People in this video: Dr. James Griffith, the Leon M. Yochelson Professor of Psychiatry and Behavioral Sciences, and chair of psychiatry and psychosomatic medicine at George Washington University School of Medicine, Washington; Whitney McKnight, cohost and producer of Mental Health Consult.

Whitney: I think we need to step back and define mental illness. For that, I’m going to go to you, Griff, because I think it’s important that we remember not all primary care doctors really do have an understanding of the nuances to definitions of mental health.

You and I were having a discussion about “How do you define depression?” There’s clinical diagnosis of it, but then there are other ways that it gets used.

Dr. James Griffith: There’s a big push in medical education to shorten it, to do more in less time, but this is complex. There has not been much acknowledgment of the complexity. I’ll give you two difficult scenarios.

“Huge numbers of people treated in primary care who would have high scores on the PHQ-9 are in fact just lonely.” – Dr. James GriffithOne is disorder versus distress. If you simply download a Patient Health Questionnaire-9 off the Internet, give it to people: They have a high score; we say they’re depressed, give them an antidepressant. Huge numbers of people in primary care who would have high depression scores, in fact, are lonely; they’re in abusive relationships; they’re grieving losses; they are demoralized because their aspirations in life won’t take place – none of these problems are helped by an antidepressant.

Medical students, or for that matter, psychiatry residents, are not well taught in how to distinguish disorder from distress. All of these are solvable problems. There’s sort of a myth of the depressed patient that if only we would recognize depressed people, give them a prescription, everything would be okay, but it doesn’t.

Whitney: How do you teach that, then? What is missing in the curriculum?

Dr. Griffith: It’s a little bit like what Dr. Kirschner said about money and teams. You don’t have teams, if you don’t have funding. You don’t have teaching, if you don’t have time, and that’s one of our first issues.

People in this video: Dr. James Griffith, the Leon M. Yochelson Professor of Psychiatry and Behavioral Sciences, and chair of psychiatry and psychosomatic medicine at George Washington University School of Medicine, Washington; Whitney McKnight, cohost and producer of Mental Health Consult.

Whitney: I think we need to step back and define mental illness. For that, I’m going to go to you, Griff, because I think it’s important that we remember not all primary care doctors really do have an understanding of the nuances to definitions of mental health.

You and I were having a discussion about “How do you define depression?” There’s clinical diagnosis of it, but then there are other ways that it gets used.

Dr. James Griffith: There’s a big push in medical education to shorten it, to do more in less time, but this is complex. There has not been much acknowledgment of the complexity. I’ll give you two difficult scenarios.

“Huge numbers of people treated in primary care who would have high scores on the PHQ-9 are in fact just lonely.” – Dr. James GriffithOne is disorder versus distress. If you simply download a Patient Health Questionnaire-9 off the Internet, give it to people: They have a high score; we say they’re depressed, give them an antidepressant. Huge numbers of people in primary care who would have high depression scores, in fact, are lonely; they’re in abusive relationships; they’re grieving losses; they are demoralized because their aspirations in life won’t take place – none of these problems are helped by an antidepressant.

Medical students, or for that matter, psychiatry residents, are not well taught in how to distinguish disorder from distress. All of these are solvable problems. There’s sort of a myth of the depressed patient that if only we would recognize depressed people, give them a prescription, everything would be okay, but it doesn’t.

Whitney: How do you teach that, then? What is missing in the curriculum?

Dr. Griffith: It’s a little bit like what Dr. Kirschner said about money and teams. You don’t have teams, if you don’t have funding. You don’t have teaching, if you don’t have time, and that’s one of our first issues.

People in this video: Dr. James Griffith, the Leon M. Yochelson Professor of Psychiatry and Behavioral Sciences, and chair of psychiatry and psychosomatic medicine at George Washington University School of Medicine, Washington; Whitney McKnight, cohost and producer of Mental Health Consult.

Whitney: I think we need to step back and define mental illness. For that, I’m going to go to you, Griff, because I think it’s important that we remember not all primary care doctors really do have an understanding of the nuances to definitions of mental health.

You and I were having a discussion about “How do you define depression?” There’s clinical diagnosis of it, but then there are other ways that it gets used.

Dr. James Griffith: There’s a big push in medical education to shorten it, to do more in less time, but this is complex. There has not been much acknowledgment of the complexity. I’ll give you two difficult scenarios.

“Huge numbers of people treated in primary care who would have high scores on the PHQ-9 are in fact just lonely.” – Dr. James GriffithOne is disorder versus distress. If you simply download a Patient Health Questionnaire-9 off the Internet, give it to people: They have a high score; we say they’re depressed, give them an antidepressant. Huge numbers of people in primary care who would have high depression scores, in fact, are lonely; they’re in abusive relationships; they’re grieving losses; they are demoralized because their aspirations in life won’t take place – none of these problems are helped by an antidepressant.

Medical students, or for that matter, psychiatry residents, are not well taught in how to distinguish disorder from distress. All of these are solvable problems. There’s sort of a myth of the depressed patient that if only we would recognize depressed people, give them a prescription, everything would be okay, but it doesn’t.

Whitney: How do you teach that, then? What is missing in the curriculum?

Dr. Griffith: It’s a little bit like what Dr. Kirschner said about money and teams. You don’t have teams, if you don’t have funding. You don’t have teaching, if you don’t have time, and that’s one of our first issues.

People in this video: Whitney McKnight, cohost and producer of Mental Health Consult; Dr. Lorenzo Norris, editorial board member of Clinical Psychiatry News and cohost of Mental Health Consult, and assistant professor of psychiatry and behavioral sciences, assistant dean of student affairs at G.W. University School of Medicine & Health Sciences, and the medical director of psychiatric and behavioral services at G.W.U. Hospital, Washington; Dr. Lillian Beard, pediatrician with Children’s National Hospital Network, Washington, and a Pediatric News editorial board member; Dr. David Pickar, adjunct professor of psychiatry at Johns Hopkins University School of Medicine, Baltimore, and at the Uniformed Services University of the Health Sciences in Bethesda, Md.; Dr. April Barbour, an associate professor of medicine and the director of general internal medicine and of the primary care residency program at G.W.U. School of Medicine, Washington.

Dr. Beard: This is one of the major frustrations. You've hit it right on the head. I will take anywhere from 45-50 minutes to do this, and I will have others who are waiting in my reception area or I will have a tap on the door. It takes that kind of time and the unfortunate thing is, I am never adequately reimbursed for the time that it really takes. Often, what I do is ask my front desk to screen patients when they call. If they say it is a routine check-up, the front desk knows to ask, "Are there any particular concerns that you have this year. Anything you would like the doctor to focus on?" If they do, then what I have to do is block out three of my regular times and that is very costly.
 
Whitney: As we move into a world in which it is not fee-for-service—based and “I think if it’s possible to have a mental health professional on site [in your practice], it is a win-win situation.” – Dr. Lillian Beardwe have to create these new metrics, I say “we,” but the health care system is moving toward setting up new accountable care organizations or other sorts of bundle payments. When we have the new legislation take effect, the MACRA (Medicaid Access and CHIP Reauthorization Act) legislation, are you building into the metrics that you are going to be reimbursed through your third-party payers to include these 50-minute sessions or is there no way to do that?

Dr. Beard: I do not know of a way to do it. I really do not.

Whitney: How is that going to impact outcomes and reimbursement?

Dr. Beard: Well, it is definitely going to impact outcomes. One of the areas of interest that I have is the feasibility of having a mental health specialist in my actual primary care site. Even if it is for a few segments a week, it would be a tremendous help. Just having that individual present removes certain barriers. For example, there are times that, even during the primary care encounter, the mental health specialist is able to say to the patient’s parents, “We’ll be glad to make an appointment and discuss that with you at a future time, so we can go more in depth.” Just that introduction lowers the barrier. Otherwise, there is more resistance if I say, “I am going to refer you to Dr. Pickar he is an associate who…” They object, and want to know, “Well, what kind of doctor is Dr. Pickar? He is a psychiatrist?”  It depends on what association they have with the word “psychiatrist.” The parents might object, “My kid’s not crazy.” I have to explain that this is a mental health disorder that we can do something about, and the psychiatrist is going to assist us with that.

Dr. Pickar: That is a great model.

Whitney: Yes but is it feasible with all the new legislation that is coming down the line?

Dr. Barbour: I think there are very dramatic differences between the pediatric model of care, which tends to be more wraparound care that you are describing; (should this be “that” or “than”?) and the adult model of care, which is more consumer driven and in which we expect a lot of our patients. We find particularly that young people transitioning to their early 20s often have a hard time understanding how to interact in the adult model of care. Particularly the patients that we have worked on have had significant health problems, many of which include mental health disorders. The program that we put in place has some psychiatric services available in the clinic. That is not feasible – I think – in our current payment structure to do that everywhere, in all adult medicine clinics.

I think these patients are particularly vulnerable. They do not understand the health care systems. They come in with these diagnoses. You bring up ADHD and that is something an internist is not as comfortable in providing care for as you are, and that I think causes a lot of roadblocks for patients to get the medicines they need. It has worked well for them, but the new doctor is not as comfortable prescribing the medicine or making the diagnosis. There are issues around that.

Dr. Norris: This is one of points of the roundtable. Who should be delivering this treatment? If you can create a team based atmosphere where what Dr. Beard illustrated, just the introduction. "I want to introduce you to my colleague so that we can start treatment." That one element, just starting that can make a huge difference, but how do you make that fiscally viable? In the George Washington University Hospital Thriving After Cancer clinic, we used resident psychiatrist in training. These are senior-level residents who are very good at that or are supervised by a psychiatrist. If you were to put a psychiatrist in the TAC clinic and bill for their hours, it just would not work, Dr. Barbour is shaking her head like no way.

Dr. Barbour: I could not afford it.

Dr. Beard: What I am thinking is that this other professional, be it a psychiatrist or psychologist, a licensed clinical social worker, whatever, will have the capability of billing for his or her services. I think if it is possible to have that professional in your site it is a win/win situation.

People in this video: Whitney McKnight, cohost and producer of Mental Health Consult; Dr. Lorenzo Norris, editorial board member of Clinical Psychiatry News and cohost of Mental Health Consult, and assistant professor of psychiatry and behavioral sciences, assistant dean of student affairs at G.W. University School of Medicine & Health Sciences, and the medical director of psychiatric and behavioral services at G.W.U. Hospital, Washington; Dr. Lillian Beard, pediatrician with Children’s National Hospital Network, Washington, and a Pediatric News editorial board member; Dr. David Pickar, adjunct professor of psychiatry at Johns Hopkins University School of Medicine, Baltimore, and at the Uniformed Services University of the Health Sciences in Bethesda, Md.; Dr. April Barbour, an associate professor of medicine and the director of general internal medicine and of the primary care residency program at G.W.U. School of Medicine, Washington.

Dr. Beard: This is one of the major frustrations. You've hit it right on the head. I will take anywhere from 45-50 minutes to do this, and I will have others who are waiting in my reception area or I will have a tap on the door. It takes that kind of time and the unfortunate thing is, I am never adequately reimbursed for the time that it really takes. Often, what I do is ask my front desk to screen patients when they call. If they say it is a routine check-up, the front desk knows to ask, "Are there any particular concerns that you have this year. Anything you would like the doctor to focus on?" If they do, then what I have to do is block out three of my regular times and that is very costly.
 
Whitney: As we move into a world in which it is not fee-for-service—based and “I think if it’s possible to have a mental health professional on site [in your practice], it is a win-win situation.” – Dr. Lillian Beardwe have to create these new metrics, I say “we,” but the health care system is moving toward setting up new accountable care organizations or other sorts of bundle payments. When we have the new legislation take effect, the MACRA (Medicaid Access and CHIP Reauthorization Act) legislation, are you building into the metrics that you are going to be reimbursed through your third-party payers to include these 50-minute sessions or is there no way to do that?

Dr. Beard: I do not know of a way to do it. I really do not.

Whitney: How is that going to impact outcomes and reimbursement?

