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Scholar grants help future hospitalists explore career pathways
Editor’s note: Each month, SHM puts the spotlight on some of our most active members who are making substantial contributions to hospital medicine. Log on to www.hospitalmedicine.org/getinvolved for more information on how you can lend your expertise to help SHM improve the care of hospitalized patients.
This month, The Hospitalist spotlights Ernie L. Esquivel, MD, FACP, FHM, the clerkship director, medicine, and assistant professor of clinical medicine in the Division of General Internal Medicine at the Weill Cornell Medical College in New York City. Dr. Esquivel is involved with SHM’s Physicians in Training Committee, and has spearheaded the creation of the Student Hospitalist Scholar Grant program.
What inspired you to become a hospitalist?
I became a hospitalist serendipitously. At a critical juncture in my life about 8 years ago (when a change in career direction became necessary), I chanced upon a locum tenens position in a small community hospital in Lansdale, Pa., as a hospitalist. Having been a primary care track resident who subsequently chose to specialize in nephrology, I rediscovered my generalist inclinations during this job. I fell in love with the fast pace of the hospitalist’s work, the complexity of delivering care and the diversity of diseases, and of personal life stories on the general medicine wards and the ICU. 
Subsequently, I worked as an intensivist in Philadelphia for a year before joining the Academic Hospital Medicine Division at Weill Cornell in New York City. At Cornell, I have managed to cultivate my passion for medical education, especially for working with and mentoring students and residents, while continuing to care for patients on the general medicine wards. As the medicine clerkship director, I have had the privilege of creating an innovative curriculum that I hope prepares medical students for the challenges in, and the richness of, encounters in the practice of inpatient medicine.
How and why did you become a member of SHM and the Physicians in Training Committee (PIT)?
I joined SHM 6 years ago as I started to explore my career options more deeply. In 2010, I attended the Academic Hospitalist Academy, and that really offered me a closer look at the different ways in which SHM could help me advance. I went to my first SHM annual meeting 5 years ago; it motivated me to become involved in committee work. Because of my interest in medical education, I volunteered for the PIT Committee and it has given me the opportunity to work closely with other hospitalists around the country, and develop programming specifically targeted toward future hospitalists.
What is the PIT Committee working on?
The committee has continued to find ways for increased engagement of residents and students in SHM. Dr. Brian Kwan, an academic hospitalist at UC San Diego, and I have been developing a travel grant program for resident trainees and hospital medicine fellows to attend the annual meeting. By offering them a stipend to defray the costs of travel if their quality improvement innovation or research project is accepted, we hope that the annual meeting can become a venue for them to highlight their work, while becoming exposed to the many activities and opportunities offered by our society. In addition, it could be a way for them to network with other future hospitalists and established future mentors.
What prompted you to lead the creation of the Student Hospitalist Scholar Grant summer program?
Before I became a hospitalist, I spent about 7 years in research, studying renal genetics. I have always been fascinated by science and asked how I can help to advance our knowledge. As a hospitalist, it became clear to me early on that there are many questions that one can pose about the clinical work we do, the way we practice medicine, or ways to innovate education, and that there are many academic hospitalists who engage in advancing the field. I spearheaded this program because I would like students to see the field of hospital medicine as one in which they can develop a future career in academic medicine, not only by caring for patients, but also by involving themselves in research questions or QI projects.
Do you have any specific advice for students and residents interested in hospital medicine? In what ways can early-career hospitalists utilize SHM resources to leverage their careers?
The decision to pursue a career as a hospitalist will open up many more questions in the future, because there are so many opportunities available. I would suggest that trainees ask in which ways they see themselves growing in the future – clinical research, medical education, QI/patient safety, operations, and hospital leadership are the main avenues. When I interview future faculty, I always pose the same question to each of them: “Every year you are allocated X amount of money that you can use for CME, etc. How are you going to use this money to improve your skills in any particular area?” The ability of candidates to answer this question reflects for me their preparedness to develop themselves as career hospitalists and their willingness to contribute to their group or division in an innovative manner.
The reality is that as one gets older, most will find it difficult to sustain a 26-week/year schedule. So find ways for your energies, in whichever area, to be noticed and developed toward a position of leadership in the hospital or medical school.
As you take care of patients in the hospital or consider your education and training, identify ways in which things can be done better. Invariably, someone in the Society of Hospital Medicine is interested in the same issue(s). Explore your ideas, share them at the meeting, talk to people, go to the SHM website and identify what resources are already available.
If SHM will be your future academic home, volunteer to engage in activities at the chapter or national levels. Our society is really dedicated to identifying ways to welcome you into our exciting and continually evolving field.
Felicia Steele is SHM’s communications coordinator.
Editor’s note: Each month, SHM puts the spotlight on some of our most active members who are making substantial contributions to hospital medicine. Log on to www.hospitalmedicine.org/getinvolved for more information on how you can lend your expertise to help SHM improve the care of hospitalized patients.
This month, The Hospitalist spotlights Ernie L. Esquivel, MD, FACP, FHM, the clerkship director, medicine, and assistant professor of clinical medicine in the Division of General Internal Medicine at the Weill Cornell Medical College in New York City. Dr. Esquivel is involved with SHM’s Physicians in Training Committee, and has spearheaded the creation of the Student Hospitalist Scholar Grant program.
What inspired you to become a hospitalist?
I became a hospitalist serendipitously. At a critical juncture in my life about 8 years ago (when a change in career direction became necessary), I chanced upon a locum tenens position in a small community hospital in Lansdale, Pa., as a hospitalist. Having been a primary care track resident who subsequently chose to specialize in nephrology, I rediscovered my generalist inclinations during this job. I fell in love with the fast pace of the hospitalist’s work, the complexity of delivering care and the diversity of diseases, and of personal life stories on the general medicine wards and the ICU.
Subsequently, I worked as an intensivist in Philadelphia for a year before joining the Academic Hospital Medicine Division at Weill Cornell in New York City. At Cornell, I have managed to cultivate my passion for medical education, especially for working with and mentoring students and residents, while continuing to care for patients on the general medicine wards. As the medicine clerkship director, I have had the privilege of creating an innovative curriculum that I hope prepares medical students for the challenges in, and the richness of, encounters in the practice of inpatient medicine.
How and why did you become a member of SHM and the Physicians in Training Committee (PIT)?
I joined SHM 6 years ago as I started to explore my career options more deeply. In 2010, I attended the Academic Hospitalist Academy, and that really offered me a closer look at the different ways in which SHM could help me advance. I went to my first SHM annual meeting 5 years ago; it motivated me to become involved in committee work. Because of my interest in medical education, I volunteered for the PIT Committee and it has given me the opportunity to work closely with other hospitalists around the country, and develop programming specifically targeted toward future hospitalists.
What is the PIT Committee working on?
The committee has continued to find ways for increased engagement of residents and students in SHM. Dr. Brian Kwan, an academic hospitalist at UC San Diego, and I have been developing a travel grant program for resident trainees and hospital medicine fellows to attend the annual meeting. By offering them a stipend to defray the costs of travel if their quality improvement innovation or research project is accepted, we hope that the annual meeting can become a venue for them to highlight their work, while becoming exposed to the many activities and opportunities offered by our society. In addition, it could be a way for them to network with other future hospitalists and established future mentors.
What prompted you to lead the creation of the Student Hospitalist Scholar Grant summer program?
Before I became a hospitalist, I spent about 7 years in research, studying renal genetics. I have always been fascinated by science and asked how I can help to advance our knowledge. As a hospitalist, it became clear to me early on that there are many questions that one can pose about the clinical work we do, the way we practice medicine, or ways to innovate education, and that there are many academic hospitalists who engage in advancing the field. I spearheaded this program because I would like students to see the field of hospital medicine as one in which they can develop a future career in academic medicine, not only by caring for patients, but also by involving themselves in research questions or QI projects.
Do you have any specific advice for students and residents interested in hospital medicine? In what ways can early-career hospitalists utilize SHM resources to leverage their careers?
The decision to pursue a career as a hospitalist will open up many more questions in the future, because there are so many opportunities available. I would suggest that trainees ask in which ways they see themselves growing in the future – clinical research, medical education, QI/patient safety, operations, and hospital leadership are the main avenues. When I interview future faculty, I always pose the same question to each of them: “Every year you are allocated X amount of money that you can use for CME, etc. How are you going to use this money to improve your skills in any particular area?” The ability of candidates to answer this question reflects for me their preparedness to develop themselves as career hospitalists and their willingness to contribute to their group or division in an innovative manner.
The reality is that as one gets older, most will find it difficult to sustain a 26-week/year schedule. So find ways for your energies, in whichever area, to be noticed and developed toward a position of leadership in the hospital or medical school.
As you take care of patients in the hospital or consider your education and training, identify ways in which things can be done better. Invariably, someone in the Society of Hospital Medicine is interested in the same issue(s). Explore your ideas, share them at the meeting, talk to people, go to the SHM website and identify what resources are already available.
If SHM will be your future academic home, volunteer to engage in activities at the chapter or national levels. Our society is really dedicated to identifying ways to welcome you into our exciting and continually evolving field.
Felicia Steele is SHM’s communications coordinator.
Editor’s note: Each month, SHM puts the spotlight on some of our most active members who are making substantial contributions to hospital medicine. Log on to www.hospitalmedicine.org/getinvolved for more information on how you can lend your expertise to help SHM improve the care of hospitalized patients.
This month, The Hospitalist spotlights Ernie L. Esquivel, MD, FACP, FHM, the clerkship director, medicine, and assistant professor of clinical medicine in the Division of General Internal Medicine at the Weill Cornell Medical College in New York City. Dr. Esquivel is involved with SHM’s Physicians in Training Committee, and has spearheaded the creation of the Student Hospitalist Scholar Grant program.
What inspired you to become a hospitalist?
I became a hospitalist serendipitously. At a critical juncture in my life about 8 years ago (when a change in career direction became necessary), I chanced upon a locum tenens position in a small community hospital in Lansdale, Pa., as a hospitalist. Having been a primary care track resident who subsequently chose to specialize in nephrology, I rediscovered my generalist inclinations during this job. I fell in love with the fast pace of the hospitalist’s work, the complexity of delivering care and the diversity of diseases, and of personal life stories on the general medicine wards and the ICU.
Subsequently, I worked as an intensivist in Philadelphia for a year before joining the Academic Hospital Medicine Division at Weill Cornell in New York City. At Cornell, I have managed to cultivate my passion for medical education, especially for working with and mentoring students and residents, while continuing to care for patients on the general medicine wards. As the medicine clerkship director, I have had the privilege of creating an innovative curriculum that I hope prepares medical students for the challenges in, and the richness of, encounters in the practice of inpatient medicine.
How and why did you become a member of SHM and the Physicians in Training Committee (PIT)?
I joined SHM 6 years ago as I started to explore my career options more deeply. In 2010, I attended the Academic Hospitalist Academy, and that really offered me a closer look at the different ways in which SHM could help me advance. I went to my first SHM annual meeting 5 years ago; it motivated me to become involved in committee work. Because of my interest in medical education, I volunteered for the PIT Committee and it has given me the opportunity to work closely with other hospitalists around the country, and develop programming specifically targeted toward future hospitalists.
What is the PIT Committee working on?
The committee has continued to find ways for increased engagement of residents and students in SHM. Dr. Brian Kwan, an academic hospitalist at UC San Diego, and I have been developing a travel grant program for resident trainees and hospital medicine fellows to attend the annual meeting. By offering them a stipend to defray the costs of travel if their quality improvement innovation or research project is accepted, we hope that the annual meeting can become a venue for them to highlight their work, while becoming exposed to the many activities and opportunities offered by our society. In addition, it could be a way for them to network with other future hospitalists and established future mentors.
What prompted you to lead the creation of the Student Hospitalist Scholar Grant summer program?
Before I became a hospitalist, I spent about 7 years in research, studying renal genetics. I have always been fascinated by science and asked how I can help to advance our knowledge. As a hospitalist, it became clear to me early on that there are many questions that one can pose about the clinical work we do, the way we practice medicine, or ways to innovate education, and that there are many academic hospitalists who engage in advancing the field. I spearheaded this program because I would like students to see the field of hospital medicine as one in which they can develop a future career in academic medicine, not only by caring for patients, but also by involving themselves in research questions or QI projects.
Do you have any specific advice for students and residents interested in hospital medicine? In what ways can early-career hospitalists utilize SHM resources to leverage their careers?
The decision to pursue a career as a hospitalist will open up many more questions in the future, because there are so many opportunities available. I would suggest that trainees ask in which ways they see themselves growing in the future – clinical research, medical education, QI/patient safety, operations, and hospital leadership are the main avenues. When I interview future faculty, I always pose the same question to each of them: “Every year you are allocated X amount of money that you can use for CME, etc. How are you going to use this money to improve your skills in any particular area?” The ability of candidates to answer this question reflects for me their preparedness to develop themselves as career hospitalists and their willingness to contribute to their group or division in an innovative manner.
The reality is that as one gets older, most will find it difficult to sustain a 26-week/year schedule. So find ways for your energies, in whichever area, to be noticed and developed toward a position of leadership in the hospital or medical school.
As you take care of patients in the hospital or consider your education and training, identify ways in which things can be done better. Invariably, someone in the Society of Hospital Medicine is interested in the same issue(s). Explore your ideas, share them at the meeting, talk to people, go to the SHM website and identify what resources are already available.
If SHM will be your future academic home, volunteer to engage in activities at the chapter or national levels. Our society is really dedicated to identifying ways to welcome you into our exciting and continually evolving field.
Felicia Steele is SHM’s communications coordinator.
Postdischarge antibiotics for complicated pneumonia
Clinical question: Are oral antibiotics as effective as intravenous (IV) antibiotics in the treatment of complicated pneumonia after discharge to home?
Background: Pneumonia is the most common illness among hospitalized children and adolescents (excluding neonates). Among children admitted with community acquired pneumonia, 15% may develop a complicated pneumonia (one with a pleural effusion or empyema). Treatment for these complicated pneumonias may include a variety of invasive procedures, such as video-assisted thorascopic surgery or chest tube placement.
Typically, a long course of antibiotics is prescribed on discharge, which may be oral or parenterally administered via a peripherally inserted central catheter (PICC). Previous studies have shown that oral antibiotics are equivalent to parenteral antibiotics for outpatient treatment of osteomyelitis. However, little evidence exists comparing the effectiveness of the two routes in treating complicated pneumonia. 
The rate of PICC complications in complicated pneumonia also has not been well studied.
Study design: Retrospective cohort study.
Setting: Thirty-eight children’s hospitals affiliated with the Children’s Hospital Association.
Synopsis: Over 4 years, 7,820 encounters were identified with 2,123 patients ultimately being included in the cohort. Inclusion criteria were age 2 months to 18 years, and discharge diagnoses of pneumonia and pleural effusion. The authors excluded patients with chronic medical conditions, length of stay (LOS) less than 4 and more than 14 days, patients transferred to or from other institutions, and patients receiving no antibiotics on hospital day 1. The final criteria attempted to avoid inclusion of patients with nosocomial pneumonia. After application of these criteria, individual patient records were reviewed.
Patients were categorized as PICC or oral antibiotics based upon antibiotic route at their initial discharge. Treatment failure was defined as an ED revisit or rehospitalization that led to a change in antibiotic, lengthening of antibiotic course, or pleural drainage. Records were searched for evidence of PICC complications, adverse drug reactions, and other illness-related revisits. Patients in the PICC arm and oral arm were matched by age, race, insurance, LOS, positive vs. negative blood culture, ICU admission, and timing and type of pleural drainage.
