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New appropriate use criteria reframe severe aortic stenosis
New appropriate use criteria (AUC) for severe aortic stenosis (AS) run the full gamut of clinical scenarios and treatment options.
“Cardiology is seeing a radical change in the management of aortic stenosis. This new document incorporates all therapies currently available in the world,” said Vinod H. Thourani, MD, who served on the AUC’s writing group on behalf of the American College of Cardiology. “The AUC highlights state-of-the-art therapy for aortic stenosis and, even more importantly, helps clarify the right indications for surgical and transcatheter valve replacement.”
Surgical risk is assessed based on the Society of Thoracic Surgeons Predicted Risk of Mortality score plus additional anatomic and functional considerations that should be assessed by a multidisciplinary heart team. The AUC repeatedly emphasizes this team’s importance. “Multiple comorbidities can change the pathway of treating AS, and this determination is best made by a heart team that at least includes a noninvasive cardiologist, an interventional cardiologist, and a cardiac surgeon,” Dr. Thourani said. “That’s how patients get the best care.”
Historically, aortic stenosis typically was managed medically or with balloon aortic valvuloplasty (BAV) or open aortic valve replacement, Dr. Thourani said. However, BAV is less common now, and indications for surgical or transcatheter aortic valve replacement (SAVR or TAVR) are expanding. Balloon aortic valvuloplasty sometimes does provide palliative treatment or serve as a bridge to a decision, the AUC states. For example, for a high-risk patient with severe aortic stenosis and severe secondary mitral regurgitation, BAV can help the heart team decide whether TAVR alone will improve mitral regurgitation or whether a double valve procedure is preferable.
Regardless of risk score, the AUC considers a wait-and-see approach as potentially appropriate for patients with asymptomatic high-grade AS whose left ventricular ejection fraction is at least 50%, peak aortic valve velocity is 4.0-4.9 m/sec, and exercise stress test is normal and with no predictors of symptom onset or rapid progression. Asymptomatic patients who are likely to become symptomatic but who have a low risk of sudden death are candidates for intervention (rated “appropriate”) or medical management (“may be appropriate”). In contrast, a positive stress test in an otherwise asymptomatic patient merits consideration of SAVR or TAVR regardless of surgical risk. The recommendations for asymptomatic patients reflect a lack of head-to-head trials in this population, Dr. Thourani said. “We don’t have good randomized data to show one therapy is better than another.”
Symptomatic, high-gradient, severe AS with associated coronary artery disease merits consideration of SAVR with coronary artery bypass graft or, in some cases, TAVR with percutaneous coronary intervention, according to the AUC. Less evidence supports SAVR with PCI. “Optimal management of coronary artery disease in patients with AS is a complex decision process requiring clinical, anatomical, and technical considerations that is best achieved with close collaboration between heart team members,” the authors stress.
The document covers other valvular and structural heart conditions that commonly accompany severe AS, such as symptomatic AS with bicuspid aortic valve and ascending aortic dilation. “Although there remains an increasing prevalence of transcatheter valve usage in bicuspid aortic valve, the standard of care remains surgical therapy, especially in patients who have a dilated aorta,” Dr. Thourani said.
For the first time, the AUC also addresses failing aortic valve prostheses, presenting six relevant clinical scenarios. The AUC consistently recommends SAVR, although the use of TAVR has “dramatically increased” in these patients, Dr. Thourani said. “Long-term data are still pending, but TAVR appears to be a less morbid procedure, when done appropriately.”
The societies involved in creating the AUC statement were the American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, European Association for Cardio-Thoracic Surgery, Heart Valve Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons.
Dr. Thourani disclosed ties to Edwards Lifesciences, St. Jude Medical, Abbott, Boston Scientific, and Medtronic.
New appropriate use criteria (AUC) for severe aortic stenosis (AS) run the full gamut of clinical scenarios and treatment options.
“Cardiology is seeing a radical change in the management of aortic stenosis. This new document incorporates all therapies currently available in the world,” said Vinod H. Thourani, MD, who served on the AUC’s writing group on behalf of the American College of Cardiology. “The AUC highlights state-of-the-art therapy for aortic stenosis and, even more importantly, helps clarify the right indications for surgical and transcatheter valve replacement.”
Surgical risk is assessed based on the Society of Thoracic Surgeons Predicted Risk of Mortality score plus additional anatomic and functional considerations that should be assessed by a multidisciplinary heart team. The AUC repeatedly emphasizes this team’s importance. “Multiple comorbidities can change the pathway of treating AS, and this determination is best made by a heart team that at least includes a noninvasive cardiologist, an interventional cardiologist, and a cardiac surgeon,” Dr. Thourani said. “That’s how patients get the best care.”
Historically, aortic stenosis typically was managed medically or with balloon aortic valvuloplasty (BAV) or open aortic valve replacement, Dr. Thourani said. However, BAV is less common now, and indications for surgical or transcatheter aortic valve replacement (SAVR or TAVR) are expanding. Balloon aortic valvuloplasty sometimes does provide palliative treatment or serve as a bridge to a decision, the AUC states. For example, for a high-risk patient with severe aortic stenosis and severe secondary mitral regurgitation, BAV can help the heart team decide whether TAVR alone will improve mitral regurgitation or whether a double valve procedure is preferable.
Regardless of risk score, the AUC considers a wait-and-see approach as potentially appropriate for patients with asymptomatic high-grade AS whose left ventricular ejection fraction is at least 50%, peak aortic valve velocity is 4.0-4.9 m/sec, and exercise stress test is normal and with no predictors of symptom onset or rapid progression. Asymptomatic patients who are likely to become symptomatic but who have a low risk of sudden death are candidates for intervention (rated “appropriate”) or medical management (“may be appropriate”). In contrast, a positive stress test in an otherwise asymptomatic patient merits consideration of SAVR or TAVR regardless of surgical risk. The recommendations for asymptomatic patients reflect a lack of head-to-head trials in this population, Dr. Thourani said. “We don’t have good randomized data to show one therapy is better than another.”
Symptomatic, high-gradient, severe AS with associated coronary artery disease merits consideration of SAVR with coronary artery bypass graft or, in some cases, TAVR with percutaneous coronary intervention, according to the AUC. Less evidence supports SAVR with PCI. “Optimal management of coronary artery disease in patients with AS is a complex decision process requiring clinical, anatomical, and technical considerations that is best achieved with close collaboration between heart team members,” the authors stress.
The document covers other valvular and structural heart conditions that commonly accompany severe AS, such as symptomatic AS with bicuspid aortic valve and ascending aortic dilation. “Although there remains an increasing prevalence of transcatheter valve usage in bicuspid aortic valve, the standard of care remains surgical therapy, especially in patients who have a dilated aorta,” Dr. Thourani said.
For the first time, the AUC also addresses failing aortic valve prostheses, presenting six relevant clinical scenarios. The AUC consistently recommends SAVR, although the use of TAVR has “dramatically increased” in these patients, Dr. Thourani said. “Long-term data are still pending, but TAVR appears to be a less morbid procedure, when done appropriately.”
The societies involved in creating the AUC statement were the American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, European Association for Cardio-Thoracic Surgery, Heart Valve Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons.