Dr. Beard: Well, it is definitely going to impact outcomes. One of the areas of interest that I have is the feasibility of having a mental health specialist in my actual primary care site. Even if it is for a few segments a week, it would be a tremendous help. Just having that individual present removes certain barriers. For example, there are times that, even during the primary care encounter, the mental health specialist is able to say to the patient’s parents, “We’ll be glad to make an appointment and discuss that with you at a future time, so we can go more in depth.” Just that introduction lowers the barrier. Otherwise, there is more resistance if I say, “I am going to refer you to Dr. Pickar he is an associate who…” They object, and want to know, “Well, what kind of doctor is Dr. Pickar? He is a psychiatrist?”  It depends on what association they have with the word “psychiatrist.” The parents might object, “My kid’s not crazy.” I have to explain that this is a mental health disorder that we can do something about, and the psychiatrist is going to assist us with that.

Dr. Pickar: That is a great model.

Whitney: Yes but is it feasible with all the new legislation that is coming down the line?

Dr. Barbour: I think there are very dramatic differences between the pediatric model of care, which tends to be more wraparound care that you are describing; (should this be “that” or “than”?) and the adult model of care, which is more consumer driven and in which we expect a lot of our patients. We find particularly that young people transitioning to their early 20s often have a hard time understanding how to interact in the adult model of care. Particularly the patients that we have worked on have had significant health problems, many of which include mental health disorders. The program that we put in place has some psychiatric services available in the clinic. That is not feasible – I think – in our current payment structure to do that everywhere, in all adult medicine clinics.

I think these patients are particularly vulnerable. They do not understand the health care systems. They come in with these diagnoses. You bring up ADHD and that is something an internist is not as comfortable in providing care for as you are, and that I think causes a lot of roadblocks for patients to get the medicines they need. It has worked well for them, but the new doctor is not as comfortable prescribing the medicine or making the diagnosis. There are issues around that.

Dr. Norris: This is one of points of the roundtable. Who should be delivering this treatment? If you can create a team based atmosphere where what Dr. Beard illustrated, just the introduction. "I want to introduce you to my colleague so that we can start treatment." That one element, just starting that can make a huge difference, but how do you make that fiscally viable? In the George Washington University Hospital Thriving After Cancer clinic, we used resident psychiatrist in training. These are senior-level residents who are very good at that or are supervised by a psychiatrist. If you were to put a psychiatrist in the TAC clinic and bill for their hours, it just would not work, Dr. Barbour is shaking her head like no way.

Dr. Barbour: I could not afford it.

Dr. Beard: What I am thinking is that this other professional, be it a psychiatrist or psychologist, a licensed clinical social worker, whatever, will have the capability of billing for his or her services. I think if it is possible to have that professional in your site it is a win/win situation.

People in this video: Whitney McKnight, cohost and producer of Mental Health Consult; Dr. Lorenzo Norris, editorial board member of Clinical Psychiatry News and cohost of Mental Health Consult, and assistant professor of psychiatry and behavioral sciences, assistant dean of student affairs at G.W. University School of Medicine & Health Sciences, and the medical director of psychiatric and behavioral services at G.W.U. Hospital, Washington; Dr. Lillian Beard, pediatrician with Children’s National Hospital Network, Washington, and a Pediatric News editorial board member; Dr. David Pickar, adjunct professor of psychiatry at Johns Hopkins University School of Medicine, Baltimore, and at the Uniformed Services University of the Health Sciences in Bethesda, Md.; Dr. April Barbour, an associate professor of medicine and the director of general internal medicine and of the primary care residency program at G.W.U. School of Medicine, Washington.

Dr. Beard: This is one of the major frustrations. You've hit it right on the head. I will take anywhere from 45-50 minutes to do this, and I will have others who are waiting in my reception area or I will have a tap on the door. It takes that kind of time and the unfortunate thing is, I am never adequately reimbursed for the time that it really takes. Often, what I do is ask my front desk to screen patients when they call. If they say it is a routine check-up, the front desk knows to ask, "Are there any particular concerns that you have this year. Anything you would like the doctor to focus on?" If they do, then what I have to do is block out three of my regular times and that is very costly.
 
Whitney: As we move into a world in which it is not fee-for-service—based and “I think if it’s possible to have a mental health professional on site [in your practice], it is a win-win situation.” – Dr. Lillian Beardwe have to create these new metrics, I say “we,” but the health care system is moving toward setting up new accountable care organizations or other sorts of bundle payments. When we have the new legislation take effect, the MACRA (Medicaid Access and CHIP Reauthorization Act) legislation, are you building into the metrics that you are going to be reimbursed through your third-party payers to include these 50-minute sessions or is there no way to do that?

Dr. Beard: I do not know of a way to do it. I really do not.

Whitney: How is that going to impact outcomes and reimbursement?

Dr. Beard: Well, it is definitely going to impact outcomes. One of the areas of interest that I have is the feasibility of having a mental health specialist in my actual primary care site. Even if it is for a few segments a week, it would be a tremendous help. Just having that individual present removes certain barriers. For example, there are times that, even during the primary care encounter, the mental health specialist is able to say to the patient’s parents, “We’ll be glad to make an appointment and discuss that with you at a future time, so we can go more in depth.” Just that introduction lowers the barrier. Otherwise, there is more resistance if I say, “I am going to refer you to Dr. Pickar he is an associate who…” They object, and want to know, “Well, what kind of doctor is Dr. Pickar? He is a psychiatrist?”  It depends on what association they have with the word “psychiatrist.” The parents might object, “My kid’s not crazy.” I have to explain that this is a mental health disorder that we can do something about, and the psychiatrist is going to assist us with that.

Dr. Pickar: That is a great model.

Whitney: Yes but is it feasible with all the new legislation that is coming down the line?

Dr. Barbour: I think there are very dramatic differences between the pediatric model of care, which tends to be more wraparound care that you are describing; (should this be “that” or “than”?) and the adult model of care, which is more consumer driven and in which we expect a lot of our patients. We find particularly that young people transitioning to their early 20s often have a hard time understanding how to interact in the adult model of care. Particularly the patients that we have worked on have had significant health problems, many of which include mental health disorders. The program that we put in place has some psychiatric services available in the clinic. That is not feasible – I think – in our current payment structure to do that everywhere, in all adult medicine clinics.

I think these patients are particularly vulnerable. They do not understand the health care systems. They come in with these diagnoses. You bring up ADHD and that is something an internist is not as comfortable in providing care for as you are, and that I think causes a lot of roadblocks for patients to get the medicines they need. It has worked well for them, but the new doctor is not as comfortable prescribing the medicine or making the diagnosis. There are issues around that.

Dr. Norris: This is one of points of the roundtable. Who should be delivering this treatment? If you can create a team based atmosphere where what Dr. Beard illustrated, just the introduction. "I want to introduce you to my colleague so that we can start treatment." That one element, just starting that can make a huge difference, but how do you make that fiscally viable? In the George Washington University Hospital Thriving After Cancer clinic, we used resident psychiatrist in training. These are senior-level residents who are very good at that or are supervised by a psychiatrist. If you were to put a psychiatrist in the TAC clinic and bill for their hours, it just would not work, Dr. Barbour is shaking her head like no way.

Dr. Barbour: I could not afford it.

Dr. Beard: What I am thinking is that this other professional, be it a psychiatrist or psychologist, a licensed clinical social worker, whatever, will have the capability of billing for his or her services. I think if it is possible to have that professional in your site it is a win/win situation.

When I think of the word “relationship,” I imagine gazing into the loving eyes of my husband, playing hide and seek with my children, or texting my best friend for no good reason other than to just say hello.

There is a special comfort zone we expect from people who are close to us; a feeling of love and acceptance that we can’t find elsewhere.

But in a much broader sense, our important relationships extend far beyond our inner circle to include every single person who is involved with our health care team. Our team includes the hospital executives who create new safety initiatives, develop budgets, and oversee a host of other patient care and fiscal functions. The physical therapists who evaluate our patients and make recommendations on how to safely transition them out of the hospital are on our team. The housekeepers who scrub the toilets and wash the linens to prevent nosocomial infections are on our team. They, along with many others, play a pivotal role in our patients’ care, although many important players make their impact behind the scenes.

Yet, of course, our most important professional relationships are not with the CEO, the pharmacist, or even the nursing staff. Our most important relationships are with our patients and their families. I recently attended an all-day conference on a little-known gem called Relationship-Based Care (RBC), a culture transformation and operational model that is gaining steam globally. The RBC model focuses not only on well-known metrics, such as patient safety, quality care, and patient satisfaction; it also emphasizes staff satisfaction by improving each and every relationship. Specifically, it creates therapeutic relationships between caregivers and the patients and families they serve, strengthens relationships between members of the health care team, and last, but certainly not least, it nurtures each caregiver’s relationship with himself or herself. What a novel, and much needed concept!

Numerous hospitals that have implemented this training model have achieved impressive outcomes, including significant improvement in HCAHPS (Hospital Consumer Assessment of Healthcare Providers and Systems) scores, and staff satisfaction survey scores so high that one hospital gained national recognition as one of the best places to work in America.

I look forward to future training on RBC and am glad to see that addressing the needs of caregivers, not just care receivers, is starting to take center stage, as it rightfully should. After all, how can we give our all to our patients when we are not whole?

Dr. Hester is a hospitalist at Baltimore-Washington Medical Center in Glen Burnie, Md. She is the creator of the Patient Whiz, a patient-engagement app for iOS. Reach her at healthsavvy@aol.com.

When I think of the word “relationship,” I imagine gazing into the loving eyes of my husband, playing hide and seek with my children, or texting my best friend for no good reason other than to just say hello.

There is a special comfort zone we expect from people who are close to us; a feeling of love and acceptance that we can’t find elsewhere.

But in a much broader sense, our important relationships extend far beyond our inner circle to include every single person who is involved with our health care team. Our team includes the hospital executives who create new safety initiatives, develop budgets, and oversee a host of other patient care and fiscal functions. The physical therapists who evaluate our patients and make recommendations on how to safely transition them out of the hospital are on our team. The housekeepers who scrub the toilets and wash the linens to prevent nosocomial infections are on our team. They, along with many others, play a pivotal role in our patients’ care, although many important players make their impact behind the scenes.

Yet, of course, our most important professional relationships are not with the CEO, the pharmacist, or even the nursing staff. Our most important relationships are with our patients and their families. I recently attended an all-day conference on a little-known gem called Relationship-Based Care (RBC), a culture transformation and operational model that is gaining steam globally. The RBC model focuses not only on well-known metrics, such as patient safety, quality care, and patient satisfaction; it also emphasizes staff satisfaction by improving each and every relationship. Specifically, it creates therapeutic relationships between caregivers and the patients and families they serve, strengthens relationships between members of the health care team, and last, but certainly not least, it nurtures each caregiver’s relationship with himself or herself. What a novel, and much needed concept!

Numerous hospitals that have implemented this training model have achieved impressive outcomes, including significant improvement in HCAHPS (Hospital Consumer Assessment of Healthcare Providers and Systems) scores, and staff satisfaction survey scores so high that one hospital gained national recognition as one of the best places to work in America.

I look forward to future training on RBC and am glad to see that addressing the needs of caregivers, not just care receivers, is starting to take center stage, as it rightfully should. After all, how can we give our all to our patients when we are not whole?

Dr. Hester is a hospitalist at Baltimore-Washington Medical Center in Glen Burnie, Md. She is the creator of the Patient Whiz, a patient-engagement app for iOS. Reach her at healthsavvy@aol.com.

When I think of the word “relationship,” I imagine gazing into the loving eyes of my husband, playing hide and seek with my children, or texting my best friend for no good reason other than to just say hello.

There is a special comfort zone we expect from people who are close to us; a feeling of love and acceptance that we can’t find elsewhere.

But in a much broader sense, our important relationships extend far beyond our inner circle to include every single person who is involved with our health care team. Our team includes the hospital executives who create new safety initiatives, develop budgets, and oversee a host of other patient care and fiscal functions. The physical therapists who evaluate our patients and make recommendations on how to safely transition them out of the hospital are on our team. The housekeepers who scrub the toilets and wash the linens to prevent nosocomial infections are on our team. They, along with many others, play a pivotal role in our patients’ care, although many important players make their impact behind the scenes.