Fifty-seven patients had treatment failure (2.7%). In matched analysis, there was no difference in treatment failure between PICC and oral routes (PICC treatment failure OR, 1.26 95% CI, 0.54-2.94). PICC complications were found in 7.1% of patients. Patients with PICC had significantly higher rates of adverse drug reactions (OR, 19.1 95% CI, 4.2-87.3) and illness-related revisits (OR 3.27 95% CI, 1.65-6.48), and all revisits (OR, 4.71 95% CI, 2.97-7.46).
PICC use varied markedly across geographic regions and institutions, with rates varying from less than 10% of cases to approximately 70%. Of geographic regions, the Mid-Atlantic used PICCs least often while the East North Central used them the most.
Bottom line: Treatment failure with both oral and PICC treatment of complicated pneumonia occur at the same rate, and are uncommon. Patients with PICCs had an increased rate of complications, including adverse drug reactions and revisits.
Citation: Shah SS, Srivastava R, Wu S, et al. Intravenous versus oral antibiotics for postdischarge treatment of complicated pneumonia. Pediatrics. 2016;138(6):e20161692. doi: 10.1542/peds.2016-1692.
Dr. Stubblefield is a pediatric hospitalist at Nemours/Alfred I. duPont Hospital for Children in Wilmington, Del., and clinical assistant professor of pediatrics at Sidney Kimmel Medical College at Thomas Jefferson University in Philadelphia.
Clinical question: Are oral antibiotics as effective as intravenous (IV) antibiotics in the treatment of complicated pneumonia after discharge to home?
Background: Pneumonia is the most common illness among hospitalized children and adolescents (excluding neonates). Among children admitted with community acquired pneumonia, 15% may develop a complicated pneumonia (one with a pleural effusion or empyema). Treatment for these complicated pneumonias may include a variety of invasive procedures, such as video-assisted thorascopic surgery or chest tube placement.
Typically, a long course of antibiotics is prescribed on discharge, which may be oral or parenterally administered via a peripherally inserted central catheter (PICC). Previous studies have shown that oral antibiotics are equivalent to parenteral antibiotics for outpatient treatment of osteomyelitis. However, little evidence exists comparing the effectiveness of the two routes in treating complicated pneumonia.
The rate of PICC complications in complicated pneumonia also has not been well studied.
Study design: Retrospective cohort study.
Setting: Thirty-eight children’s hospitals affiliated with the Children’s Hospital Association.
Synopsis: Over 4 years, 7,820 encounters were identified with 2,123 patients ultimately being included in the cohort. Inclusion criteria were age 2 months to 18 years, and discharge diagnoses of pneumonia and pleural effusion. The authors excluded patients with chronic medical conditions, length of stay (LOS) less than 4 and more than 14 days, patients transferred to or from other institutions, and patients receiving no antibiotics on hospital day 1. The final criteria attempted to avoid inclusion of patients with nosocomial pneumonia. After application of these criteria, individual patient records were reviewed.
Patients were categorized as PICC or oral antibiotics based upon antibiotic route at their initial discharge. Treatment failure was defined as an ED revisit or rehospitalization that led to a change in antibiotic, lengthening of antibiotic course, or pleural drainage. Records were searched for evidence of PICC complications, adverse drug reactions, and other illness-related revisits. Patients in the PICC arm and oral arm were matched by age, race, insurance, LOS, positive vs. negative blood culture, ICU admission, and timing and type of pleural drainage.
Fifty-seven patients had treatment failure (2.7%). In matched analysis, there was no difference in treatment failure between PICC and oral routes (PICC treatment failure OR, 1.26 95% CI, 0.54-2.94). PICC complications were found in 7.1% of patients. Patients with PICC had significantly higher rates of adverse drug reactions (OR, 19.1 95% CI, 4.2-87.3) and illness-related revisits (OR 3.27 95% CI, 1.65-6.48), and all revisits (OR, 4.71 95% CI, 2.97-7.46).
PICC use varied markedly across geographic regions and institutions, with rates varying from less than 10% of cases to approximately 70%. Of geographic regions, the Mid-Atlantic used PICCs least often while the East North Central used them the most.
Bottom line: Treatment failure with both oral and PICC treatment of complicated pneumonia occur at the same rate, and are uncommon. Patients with PICCs had an increased rate of complications, including adverse drug reactions and revisits.
Citation: Shah SS, Srivastava R, Wu S, et al. Intravenous versus oral antibiotics for postdischarge treatment of complicated pneumonia. Pediatrics. 2016;138(6):e20161692. doi: 10.1542/peds.2016-1692.
Dr. Stubblefield is a pediatric hospitalist at Nemours/Alfred I. duPont Hospital for Children in Wilmington, Del., and clinical assistant professor of pediatrics at Sidney Kimmel Medical College at Thomas Jefferson University in Philadelphia.
Clinical question: Are oral antibiotics as effective as intravenous (IV) antibiotics in the treatment of complicated pneumonia after discharge to home?
Background: Pneumonia is the most common illness among hospitalized children and adolescents (excluding neonates). Among children admitted with community acquired pneumonia, 15% may develop a complicated pneumonia (one with a pleural effusion or empyema). Treatment for these complicated pneumonias may include a variety of invasive procedures, such as video-assisted thorascopic surgery or chest tube placement.
Typically, a long course of antibiotics is prescribed on discharge, which may be oral or parenterally administered via a peripherally inserted central catheter (PICC). Previous studies have shown that oral antibiotics are equivalent to parenteral antibiotics for outpatient treatment of osteomyelitis. However, little evidence exists comparing the effectiveness of the two routes in treating complicated pneumonia.
The rate of PICC complications in complicated pneumonia also has not been well studied.
Study design: Retrospective cohort study.
Setting: Thirty-eight children’s hospitals affiliated with the Children’s Hospital Association.
Synopsis: Over 4 years, 7,820 encounters were identified with 2,123 patients ultimately being included in the cohort. Inclusion criteria were age 2 months to 18 years, and discharge diagnoses of pneumonia and pleural effusion. The authors excluded patients with chronic medical conditions, length of stay (LOS) less than 4 and more than 14 days, patients transferred to or from other institutions, and patients receiving no antibiotics on hospital day 1. The final criteria attempted to avoid inclusion of patients with nosocomial pneumonia. After application of these criteria, individual patient records were reviewed.
Patients were categorized as PICC or oral antibiotics based upon antibiotic route at their initial discharge. Treatment failure was defined as an ED revisit or rehospitalization that led to a change in antibiotic, lengthening of antibiotic course, or pleural drainage. Records were searched for evidence of PICC complications, adverse drug reactions, and other illness-related revisits. Patients in the PICC arm and oral arm were matched by age, race, insurance, LOS, positive vs. negative blood culture, ICU admission, and timing and type of pleural drainage.
Fifty-seven patients had treatment failure (2.7%). In matched analysis, there was no difference in treatment failure between PICC and oral routes (PICC treatment failure OR, 1.26 95% CI, 0.54-2.94). PICC complications were found in 7.1% of patients. Patients with PICC had significantly higher rates of adverse drug reactions (OR, 19.1 95% CI, 4.2-87.3) and illness-related revisits (OR 3.27 95% CI, 1.65-6.48), and all revisits (OR, 4.71 95% CI, 2.97-7.46).
PICC use varied markedly across geographic regions and institutions, with rates varying from less than 10% of cases to approximately 70%. Of geographic regions, the Mid-Atlantic used PICCs least often while the East North Central used them the most.
Bottom line: Treatment failure with both oral and PICC treatment of complicated pneumonia occur at the same rate, and are uncommon. Patients with PICCs had an increased rate of complications, including adverse drug reactions and revisits.
Citation: Shah SS, Srivastava R, Wu S, et al. Intravenous versus oral antibiotics for postdischarge treatment of complicated pneumonia. Pediatrics. 2016;138(6):e20161692. doi: 10.1542/peds.2016-1692.
Dr. Stubblefield is a pediatric hospitalist at Nemours/Alfred I. duPont Hospital for Children in Wilmington, Del., and clinical assistant professor of pediatrics at Sidney Kimmel Medical College at Thomas Jefferson University in Philadelphia.
Guideline: CRC patients should receive RAS mutation testing
Current evidence supports testing colorectal cancers for genetic mutations in the epidermal growth factor receptor (EGFR) signaling pathway because the results provide clinically actionable information, according to a new clinical practice guideline published in the Journal of Clinical Oncology.
In contrast, the evidence is inadequate at this time to recommend either for or against several other mutational analyses, such as PIK3CA, PTEN, or BRAF V600 testing. This guideline is intended “to help establish standard molecular biomarker testing, guide targeted therapies, and advance personalized care for colorectal cancer patients,” said Antonia R. Sepulveda, MD, PhD, and her associates on the guideline committee.
The guideline is meant for use by oncologists and other clinicians, pathologists, laboratory employees, molecular diagnostics professionals, scientists, government agencies, nonprofit organizations, patients, and patient advocates. It includes 21 recommendations and was developed jointly by the American Society for Clinical Pathology, the College of American Pathologists, the Association for Molecular Pathology, and the American Society of Clinical Oncology. The groups based these recommendations on a comprehensive review of 123 randomized controlled studies, comparative studies, existing practice guidelines, consensus documents, and meta-analyses published in the medical literature or presented at meetings since 2008, said Dr. Sepulveda, professor of pathology and cell biology at Columbia University, New York, and her associates (J Clin Oncol. 2017 Feb 6. doi: 10.1200/JCO.2016.71.9807.
Among the strongest recommendations based on the highest-quality evidence:
• Patients with colorectal carcinoma who are being considered for anti-EGFR therapy must undergo RAS mutational testing, and KRAS and NRAS mutations are reliable predictors that this therapy will not be beneficial.
• Analysis of BRAF and MMR mutations have clear prognostic value, and MMR status is emerging as predictive in patients with advanced disease being considered for anti-PD-1/PD-L1 treatment.
• Laboratories must use validated molecular testing methods and follow accepted standards for molecular diagnostic tests. They should include in their reports a “results and interpretation” section readily understandable to oncologists and pathologists.
• Laboratories must incorporate colorectal carcinoma molecular biomarker testing methods into their overall quality improvement programs and must participate in formal proficiency testing programs or an appropriate alternative.
Several recommendations address the importance of timeliness in performing genetic testing on colorectal cancers. Professionals and staff must expedite sending specimens to specialty laboratories, performing all biomarker tests, and reporting all test results to clinicians. It is “suggested” that molecular diagnostics laboratories aim for a benchmark of 90% of reports available within 10 working days from date of receipt of the specimen.
Current evidence supports testing colorectal cancers for genetic mutations in the epidermal growth factor receptor (EGFR) signaling pathway because the results provide clinically actionable information, according to a new clinical practice guideline published in the Journal of Clinical Oncology.
In contrast, the evidence is inadequate at this time to recommend either for or against several other mutational analyses, such as PIK3CA, PTEN, or BRAF V600 testing. This guideline is intended “to help establish standard molecular biomarker testing, guide targeted therapies, and advance personalized care for colorectal cancer patients,” said Antonia R. Sepulveda, MD, PhD, and her associates on the guideline committee.
The guideline is meant for use by oncologists and other clinicians, pathologists, laboratory employees, molecular diagnostics professionals, scientists, government agencies, nonprofit organizations, patients, and patient advocates. It includes 21 recommendations and was developed jointly by the American Society for Clinical Pathology, the College of American Pathologists, the Association for Molecular Pathology, and the American Society of Clinical Oncology. The groups based these recommendations on a comprehensive review of 123 randomized controlled studies, comparative studies, existing practice guidelines, consensus documents, and meta-analyses published in the medical literature or presented at meetings since 2008, said Dr. Sepulveda, professor of pathology and cell biology at Columbia University, New York, and her associates (J Clin Oncol. 2017 Feb 6. doi: 10.1200/JCO.2016.71.9807.
Among the strongest recommendations based on the highest-quality evidence:
• Patients with colorectal carcinoma who are being considered for anti-EGFR therapy must undergo RAS mutational testing, and KRAS and NRAS mutations are reliable predictors that this therapy will not be beneficial.
• Analysis of BRAF and MMR mutations have clear prognostic value, and MMR status is emerging as predictive in patients with advanced disease being considered for anti-PD-1/PD-L1 treatment.
• Laboratories must use validated molecular testing methods and follow accepted standards for molecular diagnostic tests. They should include in their reports a “results and interpretation” section readily understandable to oncologists and pathologists.
• Laboratories must incorporate colorectal carcinoma molecular biomarker testing methods into their overall quality improvement programs and must participate in formal proficiency testing programs or an appropriate alternative.
Several recommendations address the importance of timeliness in performing genetic testing on colorectal cancers. Professionals and staff must expedite sending specimens to specialty laboratories, performing all biomarker tests, and reporting all test results to clinicians. It is “suggested” that molecular diagnostics laboratories aim for a benchmark of 90% of reports available within 10 working days from date of receipt of the specimen.
Current evidence supports testing colorectal cancers for genetic mutations in the epidermal growth factor receptor (EGFR) signaling pathway because the results provide clinically actionable information, according to a new clinical practice guideline published in the Journal of Clinical Oncology.
In contrast, the evidence is inadequate at this time to recommend either for or against several other mutational analyses, such as PIK3CA, PTEN, or BRAF V600 testing. This guideline is intended “to help establish standard molecular biomarker testing, guide targeted therapies, and advance personalized care for colorectal cancer patients,” said Antonia R. Sepulveda, MD, PhD, and her associates on the guideline committee.
The guideline is meant for use by oncologists and other clinicians, pathologists, laboratory employees, molecular diagnostics professionals, scientists, government agencies, nonprofit organizations, patients, and patient advocates. It includes 21 recommendations and was developed jointly by the American Society for Clinical Pathology, the College of American Pathologists, the Association for Molecular Pathology, and the American Society of Clinical Oncology. The groups based these recommendations on a comprehensive review of 123 randomized controlled studies, comparative studies, existing practice guidelines, consensus documents, and meta-analyses published in the medical literature or presented at meetings since 2008, said Dr. Sepulveda, professor of pathology and cell biology at Columbia University, New York, and her associates (J Clin Oncol. 2017 Feb 6. doi: 10.1200/JCO.2016.71.9807.
Among the strongest recommendations based on the highest-quality evidence:
• Patients with colorectal carcinoma who are being considered for anti-EGFR therapy must undergo RAS mutational testing, and KRAS and NRAS mutations are reliable predictors that this therapy will not be beneficial.
• Analysis of BRAF and MMR mutations have clear prognostic value, and MMR status is emerging as predictive in patients with advanced disease being considered for anti-PD-1/PD-L1 treatment.
• Laboratories must use validated molecular testing methods and follow accepted standards for molecular diagnostic tests. They should include in their reports a “results and interpretation” section readily understandable to oncologists and pathologists.
• Laboratories must incorporate colorectal carcinoma molecular biomarker testing methods into their overall quality improvement programs and must participate in formal proficiency testing programs or an appropriate alternative.
Several recommendations address the importance of timeliness in performing genetic testing on colorectal cancers. Professionals and staff must expedite sending specimens to specialty laboratories, performing all biomarker tests, and reporting all test results to clinicians. It is “suggested” that molecular diagnostics laboratories aim for a benchmark of 90% of reports available within 10 working days from date of receipt of the specimen.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: The current evidence supports testing colorectal cancers for mutations of genes in the EGFR signaling pathway.
Key numerical finding: Molecular diagnostics laboratories should aim for a benchmark of 90% of reports available to pathologists and clinicians within 10 working days from the date of receipt of the colorectal cancer specimen.