Dr. Thourani disclosed ties to Edwards Lifesciences, St. Jude Medical, Abbott, Boston Scientific, and Medtronic.
New appropriate use criteria (AUC) for severe aortic stenosis (AS) run the full gamut of clinical scenarios and treatment options.
“Cardiology is seeing a radical change in the management of aortic stenosis. This new document incorporates all therapies currently available in the world,” said Vinod H. Thourani, MD, who served on the AUC’s writing group on behalf of the American College of Cardiology. “The AUC highlights state-of-the-art therapy for aortic stenosis and, even more importantly, helps clarify the right indications for surgical and transcatheter valve replacement.”
Surgical risk is assessed based on the Society of Thoracic Surgeons Predicted Risk of Mortality score plus additional anatomic and functional considerations that should be assessed by a multidisciplinary heart team. The AUC repeatedly emphasizes this team’s importance. “Multiple comorbidities can change the pathway of treating AS, and this determination is best made by a heart team that at least includes a noninvasive cardiologist, an interventional cardiologist, and a cardiac surgeon,” Dr. Thourani said. “That’s how patients get the best care.”
Historically, aortic stenosis typically was managed medically or with balloon aortic valvuloplasty (BAV) or open aortic valve replacement, Dr. Thourani said. However, BAV is less common now, and indications for surgical or transcatheter aortic valve replacement (SAVR or TAVR) are expanding. Balloon aortic valvuloplasty sometimes does provide palliative treatment or serve as a bridge to a decision, the AUC states. For example, for a high-risk patient with severe aortic stenosis and severe secondary mitral regurgitation, BAV can help the heart team decide whether TAVR alone will improve mitral regurgitation or whether a double valve procedure is preferable.
Regardless of risk score, the AUC considers a wait-and-see approach as potentially appropriate for patients with asymptomatic high-grade AS whose left ventricular ejection fraction is at least 50%, peak aortic valve velocity is 4.0-4.9 m/sec, and exercise stress test is normal and with no predictors of symptom onset or rapid progression. Asymptomatic patients who are likely to become symptomatic but who have a low risk of sudden death are candidates for intervention (rated “appropriate”) or medical management (“may be appropriate”). In contrast, a positive stress test in an otherwise asymptomatic patient merits consideration of SAVR or TAVR regardless of surgical risk. The recommendations for asymptomatic patients reflect a lack of head-to-head trials in this population, Dr. Thourani said. “We don’t have good randomized data to show one therapy is better than another.”
Symptomatic, high-gradient, severe AS with associated coronary artery disease merits consideration of SAVR with coronary artery bypass graft or, in some cases, TAVR with percutaneous coronary intervention, according to the AUC. Less evidence supports SAVR with PCI. “Optimal management of coronary artery disease in patients with AS is a complex decision process requiring clinical, anatomical, and technical considerations that is best achieved with close collaboration between heart team members,” the authors stress.
The document covers other valvular and structural heart conditions that commonly accompany severe AS, such as symptomatic AS with bicuspid aortic valve and ascending aortic dilation. “Although there remains an increasing prevalence of transcatheter valve usage in bicuspid aortic valve, the standard of care remains surgical therapy, especially in patients who have a dilated aorta,” Dr. Thourani said.
For the first time, the AUC also addresses failing aortic valve prostheses, presenting six relevant clinical scenarios. The AUC consistently recommends SAVR, although the use of TAVR has “dramatically increased” in these patients, Dr. Thourani said. “Long-term data are still pending, but TAVR appears to be a less morbid procedure, when done appropriately.”
The societies involved in creating the AUC statement were the American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, European Association for Cardio-Thoracic Surgery, Heart Valve Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons.
Dr. Thourani disclosed ties to Edwards Lifesciences, St. Jude Medical, Abbott, Boston Scientific, and Medtronic.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
What Is the Nocebo Effect?
T-VEC improves melanoma response without toxicity increase
In patients with advanced, unresectable melanoma, the combination of talimogene laherparepvec (T-VEC) and ipilimumab yielded a higher objective response rate vs. ipilimumab alone, with a similar rate of severe or life-threatening ipilimumab-related toxicities, according to results of a 198-patient randomized phase II study.
Moreover, the incidence of grade 3/4 toxicities attributed to ipilimumab was similar between the two arms of the study, with no unexpected increases in treatment-related adverse events (AEs), reported Jason A. Chesney, MD, PhD, of the James Graham Brown Cancer Center, University of Louisville (Ky.), and his coinvestigators.
Taken together, the efficacy and safety findings suggest that the combination of T-VEC and ipilimumab “may have significant clinical utility in treatment of advanced melanoma,” Dr. Chesney and his colleagues wrote (J Clin Oncol. 2017 Oct. 5 doi: 10.1200/JCO.2017.73.7379).
The study included patients with unresectable stage IIIB/IV melanoma who had received no more than one previous treatment if BRAF wild type and no more than two treatments if BRAF mutant. Patients randomized to the combination arm received T-VEC starting in week 1 of the study and ipilimumab starting on week 6, while those in the single-agent arm received ipilimumab starting on week 1.
The primary endpoint of the phase II study was objective response rate by immune-related response criteria. Objective responses were seen in 38 of the 98 patients (39%) receiving T-VEC/ipilimumab, vs. 18 of the 100 patients (18%) who received ipilimumab alone (P = 0.002), the investigators said.
The incidence of grade 3 or greater AEs was 45% for the combination arm and 35% for the single-agent arm. There were three fatal AEs in the combination arm, but none was related to treatment, according to the investigators.
“Overall, combination treatment was not associated with unexpected AEs or increase in incidence or severity of AEs, suggesting that the combination therapy is tolerable for patients with advanced melanoma,” Dr. Chesney and his associates wrote.
Median progression-free survival (PFS) was 8.2 months for the combination arm and 6.4 months for ipilimumab alone (P = .35). Although the difference was not statistically significant, investigators remarked that ipilimumab was started later in the combination arm, per study design. Moreover, the 8.2-month median PFS exceeds the 2.8- to 2.9-month median PFS seen in previous ipilimumab studies, they said.
Combination immunotherapy is of great interest now in melanoma research. Ipilimumab is an anticytotoxic T-lymphocyte antigen-4 antibody, while T-VEC is an attenuated herpes simplex 1 virus that expresses the immunostimulatory cytokine granulocyte–macrophage colony-stimulating factor. Some other combinations have shown promise, but with higher rates of toxicity, including the combination of ipilimumab plus nivolumab, which resulted in an increase in clinically significant AEs of grade 3 or greater, Dr. Chesney and his colleagues said.
“Combination regimens with lower toxicity may allow for their use in a broader range of patients,” they added.
The study was funded by Amgen, which manufactures talimogene laherparepvec. Dr. Chesney has a relationship with Amgen that involves consulting or advising; research funding; and travel, accommodation, and expenses. His associates reported financial relationships with Amgen and other companies; three of the investigators are Amgen employees.
In patients with advanced, unresectable melanoma, the combination of talimogene laherparepvec (T-VEC) and ipilimumab yielded a higher objective response rate vs. ipilimumab alone, with a similar rate of severe or life-threatening ipilimumab-related toxicities, according to results of a 198-patient randomized phase II study.