Yet, of course, our most important professional relationships are not with the CEO, the pharmacist, or even the nursing staff. Our most important relationships are with our patients and their families. I recently attended an all-day conference on a little-known gem called Relationship-Based Care (RBC), a culture transformation and operational model that is gaining steam globally. The RBC model focuses not only on well-known metrics, such as patient safety, quality care, and patient satisfaction; it also emphasizes staff satisfaction by improving each and every relationship. Specifically, it creates therapeutic relationships between caregivers and the patients and families they serve, strengthens relationships between members of the health care team, and last, but certainly not least, it nurtures each caregiver’s relationship with himself or herself. What a novel, and much needed concept!

Numerous hospitals that have implemented this training model have achieved impressive outcomes, including significant improvement in HCAHPS (Hospital Consumer Assessment of Healthcare Providers and Systems) scores, and staff satisfaction survey scores so high that one hospital gained national recognition as one of the best places to work in America.

I look forward to future training on RBC and am glad to see that addressing the needs of caregivers, not just care receivers, is starting to take center stage, as it rightfully should. After all, how can we give our all to our patients when we are not whole?

Dr. Hester is a hospitalist at Baltimore-Washington Medical Center in Glen Burnie, Md. She is the creator of the Patient Whiz, a patient-engagement app for iOS. Reach her at healthsavvy@aol.com.

Radiography detected up to 16% of cases of hip osteoarthritis among older patients with frequent hip pain in an analysis of participants in the Framingham Osteoarthritis Study and the Osteoarthritis Initiative.

“In older patients, inadequate recognition of osteoarthritis has consequences. Decreased functional status from osteoarthritis significantly increases morbidity from coronary heart disease, lung disease, diabetes, obesity, falls, frailty, and various other ailments,” said Dr. Chan Kim of Boston University and his associates. “Because many patients with hip pain do not have radiographic hip osteoarthritis, a health professional should continue with the evaluation and treatment of osteoarthritis, despite negative radiographic findings.”

© iStock / ThinkStockPhotos.com

Radiographic pathology often is detected late in the course of knee OA and correlates poorly with knee pain, but few studies have examined these trends for the hip. The researchers analyzed pelvic radiographs and hip pain among 946 participants in the Framingham Osteoarthritis Study and 4,366 participants in the Osteoarthritis Initiative. They defined radiographic hip OA as a Kellgren-Lawrence grade of 2 or more – that is, definite superolateral or superomedial joint space narrowing and a definite osteophyte. They used various clinical symptoms of hip OA for comparison. Participants in both studies were older than 45 years, and tended to be in their early 60s (BMJ 2015 Dec 2. doi: 10.1136/bmj.h5983).

The most sensitive criterion in the study was groin pain, for which radiography was positive in 37% of hips in the Framingham Study and 17% of hips in the Osteoarthritis Initiative, the researchers said. Other clinical criteria were less sensitive, including anterior thigh pain, frequent hip pain, and painful internal rotation. Moreover, about 21%-24% of hips with radiographic OA were frequently painful.

The study did not evaluate MRI findings, the investigators noted. They suggested that such results would resemble those for the knee, in which MRI is “more sensitive than radiography, [but] it is far less specific for abnormalities suggestive of osteoarthritis in most middle-aged and older people.”

The National Institute of Arthritis and Musculoskeletal and Skin Diseases funded the study. The Osteoarthritis Initiative is funded by the National Institutes of Health, Merck Research Laboratories, Novartis, GlaxoSmithKline, and Pfizer. The researchers had no disclosures.

Radiography detected up to 16% of cases of hip osteoarthritis among older patients with frequent hip pain in an analysis of participants in the Framingham Osteoarthritis Study and the Osteoarthritis Initiative.

“In older patients, inadequate recognition of osteoarthritis has consequences. Decreased functional status from osteoarthritis significantly increases morbidity from coronary heart disease, lung disease, diabetes, obesity, falls, frailty, and various other ailments,” said Dr. Chan Kim of Boston University and his associates. “Because many patients with hip pain do not have radiographic hip osteoarthritis, a health professional should continue with the evaluation and treatment of osteoarthritis, despite negative radiographic findings.”

© iStock / ThinkStockPhotos.com

Radiographic pathology often is detected late in the course of knee OA and correlates poorly with knee pain, but few studies have examined these trends for the hip. The researchers analyzed pelvic radiographs and hip pain among 946 participants in the Framingham Osteoarthritis Study and 4,366 participants in the Osteoarthritis Initiative. They defined radiographic hip OA as a Kellgren-Lawrence grade of 2 or more – that is, definite superolateral or superomedial joint space narrowing and a definite osteophyte. They used various clinical symptoms of hip OA for comparison. Participants in both studies were older than 45 years, and tended to be in their early 60s (BMJ 2015 Dec 2. doi: 10.1136/bmj.h5983).

The most sensitive criterion in the study was groin pain, for which radiography was positive in 37% of hips in the Framingham Study and 17% of hips in the Osteoarthritis Initiative, the researchers said. Other clinical criteria were less sensitive, including anterior thigh pain, frequent hip pain, and painful internal rotation. Moreover, about 21%-24% of hips with radiographic OA were frequently painful.

The study did not evaluate MRI findings, the investigators noted. They suggested that such results would resemble those for the knee, in which MRI is “more sensitive than radiography, [but] it is far less specific for abnormalities suggestive of osteoarthritis in most middle-aged and older people.”

The National Institute of Arthritis and Musculoskeletal and Skin Diseases funded the study. The Osteoarthritis Initiative is funded by the National Institutes of Health, Merck Research Laboratories, Novartis, GlaxoSmithKline, and Pfizer. The researchers had no disclosures.

Radiography detected up to 16% of cases of hip osteoarthritis among older patients with frequent hip pain in an analysis of participants in the Framingham Osteoarthritis Study and the Osteoarthritis Initiative.

“In older patients, inadequate recognition of osteoarthritis has consequences. Decreased functional status from osteoarthritis significantly increases morbidity from coronary heart disease, lung disease, diabetes, obesity, falls, frailty, and various other ailments,” said Dr. Chan Kim of Boston University and his associates. “Because many patients with hip pain do not have radiographic hip osteoarthritis, a health professional should continue with the evaluation and treatment of osteoarthritis, despite negative radiographic findings.”

© iStock / ThinkStockPhotos.com

Radiographic pathology often is detected late in the course of knee OA and correlates poorly with knee pain, but few studies have examined these trends for the hip. The researchers analyzed pelvic radiographs and hip pain among 946 participants in the Framingham Osteoarthritis Study and 4,366 participants in the Osteoarthritis Initiative. They defined radiographic hip OA as a Kellgren-Lawrence grade of 2 or more – that is, definite superolateral or superomedial joint space narrowing and a definite osteophyte. They used various clinical symptoms of hip OA for comparison. Participants in both studies were older than 45 years, and tended to be in their early 60s (BMJ 2015 Dec 2. doi: 10.1136/bmj.h5983).

The most sensitive criterion in the study was groin pain, for which radiography was positive in 37% of hips in the Framingham Study and 17% of hips in the Osteoarthritis Initiative, the researchers said. Other clinical criteria were less sensitive, including anterior thigh pain, frequent hip pain, and painful internal rotation. Moreover, about 21%-24% of hips with radiographic OA were frequently painful.

The study did not evaluate MRI findings, the investigators noted. They suggested that such results would resemble those for the knee, in which MRI is “more sensitive than radiography, [but] it is far less specific for abnormalities suggestive of osteoarthritis in most middle-aged and older people.”

The National Institute of Arthritis and Musculoskeletal and Skin Diseases funded the study. The Osteoarthritis Initiative is funded by the National Institutes of Health, Merck Research Laboratories, Novartis, GlaxoSmithKline, and Pfizer. The researchers had no disclosures.

Lateral wedge insoles worn by people with medial knee osteoarthritis (OA) provide a limited amount of immediate biomechanical improvement during walking and may be best suited to people who have biomechanical phenotypes that would benefit the most, according to findings from a systematic review and meta-analysis of studies examining the intraindividual effects of the insoles.

“This review is ... the most definitive, up-to-date and comprehensive analysis on this issue to clarify the effects of lateral wedge insoles on biomechanical risk factors for knee OA progression,” wrote lead investigator John Arnold, Ph.D., of the University of South Australia, Adelaide, and his colleagues (Arthritis Care Res. 2015 Nov 25. doi: 10.1002/acr.22797).

Courtesy National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

The investigators reviewed 18 studies with a total of 534 participants and found small, but statistically significant reductions in estimates of knee joint loading based on the surrogate measures of external knee adduction moment (EKAM) and the knee adduction angular impulse (KAAI).

Most studies (14) tested full-length insoles, and the remaining four allowed a customized amount based on comfort and/or pain level. Another two used heel wedges, and two others tested both. The inclination angle of the insoles was most commonly 5 degrees, but ranged from 4 to 11 degrees. Some studies used a concomitant medial arch support; these were of a generic design in four studies and were made to order in another three. The lateral wedge insoles were compared against flat insoles, the patients’ own footwear, or standardized footwear.

The pooled effect sizes of both the first and second peak EKAM reductions were small, with standard mean differences of –0.20 to –0.25. For the first EKAM, the effect sizes did not vary according to whether studies used flat insoles or shoes only as comparators, whereas for the eight studies that reported second EKAM outcomes, there was a larger pooled effect size for comparisons against shoe-only than for one study that made flat insole comparisons. The pooled estimate for the standard mean difference in nine studies that reported KAAI was –0.14.

There was only weak evidence for publication bias in all the comparisons for the surrogate measures, and most had a low level of statistical heterogeneity between the outcomes of the studies.

The investigators noted that this meta-analysis of surrogate measures for knee joint loading does not take cumulative loading into account, so that even though the reduction in peak EKAM and KAAI was small, it may amount “to a large cumulative effect imparted on the knee over the course of the day. This should be considered when interpreting the findings of this review and future research on load modifying interventions in knee osteoarthritis.” They said that while EKAM has been associated with OA progression, KAAI has been thought to be a better measure of the duration and magnitude of loading in knee OA and has been associated with medial tibiofemoral cartilage loss over 1-2 years.

“Prescription [for lateral wedge insoles] based on biomechanical response and use of insoles only in individuals who show reductions in knee joint loading (biomechanical phenotypes) appears more appropriate to increase the likelihood of a favorable long-term response regarding the attenuation of structural changes. This would limit their application and benefit to a smaller number of individuals, but is still likely to be significant considering the overall prevalence of knee OA and projected rise due to population aging and rising obesity levels,” the authors concluded.

The investigators had no outside funding source for their systematic review. One of the authors may receive royalties from Salford Insole, a manufacturer of lateral wedge insoles.

jevans@frontlinemedcom.com

Lateral wedge insoles worn by people with medial knee osteoarthritis (OA) provide a limited amount of immediate biomechanical improvement during walking and may be best suited to people who have biomechanical phenotypes that would benefit the most, according to findings from a systematic review and meta-analysis of studies examining the intraindividual effects of the insoles.

“This review is ... the most definitive, up-to-date and comprehensive analysis on this issue to clarify the effects of lateral wedge insoles on biomechanical risk factors for knee OA progression,” wrote lead investigator John Arnold, Ph.D., of the University of South Australia, Adelaide, and his colleagues (Arthritis Care Res. 2015 Nov 25. doi: 10.1002/acr.22797).

Courtesy National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

The investigators reviewed 18 studies with a total of 534 participants and found small, but statistically significant reductions in estimates of knee joint loading based on the surrogate measures of external knee adduction moment (EKAM) and the knee adduction angular impulse (KAAI).

Most studies (14) tested full-length insoles, and the remaining four allowed a customized amount based on comfort and/or pain level. Another two used heel wedges, and two others tested both. The inclination angle of the insoles was most commonly 5 degrees, but ranged from 4 to 11 degrees. Some studies used a concomitant medial arch support; these were of a generic design in four studies and were made to order in another three. The lateral wedge insoles were compared against flat insoles, the patients’ own footwear, or standardized footwear.

The pooled effect sizes of both the first and second peak EKAM reductions were small, with standard mean differences of –0.20 to –0.25. For the first EKAM, the effect sizes did not vary according to whether studies used flat insoles or shoes only as comparators, whereas for the eight studies that reported second EKAM outcomes, there was a larger pooled effect size for comparisons against shoe-only than for one study that made flat insole comparisons. The pooled estimate for the standard mean difference in nine studies that reported KAAI was –0.14.

There was only weak evidence for publication bias in all the comparisons for the surrogate measures, and most had a low level of statistical heterogeneity between the outcomes of the studies.