Data source: A review of 123 reports in the literature and a compilation of 21 recommendations regarding molecular testing of colorectal cancers.
Disclosures: No industry funds were used in the development of this guideline.
Aspirin reduces recurrent preeclampsia in real-world study
LAS VEGAS – Using low-dose aspirin during pregnancy significantly reduced the risk of recurrent preeclampsia, according to results of a new study.
“The net benefit of aspirin is substantial,” Mary Catherine Tolcher, MD, the study’s lead author said. “The number needed to treat to prevent one case of recurrent preeclampsia is six... The cost of daily low-dose aspirin for the duration of one pregnancy is about $4.00. Comparatively, the cost to prevent one case of eclampsia is approximately $21,000.”
Dr. Tolcher, a postdoctorate fellow in ob.gyn. at Baylor College of Medicine, Houston, and her colleagues found a total of 417 at-risk women in the institution’s labor and delivery database during the August 2011–June 2016 study period; 284 were identified before the guidelines were implemented in 2014, while 133 women were identified as high-risk after guideline implementation.
While nearly one-third (32.4%) of women with a history of preeclampsia had a recurrence in the before group, the recurrence rate fell to 16.5% in the after group, who had been instructed to take low-dose aspirin in accordance with the guidelines. When the investigators calculated the fully adjusted odds ratio for recurrent preeclampsia, they found a reduction of about 30% in recurrent preeclampsia [aOR, 0.71; 95% confidence interval, 0.52-0.95].
“This decrease is greater than the approximately 10 to 15 percent reduction that has been previously reported in clinical trials, and different from the meta-analysis that prompted the national recommendations,” Dr. Tolcher said at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.
She and her colleagues hypothesize that the greater effect size may be attributable to limiting the study population to the higher-risk group of women with a history of preeclampsia. Alternatively, she said, aspirin’s pharmacodynamics can differ by race, so racial differences between study populations may also be at play.
One of the causative mechanisms for preeclampsia is thought to be impaired trophoblastic remodeling that impedes development of the low-resistance vascular system of the maternal-fetal unit. “The resulting pathophysiology is multisystemic and includes vascular and endothelial dysfunction, placental ischemia, and an inflammatory and stress response,” Dr. Tolcher said. Overproduction of thromboxanes, she said, plays a role in this process. Aspirin’s inhibition of cyclooxygenase-2 (COX-2) enzymes and thromboxanes is thought to mitigate the vasoconstriction and endothelial dysfunction seen in preeclampsia, she said.
A secondary outcome measure in the study was use of magnesium sulfate, and after guideline implementation “there was a trend toward reduced use of magnesium sulfate, which we reserved for preeclampsia with severe features,” Dr. Tolcher said.
There was no difference in the incidence of preterm deliveries, another secondary outcome measure, after the aspirin guidelines were implemented.
There were some differences in characteristics between the before and after groups: the ratio of Hispanic women with preeclampsia was significantly lower in the after group (P less than .0001). The distribution of method of payment shifted, with more private pay patients, fewer Children’s Health Insurance Program (CHIP) patients, and fewer “other” payment method patients in the after group. Though Dr. Tolcher reported that type 1 diabetes was seen more often in the after group, the rates of any kind of pre-pregnancy diabetes were similar between the groups (6.33% before; 4.26% after).
Potentially confounding variables were controlled by means of logistic regression analysis. Women with multiple gestations were excluded, and only the first pregnancy after a previous episode of preeclampsia was studied.
Otherwise, demographics and other patient characteristics – including rates of chronic hypertension, were similar between the before and after groups. About a quarter of the patients in each group had a history of preterm delivery, and the median age at delivery for both was 38 years.
Within the total group that had recurrent preeclampsia, “maternal age greater than 35, type 2 diabetes, chronic hypertension, and a history of preterm preeclampsia were significantly associated with recurrent preeclampsia,” Dr. Tolcher said.
Study limitations included the retrospective nature, the inclusion of only women who had a prior history of preeclampsia, and the investigators’ inability to determine whether patients were adherent to recommendations for aspirin use. However, the study represents actual clinical use, Dr. Tolcher said, and addresses a real need. “Preeclampsia is responsible for 75,000 maternal deaths annually, and accounts for 15% of the preterm births in the U.S.,” she said.
Dr. Tolcher reported having no relevant financial disclosures.
[email protected]
On Twitter @karioakes
LAS VEGAS – Using low-dose aspirin during pregnancy significantly reduced the risk of recurrent preeclampsia, according to results of a new study.
“The net benefit of aspirin is substantial,” Mary Catherine Tolcher, MD, the study’s lead author said. “The number needed to treat to prevent one case of recurrent preeclampsia is six... The cost of daily low-dose aspirin for the duration of one pregnancy is about $4.00. Comparatively, the cost to prevent one case of eclampsia is approximately $21,000.”
Dr. Tolcher, a postdoctorate fellow in ob.gyn. at Baylor College of Medicine, Houston, and her colleagues found a total of 417 at-risk women in the institution’s labor and delivery database during the August 2011–June 2016 study period; 284 were identified before the guidelines were implemented in 2014, while 133 women were identified as high-risk after guideline implementation.
While nearly one-third (32.4%) of women with a history of preeclampsia had a recurrence in the before group, the recurrence rate fell to 16.5% in the after group, who had been instructed to take low-dose aspirin in accordance with the guidelines. When the investigators calculated the fully adjusted odds ratio for recurrent preeclampsia, they found a reduction of about 30% in recurrent preeclampsia [aOR, 0.71; 95% confidence interval, 0.52-0.95].
“This decrease is greater than the approximately 10 to 15 percent reduction that has been previously reported in clinical trials, and different from the meta-analysis that prompted the national recommendations,” Dr. Tolcher said at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.
She and her colleagues hypothesize that the greater effect size may be attributable to limiting the study population to the higher-risk group of women with a history of preeclampsia. Alternatively, she said, aspirin’s pharmacodynamics can differ by race, so racial differences between study populations may also be at play.
One of the causative mechanisms for preeclampsia is thought to be impaired trophoblastic remodeling that impedes development of the low-resistance vascular system of the maternal-fetal unit. “The resulting pathophysiology is multisystemic and includes vascular and endothelial dysfunction, placental ischemia, and an inflammatory and stress response,” Dr. Tolcher said. Overproduction of thromboxanes, she said, plays a role in this process. Aspirin’s inhibition of cyclooxygenase-2 (COX-2) enzymes and thromboxanes is thought to mitigate the vasoconstriction and endothelial dysfunction seen in preeclampsia, she said.
A secondary outcome measure in the study was use of magnesium sulfate, and after guideline implementation “there was a trend toward reduced use of magnesium sulfate, which we reserved for preeclampsia with severe features,” Dr. Tolcher said.
There was no difference in the incidence of preterm deliveries, another secondary outcome measure, after the aspirin guidelines were implemented.
There were some differences in characteristics between the before and after groups: the ratio of Hispanic women with preeclampsia was significantly lower in the after group (P less than .0001). The distribution of method of payment shifted, with more private pay patients, fewer Children’s Health Insurance Program (CHIP) patients, and fewer “other” payment method patients in the after group. Though Dr. Tolcher reported that type 1 diabetes was seen more often in the after group, the rates of any kind of pre-pregnancy diabetes were similar between the groups (6.33% before; 4.26% after).
Potentially confounding variables were controlled by means of logistic regression analysis. Women with multiple gestations were excluded, and only the first pregnancy after a previous episode of preeclampsia was studied.
Otherwise, demographics and other patient characteristics – including rates of chronic hypertension, were similar between the before and after groups. About a quarter of the patients in each group had a history of preterm delivery, and the median age at delivery for both was 38 years.
Within the total group that had recurrent preeclampsia, “maternal age greater than 35, type 2 diabetes, chronic hypertension, and a history of preterm preeclampsia were significantly associated with recurrent preeclampsia,” Dr. Tolcher said.
Study limitations included the retrospective nature, the inclusion of only women who had a prior history of preeclampsia, and the investigators’ inability to determine whether patients were adherent to recommendations for aspirin use. However, the study represents actual clinical use, Dr. Tolcher said, and addresses a real need. “Preeclampsia is responsible for 75,000 maternal deaths annually, and accounts for 15% of the preterm births in the U.S.,” she said.
Dr. Tolcher reported having no relevant financial disclosures.
[email protected]
On Twitter @karioakes
LAS VEGAS – Using low-dose aspirin during pregnancy significantly reduced the risk of recurrent preeclampsia, according to results of a new study.
“The net benefit of aspirin is substantial,” Mary Catherine Tolcher, MD, the study’s lead author said. “The number needed to treat to prevent one case of recurrent preeclampsia is six... The cost of daily low-dose aspirin for the duration of one pregnancy is about $4.00. Comparatively, the cost to prevent one case of eclampsia is approximately $21,000.”
Dr. Tolcher, a postdoctorate fellow in ob.gyn. at Baylor College of Medicine, Houston, and her colleagues found a total of 417 at-risk women in the institution’s labor and delivery database during the August 2011–June 2016 study period; 284 were identified before the guidelines were implemented in 2014, while 133 women were identified as high-risk after guideline implementation.
While nearly one-third (32.4%) of women with a history of preeclampsia had a recurrence in the before group, the recurrence rate fell to 16.5% in the after group, who had been instructed to take low-dose aspirin in accordance with the guidelines. When the investigators calculated the fully adjusted odds ratio for recurrent preeclampsia, they found a reduction of about 30% in recurrent preeclampsia [aOR, 0.71; 95% confidence interval, 0.52-0.95].
“This decrease is greater than the approximately 10 to 15 percent reduction that has been previously reported in clinical trials, and different from the meta-analysis that prompted the national recommendations,” Dr. Tolcher said at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.
She and her colleagues hypothesize that the greater effect size may be attributable to limiting the study population to the higher-risk group of women with a history of preeclampsia. Alternatively, she said, aspirin’s pharmacodynamics can differ by race, so racial differences between study populations may also be at play.
One of the causative mechanisms for preeclampsia is thought to be impaired trophoblastic remodeling that impedes development of the low-resistance vascular system of the maternal-fetal unit. “The resulting pathophysiology is multisystemic and includes vascular and endothelial dysfunction, placental ischemia, and an inflammatory and stress response,” Dr. Tolcher said. Overproduction of thromboxanes, she said, plays a role in this process. Aspirin’s inhibition of cyclooxygenase-2 (COX-2) enzymes and thromboxanes is thought to mitigate the vasoconstriction and endothelial dysfunction seen in preeclampsia, she said.
A secondary outcome measure in the study was use of magnesium sulfate, and after guideline implementation “there was a trend toward reduced use of magnesium sulfate, which we reserved for preeclampsia with severe features,” Dr. Tolcher said.
There was no difference in the incidence of preterm deliveries, another secondary outcome measure, after the aspirin guidelines were implemented.
There were some differences in characteristics between the before and after groups: the ratio of Hispanic women with preeclampsia was significantly lower in the after group (P less than .0001). The distribution of method of payment shifted, with more private pay patients, fewer Children’s Health Insurance Program (CHIP) patients, and fewer “other” payment method patients in the after group. Though Dr. Tolcher reported that type 1 diabetes was seen more often in the after group, the rates of any kind of pre-pregnancy diabetes were similar between the groups (6.33% before; 4.26% after).
Potentially confounding variables were controlled by means of logistic regression analysis. Women with multiple gestations were excluded, and only the first pregnancy after a previous episode of preeclampsia was studied.
Otherwise, demographics and other patient characteristics – including rates of chronic hypertension, were similar between the before and after groups. About a quarter of the patients in each group had a history of preterm delivery, and the median age at delivery for both was 38 years.
Within the total group that had recurrent preeclampsia, “maternal age greater than 35, type 2 diabetes, chronic hypertension, and a history of preterm preeclampsia were significantly associated with recurrent preeclampsia,” Dr. Tolcher said.
Study limitations included the retrospective nature, the inclusion of only women who had a prior history of preeclampsia, and the investigators’ inability to determine whether patients were adherent to recommendations for aspirin use. However, the study represents actual clinical use, Dr. Tolcher said, and addresses a real need. “Preeclampsia is responsible for 75,000 maternal deaths annually, and accounts for 15% of the preterm births in the U.S.,” she said.
Dr. Tolcher reported having no relevant financial disclosures.
[email protected]
On Twitter @karioakes
AT THE PREGNANCY MEETING
Key clinical point:
Major finding: The adjusted odds ratio for recurrent preeclampsia was 0.71 after implementing U.S. Preventive Services Task Force (USPSTF) guidelines for aspirin administration.
Data source: Retrospective cohort study of 17,256 deliveries at a single academic medical center before and after implementation of USPSTF aspirin guidelines, with 417 cases of recurrent preeclampsia identified.
Disclosures: Dr. Tolcher reported having no relevant financial disclosures.
Children with psychotic illness aren’t treated soon enough
SAN FRANCISCO – Early detection and treatment of psychotic illness is critical in children, according to Devanand Manoli, MD, PhD, of the University of California, San Francisco.
“After the conversion to psychotic illness, one of the most important prognostic factors is the duration of untreated psychosis.” A longer duration is associated with a greater symptom burden and lower functioning, which have “significant prognostic implications,” but sometimes treatment doesn’t come for a year or more. “There are many patients out there not receiving treatment,” the pediatric psychiatrist said at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.
The impact of early treatment raises the question of what to do with those who seem to be at risk, but don’t meet criteria for formal diagnosis.
It’s tough to be sure who exactly is at risk. Signs and symptoms can be nonspecific in adolescents, including disorganized communication, suspiciousness, verbal memory deficiencies, and decline in social functioning.
It’s even a tougher call in younger children. Most who exhibit psychotic or psychoticlike symptoms do not have a true psychotic disorder. Loose associations and illogical thinking are fairly common in early childhood, and preschool children can have transient tactile, visual, and other hallucinations that are benign. If there does seem to be a problem, metabolic issues are the most likely culprit before the age of 6 or so.
Again, comprehensive early intervention – including reducing environmental stressors – helps with functioning, symptoms, and other issues even before a formal diagnosis. However, antipsychotics do not decrease the rate of conversion to psychotic illness in truly high-risk children; their use is for symptom management, Dr. Manoli said.
It’s important adolescents avoid cannabis; it’s become clear in recent years that marijuana increases the risk of conversion to schizophrenia and the risk of relapse. “It’s a very important thing to emphasize. Cannabis use is something to counsel against,” he said.
Atypicals seem to be about equally effective, so their selection mostly comes down to side effects and cost. An exception might be clozapine. “It’s a medication we are very resistant to prescribe” because of the need for aggressive neutrophil monitoring and other issues, “but in patients with acute psychotic symptoms, it can be very effective” in both treatment-naïve and treatment-resistant children and help with aggression, he said, noting also that it’s important to remember children are more sensitive than adults to akathisia and other extrapyramidal symptoms with antipsychotics.
In response to audience questions, Dr. Manoli said there isn’t really a need to monitor for prolactin elevations with atypical antipsychotics unless there are symptoms, such as inappropriate breast tissue or lactation. In those cases, augmentation with aripiprazole can normalize levels.
He also noted that he and his colleagues do order baseline and follow-up ECGs when prescribing ziprasidone; prolonged QTc interval is a concern, regardless of family cardiac history.
Dr. Manoli reported research funding from the Brain & Behavior Research Foundation, the One Mind Institute, the National Institutes of Health, and other sources.
SAN FRANCISCO – Early detection and treatment of psychotic illness is critical in children, according to Devanand Manoli, MD, PhD, of the University of California, San Francisco.