Moreover, the incidence of grade 3/4 toxicities attributed to ipilimumab was similar between the two arms of the study, with no unexpected increases in treatment-related adverse events (AEs), reported Jason A. Chesney, MD, PhD, of the James Graham Brown Cancer Center, University of Louisville (Ky.), and his coinvestigators.
Taken together, the efficacy and safety findings suggest that the combination of T-VEC and ipilimumab “may have significant clinical utility in treatment of advanced melanoma,” Dr. Chesney and his colleagues wrote (J Clin Oncol. 2017 Oct. 5 doi: 10.1200/JCO.2017.73.7379).
The study included patients with unresectable stage IIIB/IV melanoma who had received no more than one previous treatment if BRAF wild type and no more than two treatments if BRAF mutant. Patients randomized to the combination arm received T-VEC starting in week 1 of the study and ipilimumab starting on week 6, while those in the single-agent arm received ipilimumab starting on week 1.
The primary endpoint of the phase II study was objective response rate by immune-related response criteria. Objective responses were seen in 38 of the 98 patients (39%) receiving T-VEC/ipilimumab, vs. 18 of the 100 patients (18%) who received ipilimumab alone (P = 0.002), the investigators said.
The incidence of grade 3 or greater AEs was 45% for the combination arm and 35% for the single-agent arm. There were three fatal AEs in the combination arm, but none was related to treatment, according to the investigators.
“Overall, combination treatment was not associated with unexpected AEs or increase in incidence or severity of AEs, suggesting that the combination therapy is tolerable for patients with advanced melanoma,” Dr. Chesney and his associates wrote.
Median progression-free survival (PFS) was 8.2 months for the combination arm and 6.4 months for ipilimumab alone (P = .35). Although the difference was not statistically significant, investigators remarked that ipilimumab was started later in the combination arm, per study design. Moreover, the 8.2-month median PFS exceeds the 2.8- to 2.9-month median PFS seen in previous ipilimumab studies, they said.
Combination immunotherapy is of great interest now in melanoma research. Ipilimumab is an anticytotoxic T-lymphocyte antigen-4 antibody, while T-VEC is an attenuated herpes simplex 1 virus that expresses the immunostimulatory cytokine granulocyte–macrophage colony-stimulating factor. Some other combinations have shown promise, but with higher rates of toxicity, including the combination of ipilimumab plus nivolumab, which resulted in an increase in clinically significant AEs of grade 3 or greater, Dr. Chesney and his colleagues said.
“Combination regimens with lower toxicity may allow for their use in a broader range of patients,” they added.
The study was funded by Amgen, which manufactures talimogene laherparepvec. Dr. Chesney has a relationship with Amgen that involves consulting or advising; research funding; and travel, accommodation, and expenses. His associates reported financial relationships with Amgen and other companies; three of the investigators are Amgen employees.
In patients with advanced, unresectable melanoma, the combination of talimogene laherparepvec (T-VEC) and ipilimumab yielded a higher objective response rate vs. ipilimumab alone, with a similar rate of severe or life-threatening ipilimumab-related toxicities, according to results of a 198-patient randomized phase II study.
Moreover, the incidence of grade 3/4 toxicities attributed to ipilimumab was similar between the two arms of the study, with no unexpected increases in treatment-related adverse events (AEs), reported Jason A. Chesney, MD, PhD, of the James Graham Brown Cancer Center, University of Louisville (Ky.), and his coinvestigators.
Taken together, the efficacy and safety findings suggest that the combination of T-VEC and ipilimumab “may have significant clinical utility in treatment of advanced melanoma,” Dr. Chesney and his colleagues wrote (J Clin Oncol. 2017 Oct. 5 doi: 10.1200/JCO.2017.73.7379).
The study included patients with unresectable stage IIIB/IV melanoma who had received no more than one previous treatment if BRAF wild type and no more than two treatments if BRAF mutant. Patients randomized to the combination arm received T-VEC starting in week 1 of the study and ipilimumab starting on week 6, while those in the single-agent arm received ipilimumab starting on week 1.
The primary endpoint of the phase II study was objective response rate by immune-related response criteria. Objective responses were seen in 38 of the 98 patients (39%) receiving T-VEC/ipilimumab, vs. 18 of the 100 patients (18%) who received ipilimumab alone (P = 0.002), the investigators said.
The incidence of grade 3 or greater AEs was 45% for the combination arm and 35% for the single-agent arm. There were three fatal AEs in the combination arm, but none was related to treatment, according to the investigators.
“Overall, combination treatment was not associated with unexpected AEs or increase in incidence or severity of AEs, suggesting that the combination therapy is tolerable for patients with advanced melanoma,” Dr. Chesney and his associates wrote.
Median progression-free survival (PFS) was 8.2 months for the combination arm and 6.4 months for ipilimumab alone (P = .35). Although the difference was not statistically significant, investigators remarked that ipilimumab was started later in the combination arm, per study design. Moreover, the 8.2-month median PFS exceeds the 2.8- to 2.9-month median PFS seen in previous ipilimumab studies, they said.
Combination immunotherapy is of great interest now in melanoma research. Ipilimumab is an anticytotoxic T-lymphocyte antigen-4 antibody, while T-VEC is an attenuated herpes simplex 1 virus that expresses the immunostimulatory cytokine granulocyte–macrophage colony-stimulating factor. Some other combinations have shown promise, but with higher rates of toxicity, including the combination of ipilimumab plus nivolumab, which resulted in an increase in clinically significant AEs of grade 3 or greater, Dr. Chesney and his colleagues said.
“Combination regimens with lower toxicity may allow for their use in a broader range of patients,” they added.
The study was funded by Amgen, which manufactures talimogene laherparepvec. Dr. Chesney has a relationship with Amgen that involves consulting or advising; research funding; and travel, accommodation, and expenses. His associates reported financial relationships with Amgen and other companies; three of the investigators are Amgen employees.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point:
Major finding: Of the 98 patients receiving T-VEC/ipilimumab, 38 (39%) had objective responses, vs. 18 of the 100 patients receiving ipilimumab alone (P = .002).
Data source: Analysis of a 198-patient randomized, open-label phase II study of T-VEC/ipilimumab vs. ipilimumab alone.
Disclosures: The study was funded by Amgen, which manufactures talimogene laherparepvec. Dr. Chesney has a relationship with Amgen that involves consulting or advising; research funding; and travel, accommodation, and expenses. His associates reported financial relationships with Amgen and other companies; three of the investigators are Amgen employees.
Thinking about productivity: Survey data 2017
The 2017 MGMA survey data on compensation and productivity were released last June. While the numbers aren’t surprising, reviewing them always gets me thinking about factors that influence reasonable expectations for compensation and productivity in any individual hospitalist group.
The data were collected in early 2017, reflecting work done in 2016, and show a national median hospitalist compensation for internal medicine physicians of $284,000, up from $278,500 the year before. Since MGMA added a hospitalist category to the survey, compensation has been growing significantly faster than inflation, even though productivity has been essentially flat. I’ve always thought that the high demand for hospitalists, which isn’t letting up much, in the face of a limited supply is probably the most significant force causing hospitalist compensation to rise faster than in most other specialties.