The investigators noted that this meta-analysis of surrogate measures for knee joint loading does not take cumulative loading into account, so that even though the reduction in peak EKAM and KAAI was small, it may amount “to a large cumulative effect imparted on the knee over the course of the day. This should be considered when interpreting the findings of this review and future research on load modifying interventions in knee osteoarthritis.” They said that while EKAM has been associated with OA progression, KAAI has been thought to be a better measure of the duration and magnitude of loading in knee OA and has been associated with medial tibiofemoral cartilage loss over 1-2 years.

“Prescription [for lateral wedge insoles] based on biomechanical response and use of insoles only in individuals who show reductions in knee joint loading (biomechanical phenotypes) appears more appropriate to increase the likelihood of a favorable long-term response regarding the attenuation of structural changes. This would limit their application and benefit to a smaller number of individuals, but is still likely to be significant considering the overall prevalence of knee OA and projected rise due to population aging and rising obesity levels,” the authors concluded.

The investigators had no outside funding source for their systematic review. One of the authors may receive royalties from Salford Insole, a manufacturer of lateral wedge insoles.

jevans@frontlinemedcom.com

Lateral wedge insoles worn by people with medial knee osteoarthritis (OA) provide a limited amount of immediate biomechanical improvement during walking and may be best suited to people who have biomechanical phenotypes that would benefit the most, according to findings from a systematic review and meta-analysis of studies examining the intraindividual effects of the insoles.

“This review is ... the most definitive, up-to-date and comprehensive analysis on this issue to clarify the effects of lateral wedge insoles on biomechanical risk factors for knee OA progression,” wrote lead investigator John Arnold, Ph.D., of the University of South Australia, Adelaide, and his colleagues (Arthritis Care Res. 2015 Nov 25. doi: 10.1002/acr.22797).

Courtesy National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

The investigators reviewed 18 studies with a total of 534 participants and found small, but statistically significant reductions in estimates of knee joint loading based on the surrogate measures of external knee adduction moment (EKAM) and the knee adduction angular impulse (KAAI).

Most studies (14) tested full-length insoles, and the remaining four allowed a customized amount based on comfort and/or pain level. Another two used heel wedges, and two others tested both. The inclination angle of the insoles was most commonly 5 degrees, but ranged from 4 to 11 degrees. Some studies used a concomitant medial arch support; these were of a generic design in four studies and were made to order in another three. The lateral wedge insoles were compared against flat insoles, the patients’ own footwear, or standardized footwear.

The pooled effect sizes of both the first and second peak EKAM reductions were small, with standard mean differences of –0.20 to –0.25. For the first EKAM, the effect sizes did not vary according to whether studies used flat insoles or shoes only as comparators, whereas for the eight studies that reported second EKAM outcomes, there was a larger pooled effect size for comparisons against shoe-only than for one study that made flat insole comparisons. The pooled estimate for the standard mean difference in nine studies that reported KAAI was –0.14.

There was only weak evidence for publication bias in all the comparisons for the surrogate measures, and most had a low level of statistical heterogeneity between the outcomes of the studies.

The investigators noted that this meta-analysis of surrogate measures for knee joint loading does not take cumulative loading into account, so that even though the reduction in peak EKAM and KAAI was small, it may amount “to a large cumulative effect imparted on the knee over the course of the day. This should be considered when interpreting the findings of this review and future research on load modifying interventions in knee osteoarthritis.” They said that while EKAM has been associated with OA progression, KAAI has been thought to be a better measure of the duration and magnitude of loading in knee OA and has been associated with medial tibiofemoral cartilage loss over 1-2 years.

“Prescription [for lateral wedge insoles] based on biomechanical response and use of insoles only in individuals who show reductions in knee joint loading (biomechanical phenotypes) appears more appropriate to increase the likelihood of a favorable long-term response regarding the attenuation of structural changes. This would limit their application and benefit to a smaller number of individuals, but is still likely to be significant considering the overall prevalence of knee OA and projected rise due to population aging and rising obesity levels,” the authors concluded.

The investigators had no outside funding source for their systematic review. One of the authors may receive royalties from Salford Insole, a manufacturer of lateral wedge insoles.

jevans@frontlinemedcom.com

James N. Kochenderfer, MD

Photo courtesy of ASH

ORLANDO, FL—Allogeneic chimeric antigen receptor (CAR) T cells directed against CD19 can have “significant” activity against resistant B-cell malignancies, even when given without prior chemotherapy, according to a presentation at the 2015 ASH Annual Meeting.

Nine of 20 patients responded to treatment with the CAR T cells, despite having failed prior allogeneic transplant. The best responses were observed in patients with acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL).

“Malignancies that were resistant to allogeneic transplants and standard donor lymphocyte infusions regressed after infusions of allogeneic anti-CD19 CAR T cells,” said James N. Kochenderfer, MD, of the National Cancer Institute in Bethesda, Maryland.

“Allogeneic anti-CD19 CAR T cells seem to be particularly effective against ALL and CLL, suggesting a possible antigenic stimulation that may be more pronounced in these malignancies.”

Adverse events associated with these CAR T cells included severe but reversible cytokine release syndrome, mild aphasia, and muscle damage. There were no cases of acute graft-vs-host disease (GVHD).

Dr Kochenderfer presented these results at ASH as abstract 99.

For this phase 1 study, researchers tested a CAR T-cell therapy that was originally developed by Dr Kochenderfer and his colleagues. The therapy is now known as KTE-C19 and is under development by Kite Pharmaceuticals. However, the company did not sponsor this trial.

The study was open to patients with any CD19+ B-cell malignancy that persisted after allogeneic transplant.

All patients except those with ALL were required to have received at least one standard donor lymphocyte infusion. In addition, patients were only eligible if they had minimal or no GVHD and were not receiving any systemic immunosuppressive drugs.

The trial included 20 patients—5 each with ALL, CLL, mantle cell lymphoma (MCL), and diffuse large B-cell lymphoma (DLBCL).

All patients received a single infusion of CAR T cells derived from their original transplant donor. Production of these cells took 8 days. The highest dose of CAR T cells given was 10⁷ cells/kg.

Four of the ALL patients obtained a minimal-residual disease-negative complete response (CR), but 2 of these patients subsequently relapsed. Of the other 2 patients, 1 remains in CR at 18 months of follow-up, and the other went on to receive a second allogeneic transplant. That patient remains in CR today.

Among the CLL patients, 1 achieved a CR, and 1 achieved a partial response (PR). One patient had stable disease (SD), and the other 2 progressed. Both the CR and the PR are ongoing at 36 and 18 months of follow-up, respectively.

One MCL patient achieved a CR, 1 had a PR, and 3 had SD. The CR is ongoing at 31 months. One DLBCL patient achieved a CR, 3 had SD, and 1 progressed.

Dr Kochenderfer noted that response was associated with higher blood CAR T-cell levels. There was a significant difference in CAR T-cell levels between responders and nonresponders (P=0.001).

In addition, the presence of blood B-cell levels before CAR T-cell infusion was associated with higher blood CAR T-cell levels. Patients with normal or high B lymphocytes had higher levels of CAR T cells in their blood (P=0.04).

Patients with high tumor burdens developed severe cytokine-release syndrome with fever, tachycardia, and hypotension. The ALL patients were particularly susceptible to cytokine-release syndrome.

Dr Kochenderfer said neurologic toxicity was rare and mild. There was 1 case of mild aphasia.

There were 2 patients with elevations in CPK, indicating muscle damage. Those patients also reported muscle pain, and 1 patient reported weakness.

“This is one of the first reports, I think, of muscle damage in CAR T-cell patients,” Dr Kochenderfer said.

None of the patients developed acute GVHD after CAR T-cell therapy. One patient had continued worsening of pre-existing chronic GVHD after treatment, and 1 patient developed mild chronic eye GVHD more than a year after CAR T-cell infusion.

Dr Kochenderfer said additional details from this trial will be published in an upcoming issue of the Journal of Clinical Oncology.

James N. Kochenderfer, MD

Photo courtesy of ASH

ORLANDO, FL—Allogeneic chimeric antigen receptor (CAR) T cells directed against CD19 can have “significant” activity against resistant B-cell malignancies, even when given without prior chemotherapy, according to a presentation at the 2015 ASH Annual Meeting.

Nine of 20 patients responded to treatment with the CAR T cells, despite having failed prior allogeneic transplant. The best responses were observed in patients with acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL).

“Malignancies that were resistant to allogeneic transplants and standard donor lymphocyte infusions regressed after infusions of allogeneic anti-CD19 CAR T cells,” said James N. Kochenderfer, MD, of the National Cancer Institute in Bethesda, Maryland.

“Allogeneic anti-CD19 CAR T cells seem to be particularly effective against ALL and CLL, suggesting a possible antigenic stimulation that may be more pronounced in these malignancies.”

Adverse events associated with these CAR T cells included severe but reversible cytokine release syndrome, mild aphasia, and muscle damage. There were no cases of acute graft-vs-host disease (GVHD).

Dr Kochenderfer presented these results at ASH as abstract 99.

For this phase 1 study, researchers tested a CAR T-cell therapy that was originally developed by Dr Kochenderfer and his colleagues. The therapy is now known as KTE-C19 and is under development by Kite Pharmaceuticals. However, the company did not sponsor this trial.

The study was open to patients with any CD19+ B-cell malignancy that persisted after allogeneic transplant.

All patients except those with ALL were required to have received at least one standard donor lymphocyte infusion. In addition, patients were only eligible if they had minimal or no GVHD and were not receiving any systemic immunosuppressive drugs.

The trial included 20 patients—5 each with ALL, CLL, mantle cell lymphoma (MCL), and diffuse large B-cell lymphoma (DLBCL).

All patients received a single infusion of CAR T cells derived from their original transplant donor. Production of these cells took 8 days. The highest dose of CAR T cells given was 10⁷ cells/kg.

Four of the ALL patients obtained a minimal-residual disease-negative complete response (CR), but 2 of these patients subsequently relapsed. Of the other 2 patients, 1 remains in CR at 18 months of follow-up, and the other went on to receive a second allogeneic transplant. That patient remains in CR today.

Among the CLL patients, 1 achieved a CR, and 1 achieved a partial response (PR). One patient had stable disease (SD), and the other 2 progressed. Both the CR and the PR are ongoing at 36 and 18 months of follow-up, respectively.

One MCL patient achieved a CR, 1 had a PR, and 3 had SD. The CR is ongoing at 31 months. One DLBCL patient achieved a CR, 3 had SD, and 1 progressed.

Dr Kochenderfer noted that response was associated with higher blood CAR T-cell levels. There was a significant difference in CAR T-cell levels between responders and nonresponders (P=0.001).

In addition, the presence of blood B-cell levels before CAR T-cell infusion was associated with higher blood CAR T-cell levels. Patients with normal or high B lymphocytes had higher levels of CAR T cells in their blood (P=0.04).

Patients with high tumor burdens developed severe cytokine-release syndrome with fever, tachycardia, and hypotension. The ALL patients were particularly susceptible to cytokine-release syndrome.

Dr Kochenderfer said neurologic toxicity was rare and mild. There was 1 case of mild aphasia.

There were 2 patients with elevations in CPK, indicating muscle damage. Those patients also reported muscle pain, and 1 patient reported weakness.

“This is one of the first reports, I think, of muscle damage in CAR T-cell patients,” Dr Kochenderfer said.

None of the patients developed acute GVHD after CAR T-cell therapy. One patient had continued worsening of pre-existing chronic GVHD after treatment, and 1 patient developed mild chronic eye GVHD more than a year after CAR T-cell infusion.

Dr Kochenderfer said additional details from this trial will be published in an upcoming issue of the Journal of Clinical Oncology.

James N. Kochenderfer, MD

Photo courtesy of ASH

ORLANDO, FL—Allogeneic chimeric antigen receptor (CAR) T cells directed against CD19 can have “significant” activity against resistant B-cell malignancies, even when given without prior chemotherapy, according to a presentation at the 2015 ASH Annual Meeting.

Nine of 20 patients responded to treatment with the CAR T cells, despite having failed prior allogeneic transplant. The best responses were observed in patients with acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL).