“After the conversion to psychotic illness, one of the most important prognostic factors is the duration of untreated psychosis.” A longer duration is associated with a greater symptom burden and lower functioning, which have “significant prognostic implications,” but sometimes treatment doesn’t come for a year or more. “There are many patients out there not receiving treatment,” the pediatric psychiatrist said at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.
The impact of early treatment raises the question of what to do with those who seem to be at risk, but don’t meet criteria for formal diagnosis.
It’s tough to be sure who exactly is at risk. Signs and symptoms can be nonspecific in adolescents, including disorganized communication, suspiciousness, verbal memory deficiencies, and decline in social functioning.
It’s even a tougher call in younger children. Most who exhibit psychotic or psychoticlike symptoms do not have a true psychotic disorder. Loose associations and illogical thinking are fairly common in early childhood, and preschool children can have transient tactile, visual, and other hallucinations that are benign. If there does seem to be a problem, metabolic issues are the most likely culprit before the age of 6 or so.
Again, comprehensive early intervention – including reducing environmental stressors – helps with functioning, symptoms, and other issues even before a formal diagnosis. However, antipsychotics do not decrease the rate of conversion to psychotic illness in truly high-risk children; their use is for symptom management, Dr. Manoli said.
It’s important adolescents avoid cannabis; it’s become clear in recent years that marijuana increases the risk of conversion to schizophrenia and the risk of relapse. “It’s a very important thing to emphasize. Cannabis use is something to counsel against,” he said.
Atypicals seem to be about equally effective, so their selection mostly comes down to side effects and cost. An exception might be clozapine. “It’s a medication we are very resistant to prescribe” because of the need for aggressive neutrophil monitoring and other issues, “but in patients with acute psychotic symptoms, it can be very effective” in both treatment-naïve and treatment-resistant children and help with aggression, he said, noting also that it’s important to remember children are more sensitive than adults to akathisia and other extrapyramidal symptoms with antipsychotics.
In response to audience questions, Dr. Manoli said there isn’t really a need to monitor for prolactin elevations with atypical antipsychotics unless there are symptoms, such as inappropriate breast tissue or lactation. In those cases, augmentation with aripiprazole can normalize levels.
He also noted that he and his colleagues do order baseline and follow-up ECGs when prescribing ziprasidone; prolonged QTc interval is a concern, regardless of family cardiac history.
Dr. Manoli reported research funding from the Brain & Behavior Research Foundation, the One Mind Institute, the National Institutes of Health, and other sources.
SAN FRANCISCO – Early detection and treatment of psychotic illness is critical in children, according to Devanand Manoli, MD, PhD, of the University of California, San Francisco.
“After the conversion to psychotic illness, one of the most important prognostic factors is the duration of untreated psychosis.” A longer duration is associated with a greater symptom burden and lower functioning, which have “significant prognostic implications,” but sometimes treatment doesn’t come for a year or more. “There are many patients out there not receiving treatment,” the pediatric psychiatrist said at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.
The impact of early treatment raises the question of what to do with those who seem to be at risk, but don’t meet criteria for formal diagnosis.
It’s tough to be sure who exactly is at risk. Signs and symptoms can be nonspecific in adolescents, including disorganized communication, suspiciousness, verbal memory deficiencies, and decline in social functioning.
It’s even a tougher call in younger children. Most who exhibit psychotic or psychoticlike symptoms do not have a true psychotic disorder. Loose associations and illogical thinking are fairly common in early childhood, and preschool children can have transient tactile, visual, and other hallucinations that are benign. If there does seem to be a problem, metabolic issues are the most likely culprit before the age of 6 or so.
Again, comprehensive early intervention – including reducing environmental stressors – helps with functioning, symptoms, and other issues even before a formal diagnosis. However, antipsychotics do not decrease the rate of conversion to psychotic illness in truly high-risk children; their use is for symptom management, Dr. Manoli said.
It’s important adolescents avoid cannabis; it’s become clear in recent years that marijuana increases the risk of conversion to schizophrenia and the risk of relapse. “It’s a very important thing to emphasize. Cannabis use is something to counsel against,” he said.
Atypicals seem to be about equally effective, so their selection mostly comes down to side effects and cost. An exception might be clozapine. “It’s a medication we are very resistant to prescribe” because of the need for aggressive neutrophil monitoring and other issues, “but in patients with acute psychotic symptoms, it can be very effective” in both treatment-naïve and treatment-resistant children and help with aggression, he said, noting also that it’s important to remember children are more sensitive than adults to akathisia and other extrapyramidal symptoms with antipsychotics.
In response to audience questions, Dr. Manoli said there isn’t really a need to monitor for prolactin elevations with atypical antipsychotics unless there are symptoms, such as inappropriate breast tissue or lactation. In those cases, augmentation with aripiprazole can normalize levels.
He also noted that he and his colleagues do order baseline and follow-up ECGs when prescribing ziprasidone; prolonged QTc interval is a concern, regardless of family cardiac history.
Dr. Manoli reported research funding from the Brain & Behavior Research Foundation, the One Mind Institute, the National Institutes of Health, and other sources.
EXPERT ANALYSIS FROM THE PSYCHOPHARMACOLOGY UPDATE INSTITUTE
Teen vaccines: Where we are now, and how can we go further?
Adolescents remain undervaccinated for several diseases, and clinicians need to lead the charge to change this reality, according to new clinical reports issued by the American Academy of Pediatrics Committee on Infectious Diseases.
Teens are lagging behind the Healthy People 2020 vaccination goals for the Tdap, quadrivalent meningococcal conjugate (menACWY), and human papillomavirus (HPV) vaccines, lead authors Henry H. Bernstein, DO, and Joseph A. Bocchini Jr., MD, wrote in the Feb. 6 issue of Pediatrics.
“Although HPV vaccination rates are slowly improving, they continue to lag far behind Tdap and menACWY rates for both boys and girls,” the authors wrote. Only 63% of girls and 50% of boys have gotten at least one HPV vaccine dose; just 42% of girls and 28% of boys finished the entire three-dose series in 2015.
A recent study found that parents declined the HPV vaccine 56% of the time. The three most common reasons were the belief that their child had a low risk of acquiring HPV; fear that the risk of adverse events was too great and belief that the vaccine wasn’t well researched and hasn’t been on the market long enough.
But teens also are falling behind with less controversial vaccines, the report noted. Fewer than half of teens got a flu shot in the 2015-2016 season. Rates for the MenACWY and Tdap are better, but not optimal (81% and 86%, respectively).
Barriers to optimal immunization
The clinical report puts clinicians on the first line of responsibility and makes no apologies for that.
“One of the greatest challenges is health care provider recommendation, which often lacks consistency and urgency,” the authors said. “Many health care providers do not universally recommend vaccines to eligible populations and do not offer concomitant vaccination with indicated vaccines during a single patient encounter.”
In fact, they noted, a recent physician survey found that only about 60% of pediatricians and family doctors strongly recommend the HPV vaccine for 11- and 12-year-old girls. Several parent surveys have determined that lack of provider recommendation is a leading reason for undervaccination among adolescents.
A companion clinical report, also authored by Dr. Bernstein and Dr. Bocchini, discusses practical ways to confront these barriers (Pediatrics. 2017 Feb 6. doi: 10.1542/peds.2016-4187). It opens with a strong call to physicians to lead the charge in increasing immunization rates.
“Up to 65% of parents have reported not receiving a recommendation … for immunizations. The major reason for nonreceipt [of Tdap and menACWY] was lack of a health care provider recommendation,” they said.
Overcoming parental vaccine hesitancy is a thorny struggle, the authors acknowledge. But they offer some helpful suggestions, including:
• Don’t offer immunizations as “optional.” This opens the door to vaccine dismissal. Instead, “strongly endorse all universally recommended vaccines as important for adolescents’ health.”
• Ask open-ended questions to get at the root of parental hesitancy. Give fact-based, medically sound information. Stress that doctors are parent partners in raising healthy children and protecting them from disease.
• Stress the big-picture benefits of vaccines. Telling parents that the HPV vaccine prevents cancer lifelong is a powerful message. “Up-to-date information on current events and disease outbreaks is a tool to bring into the conversation about vaccines as well.”
• Review the vaccine timeline. Do everything possible to ensure parents follow up and complete each series. “Follow-up immunization visits should be scheduled before the family leaves the care setting.”
• Don’t give up when a parent refuses a vaccine. “Although it may be challenging, it’s important that health care providers offer the vaccine at the next most appropriate time. Perseverance is critical for vaccine uptake and immunization rates.”
Dr. Bernstein and Dr. Bocchini also suggest that vaccine uptake could be boosted by a mental re-set of the office visit. “Missed opportunities for adolescent immunizations,” such as sick calls, are a prime example. “The majority of vaccines are administered during well-child visit [sports or camp physicals]. … However, acute care visits or sick visits in the patient-centered medical home are also an opportunity to deliver vaccines or to discuss upcoming vaccines,” they said.
Education and communication are essential to improving vaccine uptake, the report concludes. “Appropriate techniques for approaching adolescent patients and their parents in the office to encourage immunizations are important skills for healthcare providers. The key to increasing immunization rates and decreasing vaccine-preventable disease … is to focus on educating adolescents and strengthening health care providers’ recommendations by using all clinical opportunities to assess immunization status and provide needed vaccinations.”
Neither Dr Bernstein nor Dr. Bocchini had any financial disclosures.
Need help talking about teen vaccines? Check out these resources
The American Academy of Pediatrics offered the following resources designed to help clinicians communicate effectively when talking to patients and parents about vaccines:
• Talking to parents about the HPV vaccine. This website hosted by the Centers for Disease Control and Prevention includes a link to the latest vaccination recommendations, as well as a tip sheet with HPV vaccine talking points, a fact sheet on the vaccine’s safety data, and a video with four clinical vignettes that model effective communication.
• The HPV Champion Toolkit. This contains numerous resources to help clinicians learn to educate other health care professionals, discuss HPV vaccination with parents, and make practice changes to increase HPV vaccine uptake.
• You Are the Key to HPV Prevention. This CDC video presents up-to-date information on HPV infection and disease, the HPV vaccine, and ways to successfully communicate with patients and their parents about HPV vaccination.
• Adolescentvaccination.org. The National Foundation for Infectious Diseases maintains a website is entirely devoted to adolescent vaccination issues. It contains resources for clinicians, and parents.
• Top Strategies for Increasing Vaccine Coverage. This is a report by the American Academy of Pediatrics.
• You Call the Shots. This is an interactive, Web-based immunization training course created by the CDC.
• Suggestions to Improve Your Immunization Services. This is a checklist of suggestions, by the Immunization Action.
[email protected]
On Twitter @Alz_Gal
Adolescents remain undervaccinated for several diseases, and clinicians need to lead the charge to change this reality, according to new clinical reports issued by the American Academy of Pediatrics Committee on Infectious Diseases.
Teens are lagging behind the Healthy People 2020 vaccination goals for the Tdap, quadrivalent meningococcal conjugate (menACWY), and human papillomavirus (HPV) vaccines, lead authors Henry H. Bernstein, DO, and Joseph A. Bocchini Jr., MD, wrote in the Feb. 6 issue of Pediatrics.
“Although HPV vaccination rates are slowly improving, they continue to lag far behind Tdap and menACWY rates for both boys and girls,” the authors wrote. Only 63% of girls and 50% of boys have gotten at least one HPV vaccine dose; just 42% of girls and 28% of boys finished the entire three-dose series in 2015.
A recent study found that parents declined the HPV vaccine 56% of the time. The three most common reasons were the belief that their child had a low risk of acquiring HPV; fear that the risk of adverse events was too great and belief that the vaccine wasn’t well researched and hasn’t been on the market long enough.
But teens also are falling behind with less controversial vaccines, the report noted. Fewer than half of teens got a flu shot in the 2015-2016 season. Rates for the MenACWY and Tdap are better, but not optimal (81% and 86%, respectively).
Barriers to optimal immunization
The clinical report puts clinicians on the first line of responsibility and makes no apologies for that.
“One of the greatest challenges is health care provider recommendation, which often lacks consistency and urgency,” the authors said. “Many health care providers do not universally recommend vaccines to eligible populations and do not offer concomitant vaccination with indicated vaccines during a single patient encounter.”
In fact, they noted, a recent physician survey found that only about 60% of pediatricians and family doctors strongly recommend the HPV vaccine for 11- and 12-year-old girls. Several parent surveys have determined that lack of provider recommendation is a leading reason for undervaccination among adolescents.
A companion clinical report, also authored by Dr. Bernstein and Dr. Bocchini, discusses practical ways to confront these barriers (Pediatrics. 2017 Feb 6. doi: 10.1542/peds.2016-4187). It opens with a strong call to physicians to lead the charge in increasing immunization rates.
“Up to 65% of parents have reported not receiving a recommendation … for immunizations. The major reason for nonreceipt [of Tdap and menACWY] was lack of a health care provider recommendation,” they said.
Overcoming parental vaccine hesitancy is a thorny struggle, the authors acknowledge. But they offer some helpful suggestions, including:
• Don’t offer immunizations as “optional.” This opens the door to vaccine dismissal. Instead, “strongly endorse all universally recommended vaccines as important for adolescents’ health.”
• Ask open-ended questions to get at the root of parental hesitancy. Give fact-based, medically sound information. Stress that doctors are parent partners in raising healthy children and protecting them from disease.
• Stress the big-picture benefits of vaccines. Telling parents that the HPV vaccine prevents cancer lifelong is a powerful message. “Up-to-date information on current events and disease outbreaks is a tool to bring into the conversation about vaccines as well.”
• Review the vaccine timeline. Do everything possible to ensure parents follow up and complete each series. “Follow-up immunization visits should be scheduled before the family leaves the care setting.”
• Don’t give up when a parent refuses a vaccine. “Although it may be challenging, it’s important that health care providers offer the vaccine at the next most appropriate time. Perseverance is critical for vaccine uptake and immunization rates.”
Dr. Bernstein and Dr. Bocchini also suggest that vaccine uptake could be boosted by a mental re-set of the office visit. “Missed opportunities for adolescent immunizations,” such as sick calls, are a prime example. “The majority of vaccines are administered during well-child visit [sports or camp physicals]. … However, acute care visits or sick visits in the patient-centered medical home are also an opportunity to deliver vaccines or to discuss upcoming vaccines,” they said.
Education and communication are essential to improving vaccine uptake, the report concludes. “Appropriate techniques for approaching adolescent patients and their parents in the office to encourage immunizations are important skills for healthcare providers. The key to increasing immunization rates and decreasing vaccine-preventable disease … is to focus on educating adolescents and strengthening health care providers’ recommendations by using all clinical opportunities to assess immunization status and provide needed vaccinations.”
Neither Dr Bernstein nor Dr. Bocchini had any financial disclosures.
Need help talking about teen vaccines? Check out these resources
The American Academy of Pediatrics offered the following resources designed to help clinicians communicate effectively when talking to patients and parents about vaccines:
• Talking to parents about the HPV vaccine. This website hosted by the Centers for Disease Control and Prevention includes a link to the latest vaccination recommendations, as well as a tip sheet with HPV vaccine talking points, a fact sheet on the vaccine’s safety data, and a video with four clinical vignettes that model effective communication.
• The HPV Champion Toolkit. This contains numerous resources to help clinicians learn to educate other health care professionals, discuss HPV vaccination with parents, and make practice changes to increase HPV vaccine uptake.
• You Are the Key to HPV Prevention. This CDC video presents up-to-date information on HPV infection and disease, the HPV vaccine, and ways to successfully communicate with patients and their parents about HPV vaccination.
• Adolescentvaccination.org. The National Foundation for Infectious Diseases maintains a website is entirely devoted to adolescent vaccination issues. It contains resources for clinicians, and parents.