The survey shows a median of 2,114 billed encounters and 4,159 wRVUs (work relative value units) generated per internal medicine hospitalist annually (family medicine hospitalists are reported separately). These numbers have been pretty stable for many years.
Whether it is reasonable to expect hospitalists in your group to produce at this level is a question that can unspool into a lengthy conversation. Below are several assertions I regularly hear others make about productivity, and following each is my commentary.
“Surveys show only what is most typical, not what is optimal. Our field suffers from concerning levels of burnout, essentially proving that median levels of productivity shown in surveys is too high.”
I share this concern, but this is a complicated issue. You’ll have to make up your own mind regarding how significantly workload influences hospitalist burnout. But the modest amount of published research on this topic suggests that workload itself isn’t as strongly associated with burnout as you might think. I’m certain workload does play a role, but other factors such as “occupational solidarity” seem to matter more. Lowering workload in some settings might be appropriate, but without other interventions may not influence work-related stress and burnout as much as might be hoped.
“Surveys don’t capture unbillable activities (‘unbillable wRVUs’), so are a poor frame of reference when thinking about productivity expectations in our own group.”
It’s true that hospitalists do a lot of work that isn’t captured in wRVUs. My work with many groups around the country suggests the amount and difficulty of this unbillable work is reasonably similar across most groups. We all spend time with handoffs, managing paperwork such as charge capture and completing forms, responding to a rapid response call that doesn’t lead to a billable charge, etc. The average amount of this sort of work is built into the survey. Clearly some groups are outliers with meaningfully more unbillable work than elsewhere, but that can be a difficult or impossible thing to prove.
“My hospital has unique barriers to efficiency/productivity, so it’s more difficult to achieve levels of productivity shown in surveys.”
This is another way of expressing the previous issue. To support this assertion hospitalists will mention that it is tougher to be productive at their hospital because they’re a referral center with unusually sick and complicated patients; they teach trainees in addition to clinical care; and/or their patients and families are unusually demanding, so they take much more time than at other places.
Yet for each of these issues I also hear the reverse argument regularly. Hospitalists point out that because they’re a small hospital (not a referral center) they lack the support of other specialties so must manage all aspects of care themselves; they don’t have residents to help do some of the work; and their patients are unsophisticated and lack social support. For these reasons, the argument goes, they shouldn’t be expected to achieve levels of productivity shown in surveys.
I have worked with hospitalist groups that I am convinced do face unusual barriers to efficiency that are meaningful enough that unless the barriers can be addressed, I think productivity expectations should be lower than survey benchmarks. For example, in most academic medical centers and a very small number of nonacademic hospitals, only the attending physician writes orders; consulting doctors don’t. This means that the attending hospitalist must check a patient’s chart repeatedly through the day just to see if the consultant proposed even small things like ordering a routine lab test, advancing the diet, etc., that the hospitalist must order.
A separate daytime admitter shift is a modest barrier to efficiency that is so common it is clearly factored into survey results. Most hospitalist groups with more than about five doctors working daily have one doctor (or more than one in large groups) manage admissions while the rest round and are protected from admissions. While this may have a number of benefits, overall hospitalist efficiency isn’t one of them. It means that all patients, not just those admitted at night, will have a handoff from the admitting provider to a new attending for the first rounding visit. This new attending will spend additional time becoming familiar with the patient – time that wouldn’t be necessary had that doctor performed the admission visit herself.
“Our hospitalist group is always being asked to take on more duties, such as managing med reconciliation, taking referrals from an additional PCP group, or serving as admitting and attending physician for patients previously admitted by a different specialty (which now serves in the consultant role). For this reason, it’s necessary to steadily lower hospitalist productivity expectations over time.”
A hospitalist today probably spends a quarter of the day doing things I didn’t have to do at the outset of my career in the 1980s. So my impulse is to agree that as the breadth of our responsibilities expands, expected wRVU productivity should fall. But surveys over the last 15-20 years don’t show this happening, and the pressure to maintain productivity levels isn’t likely to let up. Rather than generating fewer wRVUs (seeing fewer patients), hospital medicine, like health care as a whole, faces the challenge of continually improving our efficiency.
“Surveys are only one frame of reference for determining expectations at my particular hospitalist group. There are other factors to consider as well.”
This is absolutely true. There may be many reasons for your group to set expectations that are meaningfully different from survey figures. Just make sure your rationale for doing so is well considered and effectively communicated to other stakeholders, such as those in finance and organizational leadership at your organization.
Dr. Nelson has had a career in clinical practice as a hospitalist starting in 1988. He is cofounder and past president of SHM, and principal in Nelson Flores Hospital Medicine Consultants. He is codirector for SHM’s practice management courses. [email protected]
The 2017 MGMA survey data on compensation and productivity were released last June. While the numbers aren’t surprising, reviewing them always gets me thinking about factors that influence reasonable expectations for compensation and productivity in any individual hospitalist group.
The data were collected in early 2017, reflecting work done in 2016, and show a national median hospitalist compensation for internal medicine physicians of $284,000, up from $278,500 the year before. Since MGMA added a hospitalist category to the survey, compensation has been growing significantly faster than inflation, even though productivity has been essentially flat. I’ve always thought that the high demand for hospitalists, which isn’t letting up much, in the face of a limited supply is probably the most significant force causing hospitalist compensation to rise faster than in most other specialties.
The survey shows a median of 2,114 billed encounters and 4,159 wRVUs (work relative value units) generated per internal medicine hospitalist annually (family medicine hospitalists are reported separately). These numbers have been pretty stable for many years.
Whether it is reasonable to expect hospitalists in your group to produce at this level is a question that can unspool into a lengthy conversation. Below are several assertions I regularly hear others make about productivity, and following each is my commentary.
“Surveys show only what is most typical, not what is optimal. Our field suffers from concerning levels of burnout, essentially proving that median levels of productivity shown in surveys is too high.”
I share this concern, but this is a complicated issue. You’ll have to make up your own mind regarding how significantly workload influences hospitalist burnout. But the modest amount of published research on this topic suggests that workload itself isn’t as strongly associated with burnout as you might think. I’m certain workload does play a role, but other factors such as “occupational solidarity” seem to matter more. Lowering workload in some settings might be appropriate, but without other interventions may not influence work-related stress and burnout as much as might be hoped.
“Surveys don’t capture unbillable activities (‘unbillable wRVUs’), so are a poor frame of reference when thinking about productivity expectations in our own group.”
It’s true that hospitalists do a lot of work that isn’t captured in wRVUs. My work with many groups around the country suggests the amount and difficulty of this unbillable work is reasonably similar across most groups. We all spend time with handoffs, managing paperwork such as charge capture and completing forms, responding to a rapid response call that doesn’t lead to a billable charge, etc. The average amount of this sort of work is built into the survey. Clearly some groups are outliers with meaningfully more unbillable work than elsewhere, but that can be a difficult or impossible thing to prove.
“My hospital has unique barriers to efficiency/productivity, so it’s more difficult to achieve levels of productivity shown in surveys.”
This is another way of expressing the previous issue. To support this assertion hospitalists will mention that it is tougher to be productive at their hospital because they’re a referral center with unusually sick and complicated patients; they teach trainees in addition to clinical care; and/or their patients and families are unusually demanding, so they take much more time than at other places.