“Malignancies that were resistant to allogeneic transplants and standard donor lymphocyte infusions regressed after infusions of allogeneic anti-CD19 CAR T cells,” said James N. Kochenderfer, MD, of the National Cancer Institute in Bethesda, Maryland.

“Allogeneic anti-CD19 CAR T cells seem to be particularly effective against ALL and CLL, suggesting a possible antigenic stimulation that may be more pronounced in these malignancies.”

Adverse events associated with these CAR T cells included severe but reversible cytokine release syndrome, mild aphasia, and muscle damage. There were no cases of acute graft-vs-host disease (GVHD).

Dr Kochenderfer presented these results at ASH as abstract 99.

For this phase 1 study, researchers tested a CAR T-cell therapy that was originally developed by Dr Kochenderfer and his colleagues. The therapy is now known as KTE-C19 and is under development by Kite Pharmaceuticals. However, the company did not sponsor this trial.

The study was open to patients with any CD19+ B-cell malignancy that persisted after allogeneic transplant.

All patients except those with ALL were required to have received at least one standard donor lymphocyte infusion. In addition, patients were only eligible if they had minimal or no GVHD and were not receiving any systemic immunosuppressive drugs.

The trial included 20 patients—5 each with ALL, CLL, mantle cell lymphoma (MCL), and diffuse large B-cell lymphoma (DLBCL).

All patients received a single infusion of CAR T cells derived from their original transplant donor. Production of these cells took 8 days. The highest dose of CAR T cells given was 10⁷ cells/kg.

Four of the ALL patients obtained a minimal-residual disease-negative complete response (CR), but 2 of these patients subsequently relapsed. Of the other 2 patients, 1 remains in CR at 18 months of follow-up, and the other went on to receive a second allogeneic transplant. That patient remains in CR today.

Among the CLL patients, 1 achieved a CR, and 1 achieved a partial response (PR). One patient had stable disease (SD), and the other 2 progressed. Both the CR and the PR are ongoing at 36 and 18 months of follow-up, respectively.

One MCL patient achieved a CR, 1 had a PR, and 3 had SD. The CR is ongoing at 31 months. One DLBCL patient achieved a CR, 3 had SD, and 1 progressed.

Dr Kochenderfer noted that response was associated with higher blood CAR T-cell levels. There was a significant difference in CAR T-cell levels between responders and nonresponders (P=0.001).

In addition, the presence of blood B-cell levels before CAR T-cell infusion was associated with higher blood CAR T-cell levels. Patients with normal or high B lymphocytes had higher levels of CAR T cells in their blood (P=0.04).

Patients with high tumor burdens developed severe cytokine-release syndrome with fever, tachycardia, and hypotension. The ALL patients were particularly susceptible to cytokine-release syndrome.

Dr Kochenderfer said neurologic toxicity was rare and mild. There was 1 case of mild aphasia.

There were 2 patients with elevations in CPK, indicating muscle damage. Those patients also reported muscle pain, and 1 patient reported weakness.

“This is one of the first reports, I think, of muscle damage in CAR T-cell patients,” Dr Kochenderfer said.

None of the patients developed acute GVHD after CAR T-cell therapy. One patient had continued worsening of pre-existing chronic GVHD after treatment, and 1 patient developed mild chronic eye GVHD more than a year after CAR T-cell infusion.

Dr Kochenderfer said additional details from this trial will be published in an upcoming issue of the Journal of Clinical Oncology.

Warfarin tablets

A retrospective study published in The BMJ suggests the possibility of a significant drug interaction between warfarin and the sulfonylureas glipizide and glimepiride.

Taking either of these diabetes drugs in conjunction with warfarin was linked to increased hospitalizations for falls, altered mental state, and insulin shock among patients 65 and older.

Hospital admissions or emergency room visits were nearly 22% higher for patients who were taking warfarin with glipizide or glimepiride, compared to patients taking the diabetes drugs alone.

Clinical references warn doctors of a potential interaction between these drugs, but evidence of it has been thin, according to lead study author John Romley, PhD, of the University of Southern California (USC) in Los Angeles.

He and his colleagues said that, in their study, evidence of the drug-to-drug interaction was clear.

When taken with glipizide or glimepiride, warfarin can intensify their effects and send blood sugar levels crashing. Patients experiencing hypoglycemia may seem drunk, lightheaded, and confused, and are at risk of falling.

“The take-home message is simply that an interaction can occur that has clinical significance, so providers need to be aware in order to prevent a low blood sugar issue from occurring,” said Anne Peters, MD, also of USC.

“Sometimes this means having the patient monitor their blood sugar levels more often. There are many ways to deal with the issue if one is forewarned.”

Pharmacists don’t need to change patient instructions, added Bradley Williams, PharmD, of USC.

“What it does require is for pharmacists and other clinicians to be more vigilant when a sulfonylurea is added to a regimen that includes warfarin, as well as when a patient who is taking both has a change in their medical status,” Dr Williams said.

“I think additional research into the potential interactions between medications for diabetes and warfarin, as well as other drugs that affect blood clotting, is warranted because of the potential consequences of excessive bleeding.”

For the current study, the researchers analyzed a random sample of 465,918 Medicare beneficiaries with diabetes who filled a prescription for glipizide or glimepiride between 2006 and 2011. About 15% of these patients (n=71,895) also filled a prescription for warfarin.

The researchers found that hospital admissions or emergency department visits for hypoglycemia were more common with concurrent warfarin and glipizide/glimepiride use than with glipizide/glimepiride use alone. The adjusted odds ratio (AOR) was 1.22.

The risk of hypoglycemia associated with concurrent use was higher among patients taking warfarin for the first time, as well as in patients ages 65 to 74.

Concurrent use of warfarin and glipizide/glimepiride was also associated with hospital admission or emergency department visits for fall-related fractures (AOR=1.47) and altered consciousness/mental status (AOR=1.22).

The researchers said these findings may not be generalizable beyond the elderly Medicare population.

They also noted that their findings could be confounded by some unmeasured characteristics in patients that may be connected to warfarin use or a risk for hypoglycemia. Another limitation of this study is that the researchers did not measure drug use directly.

Warfarin tablets

A retrospective study published in The BMJ suggests the possibility of a significant drug interaction between warfarin and the sulfonylureas glipizide and glimepiride.

Taking either of these diabetes drugs in conjunction with warfarin was linked to increased hospitalizations for falls, altered mental state, and insulin shock among patients 65 and older.

Hospital admissions or emergency room visits were nearly 22% higher for patients who were taking warfarin with glipizide or glimepiride, compared to patients taking the diabetes drugs alone.

Clinical references warn doctors of a potential interaction between these drugs, but evidence of it has been thin, according to lead study author John Romley, PhD, of the University of Southern California (USC) in Los Angeles.

He and his colleagues said that, in their study, evidence of the drug-to-drug interaction was clear.

When taken with glipizide or glimepiride, warfarin can intensify their effects and send blood sugar levels crashing. Patients experiencing hypoglycemia may seem drunk, lightheaded, and confused, and are at risk of falling.

“The take-home message is simply that an interaction can occur that has clinical significance, so providers need to be aware in order to prevent a low blood sugar issue from occurring,” said Anne Peters, MD, also of USC.

“Sometimes this means having the patient monitor their blood sugar levels more often. There are many ways to deal with the issue if one is forewarned.”

Pharmacists don’t need to change patient instructions, added Bradley Williams, PharmD, of USC.

“What it does require is for pharmacists and other clinicians to be more vigilant when a sulfonylurea is added to a regimen that includes warfarin, as well as when a patient who is taking both has a change in their medical status,” Dr Williams said.

“I think additional research into the potential interactions between medications for diabetes and warfarin, as well as other drugs that affect blood clotting, is warranted because of the potential consequences of excessive bleeding.”

For the current study, the researchers analyzed a random sample of 465,918 Medicare beneficiaries with diabetes who filled a prescription for glipizide or glimepiride between 2006 and 2011. About 15% of these patients (n=71,895) also filled a prescription for warfarin.

The researchers found that hospital admissions or emergency department visits for hypoglycemia were more common with concurrent warfarin and glipizide/glimepiride use than with glipizide/glimepiride use alone. The adjusted odds ratio (AOR) was 1.22.

The risk of hypoglycemia associated with concurrent use was higher among patients taking warfarin for the first time, as well as in patients ages 65 to 74.

Concurrent use of warfarin and glipizide/glimepiride was also associated with hospital admission or emergency department visits for fall-related fractures (AOR=1.47) and altered consciousness/mental status (AOR=1.22).

The researchers said these findings may not be generalizable beyond the elderly Medicare population.

They also noted that their findings could be confounded by some unmeasured characteristics in patients that may be connected to warfarin use or a risk for hypoglycemia. Another limitation of this study is that the researchers did not measure drug use directly.

Warfarin tablets

A retrospective study published in The BMJ suggests the possibility of a significant drug interaction between warfarin and the sulfonylureas glipizide and glimepiride.

Taking either of these diabetes drugs in conjunction with warfarin was linked to increased hospitalizations for falls, altered mental state, and insulin shock among patients 65 and older.

Hospital admissions or emergency room visits were nearly 22% higher for patients who were taking warfarin with glipizide or glimepiride, compared to patients taking the diabetes drugs alone.

Clinical references warn doctors of a potential interaction between these drugs, but evidence of it has been thin, according to lead study author John Romley, PhD, of the University of Southern California (USC) in Los Angeles.

He and his colleagues said that, in their study, evidence of the drug-to-drug interaction was clear.

When taken with glipizide or glimepiride, warfarin can intensify their effects and send blood sugar levels crashing. Patients experiencing hypoglycemia may seem drunk, lightheaded, and confused, and are at risk of falling.

“The take-home message is simply that an interaction can occur that has clinical significance, so providers need to be aware in order to prevent a low blood sugar issue from occurring,” said Anne Peters, MD, also of USC.

“Sometimes this means having the patient monitor their blood sugar levels more often. There are many ways to deal with the issue if one is forewarned.”

Pharmacists don’t need to change patient instructions, added Bradley Williams, PharmD, of USC.

“What it does require is for pharmacists and other clinicians to be more vigilant when a sulfonylurea is added to a regimen that includes warfarin, as well as when a patient who is taking both has a change in their medical status,” Dr Williams said.

“I think additional research into the potential interactions between medications for diabetes and warfarin, as well as other drugs that affect blood clotting, is warranted because of the potential consequences of excessive bleeding.”

For the current study, the researchers analyzed a random sample of 465,918 Medicare beneficiaries with diabetes who filled a prescription for glipizide or glimepiride between 2006 and 2011. About 15% of these patients (n=71,895) also filled a prescription for warfarin.

The researchers found that hospital admissions or emergency department visits for hypoglycemia were more common with concurrent warfarin and glipizide/glimepiride use than with glipizide/glimepiride use alone. The adjusted odds ratio (AOR) was 1.22.

The risk of hypoglycemia associated with concurrent use was higher among patients taking warfarin for the first time, as well as in patients ages 65 to 74.

Concurrent use of warfarin and glipizide/glimepiride was also associated with hospital admission or emergency department visits for fall-related fractures (AOR=1.47) and altered consciousness/mental status (AOR=1.22).

The researchers said these findings may not be generalizable beyond the elderly Medicare population.

They also noted that their findings could be confounded by some unmeasured characteristics in patients that may be connected to warfarin use or a risk for hypoglycemia. Another limitation of this study is that the researchers did not measure drug use directly.

The US Food and Drug Administration (FDA) has approved a recombinant von Willebrand factor product, Vonvendi (formerly BAX 111), for use in adults with von Willebrand disease (VWD).

Vonvendi is the first FDA-approved recombinant von Willebrand factor.

It is now approved for the on-demand treatment and control of bleeding episodes in VWD patients 18 years of age and older.

Vonvendi is expected to be broadly available in the US in late 2016.

Compared to other marketed von Willebrand factor concentrates, Vonvendi contains a more consistent concentration of ultra-large-molecular-weight multimers. And the product is developed using a plasma- and albumin-free manufacturing method.

Vonvendi is the first von Willebrand factor concentrate in the US that contains only trace amounts of factor VIII (FVIII), offering the flexibility to administer FVIII only when needed.

The FDA’s approval of Vonvendi was based on results from a phase 3 trial recently published in Blood. The study included 49 patients with WWD who received Vonvendi with and without recombinant FVIII.