• Top Strategies for Increasing Vaccine Coverage. This is a report by the American Academy of Pediatrics.
• You Call the Shots. This is an interactive, Web-based immunization training course created by the CDC.
• Suggestions to Improve Your Immunization Services. This is a checklist of suggestions, by the Immunization Action.
[email protected]
On Twitter @Alz_Gal
Adolescents remain undervaccinated for several diseases, and clinicians need to lead the charge to change this reality, according to new clinical reports issued by the American Academy of Pediatrics Committee on Infectious Diseases.
Teens are lagging behind the Healthy People 2020 vaccination goals for the Tdap, quadrivalent meningococcal conjugate (menACWY), and human papillomavirus (HPV) vaccines, lead authors Henry H. Bernstein, DO, and Joseph A. Bocchini Jr., MD, wrote in the Feb. 6 issue of Pediatrics.
“Although HPV vaccination rates are slowly improving, they continue to lag far behind Tdap and menACWY rates for both boys and girls,” the authors wrote. Only 63% of girls and 50% of boys have gotten at least one HPV vaccine dose; just 42% of girls and 28% of boys finished the entire three-dose series in 2015.
A recent study found that parents declined the HPV vaccine 56% of the time. The three most common reasons were the belief that their child had a low risk of acquiring HPV; fear that the risk of adverse events was too great and belief that the vaccine wasn’t well researched and hasn’t been on the market long enough.
But teens also are falling behind with less controversial vaccines, the report noted. Fewer than half of teens got a flu shot in the 2015-2016 season. Rates for the MenACWY and Tdap are better, but not optimal (81% and 86%, respectively).
Barriers to optimal immunization
The clinical report puts clinicians on the first line of responsibility and makes no apologies for that.
“One of the greatest challenges is health care provider recommendation, which often lacks consistency and urgency,” the authors said. “Many health care providers do not universally recommend vaccines to eligible populations and do not offer concomitant vaccination with indicated vaccines during a single patient encounter.”
In fact, they noted, a recent physician survey found that only about 60% of pediatricians and family doctors strongly recommend the HPV vaccine for 11- and 12-year-old girls. Several parent surveys have determined that lack of provider recommendation is a leading reason for undervaccination among adolescents.
A companion clinical report, also authored by Dr. Bernstein and Dr. Bocchini, discusses practical ways to confront these barriers (Pediatrics. 2017 Feb 6. doi: 10.1542/peds.2016-4187). It opens with a strong call to physicians to lead the charge in increasing immunization rates.
“Up to 65% of parents have reported not receiving a recommendation … for immunizations. The major reason for nonreceipt [of Tdap and menACWY] was lack of a health care provider recommendation,” they said.
Overcoming parental vaccine hesitancy is a thorny struggle, the authors acknowledge. But they offer some helpful suggestions, including:
• Don’t offer immunizations as “optional.” This opens the door to vaccine dismissal. Instead, “strongly endorse all universally recommended vaccines as important for adolescents’ health.”
• Ask open-ended questions to get at the root of parental hesitancy. Give fact-based, medically sound information. Stress that doctors are parent partners in raising healthy children and protecting them from disease.
• Stress the big-picture benefits of vaccines. Telling parents that the HPV vaccine prevents cancer lifelong is a powerful message. “Up-to-date information on current events and disease outbreaks is a tool to bring into the conversation about vaccines as well.”
• Review the vaccine timeline. Do everything possible to ensure parents follow up and complete each series. “Follow-up immunization visits should be scheduled before the family leaves the care setting.”
• Don’t give up when a parent refuses a vaccine. “Although it may be challenging, it’s important that health care providers offer the vaccine at the next most appropriate time. Perseverance is critical for vaccine uptake and immunization rates.”
Dr. Bernstein and Dr. Bocchini also suggest that vaccine uptake could be boosted by a mental re-set of the office visit. “Missed opportunities for adolescent immunizations,” such as sick calls, are a prime example. “The majority of vaccines are administered during well-child visit [sports or camp physicals]. … However, acute care visits or sick visits in the patient-centered medical home are also an opportunity to deliver vaccines or to discuss upcoming vaccines,” they said.
Education and communication are essential to improving vaccine uptake, the report concludes. “Appropriate techniques for approaching adolescent patients and their parents in the office to encourage immunizations are important skills for healthcare providers. The key to increasing immunization rates and decreasing vaccine-preventable disease … is to focus on educating adolescents and strengthening health care providers’ recommendations by using all clinical opportunities to assess immunization status and provide needed vaccinations.”
Neither Dr Bernstein nor Dr. Bocchini had any financial disclosures.
Need help talking about teen vaccines? Check out these resources
The American Academy of Pediatrics offered the following resources designed to help clinicians communicate effectively when talking to patients and parents about vaccines:
• Talking to parents about the HPV vaccine. This website hosted by the Centers for Disease Control and Prevention includes a link to the latest vaccination recommendations, as well as a tip sheet with HPV vaccine talking points, a fact sheet on the vaccine’s safety data, and a video with four clinical vignettes that model effective communication.
• The HPV Champion Toolkit. This contains numerous resources to help clinicians learn to educate other health care professionals, discuss HPV vaccination with parents, and make practice changes to increase HPV vaccine uptake.
• You Are the Key to HPV Prevention. This CDC video presents up-to-date information on HPV infection and disease, the HPV vaccine, and ways to successfully communicate with patients and their parents about HPV vaccination.
• Adolescentvaccination.org. The National Foundation for Infectious Diseases maintains a website is entirely devoted to adolescent vaccination issues. It contains resources for clinicians, and parents.
• Top Strategies for Increasing Vaccine Coverage. This is a report by the American Academy of Pediatrics.
• You Call the Shots. This is an interactive, Web-based immunization training course created by the CDC.
• Suggestions to Improve Your Immunization Services. This is a checklist of suggestions, by the Immunization Action.
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ACIP releases updated guidance for adult vaccinations
, according to the newly issued 2017 adult Recommended Immunization Schedule released by the CDC’s Advisory Committee on Immunization Practices (ACIP).
“Changes are related to concerns regarding low effectiveness of [LAIV] (FluMist, MedImmune) against influenza A(H1N1)pdm09 in the United States during the 2013-2014 and 2015-2016 influenza seasons,” wrote the authors of the report, published in Annals of Internal Medicine and led by David K. Kim, MD, of the CDC’s Immunization Services Division in Atlanta. 
Another major change involves vaccination of adults with mild or severe egg allergy. The new guidance states that those with a mild egg allergy should receive either inactivated influenza vaccine or recombinant influenza vaccine, while those with severe allergies should be given one of the same vaccinations but only in a health care setting, so a clinician can monitor any signs of reaction and treat the patient accordingly.
Vaccine doses should be administered based on the patient’s age; a patient with “severe” egg allergy is one who exhibits angioedema, respiratory distress, lightheadedness, or recurrent emesis; requires epinephrine; or requires emergency medical care of any kind after consuming egg products.
Human papillomavirus (HPV) schedules have also been noticeably altered, with the CDC now considering all men and women through the ages of 21 and 26 years, respectively, who received a two-dose series of HPV vaccinations before the age of 15 to be adequately protected. Those who took only one of those two doses still need to take another dose, while men and women who have not been vaccinated should received a three-dose series at 0, 1-2, and 6 months.
Hepatitis B recommendations were also updated, with the CDC now advising: “Adults with chronic liver disease, including, but not limited to, hepatitis C virus infection, cirrhosis, fatty liver disease, alcoholic liver disease, autoimmune hepatitis, and an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level greater than twice the upper limit of normal, should receive a HepB series.”
Meningococcal vaccination guidelines also underwent a number of small changes pertaining to adults with anatomical or functional asplenia and human immunodeficiency virus, among other risk factors.
A number of small changes to the schedule chart were implemented to help make the immunization schedule more “clean and streamlined,” according to the CDC.
“Physicians should pay careful attention to the details found in the footnotes,” the CDC said in a statement. “The footnotes clarify who needs what vaccine, when, and at what dose.”
, according to the newly issued 2017 adult Recommended Immunization Schedule released by the CDC’s Advisory Committee on Immunization Practices (ACIP).
“Changes are related to concerns regarding low effectiveness of [LAIV] (FluMist, MedImmune) against influenza A(H1N1)pdm09 in the United States during the 2013-2014 and 2015-2016 influenza seasons,” wrote the authors of the report, published in Annals of Internal Medicine and led by David K. Kim, MD, of the CDC’s Immunization Services Division in Atlanta.
Another major change involves vaccination of adults with mild or severe egg allergy. The new guidance states that those with a mild egg allergy should receive either inactivated influenza vaccine or recombinant influenza vaccine, while those with severe allergies should be given one of the same vaccinations but only in a health care setting, so a clinician can monitor any signs of reaction and treat the patient accordingly.
Vaccine doses should be administered based on the patient’s age; a patient with “severe” egg allergy is one who exhibits angioedema, respiratory distress, lightheadedness, or recurrent emesis; requires epinephrine; or requires emergency medical care of any kind after consuming egg products.
Human papillomavirus (HPV) schedules have also been noticeably altered, with the CDC now considering all men and women through the ages of 21 and 26 years, respectively, who received a two-dose series of HPV vaccinations before the age of 15 to be adequately protected. Those who took only one of those two doses still need to take another dose, while men and women who have not been vaccinated should received a three-dose series at 0, 1-2, and 6 months.
Hepatitis B recommendations were also updated, with the CDC now advising: “Adults with chronic liver disease, including, but not limited to, hepatitis C virus infection, cirrhosis, fatty liver disease, alcoholic liver disease, autoimmune hepatitis, and an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level greater than twice the upper limit of normal, should receive a HepB series.”
Meningococcal vaccination guidelines also underwent a number of small changes pertaining to adults with anatomical or functional asplenia and human immunodeficiency virus, among other risk factors.
A number of small changes to the schedule chart were implemented to help make the immunization schedule more “clean and streamlined,” according to the CDC.
“Physicians should pay careful attention to the details found in the footnotes,” the CDC said in a statement. “The footnotes clarify who needs what vaccine, when, and at what dose.”
, according to the newly issued 2017 adult Recommended Immunization Schedule released by the CDC’s Advisory Committee on Immunization Practices (ACIP).
“Changes are related to concerns regarding low effectiveness of [LAIV] (FluMist, MedImmune) against influenza A(H1N1)pdm09 in the United States during the 2013-2014 and 2015-2016 influenza seasons,” wrote the authors of the report, published in Annals of Internal Medicine and led by David K. Kim, MD, of the CDC’s Immunization Services Division in Atlanta.
Another major change involves vaccination of adults with mild or severe egg allergy. The new guidance states that those with a mild egg allergy should receive either inactivated influenza vaccine or recombinant influenza vaccine, while those with severe allergies should be given one of the same vaccinations but only in a health care setting, so a clinician can monitor any signs of reaction and treat the patient accordingly.
Vaccine doses should be administered based on the patient’s age; a patient with “severe” egg allergy is one who exhibits angioedema, respiratory distress, lightheadedness, or recurrent emesis; requires epinephrine; or requires emergency medical care of any kind after consuming egg products.
Human papillomavirus (HPV) schedules have also been noticeably altered, with the CDC now considering all men and women through the ages of 21 and 26 years, respectively, who received a two-dose series of HPV vaccinations before the age of 15 to be adequately protected. Those who took only one of those two doses still need to take another dose, while men and women who have not been vaccinated should received a three-dose series at 0, 1-2, and 6 months.
Hepatitis B recommendations were also updated, with the CDC now advising: “Adults with chronic liver disease, including, but not limited to, hepatitis C virus infection, cirrhosis, fatty liver disease, alcoholic liver disease, autoimmune hepatitis, and an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level greater than twice the upper limit of normal, should receive a HepB series.”
Meningococcal vaccination guidelines also underwent a number of small changes pertaining to adults with anatomical or functional asplenia and human immunodeficiency virus, among other risk factors.
A number of small changes to the schedule chart were implemented to help make the immunization schedule more “clean and streamlined,” according to the CDC.
“Physicians should pay careful attention to the details found in the footnotes,” the CDC said in a statement. “The footnotes clarify who needs what vaccine, when, and at what dose.”
FROM ANNALS OF INTERNAL MEDICINE
Intentional weight loss protects against endometrial cancer
Among postmenopausal women, intentional weight loss protects against endometrial cancer, even if that loss is modest (5% or more), according to a report in the Journal of Clinical Oncology.
Endometrial cancer is the malignancy most strongly associated with obesity, but to date few studies have examined the effect of intentional weight loss on risk. Researchers analyzed data from the prospective Women’s Health Initiative to assess this relationship in a large, ethnically diverse population of postmenopausal women with detailed records on potentially confounding factors such as body mass index, smoking status, physical activity level, hormone therapy use, parity, age at menarche, age at first birth, and family history.
They focused on 36,793 women who participated in the WHI and who reported whether they had maintained a stable weight, lost 5% or more of their total weight, or gained 5% or more of their total weight during the first 3 years after enrollment. During a mean of 11.4 years of follow-up, 566 of these women developed endometrial cancer, said Juhua Luo, PhD, of the department of epidemiology and biostatistics, Indiana University School of Public Health, Bloomington, and her associates.
Women who lost weight intentionally showed a significantly lower risk of endometrial cancer than did those who had stable weight (HR, 0.71). This association was most pronounced among obese women: Those who lost at least 5% of their body weight intentionally showed a dramatic reduction in endometrial cancer risk (HR, 0.44). In contrast, unintentional weight loss was not associated with a lower risk of endometrial cancer. And women who gained 10 pounds or more during the first 3 years of the study showed a significantly higher risk of endometrial cancer, the investigators said (J Clin Oncol. 2017 Feb 6. doi: 10.1200/JCO.2016.70.5822).
In a sensitivity analysis, women who intentionally lost weight and achieved a normal BMI showed the same risk of endometrial cancer as that of those who had maintained a stable BMI throughout the study.
Luo et al. showed that women who deliberately lost 5% or more of their body weight during a 3-year period reduced their long-term risk of endometrial cancer by nearly 30%, and obese women did so by 56%. At a minimum, clinicians should inform their patients about this association, especially because the link between obesity and endometrial cancer is clearly underrecognized.
But given the difficulty of losing weight, more aggressive strategies may be beneficial. Bariatric surgery and the use of progestational agents such as levonorgestrel IUDs warrant consideration.
Screening for endometrial cancer currently is very limited, so it also should be reassessed. Endometrial sampling and transvaginal ultrasound have drawbacks, including a lack of sensitivity and specificity in asymptomatic women. If more novel strategies prove reliable and cost-effective, including uterine lavage and collection of exfoliated cells from the cervix, they can be widely adapted into clinical practice.
Jason D. Wright, MD, is in the division of gynecologic oncology at Columbia University, New York, and New York Presbyterian Hospital. He reported having no relevant financial disclosures. Dr. Wright made these remarks in an editorial accompanying Dr. Luo’s report (J Clin Oncol. 2017 Feb 6. doi: 10.1200/JCO.2016.71.7991).
Luo et al. showed that women who deliberately lost 5% or more of their body weight during a 3-year period reduced their long-term risk of endometrial cancer by nearly 30%, and obese women did so by 56%. At a minimum, clinicians should inform their patients about this association, especially because the link between obesity and endometrial cancer is clearly underrecognized.
But given the difficulty of losing weight, more aggressive strategies may be beneficial. Bariatric surgery and the use of progestational agents such as levonorgestrel IUDs warrant consideration.