Yet for each of these issues I also hear the reverse argument regularly. Hospitalists point out that because they’re a small hospital (not a referral center) they lack the support of other specialties so must manage all aspects of care themselves; they don’t have residents to help do some of the work; and their patients are unsophisticated and lack social support. For these reasons, the argument goes, they shouldn’t be expected to achieve levels of productivity shown in surveys.
I have worked with hospitalist groups that I am convinced do face unusual barriers to efficiency that are meaningful enough that unless the barriers can be addressed, I think productivity expectations should be lower than survey benchmarks. For example, in most academic medical centers and a very small number of nonacademic hospitals, only the attending physician writes orders; consulting doctors don’t. This means that the attending hospitalist must check a patient’s chart repeatedly through the day just to see if the consultant proposed even small things like ordering a routine lab test, advancing the diet, etc., that the hospitalist must order.
A separate daytime admitter shift is a modest barrier to efficiency that is so common it is clearly factored into survey results. Most hospitalist groups with more than about five doctors working daily have one doctor (or more than one in large groups) manage admissions while the rest round and are protected from admissions. While this may have a number of benefits, overall hospitalist efficiency isn’t one of them. It means that all patients, not just those admitted at night, will have a handoff from the admitting provider to a new attending for the first rounding visit. This new attending will spend additional time becoming familiar with the patient – time that wouldn’t be necessary had that doctor performed the admission visit herself.
“Our hospitalist group is always being asked to take on more duties, such as managing med reconciliation, taking referrals from an additional PCP group, or serving as admitting and attending physician for patients previously admitted by a different specialty (which now serves in the consultant role). For this reason, it’s necessary to steadily lower hospitalist productivity expectations over time.”
A hospitalist today probably spends a quarter of the day doing things I didn’t have to do at the outset of my career in the 1980s. So my impulse is to agree that as the breadth of our responsibilities expands, expected wRVU productivity should fall. But surveys over the last 15-20 years don’t show this happening, and the pressure to maintain productivity levels isn’t likely to let up. Rather than generating fewer wRVUs (seeing fewer patients), hospital medicine, like health care as a whole, faces the challenge of continually improving our efficiency.
“Surveys are only one frame of reference for determining expectations at my particular hospitalist group. There are other factors to consider as well.”
This is absolutely true. There may be many reasons for your group to set expectations that are meaningfully different from survey figures. Just make sure your rationale for doing so is well considered and effectively communicated to other stakeholders, such as those in finance and organizational leadership at your organization.
Dr. Nelson has had a career in clinical practice as a hospitalist starting in 1988. He is cofounder and past president of SHM, and principal in Nelson Flores Hospital Medicine Consultants. He is codirector for SHM’s practice management courses. [email protected]
The 2017 MGMA survey data on compensation and productivity were released last June. While the numbers aren’t surprising, reviewing them always gets me thinking about factors that influence reasonable expectations for compensation and productivity in any individual hospitalist group.
The data were collected in early 2017, reflecting work done in 2016, and show a national median hospitalist compensation for internal medicine physicians of $284,000, up from $278,500 the year before. Since MGMA added a hospitalist category to the survey, compensation has been growing significantly faster than inflation, even though productivity has been essentially flat. I’ve always thought that the high demand for hospitalists, which isn’t letting up much, in the face of a limited supply is probably the most significant force causing hospitalist compensation to rise faster than in most other specialties.
The survey shows a median of 2,114 billed encounters and 4,159 wRVUs (work relative value units) generated per internal medicine hospitalist annually (family medicine hospitalists are reported separately). These numbers have been pretty stable for many years.
Whether it is reasonable to expect hospitalists in your group to produce at this level is a question that can unspool into a lengthy conversation. Below are several assertions I regularly hear others make about productivity, and following each is my commentary.
“Surveys show only what is most typical, not what is optimal. Our field suffers from concerning levels of burnout, essentially proving that median levels of productivity shown in surveys is too high.”
I share this concern, but this is a complicated issue. You’ll have to make up your own mind regarding how significantly workload influences hospitalist burnout. But the modest amount of published research on this topic suggests that workload itself isn’t as strongly associated with burnout as you might think. I’m certain workload does play a role, but other factors such as “occupational solidarity” seem to matter more. Lowering workload in some settings might be appropriate, but without other interventions may not influence work-related stress and burnout as much as might be hoped.
“Surveys don’t capture unbillable activities (‘unbillable wRVUs’), so are a poor frame of reference when thinking about productivity expectations in our own group.”
It’s true that hospitalists do a lot of work that isn’t captured in wRVUs. My work with many groups around the country suggests the amount and difficulty of this unbillable work is reasonably similar across most groups. We all spend time with handoffs, managing paperwork such as charge capture and completing forms, responding to a rapid response call that doesn’t lead to a billable charge, etc. The average amount of this sort of work is built into the survey. Clearly some groups are outliers with meaningfully more unbillable work than elsewhere, but that can be a difficult or impossible thing to prove.
“My hospital has unique barriers to efficiency/productivity, so it’s more difficult to achieve levels of productivity shown in surveys.”
This is another way of expressing the previous issue. To support this assertion hospitalists will mention that it is tougher to be productive at their hospital because they’re a referral center with unusually sick and complicated patients; they teach trainees in addition to clinical care; and/or their patients and families are unusually demanding, so they take much more time than at other places.
Yet for each of these issues I also hear the reverse argument regularly. Hospitalists point out that because they’re a small hospital (not a referral center) they lack the support of other specialties so must manage all aspects of care themselves; they don’t have residents to help do some of the work; and their patients are unsophisticated and lack social support. For these reasons, the argument goes, they shouldn’t be expected to achieve levels of productivity shown in surveys.
I have worked with hospitalist groups that I am convinced do face unusual barriers to efficiency that are meaningful enough that unless the barriers can be addressed, I think productivity expectations should be lower than survey benchmarks. For example, in most academic medical centers and a very small number of nonacademic hospitals, only the attending physician writes orders; consulting doctors don’t. This means that the attending hospitalist must check a patient’s chart repeatedly through the day just to see if the consultant proposed even small things like ordering a routine lab test, advancing the diet, etc., that the hospitalist must order.
A separate daytime admitter shift is a modest barrier to efficiency that is so common it is clearly factored into survey results. Most hospitalist groups with more than about five doctors working daily have one doctor (or more than one in large groups) manage admissions while the rest round and are protected from admissions. While this may have a number of benefits, overall hospitalist efficiency isn’t one of them. It means that all patients, not just those admitted at night, will have a handoff from the admitting provider to a new attending for the first rounding visit. This new attending will spend additional time becoming familiar with the patient – time that wouldn’t be necessary had that doctor performed the admission visit herself.
“Our hospitalist group is always being asked to take on more duties, such as managing med reconciliation, taking referrals from an additional PCP group, or serving as admitting and attending physician for patients previously admitted by a different specialty (which now serves in the consultant role). For this reason, it’s necessary to steadily lower hospitalist productivity expectations over time.”