All participants reported successful treatment of bleeding episodes. Most (96.9%) treated bleeds (n=192 bleeds in 22 patients) achieved an “excellent” efficacy rating.

Most bleeds (81.8%) were resolved with a single infusion of Vonvendi, and the treatment had a mean half-life of 21.9 hours.

There were 8 adverse events considered related to Vonvendi, but only 2 of these were serious. One patient experienced 2 simultaneous serious adverse events—chest discomfort and increased heart rate—but these were resolved.

There were no thrombotic events in this trial, no treatment-related binding or neutralizing antibodies against von Willebrand factor, and no neutralizing antibodies against FVIII.

Vonvendi is manufactured by Baxalta Incorporated. Baxalta said it is building a robust clinical development program to optimize patient access to Vonvendi worldwide. A series of clinical programs are planned to evaluate its use for prophylaxis, surgical, and pediatric indications.

Baxalta expects to file for regulatory approvals in Europe in 2017 and in other markets around the world.

For more details on Vonvendi, see the product information.

The US Food and Drug Administration (FDA) has approved a recombinant von Willebrand factor product, Vonvendi (formerly BAX 111), for use in adults with von Willebrand disease (VWD).

Vonvendi is the first FDA-approved recombinant von Willebrand factor.

It is now approved for the on-demand treatment and control of bleeding episodes in VWD patients 18 years of age and older.

Vonvendi is expected to be broadly available in the US in late 2016.

Compared to other marketed von Willebrand factor concentrates, Vonvendi contains a more consistent concentration of ultra-large-molecular-weight multimers. And the product is developed using a plasma- and albumin-free manufacturing method.

Vonvendi is the first von Willebrand factor concentrate in the US that contains only trace amounts of factor VIII (FVIII), offering the flexibility to administer FVIII only when needed.

The FDA’s approval of Vonvendi was based on results from a phase 3 trial recently published in Blood. The study included 49 patients with WWD who received Vonvendi with and without recombinant FVIII.

All participants reported successful treatment of bleeding episodes. Most (96.9%) treated bleeds (n=192 bleeds in 22 patients) achieved an “excellent” efficacy rating.

Most bleeds (81.8%) were resolved with a single infusion of Vonvendi, and the treatment had a mean half-life of 21.9 hours.

There were 8 adverse events considered related to Vonvendi, but only 2 of these were serious. One patient experienced 2 simultaneous serious adverse events—chest discomfort and increased heart rate—but these were resolved.

There were no thrombotic events in this trial, no treatment-related binding or neutralizing antibodies against von Willebrand factor, and no neutralizing antibodies against FVIII.

Vonvendi is manufactured by Baxalta Incorporated. Baxalta said it is building a robust clinical development program to optimize patient access to Vonvendi worldwide. A series of clinical programs are planned to evaluate its use for prophylaxis, surgical, and pediatric indications.

Baxalta expects to file for regulatory approvals in Europe in 2017 and in other markets around the world.

For more details on Vonvendi, see the product information.

The US Food and Drug Administration (FDA) has approved a recombinant von Willebrand factor product, Vonvendi (formerly BAX 111), for use in adults with von Willebrand disease (VWD).

Vonvendi is the first FDA-approved recombinant von Willebrand factor.

It is now approved for the on-demand treatment and control of bleeding episodes in VWD patients 18 years of age and older.

Vonvendi is expected to be broadly available in the US in late 2016.

Compared to other marketed von Willebrand factor concentrates, Vonvendi contains a more consistent concentration of ultra-large-molecular-weight multimers. And the product is developed using a plasma- and albumin-free manufacturing method.

Vonvendi is the first von Willebrand factor concentrate in the US that contains only trace amounts of factor VIII (FVIII), offering the flexibility to administer FVIII only when needed.

The FDA’s approval of Vonvendi was based on results from a phase 3 trial recently published in Blood. The study included 49 patients with WWD who received Vonvendi with and without recombinant FVIII.

All participants reported successful treatment of bleeding episodes. Most (96.9%) treated bleeds (n=192 bleeds in 22 patients) achieved an “excellent” efficacy rating.

Most bleeds (81.8%) were resolved with a single infusion of Vonvendi, and the treatment had a mean half-life of 21.9 hours.

There were 8 adverse events considered related to Vonvendi, but only 2 of these were serious. One patient experienced 2 simultaneous serious adverse events—chest discomfort and increased heart rate—but these were resolved.

There were no thrombotic events in this trial, no treatment-related binding or neutralizing antibodies against von Willebrand factor, and no neutralizing antibodies against FVIII.

Vonvendi is manufactured by Baxalta Incorporated. Baxalta said it is building a robust clinical development program to optimize patient access to Vonvendi worldwide. A series of clinical programs are planned to evaluate its use for prophylaxis, surgical, and pediatric indications.

Baxalta expects to file for regulatory approvals in Europe in 2017 and in other markets around the world.

For more details on Vonvendi, see the product information.

Doctor examines SCD patient

Photo courtesy of St. Jude

Children’s Research Hospital

Treatment with the antiplatelet agent prasugrel does not significantly reduce the rate of pain crises or severe lung complications in children with sickle cell disease (SCD), according to one of the largest and most geographically diverse international trials on SCD to date.

The DOVE trial was a double blind, randomized, placebo-controlled phase 3 study conducted at 51 sites across 13 nations in the Americas, Europe, the Middle East, Asia, and Africa.

“Although we were disappointed that prasugrel does not appear to ease the suffering of children with sickle cell disease, the fact that this study incorporated patients in the wide range of countries where the disease occurs is hugely significant,” said Carolyn Hoppe, MD, of UCSF Benioff Children’s Hospital Oakland in California.

“The logistical challenges that we addressed in designing and implementing the study can serve as a model for future research.”

The results of the study were published in NEJM. The research was sponsored by Daiichi Sankyo Company, Ltd. and Eli Lilly and Company.

The goal of the DOVE trial was to determine whether prasugrel could significantly reduce the rate of vaso-occlusive crises (VOCs)—defined as pain crises or acute chest syndrome—in children with SCD.

The trial enrolled 341 patients. About half of them (n=170) received daily oral prasugrel for between 9 and 24 months at individualized, blinded doses intended to maintain a selected target range of platelet activity. The remaining patients received a placebo.

All patients were monitored for VOCs prompting medical visits and for any increased risk of bleeding due to reduced platelet activity. In addition, patients 4 years old and older kept a daily electronic pain diary to aid in the reporting of painful events between visits.

At the end of the study period, there was no significant difference between the treatment arms in the overall rate of VOCs. The rate was 2.3 episodes per person-year in the prasugrel arm and 2.8 episodes per person-year in the placebo arm (P=0.12).

Similarly, prasugrel did not have a significant effect on the trial’s secondary outcome measures—VOC-related hospitalization rate, duration of hospitalization, time between VOCs, incidence of ischemic attack or ischemic stroke, transfusion rate, rate of pain, intensity of pain, use of analgesics, or missed school due to SCD-related pain.

The data did reveal a trend toward reduced VOC rates among patients ages 12 to 18 (P=0.06) and among patients who were not taking hydroxyurea (P=0.06). However, these trends were not statistically significant and require further research to determine their validity.

The investigators noted no adverse events related to prasugrel.

“Even though prasugrel did not achieve significant results, the findings should not detract from the fact that this team successfully completed a rigorous, sophisticated trial in a disease where the barriers to conducting large-scale international, patient-focused research are quite high,” said Matthew M. Heeney, MD, of the Dana–Farber/Boston Children’s Cancer and Blood Disorders Center in Massachusetts.

To conduct the study successfully on such a broad geographical scale, the investigators had to address several obstacles, such as varying standards of care, local technological resources, and infrastructure challenges, such as a lack of reliable electrical power.

Doctor examines SCD patient

Photo courtesy of St. Jude

Children’s Research Hospital

Treatment with the antiplatelet agent prasugrel does not significantly reduce the rate of pain crises or severe lung complications in children with sickle cell disease (SCD), according to one of the largest and most geographically diverse international trials on SCD to date.

The DOVE trial was a double blind, randomized, placebo-controlled phase 3 study conducted at 51 sites across 13 nations in the Americas, Europe, the Middle East, Asia, and Africa.

“Although we were disappointed that prasugrel does not appear to ease the suffering of children with sickle cell disease, the fact that this study incorporated patients in the wide range of countries where the disease occurs is hugely significant,” said Carolyn Hoppe, MD, of UCSF Benioff Children’s Hospital Oakland in California.

“The logistical challenges that we addressed in designing and implementing the study can serve as a model for future research.”

The results of the study were published in NEJM. The research was sponsored by Daiichi Sankyo Company, Ltd. and Eli Lilly and Company.

The goal of the DOVE trial was to determine whether prasugrel could significantly reduce the rate of vaso-occlusive crises (VOCs)—defined as pain crises or acute chest syndrome—in children with SCD.

The trial enrolled 341 patients. About half of them (n=170) received daily oral prasugrel for between 9 and 24 months at individualized, blinded doses intended to maintain a selected target range of platelet activity. The remaining patients received a placebo.

All patients were monitored for VOCs prompting medical visits and for any increased risk of bleeding due to reduced platelet activity. In addition, patients 4 years old and older kept a daily electronic pain diary to aid in the reporting of painful events between visits.

At the end of the study period, there was no significant difference between the treatment arms in the overall rate of VOCs. The rate was 2.3 episodes per person-year in the prasugrel arm and 2.8 episodes per person-year in the placebo arm (P=0.12).

Similarly, prasugrel did not have a significant effect on the trial’s secondary outcome measures—VOC-related hospitalization rate, duration of hospitalization, time between VOCs, incidence of ischemic attack or ischemic stroke, transfusion rate, rate of pain, intensity of pain, use of analgesics, or missed school due to SCD-related pain.

The data did reveal a trend toward reduced VOC rates among patients ages 12 to 18 (P=0.06) and among patients who were not taking hydroxyurea (P=0.06). However, these trends were not statistically significant and require further research to determine their validity.

The investigators noted no adverse events related to prasugrel.

“Even though prasugrel did not achieve significant results, the findings should not detract from the fact that this team successfully completed a rigorous, sophisticated trial in a disease where the barriers to conducting large-scale international, patient-focused research are quite high,” said Matthew M. Heeney, MD, of the Dana–Farber/Boston Children’s Cancer and Blood Disorders Center in Massachusetts.

To conduct the study successfully on such a broad geographical scale, the investigators had to address several obstacles, such as varying standards of care, local technological resources, and infrastructure challenges, such as a lack of reliable electrical power.

Doctor examines SCD patient

Photo courtesy of St. Jude

Children’s Research Hospital

Treatment with the antiplatelet agent prasugrel does not significantly reduce the rate of pain crises or severe lung complications in children with sickle cell disease (SCD), according to one of the largest and most geographically diverse international trials on SCD to date.

The DOVE trial was a double blind, randomized, placebo-controlled phase 3 study conducted at 51 sites across 13 nations in the Americas, Europe, the Middle East, Asia, and Africa.

“Although we were disappointed that prasugrel does not appear to ease the suffering of children with sickle cell disease, the fact that this study incorporated patients in the wide range of countries where the disease occurs is hugely significant,” said Carolyn Hoppe, MD, of UCSF Benioff Children’s Hospital Oakland in California.

“The logistical challenges that we addressed in designing and implementing the study can serve as a model for future research.”

The results of the study were published in NEJM. The research was sponsored by Daiichi Sankyo Company, Ltd. and Eli Lilly and Company.

The goal of the DOVE trial was to determine whether prasugrel could significantly reduce the rate of vaso-occlusive crises (VOCs)—defined as pain crises or acute chest syndrome—in children with SCD.

The trial enrolled 341 patients. About half of them (n=170) received daily oral prasugrel for between 9 and 24 months at individualized, blinded doses intended to maintain a selected target range of platelet activity. The remaining patients received a placebo.

All patients were monitored for VOCs prompting medical visits and for any increased risk of bleeding due to reduced platelet activity. In addition, patients 4 years old and older kept a daily electronic pain diary to aid in the reporting of painful events between visits.

At the end of the study period, there was no significant difference between the treatment arms in the overall rate of VOCs. The rate was 2.3 episodes per person-year in the prasugrel arm and 2.8 episodes per person-year in the placebo arm (P=0.12).