Screening for endometrial cancer currently is very limited, so it also should be reassessed. Endometrial sampling and transvaginal ultrasound have drawbacks, including a lack of sensitivity and specificity in asymptomatic women. If more novel strategies prove reliable and cost-effective, including uterine lavage and collection of exfoliated cells from the cervix, they can be widely adapted into clinical practice.
Jason D. Wright, MD, is in the division of gynecologic oncology at Columbia University, New York, and New York Presbyterian Hospital. He reported having no relevant financial disclosures. Dr. Wright made these remarks in an editorial accompanying Dr. Luo’s report (J Clin Oncol. 2017 Feb 6. doi: 10.1200/JCO.2016.71.7991).
Luo et al. showed that women who deliberately lost 5% or more of their body weight during a 3-year period reduced their long-term risk of endometrial cancer by nearly 30%, and obese women did so by 56%. At a minimum, clinicians should inform their patients about this association, especially because the link between obesity and endometrial cancer is clearly underrecognized.
But given the difficulty of losing weight, more aggressive strategies may be beneficial. Bariatric surgery and the use of progestational agents such as levonorgestrel IUDs warrant consideration.
Screening for endometrial cancer currently is very limited, so it also should be reassessed. Endometrial sampling and transvaginal ultrasound have drawbacks, including a lack of sensitivity and specificity in asymptomatic women. If more novel strategies prove reliable and cost-effective, including uterine lavage and collection of exfoliated cells from the cervix, they can be widely adapted into clinical practice.
Jason D. Wright, MD, is in the division of gynecologic oncology at Columbia University, New York, and New York Presbyterian Hospital. He reported having no relevant financial disclosures. Dr. Wright made these remarks in an editorial accompanying Dr. Luo’s report (J Clin Oncol. 2017 Feb 6. doi: 10.1200/JCO.2016.71.7991).
Among postmenopausal women, intentional weight loss protects against endometrial cancer, even if that loss is modest (5% or more), according to a report in the Journal of Clinical Oncology.
Endometrial cancer is the malignancy most strongly associated with obesity, but to date few studies have examined the effect of intentional weight loss on risk. Researchers analyzed data from the prospective Women’s Health Initiative to assess this relationship in a large, ethnically diverse population of postmenopausal women with detailed records on potentially confounding factors such as body mass index, smoking status, physical activity level, hormone therapy use, parity, age at menarche, age at first birth, and family history.
They focused on 36,793 women who participated in the WHI and who reported whether they had maintained a stable weight, lost 5% or more of their total weight, or gained 5% or more of their total weight during the first 3 years after enrollment. During a mean of 11.4 years of follow-up, 566 of these women developed endometrial cancer, said Juhua Luo, PhD, of the department of epidemiology and biostatistics, Indiana University School of Public Health, Bloomington, and her associates.
Women who lost weight intentionally showed a significantly lower risk of endometrial cancer than did those who had stable weight (HR, 0.71). This association was most pronounced among obese women: Those who lost at least 5% of their body weight intentionally showed a dramatic reduction in endometrial cancer risk (HR, 0.44). In contrast, unintentional weight loss was not associated with a lower risk of endometrial cancer. And women who gained 10 pounds or more during the first 3 years of the study showed a significantly higher risk of endometrial cancer, the investigators said (J Clin Oncol. 2017 Feb 6. doi: 10.1200/JCO.2016.70.5822).
In a sensitivity analysis, women who intentionally lost weight and achieved a normal BMI showed the same risk of endometrial cancer as that of those who had maintained a stable BMI throughout the study.
Among postmenopausal women, intentional weight loss protects against endometrial cancer, even if that loss is modest (5% or more), according to a report in the Journal of Clinical Oncology.
Endometrial cancer is the malignancy most strongly associated with obesity, but to date few studies have examined the effect of intentional weight loss on risk. Researchers analyzed data from the prospective Women’s Health Initiative to assess this relationship in a large, ethnically diverse population of postmenopausal women with detailed records on potentially confounding factors such as body mass index, smoking status, physical activity level, hormone therapy use, parity, age at menarche, age at first birth, and family history.
They focused on 36,793 women who participated in the WHI and who reported whether they had maintained a stable weight, lost 5% or more of their total weight, or gained 5% or more of their total weight during the first 3 years after enrollment. During a mean of 11.4 years of follow-up, 566 of these women developed endometrial cancer, said Juhua Luo, PhD, of the department of epidemiology and biostatistics, Indiana University School of Public Health, Bloomington, and her associates.
Women who lost weight intentionally showed a significantly lower risk of endometrial cancer than did those who had stable weight (HR, 0.71). This association was most pronounced among obese women: Those who lost at least 5% of their body weight intentionally showed a dramatic reduction in endometrial cancer risk (HR, 0.44). In contrast, unintentional weight loss was not associated with a lower risk of endometrial cancer. And women who gained 10 pounds or more during the first 3 years of the study showed a significantly higher risk of endometrial cancer, the investigators said (J Clin Oncol. 2017 Feb 6. doi: 10.1200/JCO.2016.70.5822).
In a sensitivity analysis, women who intentionally lost weight and achieved a normal BMI showed the same risk of endometrial cancer as that of those who had maintained a stable BMI throughout the study.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Among postmenopausal women, intentional weight loss protects against endometrial cancer, even if that loss is modest (5% or more).
Major finding: Women who intentionally lost at least 5% of their total body weight showed a significantly lower risk of endometrial cancer than did those who had stable weight (HR, 0.71), and obese women showed a dramatically reduced risk (HR, 0.44).
Data source: A secondary analysis of data from 36,793 women participating in the Women’s Health Initiative.
Disclosures: No sponsor was cited for this study. Dr. Luo reported having no relevant financial disclosures; her associates reported ties to numerous industry sources.
Open vs. endovascular for chronic mesenteric ischemia
Chronic mesenteric ischemia is best treated in an open operation.
Chronic mesenteric ischemia is a rare disorder accounting for about 1 out of 100,000 admissions.1 Because of the rarity of this disease, diagnosis is often delayed. Patients are often evaluated for other gastrointestinal diseases and/or malignancies, which in turn contributes to significant delays in diagnosis. Additionally, there are no prospective, randomized trials on which to base decisions regarding treatment; and it is unlikely that such studies will ever be undertaken.
Chronic mesenteric ischemia develops when two or more of the mesenteric vessels (celiac, superior mesenteric [SMA], or inferior mesenteric [IMA]) become occluded or develop severe stenosis. In my experience, patients most often develop occlusion (as opposed to stenosis) of their mesenteric vessels. The atherosclerotic plaque responsible for the disease originates within the aorta and the stenosis/occlusion develops at the vessel origin.
As a whole, these comorbidities would suggest that a more minimally invasive approach would be preferred. Yet, an open operation for chronic mesenteric ischemia should not be discarded as an initial operation.
Endovascular treatment of mesenteric ischemia is not without risk. As in all endovascular procedures there are complications associated with the access vessels. The orientation of the mesenteric vessels as they arise from the aorta often favors an approach from the left arm. The brachial artery is smaller than the femoral artery, and it is more difficult to apply pressure to the brachial artery to control the puncture site. This leads to a higher rate of access site complications including hemorrhage, pseudoaneurysm and thrombosis of the vessel. Bleeding or hematoma formation within the brachial neurovascular sheath can result in significant neurologic dysfunction of the arm and hand. There is risk of stroke, especially when the access vessel is the brachial artery. There are also complications directly related to the endovascular procedure.
Atheroembolism of plaque can result in occlusion of small mesenteric vessels and focal areas of bowel necrosis. Dissection of the mesenteric vessel can occur. Oderich has advocated for the use of a covered stent.2 A covered stent could cover proximal branches, and thus, in theory, the treatment itself could cause bowel ischemia or infarction. Many series that have compared open and endovascular surgery show no difference in early outcomes, but demonstrate early restenosis, decreased primary patency, and decreased assisted primary patency with endovascular treatment as compared with open operations.3-5
Another concern regarding the treatment of mesenteric ischemia is the status of the end organ, the bowel. Successful treatment of mesenteric ischemia cannot only assess the atherosclerotic lesion, but requires the surgeon to be cognizant of the condition of the bowel.
This concern is especially true for acute mesenteric ischemia,6 but the status of the bowel must also be kept in mind for chronic mesenteric ischemia. Unlike the lower extremity where the results of treatment are easily observed by inspection (color, evidence of atheroembolization), palpation (temperature, pulse), and physiologic testing (ABI), the bowel is not accessible. There are no highly accurate tests to determine if the patient has on-going bowel ischemia or has developed infarction. Should a complication occur, physical examination findings and laboratory changes often become apparent late in the course of the disease. As previously noted, these patients are often physiologically compromised and have little reserve and may not survive such complications. An open operation allows visualization of the bowel, before and after revascularization.
Traditional teaching for the surgical treatment of chronic mesenteric ischemia has emphasized that two mesenteric vessels, usually the celiac and SMA, should be revascularized.7,8 Various approaches to revascularization have been suggested including transaortic endarterectomy and an antegrade bifurcated bypass originating from the supraceliac aorta. These operations are effective in restoring flow to the mesenteric circulation, but both of these approaches involve aortic cross-clamping and are physiologically challenging for patients.
There are alternatives for open revascularization of the mesenteric vessels. The infrarenal aorta, iliac vessels, and even renal arteries can be, and have been used as the inflow source. It has been my experience that a bypass graft using an iliac artery (common or external) as the inflow source is well tolerated by patients. I have preferentially used either great saphenous vein or femoral-popliteal vein as the conduit. In many cases, the distal anastomosis is simply the SMA. However, both the celiac and SMA can be revascularized by creating a side-side anastomosis to the SMA and an end-side anastomosis to the common or proper hepatic artery. Such procedures have been durable, providing relief of symptoms and allowing patients to regain weight.9
In reality, I believe that an endovascular approach for the treatment of chronic mesenteric ischemia has a role. Vascular surgeons are uniquely positioned to carefully evaluate each patient and recommend what they feel is most appropriate. I tend to feel that an endovascular approach is less likely to be successful for patients with occluded vessels, especially those with a flush occlusion, and so will preferentially recommend an open operation for these patients. On the other hand, in my practice, I have used an endovascular approach for patients with severe stenosis, and as Dr. Harris states, know that a bypass is always an option should this be unsuccessful or ultimately fail.
References
1. Ann Vasc Surg. 1991;5:403-6
2. J Vasc Surg. 2013;58:1316-23
3. Ann Vasc Surg. 2015:29;934-40
4. World J Gastroenerol. 2013;19:1333-7
5. J Vasc Surg. 2007;45:1162-71
6. J Vasc Surg. 2015;62:767-72
7. J Vasc Surg. 2002:35:853-9
8. Surgery. 1981;90:940-6
9. J Vasc Surg. 2000;32:37-47
Eric Endean, MD, is the director of the aortic center, Gordon L. Hyde Endowed Professor and Chair, and vascular surgery section head, vascular and endovascular surgery at UK HealthCare, University of Kentucky, Lexington. He had no relevant disclosures.
Presenting the case for endovascular intervention
Chronic mesenteric ischemia (CMI) is an uncommon, but lethal, problem when left untreated. Before the endovascular era, the only option was open revascularization, which is challenging in this chronically ill, malnourished population with diffuse, systemic, atherosclerotic disease. Morbidity and mortality was relatively high because of the comorbid conditions and chronically ill status of the patients. The first mesenteric bypass was performed in 1958 by Maynard and Shaw.1
Options for open repair include transaortic endarterectomy, antegrade bypass from the supraceliac aorta or distal thoracic aorta, or retrograde bypass from the iliac artery, all of which are major abdominal procedures. Endovascular interventions are now the most commonly performed procedures for CMI in the United States based on national studies.2
Technical success with endovascular interventions can be achieved in well over 90% of patients, and multiple vessels can be treated simultaneously from either a femoral or brachial approach. The primary concern with endovascular interventions has been long-term patency, with restenosis from intimal hyperplasia or thrombosis causing recurrent symptoms in up to 30%-50% at 3-5 years.5-7 However, these rates are based on use of bare metal stents, rather than covered stents. Recent studies8 suggest that stent grafts have markedly improved outcomes over bare metal stents for ostial lesions, decreasing recurrence. Oderich found that freedom from recurrence was 92% with stent grafts as compared with 53% for bare metal stents, with primary patency rates of 92%, at 3 years8, comparable to even the best open bypass results. Schoch first reported the use of covered stents in the mesenteric circulation, and found that no patients developed recurrent stenosis at 2 years.9 Other concerns with endovascular intervention include embolization and dissection, which have not been frequently reported.
Mortality from open surgery ranges from 5% to 15%, with morbidity of 30%-40%.4 Mortality from endovascular intervention is markedly lower, in the range of 3.56% vs. 7.23%.5 Long-term survival is not different between endovascular vs. open repair (69% vs. 65%),4 with the majority of deaths related to cardiac, pulmonary, or malignancy issues. Moghadamyeghaneh, in a review of the Nationwide Inpatient Sample database, found that open surgery was one of the major predictors for higher morbidity (odds ratio, 5.07) and mortality (OR, 5.13), despite the fact that endovascular patients were older (another risk factor for adverse outcomes) and had more comorbidities in this nonrandomized, real-world study.2
Further, if one considers cost as a metric for decision making, a Markov clinical decision model by Hogendoorn et al suggests an endovascular first approach is preferred, despite the presumed higher rate of recurrence expected with use of bare metal stents, rather than covered stents, utilized for this analysis.10 Clearly, the financial advantage would be even greater for endovascular with the lower rates of recurrence with covered stents more recently reported.
If a patient develops recurrent stenosis after endovascular intervention, open bypass may be considered as an alternate to repeat endovascular intervention, dependent on the nutritional status, life expectancy, and initial intervention undertaken. Alternately, patients who undergo open repair are not immune to restenosis, with a recurrence rate of 10%-20%.11,12 Oderich found that there was a 22% mortality in those treated with repeat open interventions, with a 47% complication rate. Endovascular interventions, however, had a significantly lower rate of complications, 16%, and mortality. For patients with recurrent disease after open revascularization for CMI, the endovascular approach should also be the preferred approach.
Any lesion which is anatomically suitable for endovascular repair should first have an attempt made via this approach, utilizing covered stents. While there is a role for open revascularization, endovascular interventions can be safely performed, with minimal morbidity and mortality, and good long-term patency, even in the sickest patients. Endovascular intervention should be the procedure of choice for chronic mesenteric ischemia and recurrent chronic mesenteric ischemia.
References
1. NEJM. 1958;258:874-8
2. Am Surg. 2015;81:1149-56
3. Cardiovasc Intervent Radiol. 1980;3:43-4
4. Ann Vasc Surg. 2009;23:700-12
5. Ann Vasc Surg. 2013;27:113-22
6. J Vasc Surg. 2011;54:1422-29
7. J Vasc Surg. 2010;51:140-7
8. J Vasc Surg. 2013;58:1316-24
9. JACS. 2001;212:668-75
10. J Vasc Surg. 2014;60;715-25
11. J Vasc Surg. 200;49:1472-9
12. J Vasc Surg. 2007;45:1162-71
Linda Harris, MD, is professor of surgery; chief, division of vascular surgery; program director, vascular surgery residency & fellowship at the State University of New York at Buffalo; and an associate medical editor for Vascular Specialist. She had no relevant disclosures.
Chronic mesenteric ischemia is best treated in an open operation.
Chronic mesenteric ischemia is a rare disorder accounting for about 1 out of 100,000 admissions.1 Because of the rarity of this disease, diagnosis is often delayed. Patients are often evaluated for other gastrointestinal diseases and/or malignancies, which in turn contributes to significant delays in diagnosis. Additionally, there are no prospective, randomized trials on which to base decisions regarding treatment; and it is unlikely that such studies will ever be undertaken.