A hospitalist today probably spends a quarter of the day doing things I didn’t have to do at the outset of my career in the 1980s. So my impulse is to agree that as the breadth of our responsibilities expands, expected wRVU productivity should fall. But surveys over the last 15-20 years don’t show this happening, and the pressure to maintain productivity levels isn’t likely to let up. Rather than generating fewer wRVUs (seeing fewer patients), hospital medicine, like health care as a whole, faces the challenge of continually improving our efficiency.
“Surveys are only one frame of reference for determining expectations at my particular hospitalist group. There are other factors to consider as well.”
This is absolutely true. There may be many reasons for your group to set expectations that are meaningfully different from survey figures. Just make sure your rationale for doing so is well considered and effectively communicated to other stakeholders, such as those in finance and organizational leadership at your organization.
Dr. Nelson has had a career in clinical practice as a hospitalist starting in 1988. He is cofounder and past president of SHM, and principal in Nelson Flores Hospital Medicine Consultants. He is codirector for SHM’s practice management courses. [email protected]
Bilirubin levels associated with transplant-free survival in PBC patients
Normal serum bilirubin concentrations in patients with primary biliary cholangitis (PBC) were associated with improved odds of transplant-free survival, according to a study presented at the annual meeting of the American Association for the Study of Liver Diseases.
In a retrospective analysis of data from the Global PBC Study group, PBC patients who had bilirubin levels between normal and the upper limit of normal at baseline (n = 2,795), at 1 year (n = 3,082), at 3 years (n = 1,657), or at 5 years (n = 1,339) were included in the study. Both ursodeoxycholic acid–treated and untreated patients were included, according to Carla Murillo Perez of Toronto General Hospital and her associates.
Each cohort was organized into quartiles, with Q1 having the lowest bilirubin levels and Q4 having the highest. In the baseline cohort, 5-year transplant-free survival rates were 97% in Q1, 95% in Q2, 96% in Q3, and 91% in Q4; similarly improved odds for transplant-free survival in lower quartiles were seen in the later cohorts.
Higher bilirubin (per 0.1 × upper limit of normal increase) was associated with an increased chance for death or transplantation, with hazard ratios of 1.14 in the baseline cohort, 1.21 in the 1-year cohort, 1.19 in the 3-year cohort, and 1.17 in the 5-year cohort, Ms. Perez and her associates said.
Dr. Cyriel Ponsioen, Dr. Christophe Corpechot, Dr. Marlyn Mayo, Dr. Annarosa Floreani, Dr. Albert Pares, Dr. Frederik Nevens, Dr. Kris Kowdley, Dr. Tony Bruns, Dr. Gideon Hirschfield, Dr. Keith Lindor, and Dr. Harry Janssen reported conflicts of interest.
Normal serum bilirubin concentrations in patients with primary biliary cholangitis (PBC) were associated with improved odds of transplant-free survival, according to a study presented at the annual meeting of the American Association for the Study of Liver Diseases.
In a retrospective analysis of data from the Global PBC Study group, PBC patients who had bilirubin levels between normal and the upper limit of normal at baseline (n = 2,795), at 1 year (n = 3,082), at 3 years (n = 1,657), or at 5 years (n = 1,339) were included in the study. Both ursodeoxycholic acid–treated and untreated patients were included, according to Carla Murillo Perez of Toronto General Hospital and her associates.
Each cohort was organized into quartiles, with Q1 having the lowest bilirubin levels and Q4 having the highest. In the baseline cohort, 5-year transplant-free survival rates were 97% in Q1, 95% in Q2, 96% in Q3, and 91% in Q4; similarly improved odds for transplant-free survival in lower quartiles were seen in the later cohorts.
Higher bilirubin (per 0.1 × upper limit of normal increase) was associated with an increased chance for death or transplantation, with hazard ratios of 1.14 in the baseline cohort, 1.21 in the 1-year cohort, 1.19 in the 3-year cohort, and 1.17 in the 5-year cohort, Ms. Perez and her associates said.
Dr. Cyriel Ponsioen, Dr. Christophe Corpechot, Dr. Marlyn Mayo, Dr. Annarosa Floreani, Dr. Albert Pares, Dr. Frederik Nevens, Dr. Kris Kowdley, Dr. Tony Bruns, Dr. Gideon Hirschfield, Dr. Keith Lindor, and Dr. Harry Janssen reported conflicts of interest.
Normal serum bilirubin concentrations in patients with primary biliary cholangitis (PBC) were associated with improved odds of transplant-free survival, according to a study presented at the annual meeting of the American Association for the Study of Liver Diseases.
In a retrospective analysis of data from the Global PBC Study group, PBC patients who had bilirubin levels between normal and the upper limit of normal at baseline (n = 2,795), at 1 year (n = 3,082), at 3 years (n = 1,657), or at 5 years (n = 1,339) were included in the study. Both ursodeoxycholic acid–treated and untreated patients were included, according to Carla Murillo Perez of Toronto General Hospital and her associates.
Each cohort was organized into quartiles, with Q1 having the lowest bilirubin levels and Q4 having the highest. In the baseline cohort, 5-year transplant-free survival rates were 97% in Q1, 95% in Q2, 96% in Q3, and 91% in Q4; similarly improved odds for transplant-free survival in lower quartiles were seen in the later cohorts.
Higher bilirubin (per 0.1 × upper limit of normal increase) was associated with an increased chance for death or transplantation, with hazard ratios of 1.14 in the baseline cohort, 1.21 in the 1-year cohort, 1.19 in the 3-year cohort, and 1.17 in the 5-year cohort, Ms. Perez and her associates said.
Dr. Cyriel Ponsioen, Dr. Christophe Corpechot, Dr. Marlyn Mayo, Dr. Annarosa Floreani, Dr. Albert Pares, Dr. Frederik Nevens, Dr. Kris Kowdley, Dr. Tony Bruns, Dr. Gideon Hirschfield, Dr. Keith Lindor, and Dr. Harry Janssen reported conflicts of interest.
FROM THE LIVER MEETING 2017
Key clinical point:
Major finding: In a baseline cohort, 5-year transplant-free survival rates were 97% in patients with the lowest bilirubin levels and 91% in patients with the highest.
Data source: A retrospective analysis of data from the Global PBC Study group database.
Disclosures: Dr. Cyriel Ponsioen, Dr. Christophe Corpechot, Dr. Marlyn Mayo, Dr. Annarosa Floreani, Dr. Albert Pares, Dr. Frederik Nevens, Dr. Kris Kowdley, Dr. Tony Bruns, Dr. Gideon Hirschfield, Dr. Keith Lindor, and Dr. Harry Janssen reported conflicts of interest.
Early liver transplant good for patients with severe alcoholic hepatitis
Early liver transplantation was associated with good short-term survival in patients with severe alcoholic hepatitis, but a significant number of patients started consuming alcohol again, according to a study presented at the annual meeting of the American Association for the Study of Liver Diseases.
The study was a retrospective review of the ACCELERATE-AH trial, utilizing a cohort of 147 patients with severe AH who underwent liver transplant prior to a 6-month abstinence period and were discharged home after surgery, said Dr. Brian Lee of the University of California, San Francisco, and his colleagues. Patients also underwent a follow-up period with a median time of 1.6 years.