Similarly, prasugrel did not have a significant effect on the trial’s secondary outcome measures—VOC-related hospitalization rate, duration of hospitalization, time between VOCs, incidence of ischemic attack or ischemic stroke, transfusion rate, rate of pain, intensity of pain, use of analgesics, or missed school due to SCD-related pain.

The data did reveal a trend toward reduced VOC rates among patients ages 12 to 18 (P=0.06) and among patients who were not taking hydroxyurea (P=0.06). However, these trends were not statistically significant and require further research to determine their validity.

The investigators noted no adverse events related to prasugrel.

“Even though prasugrel did not achieve significant results, the findings should not detract from the fact that this team successfully completed a rigorous, sophisticated trial in a disease where the barriers to conducting large-scale international, patient-focused research are quite high,” said Matthew M. Heeney, MD, of the Dana–Farber/Boston Children’s Cancer and Blood Disorders Center in Massachusetts.

To conduct the study successfully on such a broad geographical scale, the investigators had to address several obstacles, such as varying standards of care, local technological resources, and infrastructure challenges, such as a lack of reliable electrical power.

Study Overview

Objective. To determine whether in-person visits for primary care patients resulted in improved weight loss maintenance relative to monthly mailings, with both groups receiving access to portion-controlled meals.

Design. Randomized clinical trial.

Setting and participants. This study took place within 2 university-affiliated primary care clinics in Colorado. For the first phase of the study, investigators enrolled 104 obese adult patients (18–79 years; BMI 30–49.9 kg/m²) who had been diagnosed with at least one of the following: type 2 diabetes, sleep apnea, hypertension, or hyperlipidemia. Patients who had independently lost weight prior to trial entry (> 5% in 6 months), were on weight-gain–promoting medications such as steroids, or had previously undergone bariatric surgery were excluded. The trial started with a 6-month run-in phase where active weight loss was promoted using a high-intensity behavioral intervention based on the Diabetes Prevention Program as well as access to subsidized portion-controlled foods (Nutrisystem). At the end of the 6-month run-in, the remaining participants (n = 84, 79.3%) were then randomized, stratified by gender and whether or not they achieved 5% weight loss, into the 2 main study arms.

Intervention. The experimental study arm (n = 41, “intensified maintenance”) relied on monthly in-person visits and monthly phone calls to prevent weight regain (thus, these participants had twice monthly contact during maintenance). Both visit types in this arm were conducted by a graduate-level research assistant and included some structured educational content as well as problem-solving around diet and lifestyle issues. In contrast, the control arm (n = 43, “standard maintenance”) relied just on monthly mailings (or emails) of educational and support materials to promote weight loss maintenance. Participants in both groups had the opportunity to purchase subsidized portion-controlled foods/meals from Nutrisystem in order to facilitate continued adherence to the caloric restriction required for weight loss maintenance.

Main outcome measures. The primary outcome for this trial was change in weight, measured in kgs, during the 12-month maintenance period. Other biometric outcomes included changes in blood pressure, serum glucose, lipid levels, and the inflammatory marker hs-CRP. Patient-reported outcomes included changes in medication use. The investigators used intention-to-treat analysis, with mixed linear models adjusted for age and gender. No imputation techniques for missing data are reported, although complete follow-up data was obtained on 94% of patients.

Results. Participants in the standard and intensified weight maintenance arms of the trial were similar with respect to measured baseline characteristics. The average age of participants was 56 years, and three-quarters (75%) were female. The majority in both groups were white (77% in standard arm; 88% in intense), and over half had either a college or advanced degree (58.1% in standard arm, 51.2% in intense). Approximately one- third had diabetes (32.6% in standard arm, 34.1% in intense) and over half had hypertension (67.4% in standard arm, 63.4% in intense). Of the 84 participants who were randomized in the weight maintenance phase of the study, 79 completed the 12-month follow up (94%; no difference in attrition between groups).

After 12 months of maintenance, participants in the intensified maintenance arm regained just 1.6 (± 1.3) kg of lost weight, while those in the standard arm regained 5.0 (± 0.8) kg, a statistically significant difference (P = 0.01). The investigators also examined the subgroup of participants who, after the 6-month run-in, had lost at least 5% of their initial body weight. For these individuals, almost three-quarters in the intensified maintenance arm (71.9%) maintained that > 5% loss by 18 months, compared to 51.7% in the standard group. This difference between groups was not statistically significant. There was a significant difference between groups for change in hs-CRP over the 12-month maintenance period, with the intensive group’s hs-CRP ending up an average of 1.46 mg/L lower than that of the standard group (P = 0.03). Although there was a similar trend favoring the intensive intervention for other biometric measures (change in waist circumference, glucose, blood pressure, and lipids were all more favorable in this arm), the between-group differences for these measures did not reach statistical significance. No significant differences between groups were observed with respect to changes in medication use over the 12-month maintenance intervention.

Conclusion. After 5 months of active weight loss, twice-monthly contact (using one in-person and one phone visit) plus portion-controlled foods during a 12-month weight maintenance phase resulted in significantly less weight regain than monthly mail or email-based counseling plus portion-controlled foods.

Commentary

Behavioral weight loss interventions, which typically require high-intensity in-person counseling over several months to a year, may be difficult to accomplish in the average primary care practice [1]. On the other hand, it may be the case that primary care practices are well-suited to assist patients who have already lost weight, as they enter weight-loss maintenance. While numerous studies have shown that patients who adhere to calorie-restricted diets (almost regardless of diet composition) are able to achieve clinically significant weight loss, less is known about effective methods of preventing weight regain. Several large trials have suggested that, as is the case with behavioral weight loss interventions, maintenance interventions are also more successful if they include regular contact, at least some of which is face-to-face [2,3]. These visits, along with other practices such as self-weighing and food diaries, may help patients maintain the energy balance necessary to stay at their new, lower body weight. There remains a gap, however, in terms of knowing whether the maintenance interventions from large randomized trials can be translated into the sometimes messy real world of clinical practice, where clinicians and patients are typically overburdened and busy.

The current study by Tsai et al does address some aspects of this important question. By recruiting “real-world” chronically ill patients from a primary care practice to participate in the trial, the results of this study may be more likely to generalize to the patient populations seen by practicing clinicians than the typically healthier, younger, community-recruited volunteers in large trials. Additionally, although the interventions in this study were not delivered by the primary care practice per se, they were low enough in intensity that they could theoretically be translated into most clinical practice settings, assuming reimbursement is not an issue. Monthly in-person visits certainly could be done by a physician (as under current CMS reimbursement guidelines), but would not have to be (the visits in this study were done by a graduate student with no formal training in behavioral interventions), and telephone visits could easily be done by clinical support staff. Even with this low level of visit intensity, patients had significantly less weight regain than those who were receiving monthly email or postal mail support (which, realistically, would still require some work on the part of primary care practices). Furthermore, there were suggestions of numerous parallel cardiometabolic benefits that might have been statistically significant with a larger sample size. This study benefited from several strengths in addition to its highly practical point of view. It was a randomized trial with a strong control group and long follow-up duration (18 months total). It used a run-in period for weight loss so that all who entered maintenance were doing so based on exposure to the same weight loss intervention. Happily, though, the investigators did not require successful weight loss (> 5%) for entry into the maintenance phase, which likely further contributed to the generalizability of their results. Another area where the run-in likely helped was with retention of subjects—94% of those randomized for maintenance contributed complete data at the end of the 12-month study period.

As acknowledged by the authors, this study also has some important limitations. As with most weight loss/diet interventions, the participants in this study were mostly female, and mostly non-Hispanic white, and thus a substantially less diverse population than is represented by patients with obesity in the US. Furthermore, although some aspects of the patient population did promote generalizability (recruitment from primary care, chronic illness burden), these patients were fairly highly educated, which may have impacted their adherence and results.

The use of subsidized portion-controlled meals in this study, while evidence-based, may have clouded the results somewhat. Perhaps the effect of both interventions would have been less pronounced had patients not been provided with subsidies to access these foods. In their discussion, the investigators acknowledge that the study lacked a comparison group with no access to portion-controlled foods and that, in a post-hoc analysis, greater use of these foods corresponded with better weight loss and weight loss maintenance among all participants.

Finally, although it was beyond the scope of this study, this trial does not provide any information about how weight loss medications in either the weight loss or maintenance phases might impact these types of interventions. Now that the FDA has approved a number of such medications for long-term use, it would be very helpful to have more information about how medications might be integrated into these types of strategies, for interested patients, as physicians could clearly play an integral role in the pharmacologic management of weight, alongside effective behavioral interventions.

Applications for Clinical Practice

Low-to-moderate intensity in-person and telephone-based visits during weight maintenance may help to protect against weight regain, and could realistically be an option for many primary care practices and their patients. However, aside from Medicare patients, for whom monthly primary care–based weight maintenance visits are now covered, physicians would need to understand how to code and bill such visits appropriately in order to avoid having patients face unexpected charges.

—Kristina Lewis, MD, MPH

Study Overview

Objective. To determine whether in-person visits for primary care patients resulted in improved weight loss maintenance relative to monthly mailings, with both groups receiving access to portion-controlled meals.

Design. Randomized clinical trial.

Setting and participants. This study took place within 2 university-affiliated primary care clinics in Colorado. For the first phase of the study, investigators enrolled 104 obese adult patients (18–79 years; BMI 30–49.9 kg/m²) who had been diagnosed with at least one of the following: type 2 diabetes, sleep apnea, hypertension, or hyperlipidemia. Patients who had independently lost weight prior to trial entry (> 5% in 6 months), were on weight-gain–promoting medications such as steroids, or had previously undergone bariatric surgery were excluded. The trial started with a 6-month run-in phase where active weight loss was promoted using a high-intensity behavioral intervention based on the Diabetes Prevention Program as well as access to subsidized portion-controlled foods (Nutrisystem). At the end of the 6-month run-in, the remaining participants (n = 84, 79.3%) were then randomized, stratified by gender and whether or not they achieved 5% weight loss, into the 2 main study arms.

Intervention. The experimental study arm (n = 41, “intensified maintenance”) relied on monthly in-person visits and monthly phone calls to prevent weight regain (thus, these participants had twice monthly contact during maintenance). Both visit types in this arm were conducted by a graduate-level research assistant and included some structured educational content as well as problem-solving around diet and lifestyle issues. In contrast, the control arm (n = 43, “standard maintenance”) relied just on monthly mailings (or emails) of educational and support materials to promote weight loss maintenance. Participants in both groups had the opportunity to purchase subsidized portion-controlled foods/meals from Nutrisystem in order to facilitate continued adherence to the caloric restriction required for weight loss maintenance.

Main outcome measures. The primary outcome for this trial was change in weight, measured in kgs, during the 12-month maintenance period. Other biometric outcomes included changes in blood pressure, serum glucose, lipid levels, and the inflammatory marker hs-CRP. Patient-reported outcomes included changes in medication use. The investigators used intention-to-treat analysis, with mixed linear models adjusted for age and gender. No imputation techniques for missing data are reported, although complete follow-up data was obtained on 94% of patients.

Results. Participants in the standard and intensified weight maintenance arms of the trial were similar with respect to measured baseline characteristics. The average age of participants was 56 years, and three-quarters (75%) were female. The majority in both groups were white (77% in standard arm; 88% in intense), and over half had either a college or advanced degree (58.1% in standard arm, 51.2% in intense). Approximately one- third had diabetes (32.6% in standard arm, 34.1% in intense) and over half had hypertension (67.4% in standard arm, 63.4% in intense). Of the 84 participants who were randomized in the weight maintenance phase of the study, 79 completed the 12-month follow up (94%; no difference in attrition between groups).

After 12 months of maintenance, participants in the intensified maintenance arm regained just 1.6 (± 1.3) kg of lost weight, while those in the standard arm regained 5.0 (± 0.8) kg, a statistically significant difference (P = 0.01). The investigators also examined the subgroup of participants who, after the 6-month run-in, had lost at least 5% of their initial body weight. For these individuals, almost three-quarters in the intensified maintenance arm (71.9%) maintained that > 5% loss by 18 months, compared to 51.7% in the standard group. This difference between groups was not statistically significant. There was a significant difference between groups for change in hs-CRP over the 12-month maintenance period, with the intensive group’s hs-CRP ending up an average of 1.46 mg/L lower than that of the standard group (P = 0.03). Although there was a similar trend favoring the intensive intervention for other biometric measures (change in waist circumference, glucose, blood pressure, and lipids were all more favorable in this arm), the between-group differences for these measures did not reach statistical significance. No significant differences between groups were observed with respect to changes in medication use over the 12-month maintenance intervention.