Chronic mesenteric ischemia develops when two or more of the mesenteric vessels (celiac, superior mesenteric [SMA], or inferior mesenteric [IMA]) become occluded or develop severe stenosis. In my experience, patients most often develop occlusion (as opposed to stenosis) of their mesenteric vessels. The atherosclerotic plaque responsible for the disease originates within the aorta and the stenosis/occlusion develops at the vessel origin.
As a whole, these comorbidities would suggest that a more minimally invasive approach would be preferred. Yet, an open operation for chronic mesenteric ischemia should not be discarded as an initial operation.
Endovascular treatment of mesenteric ischemia is not without risk. As in all endovascular procedures there are complications associated with the access vessels. The orientation of the mesenteric vessels as they arise from the aorta often favors an approach from the left arm. The brachial artery is smaller than the femoral artery, and it is more difficult to apply pressure to the brachial artery to control the puncture site. This leads to a higher rate of access site complications including hemorrhage, pseudoaneurysm and thrombosis of the vessel. Bleeding or hematoma formation within the brachial neurovascular sheath can result in significant neurologic dysfunction of the arm and hand. There is risk of stroke, especially when the access vessel is the brachial artery. There are also complications directly related to the endovascular procedure.
Atheroembolism of plaque can result in occlusion of small mesenteric vessels and focal areas of bowel necrosis. Dissection of the mesenteric vessel can occur. Oderich has advocated for the use of a covered stent.2 A covered stent could cover proximal branches, and thus, in theory, the treatment itself could cause bowel ischemia or infarction. Many series that have compared open and endovascular surgery show no difference in early outcomes, but demonstrate early restenosis, decreased primary patency, and decreased assisted primary patency with endovascular treatment as compared with open operations.3-5
Another concern regarding the treatment of mesenteric ischemia is the status of the end organ, the bowel. Successful treatment of mesenteric ischemia cannot only assess the atherosclerotic lesion, but requires the surgeon to be cognizant of the condition of the bowel.
This concern is especially true for acute mesenteric ischemia,6 but the status of the bowel must also be kept in mind for chronic mesenteric ischemia. Unlike the lower extremity where the results of treatment are easily observed by inspection (color, evidence of atheroembolization), palpation (temperature, pulse), and physiologic testing (ABI), the bowel is not accessible. There are no highly accurate tests to determine if the patient has on-going bowel ischemia or has developed infarction. Should a complication occur, physical examination findings and laboratory changes often become apparent late in the course of the disease. As previously noted, these patients are often physiologically compromised and have little reserve and may not survive such complications. An open operation allows visualization of the bowel, before and after revascularization.
Traditional teaching for the surgical treatment of chronic mesenteric ischemia has emphasized that two mesenteric vessels, usually the celiac and SMA, should be revascularized.7,8 Various approaches to revascularization have been suggested including transaortic endarterectomy and an antegrade bifurcated bypass originating from the supraceliac aorta. These operations are effective in restoring flow to the mesenteric circulation, but both of these approaches involve aortic cross-clamping and are physiologically challenging for patients.
There are alternatives for open revascularization of the mesenteric vessels. The infrarenal aorta, iliac vessels, and even renal arteries can be, and have been used as the inflow source. It has been my experience that a bypass graft using an iliac artery (common or external) as the inflow source is well tolerated by patients. I have preferentially used either great saphenous vein or femoral-popliteal vein as the conduit. In many cases, the distal anastomosis is simply the SMA. However, both the celiac and SMA can be revascularized by creating a side-side anastomosis to the SMA and an end-side anastomosis to the common or proper hepatic artery. Such procedures have been durable, providing relief of symptoms and allowing patients to regain weight.9
In reality, I believe that an endovascular approach for the treatment of chronic mesenteric ischemia has a role. Vascular surgeons are uniquely positioned to carefully evaluate each patient and recommend what they feel is most appropriate. I tend to feel that an endovascular approach is less likely to be successful for patients with occluded vessels, especially those with a flush occlusion, and so will preferentially recommend an open operation for these patients. On the other hand, in my practice, I have used an endovascular approach for patients with severe stenosis, and as Dr. Harris states, know that a bypass is always an option should this be unsuccessful or ultimately fail.
References
1. Ann Vasc Surg. 1991;5:403-6
2. J Vasc Surg. 2013;58:1316-23
3. Ann Vasc Surg. 2015:29;934-40
4. World J Gastroenerol. 2013;19:1333-7
5. J Vasc Surg. 2007;45:1162-71
6. J Vasc Surg. 2015;62:767-72
7. J Vasc Surg. 2002:35:853-9
8. Surgery. 1981;90:940-6
9. J Vasc Surg. 2000;32:37-47
Eric Endean, MD, is the director of the aortic center, Gordon L. Hyde Endowed Professor and Chair, and vascular surgery section head, vascular and endovascular surgery at UK HealthCare, University of Kentucky, Lexington. He had no relevant disclosures.
Presenting the case for endovascular intervention
Chronic mesenteric ischemia (CMI) is an uncommon, but lethal, problem when left untreated. Before the endovascular era, the only option was open revascularization, which is challenging in this chronically ill, malnourished population with diffuse, systemic, atherosclerotic disease. Morbidity and mortality was relatively high because of the comorbid conditions and chronically ill status of the patients. The first mesenteric bypass was performed in 1958 by Maynard and Shaw.1
Options for open repair include transaortic endarterectomy, antegrade bypass from the supraceliac aorta or distal thoracic aorta, or retrograde bypass from the iliac artery, all of which are major abdominal procedures. Endovascular interventions are now the most commonly performed procedures for CMI in the United States based on national studies.2
Technical success with endovascular interventions can be achieved in well over 90% of patients, and multiple vessels can be treated simultaneously from either a femoral or brachial approach. The primary concern with endovascular interventions has been long-term patency, with restenosis from intimal hyperplasia or thrombosis causing recurrent symptoms in up to 30%-50% at 3-5 years.5-7 However, these rates are based on use of bare metal stents, rather than covered stents. Recent studies8 suggest that stent grafts have markedly improved outcomes over bare metal stents for ostial lesions, decreasing recurrence. Oderich found that freedom from recurrence was 92% with stent grafts as compared with 53% for bare metal stents, with primary patency rates of 92%, at 3 years8, comparable to even the best open bypass results. Schoch first reported the use of covered stents in the mesenteric circulation, and found that no patients developed recurrent stenosis at 2 years.9 Other concerns with endovascular intervention include embolization and dissection, which have not been frequently reported.
Mortality from open surgery ranges from 5% to 15%, with morbidity of 30%-40%.4 Mortality from endovascular intervention is markedly lower, in the range of 3.56% vs. 7.23%.5 Long-term survival is not different between endovascular vs. open repair (69% vs. 65%),4 with the majority of deaths related to cardiac, pulmonary, or malignancy issues. Moghadamyeghaneh, in a review of the Nationwide Inpatient Sample database, found that open surgery was one of the major predictors for higher morbidity (odds ratio, 5.07) and mortality (OR, 5.13), despite the fact that endovascular patients were older (another risk factor for adverse outcomes) and had more comorbidities in this nonrandomized, real-world study.2
Further, if one considers cost as a metric for decision making, a Markov clinical decision model by Hogendoorn et al suggests an endovascular first approach is preferred, despite the presumed higher rate of recurrence expected with use of bare metal stents, rather than covered stents, utilized for this analysis.10 Clearly, the financial advantage would be even greater for endovascular with the lower rates of recurrence with covered stents more recently reported.
If a patient develops recurrent stenosis after endovascular intervention, open bypass may be considered as an alternate to repeat endovascular intervention, dependent on the nutritional status, life expectancy, and initial intervention undertaken. Alternately, patients who undergo open repair are not immune to restenosis, with a recurrence rate of 10%-20%.11,12 Oderich found that there was a 22% mortality in those treated with repeat open interventions, with a 47% complication rate. Endovascular interventions, however, had a significantly lower rate of complications, 16%, and mortality. For patients with recurrent disease after open revascularization for CMI, the endovascular approach should also be the preferred approach.
Any lesion which is anatomically suitable for endovascular repair should first have an attempt made via this approach, utilizing covered stents. While there is a role for open revascularization, endovascular interventions can be safely performed, with minimal morbidity and mortality, and good long-term patency, even in the sickest patients. Endovascular intervention should be the procedure of choice for chronic mesenteric ischemia and recurrent chronic mesenteric ischemia.
References
1. NEJM. 1958;258:874-8
2. Am Surg. 2015;81:1149-56
3. Cardiovasc Intervent Radiol. 1980;3:43-4
4. Ann Vasc Surg. 2009;23:700-12
5. Ann Vasc Surg. 2013;27:113-22
6. J Vasc Surg. 2011;54:1422-29
7. J Vasc Surg. 2010;51:140-7
8. J Vasc Surg. 2013;58:1316-24
9. JACS. 2001;212:668-75
10. J Vasc Surg. 2014;60;715-25
11. J Vasc Surg. 200;49:1472-9
12. J Vasc Surg. 2007;45:1162-71
Linda Harris, MD, is professor of surgery; chief, division of vascular surgery; program director, vascular surgery residency & fellowship at the State University of New York at Buffalo; and an associate medical editor for Vascular Specialist. She had no relevant disclosures.
Chronic mesenteric ischemia is best treated in an open operation.
Chronic mesenteric ischemia is a rare disorder accounting for about 1 out of 100,000 admissions.1 Because of the rarity of this disease, diagnosis is often delayed. Patients are often evaluated for other gastrointestinal diseases and/or malignancies, which in turn contributes to significant delays in diagnosis. Additionally, there are no prospective, randomized trials on which to base decisions regarding treatment; and it is unlikely that such studies will ever be undertaken.
Chronic mesenteric ischemia develops when two or more of the mesenteric vessels (celiac, superior mesenteric [SMA], or inferior mesenteric [IMA]) become occluded or develop severe stenosis. In my experience, patients most often develop occlusion (as opposed to stenosis) of their mesenteric vessels. The atherosclerotic plaque responsible for the disease originates within the aorta and the stenosis/occlusion develops at the vessel origin.
As a whole, these comorbidities would suggest that a more minimally invasive approach would be preferred. Yet, an open operation for chronic mesenteric ischemia should not be discarded as an initial operation.
Endovascular treatment of mesenteric ischemia is not without risk. As in all endovascular procedures there are complications associated with the access vessels. The orientation of the mesenteric vessels as they arise from the aorta often favors an approach from the left arm. The brachial artery is smaller than the femoral artery, and it is more difficult to apply pressure to the brachial artery to control the puncture site. This leads to a higher rate of access site complications including hemorrhage, pseudoaneurysm and thrombosis of the vessel. Bleeding or hematoma formation within the brachial neurovascular sheath can result in significant neurologic dysfunction of the arm and hand. There is risk of stroke, especially when the access vessel is the brachial artery. There are also complications directly related to the endovascular procedure.
Atheroembolism of plaque can result in occlusion of small mesenteric vessels and focal areas of bowel necrosis. Dissection of the mesenteric vessel can occur. Oderich has advocated for the use of a covered stent.2 A covered stent could cover proximal branches, and thus, in theory, the treatment itself could cause bowel ischemia or infarction. Many series that have compared open and endovascular surgery show no difference in early outcomes, but demonstrate early restenosis, decreased primary patency, and decreased assisted primary patency with endovascular treatment as compared with open operations.3-5
Another concern regarding the treatment of mesenteric ischemia is the status of the end organ, the bowel. Successful treatment of mesenteric ischemia cannot only assess the atherosclerotic lesion, but requires the surgeon to be cognizant of the condition of the bowel.
This concern is especially true for acute mesenteric ischemia,6 but the status of the bowel must also be kept in mind for chronic mesenteric ischemia. Unlike the lower extremity where the results of treatment are easily observed by inspection (color, evidence of atheroembolization), palpation (temperature, pulse), and physiologic testing (ABI), the bowel is not accessible. There are no highly accurate tests to determine if the patient has on-going bowel ischemia or has developed infarction. Should a complication occur, physical examination findings and laboratory changes often become apparent late in the course of the disease. As previously noted, these patients are often physiologically compromised and have little reserve and may not survive such complications. An open operation allows visualization of the bowel, before and after revascularization.
Traditional teaching for the surgical treatment of chronic mesenteric ischemia has emphasized that two mesenteric vessels, usually the celiac and SMA, should be revascularized.7,8 Various approaches to revascularization have been suggested including transaortic endarterectomy and an antegrade bifurcated bypass originating from the supraceliac aorta. These operations are effective in restoring flow to the mesenteric circulation, but both of these approaches involve aortic cross-clamping and are physiologically challenging for patients.
There are alternatives for open revascularization of the mesenteric vessels. The infrarenal aorta, iliac vessels, and even renal arteries can be, and have been used as the inflow source. It has been my experience that a bypass graft using an iliac artery (common or external) as the inflow source is well tolerated by patients. I have preferentially used either great saphenous vein or femoral-popliteal vein as the conduit. In many cases, the distal anastomosis is simply the SMA. However, both the celiac and SMA can be revascularized by creating a side-side anastomosis to the SMA and an end-side anastomosis to the common or proper hepatic artery. Such procedures have been durable, providing relief of symptoms and allowing patients to regain weight.9
In reality, I believe that an endovascular approach for the treatment of chronic mesenteric ischemia has a role. Vascular surgeons are uniquely positioned to carefully evaluate each patient and recommend what they feel is most appropriate. I tend to feel that an endovascular approach is less likely to be successful for patients with occluded vessels, especially those with a flush occlusion, and so will preferentially recommend an open operation for these patients. On the other hand, in my practice, I have used an endovascular approach for patients with severe stenosis, and as Dr. Harris states, know that a bypass is always an option should this be unsuccessful or ultimately fail.
References
1. Ann Vasc Surg. 1991;5:403-6
2. J Vasc Surg. 2013;58:1316-23
3. Ann Vasc Surg. 2015:29;934-40
4. World J Gastroenerol. 2013;19:1333-7
5. J Vasc Surg. 2007;45:1162-71
6. J Vasc Surg. 2015;62:767-72
7. J Vasc Surg. 2002:35:853-9
8. Surgery. 1981;90:940-6
9. J Vasc Surg. 2000;32:37-47
Eric Endean, MD, is the director of the aortic center, Gordon L. Hyde Endowed Professor and Chair, and vascular surgery section head, vascular and endovascular surgery at UK HealthCare, University of Kentucky, Lexington. He had no relevant disclosures.
Presenting the case for endovascular intervention
Chronic mesenteric ischemia (CMI) is an uncommon, but lethal, problem when left untreated. Before the endovascular era, the only option was open revascularization, which is challenging in this chronically ill, malnourished population with diffuse, systemic, atherosclerotic disease. Morbidity and mortality was relatively high because of the comorbid conditions and chronically ill status of the patients. The first mesenteric bypass was performed in 1958 by Maynard and Shaw.1
Options for open repair include transaortic endarterectomy, antegrade bypass from the supraceliac aorta or distal thoracic aorta, or retrograde bypass from the iliac artery, all of which are major abdominal procedures. Endovascular interventions are now the most commonly performed procedures for CMI in the United States based on national studies.2
Technical success with endovascular interventions can be achieved in well over 90% of patients, and multiple vessels can be treated simultaneously from either a femoral or brachial approach. The primary concern with endovascular interventions has been long-term patency, with restenosis from intimal hyperplasia or thrombosis causing recurrent symptoms in up to 30%-50% at 3-5 years.5-7 However, these rates are based on use of bare metal stents, rather than covered stents. Recent studies8 suggest that stent grafts have markedly improved outcomes over bare metal stents for ostial lesions, decreasing recurrence. Oderich found that freedom from recurrence was 92% with stent grafts as compared with 53% for bare metal stents, with primary patency rates of 92%, at 3 years8, comparable to even the best open bypass results. Schoch first reported the use of covered stents in the mesenteric circulation, and found that no patients developed recurrent stenosis at 2 years.9 Other concerns with endovascular intervention include embolization and dissection, which have not been frequently reported.