Pretransplant abstinence time was a median of 55 days, and 54% received steroids for alcoholic hepatitis before the surgery. A total of 141 patients were discharged home after surgery, and 132 survived past 3 months. Of the nine patients who died within 3 months of their liver transplant, eight had received steroid therapy, and five died from sepsis.
No deaths were reported between 3 months and 1 year post transplant, but nine deaths were reported after 1 year, seven of which were alcohol related. The probability of alcohol use after 1 year was 25% and was 34% after 3 years.
After adjustment, a lack of self-admission into a hospital was associated with alcohol usage post transplant, with a hazard ratio of 4.3. In multivariate analysis, any alcohol use post transplant was associated with death, with a hazard ratio of 3.9, Dr. Lee and his colleagues noted.
Dr. Lee, Dr. Mehta, Dr. Platt, Dr. Gurakar, Dr. Im, Dr. Han, Dr. Victor, Dr. Rinella, Dr. Maddur, Dr. Eswaran, Dr. Hause, Dr. Foley, Dr. Dodge, Dr. Li, and Dr. Terrault reported conflicts of interest.
Early liver transplantation was associated with good short-term survival in patients with severe alcoholic hepatitis, but a significant number of patients started consuming alcohol again, according to a study presented at the annual meeting of the American Association for the Study of Liver Diseases.
The study was a retrospective review of the ACCELERATE-AH trial, utilizing a cohort of 147 patients with severe AH who underwent liver transplant prior to a 6-month abstinence period and were discharged home after surgery, said Dr. Brian Lee of the University of California, San Francisco, and his colleagues. Patients also underwent a follow-up period with a median time of 1.6 years.
Pretransplant abstinence time was a median of 55 days, and 54% received steroids for alcoholic hepatitis before the surgery. A total of 141 patients were discharged home after surgery, and 132 survived past 3 months. Of the nine patients who died within 3 months of their liver transplant, eight had received steroid therapy, and five died from sepsis.
No deaths were reported between 3 months and 1 year post transplant, but nine deaths were reported after 1 year, seven of which were alcohol related. The probability of alcohol use after 1 year was 25% and was 34% after 3 years.
After adjustment, a lack of self-admission into a hospital was associated with alcohol usage post transplant, with a hazard ratio of 4.3. In multivariate analysis, any alcohol use post transplant was associated with death, with a hazard ratio of 3.9, Dr. Lee and his colleagues noted.
Dr. Lee, Dr. Mehta, Dr. Platt, Dr. Gurakar, Dr. Im, Dr. Han, Dr. Victor, Dr. Rinella, Dr. Maddur, Dr. Eswaran, Dr. Hause, Dr. Foley, Dr. Dodge, Dr. Li, and Dr. Terrault reported conflicts of interest.
Early liver transplantation was associated with good short-term survival in patients with severe alcoholic hepatitis, but a significant number of patients started consuming alcohol again, according to a study presented at the annual meeting of the American Association for the Study of Liver Diseases.
The study was a retrospective review of the ACCELERATE-AH trial, utilizing a cohort of 147 patients with severe AH who underwent liver transplant prior to a 6-month abstinence period and were discharged home after surgery, said Dr. Brian Lee of the University of California, San Francisco, and his colleagues. Patients also underwent a follow-up period with a median time of 1.6 years.
Pretransplant abstinence time was a median of 55 days, and 54% received steroids for alcoholic hepatitis before the surgery. A total of 141 patients were discharged home after surgery, and 132 survived past 3 months. Of the nine patients who died within 3 months of their liver transplant, eight had received steroid therapy, and five died from sepsis.
No deaths were reported between 3 months and 1 year post transplant, but nine deaths were reported after 1 year, seven of which were alcohol related. The probability of alcohol use after 1 year was 25% and was 34% after 3 years.
After adjustment, a lack of self-admission into a hospital was associated with alcohol usage post transplant, with a hazard ratio of 4.3. In multivariate analysis, any alcohol use post transplant was associated with death, with a hazard ratio of 3.9, Dr. Lee and his colleagues noted.
Dr. Lee, Dr. Mehta, Dr. Platt, Dr. Gurakar, Dr. Im, Dr. Han, Dr. Victor, Dr. Rinella, Dr. Maddur, Dr. Eswaran, Dr. Hause, Dr. Foley, Dr. Dodge, Dr. Li, and Dr. Terrault reported conflicts of interest.
FROM THE LIVER MEETING 2017
Key clinical point:
Major finding: The survival rate post transplant was 94% after 1 year.
Data source: A retrospective review from the ACCELERATE-AH trial of 147 alcoholic hepatitis patients who received liver transplants.
Disclosures: Dr. Lee, Dr. Mehta, Dr. Platt, Dr. Gurakar, Dr. Im, Dr. Han, Dr. Victor, Dr. Rinella, Dr. Maddur, Dr. Eswaran, Dr. Hause, Dr. Foley, Dr. Dodge, Dr. Li, and Dr. Terrault reported conflicts of interest.
Asians have highest rate of herbal dietary supplement DILI liver transplantations
There is a significant relationship between race/ethnicity and drug-induced liver disease requiring liver transplantation caused by herbal and dietary supplements (HDS), according to a study presented at the annual meeting of the American Association for the Study of Liver Diseases.
Asian people had significantly higher rates of HDS DILI that required transplant than did blacks, Hispanics, whites, and others (American Indian/Alaskan native, multiracial, and native Hawaii/Pacific Islander). White people had significantly lower rates of HDS DILI than did blacks, Hispanics, and others.
While the proportion of white people with HDS DILI requiring transplant was much lower than other races/ethnicities, the rate from 2005 to 2015 was significantly higher in this population than in 1995-2005, Dr. Kesar and his colleagues noted.
Dr. Odin is a member of Intercept Pharmaceuticals advisory committees or review panels and is an AASLD member. Dr. Ahmad is an AASLD member.
There is a significant relationship between race/ethnicity and drug-induced liver disease requiring liver transplantation caused by herbal and dietary supplements (HDS), according to a study presented at the annual meeting of the American Association for the Study of Liver Diseases.
Asian people had significantly higher rates of HDS DILI that required transplant than did blacks, Hispanics, whites, and others (American Indian/Alaskan native, multiracial, and native Hawaii/Pacific Islander). White people had significantly lower rates of HDS DILI than did blacks, Hispanics, and others.
While the proportion of white people with HDS DILI requiring transplant was much lower than other races/ethnicities, the rate from 2005 to 2015 was significantly higher in this population than in 1995-2005, Dr. Kesar and his colleagues noted.
Dr. Odin is a member of Intercept Pharmaceuticals advisory committees or review panels and is an AASLD member. Dr. Ahmad is an AASLD member.
There is a significant relationship between race/ethnicity and drug-induced liver disease requiring liver transplantation caused by herbal and dietary supplements (HDS), according to a study presented at the annual meeting of the American Association for the Study of Liver Diseases.
Asian people had significantly higher rates of HDS DILI that required transplant than did blacks, Hispanics, whites, and others (American Indian/Alaskan native, multiracial, and native Hawaii/Pacific Islander). White people had significantly lower rates of HDS DILI than did blacks, Hispanics, and others.
While the proportion of white people with HDS DILI requiring transplant was much lower than other races/ethnicities, the rate from 2005 to 2015 was significantly higher in this population than in 1995-2005, Dr. Kesar and his colleagues noted.