Conclusion. After 5 months of active weight loss, twice-monthly contact (using one in-person and one phone visit) plus portion-controlled foods during a 12-month weight maintenance phase resulted in significantly less weight regain than monthly mail or email-based counseling plus portion-controlled foods.

Commentary

Behavioral weight loss interventions, which typically require high-intensity in-person counseling over several months to a year, may be difficult to accomplish in the average primary care practice [1]. On the other hand, it may be the case that primary care practices are well-suited to assist patients who have already lost weight, as they enter weight-loss maintenance. While numerous studies have shown that patients who adhere to calorie-restricted diets (almost regardless of diet composition) are able to achieve clinically significant weight loss, less is known about effective methods of preventing weight regain. Several large trials have suggested that, as is the case with behavioral weight loss interventions, maintenance interventions are also more successful if they include regular contact, at least some of which is face-to-face [2,3]. These visits, along with other practices such as self-weighing and food diaries, may help patients maintain the energy balance necessary to stay at their new, lower body weight. There remains a gap, however, in terms of knowing whether the maintenance interventions from large randomized trials can be translated into the sometimes messy real world of clinical practice, where clinicians and patients are typically overburdened and busy.

The current study by Tsai et al does address some aspects of this important question. By recruiting “real-world” chronically ill patients from a primary care practice to participate in the trial, the results of this study may be more likely to generalize to the patient populations seen by practicing clinicians than the typically healthier, younger, community-recruited volunteers in large trials. Additionally, although the interventions in this study were not delivered by the primary care practice per se, they were low enough in intensity that they could theoretically be translated into most clinical practice settings, assuming reimbursement is not an issue. Monthly in-person visits certainly could be done by a physician (as under current CMS reimbursement guidelines), but would not have to be (the visits in this study were done by a graduate student with no formal training in behavioral interventions), and telephone visits could easily be done by clinical support staff. Even with this low level of visit intensity, patients had significantly less weight regain than those who were receiving monthly email or postal mail support (which, realistically, would still require some work on the part of primary care practices). Furthermore, there were suggestions of numerous parallel cardiometabolic benefits that might have been statistically significant with a larger sample size. This study benefited from several strengths in addition to its highly practical point of view. It was a randomized trial with a strong control group and long follow-up duration (18 months total). It used a run-in period for weight loss so that all who entered maintenance were doing so based on exposure to the same weight loss intervention. Happily, though, the investigators did not require successful weight loss (> 5%) for entry into the maintenance phase, which likely further contributed to the generalizability of their results. Another area where the run-in likely helped was with retention of subjects—94% of those randomized for maintenance contributed complete data at the end of the 12-month study period.

As acknowledged by the authors, this study also has some important limitations. As with most weight loss/diet interventions, the participants in this study were mostly female, and mostly non-Hispanic white, and thus a substantially less diverse population than is represented by patients with obesity in the US. Furthermore, although some aspects of the patient population did promote generalizability (recruitment from primary care, chronic illness burden), these patients were fairly highly educated, which may have impacted their adherence and results.

The use of subsidized portion-controlled meals in this study, while evidence-based, may have clouded the results somewhat. Perhaps the effect of both interventions would have been less pronounced had patients not been provided with subsidies to access these foods. In their discussion, the investigators acknowledge that the study lacked a comparison group with no access to portion-controlled foods and that, in a post-hoc analysis, greater use of these foods corresponded with better weight loss and weight loss maintenance among all participants.

Finally, although it was beyond the scope of this study, this trial does not provide any information about how weight loss medications in either the weight loss or maintenance phases might impact these types of interventions. Now that the FDA has approved a number of such medications for long-term use, it would be very helpful to have more information about how medications might be integrated into these types of strategies, for interested patients, as physicians could clearly play an integral role in the pharmacologic management of weight, alongside effective behavioral interventions.

Applications for Clinical Practice

Low-to-moderate intensity in-person and telephone-based visits during weight maintenance may help to protect against weight regain, and could realistically be an option for many primary care practices and their patients. However, aside from Medicare patients, for whom monthly primary care–based weight maintenance visits are now covered, physicians would need to understand how to code and bill such visits appropriately in order to avoid having patients face unexpected charges.

—Kristina Lewis, MD, MPH

Study Overview

Objective. To determine whether in-person visits for primary care patients resulted in improved weight loss maintenance relative to monthly mailings, with both groups receiving access to portion-controlled meals.

Design. Randomized clinical trial.

Setting and participants. This study took place within 2 university-affiliated primary care clinics in Colorado. For the first phase of the study, investigators enrolled 104 obese adult patients (18–79 years; BMI 30–49.9 kg/m²) who had been diagnosed with at least one of the following: type 2 diabetes, sleep apnea, hypertension, or hyperlipidemia. Patients who had independently lost weight prior to trial entry (> 5% in 6 months), were on weight-gain–promoting medications such as steroids, or had previously undergone bariatric surgery were excluded. The trial started with a 6-month run-in phase where active weight loss was promoted using a high-intensity behavioral intervention based on the Diabetes Prevention Program as well as access to subsidized portion-controlled foods (Nutrisystem). At the end of the 6-month run-in, the remaining participants (n = 84, 79.3%) were then randomized, stratified by gender and whether or not they achieved 5% weight loss, into the 2 main study arms.

Intervention. The experimental study arm (n = 41, “intensified maintenance”) relied on monthly in-person visits and monthly phone calls to prevent weight regain (thus, these participants had twice monthly contact during maintenance). Both visit types in this arm were conducted by a graduate-level research assistant and included some structured educational content as well as problem-solving around diet and lifestyle issues. In contrast, the control arm (n = 43, “standard maintenance”) relied just on monthly mailings (or emails) of educational and support materials to promote weight loss maintenance. Participants in both groups had the opportunity to purchase subsidized portion-controlled foods/meals from Nutrisystem in order to facilitate continued adherence to the caloric restriction required for weight loss maintenance.

Main outcome measures. The primary outcome for this trial was change in weight, measured in kgs, during the 12-month maintenance period. Other biometric outcomes included changes in blood pressure, serum glucose, lipid levels, and the inflammatory marker hs-CRP. Patient-reported outcomes included changes in medication use. The investigators used intention-to-treat analysis, with mixed linear models adjusted for age and gender. No imputation techniques for missing data are reported, although complete follow-up data was obtained on 94% of patients.

Results. Participants in the standard and intensified weight maintenance arms of the trial were similar with respect to measured baseline characteristics. The average age of participants was 56 years, and three-quarters (75%) were female. The majority in both groups were white (77% in standard arm; 88% in intense), and over half had either a college or advanced degree (58.1% in standard arm, 51.2% in intense). Approximately one- third had diabetes (32.6% in standard arm, 34.1% in intense) and over half had hypertension (67.4% in standard arm, 63.4% in intense). Of the 84 participants who were randomized in the weight maintenance phase of the study, 79 completed the 12-month follow up (94%; no difference in attrition between groups).

After 12 months of maintenance, participants in the intensified maintenance arm regained just 1.6 (± 1.3) kg of lost weight, while those in the standard arm regained 5.0 (± 0.8) kg, a statistically significant difference (P = 0.01). The investigators also examined the subgroup of participants who, after the 6-month run-in, had lost at least 5% of their initial body weight. For these individuals, almost three-quarters in the intensified maintenance arm (71.9%) maintained that > 5% loss by 18 months, compared to 51.7% in the standard group. This difference between groups was not statistically significant. There was a significant difference between groups for change in hs-CRP over the 12-month maintenance period, with the intensive group’s hs-CRP ending up an average of 1.46 mg/L lower than that of the standard group (P = 0.03). Although there was a similar trend favoring the intensive intervention for other biometric measures (change in waist circumference, glucose, blood pressure, and lipids were all more favorable in this arm), the between-group differences for these measures did not reach statistical significance. No significant differences between groups were observed with respect to changes in medication use over the 12-month maintenance intervention.

Conclusion. After 5 months of active weight loss, twice-monthly contact (using one in-person and one phone visit) plus portion-controlled foods during a 12-month weight maintenance phase resulted in significantly less weight regain than monthly mail or email-based counseling plus portion-controlled foods.

Commentary

Behavioral weight loss interventions, which typically require high-intensity in-person counseling over several months to a year, may be difficult to accomplish in the average primary care practice [1]. On the other hand, it may be the case that primary care practices are well-suited to assist patients who have already lost weight, as they enter weight-loss maintenance. While numerous studies have shown that patients who adhere to calorie-restricted diets (almost regardless of diet composition) are able to achieve clinically significant weight loss, less is known about effective methods of preventing weight regain. Several large trials have suggested that, as is the case with behavioral weight loss interventions, maintenance interventions are also more successful if they include regular contact, at least some of which is face-to-face [2,3]. These visits, along with other practices such as self-weighing and food diaries, may help patients maintain the energy balance necessary to stay at their new, lower body weight. There remains a gap, however, in terms of knowing whether the maintenance interventions from large randomized trials can be translated into the sometimes messy real world of clinical practice, where clinicians and patients are typically overburdened and busy.

The current study by Tsai et al does address some aspects of this important question. By recruiting “real-world” chronically ill patients from a primary care practice to participate in the trial, the results of this study may be more likely to generalize to the patient populations seen by practicing clinicians than the typically healthier, younger, community-recruited volunteers in large trials. Additionally, although the interventions in this study were not delivered by the primary care practice per se, they were low enough in intensity that they could theoretically be translated into most clinical practice settings, assuming reimbursement is not an issue. Monthly in-person visits certainly could be done by a physician (as under current CMS reimbursement guidelines), but would not have to be (the visits in this study were done by a graduate student with no formal training in behavioral interventions), and telephone visits could easily be done by clinical support staff. Even with this low level of visit intensity, patients had significantly less weight regain than those who were receiving monthly email or postal mail support (which, realistically, would still require some work on the part of primary care practices). Furthermore, there were suggestions of numerous parallel cardiometabolic benefits that might have been statistically significant with a larger sample size. This study benefited from several strengths in addition to its highly practical point of view. It was a randomized trial with a strong control group and long follow-up duration (18 months total). It used a run-in period for weight loss so that all who entered maintenance were doing so based on exposure to the same weight loss intervention. Happily, though, the investigators did not require successful weight loss (> 5%) for entry into the maintenance phase, which likely further contributed to the generalizability of their results. Another area where the run-in likely helped was with retention of subjects—94% of those randomized for maintenance contributed complete data at the end of the 12-month study period.

As acknowledged by the authors, this study also has some important limitations. As with most weight loss/diet interventions, the participants in this study were mostly female, and mostly non-Hispanic white, and thus a substantially less diverse population than is represented by patients with obesity in the US. Furthermore, although some aspects of the patient population did promote generalizability (recruitment from primary care, chronic illness burden), these patients were fairly highly educated, which may have impacted their adherence and results.

The use of subsidized portion-controlled meals in this study, while evidence-based, may have clouded the results somewhat. Perhaps the effect of both interventions would have been less pronounced had patients not been provided with subsidies to access these foods. In their discussion, the investigators acknowledge that the study lacked a comparison group with no access to portion-controlled foods and that, in a post-hoc analysis, greater use of these foods corresponded with better weight loss and weight loss maintenance among all participants.

Finally, although it was beyond the scope of this study, this trial does not provide any information about how weight loss medications in either the weight loss or maintenance phases might impact these types of interventions. Now that the FDA has approved a number of such medications for long-term use, it would be very helpful to have more information about how medications might be integrated into these types of strategies, for interested patients, as physicians could clearly play an integral role in the pharmacologic management of weight, alongside effective behavioral interventions.

Applications for Clinical Practice

Low-to-moderate intensity in-person and telephone-based visits during weight maintenance may help to protect against weight regain, and could realistically be an option for many primary care practices and their patients. However, aside from Medicare patients, for whom monthly primary care–based weight maintenance visits are now covered, physicians would need to understand how to code and bill such visits appropriately in order to avoid having patients face unexpected charges.

—Kristina Lewis, MD, MPH