Mortality from open surgery ranges from 5% to 15%, with morbidity of 30%-40%.4 Mortality from endovascular intervention is markedly lower, in the range of 3.56% vs. 7.23%.5 Long-term survival is not different between endovascular vs. open repair (69% vs. 65%),4 with the majority of deaths related to cardiac, pulmonary, or malignancy issues. Moghadamyeghaneh, in a review of the Nationwide Inpatient Sample database, found that open surgery was one of the major predictors for higher morbidity (odds ratio, 5.07) and mortality (OR, 5.13), despite the fact that endovascular patients were older (another risk factor for adverse outcomes) and had more comorbidities in this nonrandomized, real-world study.2
Further, if one considers cost as a metric for decision making, a Markov clinical decision model by Hogendoorn et al suggests an endovascular first approach is preferred, despite the presumed higher rate of recurrence expected with use of bare metal stents, rather than covered stents, utilized for this analysis.10 Clearly, the financial advantage would be even greater for endovascular with the lower rates of recurrence with covered stents more recently reported.
If a patient develops recurrent stenosis after endovascular intervention, open bypass may be considered as an alternate to repeat endovascular intervention, dependent on the nutritional status, life expectancy, and initial intervention undertaken. Alternately, patients who undergo open repair are not immune to restenosis, with a recurrence rate of 10%-20%.11,12 Oderich found that there was a 22% mortality in those treated with repeat open interventions, with a 47% complication rate. Endovascular interventions, however, had a significantly lower rate of complications, 16%, and mortality. For patients with recurrent disease after open revascularization for CMI, the endovascular approach should also be the preferred approach.
Any lesion which is anatomically suitable for endovascular repair should first have an attempt made via this approach, utilizing covered stents. While there is a role for open revascularization, endovascular interventions can be safely performed, with minimal morbidity and mortality, and good long-term patency, even in the sickest patients. Endovascular intervention should be the procedure of choice for chronic mesenteric ischemia and recurrent chronic mesenteric ischemia.
References
1. NEJM. 1958;258:874-8
2. Am Surg. 2015;81:1149-56
3. Cardiovasc Intervent Radiol. 1980;3:43-4
4. Ann Vasc Surg. 2009;23:700-12
5. Ann Vasc Surg. 2013;27:113-22
6. J Vasc Surg. 2011;54:1422-29
7. J Vasc Surg. 2010;51:140-7
8. J Vasc Surg. 2013;58:1316-24
9. JACS. 2001;212:668-75
10. J Vasc Surg. 2014;60;715-25
11. J Vasc Surg. 200;49:1472-9
12. J Vasc Surg. 2007;45:1162-71
Linda Harris, MD, is professor of surgery; chief, division of vascular surgery; program director, vascular surgery residency & fellowship at the State University of New York at Buffalo; and an associate medical editor for Vascular Specialist. She had no relevant disclosures.
Perioperative infliximab does not increase serious infection risk
Administration of infliximab within 4 weeks of elective knee or hip arthroplasty did not have any significant effect on patients’ risk of serious infection after surgery, whereas the use of glucocorticoids increased that risk, in an analysis of a Medicare claims database.
“This increased risk with glucocorticoids has been suggested by previous studies [and] although this risk may be related in part to increased disease severity among glucocorticoid treated patients, a direct medication effect is likely. [These data suggest] that prolonged interruptions in infliximab therapy prior to surgery may be counterproductive if higher dose glucocorticoid therapy is used in substitution,” wrote the authors of the new study, led by Michael D. George, MD, of the University of Pennsylvania in Philadelphia.
Dr. George and his colleagues examined data from the U.S. Medicare claims system on 4,288 elective knee or hip arthroplasties in individuals with rheumatoid arthritis, inflammatory bowel disease, psoriasis, psoriatic arthritis, or ankylosing spondylitis who received infliximab within 6 months prior to the operation during 2007-2013 (Arthritis Care Res. 2017 Jan 27. doi: 10.1002/acr.23209).
The patients had to have received infliximab at least three times within a year of their procedure to establish that they were receiving stable therapy over a long-term period. The investigators also looked at oral prednisone, prednisolone, and methylprednisolone prescriptions and used data on average dosing to determine how much was administered to each subject.
“Although previous studies have treated TNF stopping vs. not stopping as a dichotomous exposure based on an arbitrary (and variable) stopping definition, in this study the primary analysis evaluated stop timing as a more general categorical exposure using 4-week intervals (half the standard rheumatoid arthritis dosing interval) to allow better assessment of the optimal stop timing,” the authors explained.
Stopping infliximab within 4 weeks of the operation did not significantly influence the rate of serious infection within 30 days (adjusted odds ratio, 0.90; 95% CI, 0.60-1.34) and neither did stopping within 4-8 weeks (OR, 0.95; 95% CI, 0.62-1.36) when compared against stopping 8-12 weeks before surgery. Of the 4,288 arthroplasties, 270 serious infections (6.3%) occurred within 30 days of the operation.
There also was no significant difference between stopping within 4 weeks and 8-12 weeks in the rate of prosthetic joint infection within 1 year of the operation (hazard ratio, 0.98; 95% CI, 0.52-1.87). Overall, prosthetic joint infection occurred 2.9 times per 100 person-years.
However, glucocorticoid doses of more than 10 mg per day were risky. The odds for a serious infection within 30 days after surgery more than doubled with that level of use (OR, 2.11; 95% CI, 1.30-3.40), while the risk for a prosthetic joint infection within 1 year of the surgery also rose significantly (HR, 2.70; 95% CI, 1.30-5.60).
“This is a very well done paper that adds important observational data to our understanding of perioperative medication risk,” Dr. Goodman said.
But the study results will not, at least initially, bring about any changes to the proposed guidelines for perioperative management of patients taking antirheumatic drugs that were described at the 2016 annual meeting of the American College of Rheumatology, she said.
“We were aware of the abstract, which was also presented at the ACR last fall at the time the current perioperative medication management guidelines were presented, and it won’t change guidelines at this point,” said Dr. Goodman, who is one of the lead authors of the proposed guidelines. “[But] I think [the study] could provide important background information to use in a randomized clinical trial to compare infection on [and] not on TNF inhibitors.”
The proposed guidelines conditionally recommend that all biologics should be withheld prior to surgery in patients with inflammatory arthritis, that surgery should be planned for the end of the dosing cycle, and that current daily doses of glucocorticoids, rather than supraphysiologic doses, should be continued in adults with rheumatoid arthritis, lupus, or inflammatory arthritis.
The National Institutes of Health, the Rheumatology Research Foundation, and the Department of Veterans Affairs funded the study. Dr. George did not report any relevant financial disclosures. Two coauthors disclosed receiving research grants or consulting fees from pharmaceutical companies for unrelated work.
Administration of infliximab within 4 weeks of elective knee or hip arthroplasty did not have any significant effect on patients’ risk of serious infection after surgery, whereas the use of glucocorticoids increased that risk, in an analysis of a Medicare claims database.
“This increased risk with glucocorticoids has been suggested by previous studies [and] although this risk may be related in part to increased disease severity among glucocorticoid treated patients, a direct medication effect is likely. [These data suggest] that prolonged interruptions in infliximab therapy prior to surgery may be counterproductive if higher dose glucocorticoid therapy is used in substitution,” wrote the authors of the new study, led by Michael D. George, MD, of the University of Pennsylvania in Philadelphia.
Dr. George and his colleagues examined data from the U.S. Medicare claims system on 4,288 elective knee or hip arthroplasties in individuals with rheumatoid arthritis, inflammatory bowel disease, psoriasis, psoriatic arthritis, or ankylosing spondylitis who received infliximab within 6 months prior to the operation during 2007-2013 (Arthritis Care Res. 2017 Jan 27. doi: 10.1002/acr.23209).
The patients had to have received infliximab at least three times within a year of their procedure to establish that they were receiving stable therapy over a long-term period. The investigators also looked at oral prednisone, prednisolone, and methylprednisolone prescriptions and used data on average dosing to determine how much was administered to each subject.
“Although previous studies have treated TNF stopping vs. not stopping as a dichotomous exposure based on an arbitrary (and variable) stopping definition, in this study the primary analysis evaluated stop timing as a more general categorical exposure using 4-week intervals (half the standard rheumatoid arthritis dosing interval) to allow better assessment of the optimal stop timing,” the authors explained.
Stopping infliximab within 4 weeks of the operation did not significantly influence the rate of serious infection within 30 days (adjusted odds ratio, 0.90; 95% CI, 0.60-1.34) and neither did stopping within 4-8 weeks (OR, 0.95; 95% CI, 0.62-1.36) when compared against stopping 8-12 weeks before surgery. Of the 4,288 arthroplasties, 270 serious infections (6.3%) occurred within 30 days of the operation.
There also was no significant difference between stopping within 4 weeks and 8-12 weeks in the rate of prosthetic joint infection within 1 year of the operation (hazard ratio, 0.98; 95% CI, 0.52-1.87). Overall, prosthetic joint infection occurred 2.9 times per 100 person-years.
However, glucocorticoid doses of more than 10 mg per day were risky. The odds for a serious infection within 30 days after surgery more than doubled with that level of use (OR, 2.11; 95% CI, 1.30-3.40), while the risk for a prosthetic joint infection within 1 year of the surgery also rose significantly (HR, 2.70; 95% CI, 1.30-5.60).
“This is a very well done paper that adds important observational data to our understanding of perioperative medication risk,” Dr. Goodman said.
But the study results will not, at least initially, bring about any changes to the proposed guidelines for perioperative management of patients taking antirheumatic drugs that were described at the 2016 annual meeting of the American College of Rheumatology, she said.
“We were aware of the abstract, which was also presented at the ACR last fall at the time the current perioperative medication management guidelines were presented, and it won’t change guidelines at this point,” said Dr. Goodman, who is one of the lead authors of the proposed guidelines. “[But] I think [the study] could provide important background information to use in a randomized clinical trial to compare infection on [and] not on TNF inhibitors.”
The proposed guidelines conditionally recommend that all biologics should be withheld prior to surgery in patients with inflammatory arthritis, that surgery should be planned for the end of the dosing cycle, and that current daily doses of glucocorticoids, rather than supraphysiologic doses, should be continued in adults with rheumatoid arthritis, lupus, or inflammatory arthritis.
The National Institutes of Health, the Rheumatology Research Foundation, and the Department of Veterans Affairs funded the study. Dr. George did not report any relevant financial disclosures. Two coauthors disclosed receiving research grants or consulting fees from pharmaceutical companies for unrelated work.
Administration of infliximab within 4 weeks of elective knee or hip arthroplasty did not have any significant effect on patients’ risk of serious infection after surgery, whereas the use of glucocorticoids increased that risk, in an analysis of a Medicare claims database.
“This increased risk with glucocorticoids has been suggested by previous studies [and] although this risk may be related in part to increased disease severity among glucocorticoid treated patients, a direct medication effect is likely. [These data suggest] that prolonged interruptions in infliximab therapy prior to surgery may be counterproductive if higher dose glucocorticoid therapy is used in substitution,” wrote the authors of the new study, led by Michael D. George, MD, of the University of Pennsylvania in Philadelphia.
Dr. George and his colleagues examined data from the U.S. Medicare claims system on 4,288 elective knee or hip arthroplasties in individuals with rheumatoid arthritis, inflammatory bowel disease, psoriasis, psoriatic arthritis, or ankylosing spondylitis who received infliximab within 6 months prior to the operation during 2007-2013 (Arthritis Care Res. 2017 Jan 27. doi: 10.1002/acr.23209).
The patients had to have received infliximab at least three times within a year of their procedure to establish that they were receiving stable therapy over a long-term period. The investigators also looked at oral prednisone, prednisolone, and methylprednisolone prescriptions and used data on average dosing to determine how much was administered to each subject.
“Although previous studies have treated TNF stopping vs. not stopping as a dichotomous exposure based on an arbitrary (and variable) stopping definition, in this study the primary analysis evaluated stop timing as a more general categorical exposure using 4-week intervals (half the standard rheumatoid arthritis dosing interval) to allow better assessment of the optimal stop timing,” the authors explained.
Stopping infliximab within 4 weeks of the operation did not significantly influence the rate of serious infection within 30 days (adjusted odds ratio, 0.90; 95% CI, 0.60-1.34) and neither did stopping within 4-8 weeks (OR, 0.95; 95% CI, 0.62-1.36) when compared against stopping 8-12 weeks before surgery. Of the 4,288 arthroplasties, 270 serious infections (6.3%) occurred within 30 days of the operation.
There also was no significant difference between stopping within 4 weeks and 8-12 weeks in the rate of prosthetic joint infection within 1 year of the operation (hazard ratio, 0.98; 95% CI, 0.52-1.87). Overall, prosthetic joint infection occurred 2.9 times per 100 person-years.
However, glucocorticoid doses of more than 10 mg per day were risky. The odds for a serious infection within 30 days after surgery more than doubled with that level of use (OR, 2.11; 95% CI, 1.30-3.40), while the risk for a prosthetic joint infection within 1 year of the surgery also rose significantly (HR, 2.70; 95% CI, 1.30-5.60).
“This is a very well done paper that adds important observational data to our understanding of perioperative medication risk,” Dr. Goodman said.
But the study results will not, at least initially, bring about any changes to the proposed guidelines for perioperative management of patients taking antirheumatic drugs that were described at the 2016 annual meeting of the American College of Rheumatology, she said.
“We were aware of the abstract, which was also presented at the ACR last fall at the time the current perioperative medication management guidelines were presented, and it won’t change guidelines at this point,” said Dr. Goodman, who is one of the lead authors of the proposed guidelines. “[But] I think [the study] could provide important background information to use in a randomized clinical trial to compare infection on [and] not on TNF inhibitors.”
The proposed guidelines conditionally recommend that all biologics should be withheld prior to surgery in patients with inflammatory arthritis, that surgery should be planned for the end of the dosing cycle, and that current daily doses of glucocorticoids, rather than supraphysiologic doses, should be continued in adults with rheumatoid arthritis, lupus, or inflammatory arthritis.
The National Institutes of Health, the Rheumatology Research Foundation, and the Department of Veterans Affairs funded the study. Dr. George did not report any relevant financial disclosures. Two coauthors disclosed receiving research grants or consulting fees from pharmaceutical companies for unrelated work.
FROM ARTHRITIS CARE & RESEARCH
Key clinical point:
Major finding: Subjects on glucocorticoids had an OR of 2.11 (95% CI 1.30-3.40) for serious infection within 30 days and an HR of 2.70 (95% CI 1.30-5.60) for prosthetic joint infection within 1 year.
Data source: Retrospective cohort study of 4,288 elective knee and hip arthroplasties in Medicare patients with rheumatoid arthritis, inflammatory bowel disease, psoriasis, psoriatic arthritis, or ankylosing spondylitis during 2007-2013.
Disclosures: The National Institutes of Health, the Rheumatology Research Foundation, and the Department of Veterans Affairs funded the study. Dr. George did not report any relevant financial disclosures. Two coauthors disclosed receiving research grants or consulting fees from pharmaceutical companies for unrelated work.