Dr. Odin is a member of Intercept Pharmaceuticals advisory committees or review panels and is an AASLD member. Dr. Ahmad is an AASLD member.
FROM THE LIVER MEETING 2017
Key clinical point:
Major finding: People of Asian descent were most likely to require transplantation because of drug-induced liver injury from herbal dietary supplements.
Data source: Retrospective data analysis of 645 patients from the Organ Procurement and Transplantation Network database.
Disclosures: Dr. Odin is a member of Intercept Pharmaceuticals advisory committees or review panels and is an AASLD member. Dr. Ahmad is an AASLD member.
How Do Type 2 Diabetes and Thyroid Disorder Interact?
Although studies have examined the relationship between thyroid disorder (TD) and type 1 diabetes mellitus (T1DM), the information on TD and type 2 diabetes mellitus (T2DM) is limited, say researchers from Shahid Beheshti University of Medical Sciences and Aja University of Medical Science in Tehran, Iran, who report on an 11-year follow-up from the Tehran Thyroid Study. However, undetected TDs may compromise metabolic control of patients with diabetes mellitus (DM), impaired glucose tolerance, or impaired fasting glucose, the researchers point out. Undetected TDs also may increase the risk of cardiovascular diseases. And DM and prediabetes can affect thyroid tests.
The researchers evaluated 435 patients with DM, 286 with prediabetes, and 989 healthy controls. They conducted follow-up assessments every 3 years. About 19% of both the diabetic and prediabetic groups had TD, as did about 14% of the healthy controls. However, after adjusting for age, sex, smoking, blood pressure, body mass index, thyroid peroxidase antibody (TPOAb), thyrotropin (TSH), insulin resistance index, triglycerides, and cholesterol, no significant difference was found among the 3 groups. The mean incidence of TD was 14, 18, and 21 per 1000 patients per year in patients with DM, prediabetes, and healthy controls, respectively.
As in other studies, subclinical hypothyroidism and clinical hyperthyroidism were the most and the least common TD in patients with DM. Baseline TSH > 1.94 mU/L was predictive of TD with 70% sensitivity and specificity and had better predictive value than TPOAb . The researchers say conducting screening tests in all patients is not recommended except in those with TPOAb ≥ 401 U/mL or TSH > 1.94 mU/L.
Source:
Gholampour Dehaki M, Amouzegar A, Delshad H, Mehrabi Y, Tohidi M, Azizi F. PLoS One. 2017;12(10): e0184808.
doi: 10.1371/journal.pone.0184808.
Although studies have examined the relationship between thyroid disorder (TD) and type 1 diabetes mellitus (T1DM), the information on TD and type 2 diabetes mellitus (T2DM) is limited, say researchers from Shahid Beheshti University of Medical Sciences and Aja University of Medical Science in Tehran, Iran, who report on an 11-year follow-up from the Tehran Thyroid Study. However, undetected TDs may compromise metabolic control of patients with diabetes mellitus (DM), impaired glucose tolerance, or impaired fasting glucose, the researchers point out. Undetected TDs also may increase the risk of cardiovascular diseases. And DM and prediabetes can affect thyroid tests.
The researchers evaluated 435 patients with DM, 286 with prediabetes, and 989 healthy controls. They conducted follow-up assessments every 3 years. About 19% of both the diabetic and prediabetic groups had TD, as did about 14% of the healthy controls. However, after adjusting for age, sex, smoking, blood pressure, body mass index, thyroid peroxidase antibody (TPOAb), thyrotropin (TSH), insulin resistance index, triglycerides, and cholesterol, no significant difference was found among the 3 groups. The mean incidence of TD was 14, 18, and 21 per 1000 patients per year in patients with DM, prediabetes, and healthy controls, respectively.
As in other studies, subclinical hypothyroidism and clinical hyperthyroidism were the most and the least common TD in patients with DM. Baseline TSH > 1.94 mU/L was predictive of TD with 70% sensitivity and specificity and had better predictive value than TPOAb . The researchers say conducting screening tests in all patients is not recommended except in those with TPOAb ≥ 401 U/mL or TSH > 1.94 mU/L.
Source:
Gholampour Dehaki M, Amouzegar A, Delshad H, Mehrabi Y, Tohidi M, Azizi F. PLoS One. 2017;12(10): e0184808.
doi: 10.1371/journal.pone.0184808.
Although studies have examined the relationship between thyroid disorder (TD) and type 1 diabetes mellitus (T1DM), the information on TD and type 2 diabetes mellitus (T2DM) is limited, say researchers from Shahid Beheshti University of Medical Sciences and Aja University of Medical Science in Tehran, Iran, who report on an 11-year follow-up from the Tehran Thyroid Study. However, undetected TDs may compromise metabolic control of patients with diabetes mellitus (DM), impaired glucose tolerance, or impaired fasting glucose, the researchers point out. Undetected TDs also may increase the risk of cardiovascular diseases. And DM and prediabetes can affect thyroid tests.
The researchers evaluated 435 patients with DM, 286 with prediabetes, and 989 healthy controls. They conducted follow-up assessments every 3 years. About 19% of both the diabetic and prediabetic groups had TD, as did about 14% of the healthy controls. However, after adjusting for age, sex, smoking, blood pressure, body mass index, thyroid peroxidase antibody (TPOAb), thyrotropin (TSH), insulin resistance index, triglycerides, and cholesterol, no significant difference was found among the 3 groups. The mean incidence of TD was 14, 18, and 21 per 1000 patients per year in patients with DM, prediabetes, and healthy controls, respectively.
As in other studies, subclinical hypothyroidism and clinical hyperthyroidism were the most and the least common TD in patients with DM. Baseline TSH > 1.94 mU/L was predictive of TD with 70% sensitivity and specificity and had better predictive value than TPOAb . The researchers say conducting screening tests in all patients is not recommended except in those with TPOAb ≥ 401 U/mL or TSH > 1.94 mU/L.
Source:
Gholampour Dehaki M, Amouzegar A, Delshad H, Mehrabi Y, Tohidi M, Azizi F. PLoS One. 2017;12(10): e0184808.
doi: 10.1371/journal.pone.0184808.
Eltrombopag can control ITP long-term, study suggests
Eltrombopag can provide long-term disease control for chronic/persistent immune thrombocytopenia (ITP), according to research published in Blood.
In the EXTEND study, investigators evaluated patients exposed to eltrombopag for a median of 2.4 years.
Most patients achieved a response to the drug, and more than half of them maintained that response for at least 25 weeks.
More than a third of patients were able to discontinue at least 1 concomitant ITP medication.
Most adverse events (AEs) were grade 1 or 2. However, 32% of patients had serious AEs, and 14% of patients withdrew from the study due to AEs.
This research was sponsored by GlaxoSmithKline, the company that previously owned eltrombopag. Now, the drug is a product of Novartis.
Patients
EXTEND is an open-label extension study of 4 trials (TRA100773A, TRA100773B, TRA102537/RAISE, and TRA108057/REPEAT), which enrolled 302 adults with chronic/persistent ITP.
Patients had completed the treatment and follow-up periods as defined in their previous study protocol and did not experience eltrombopag-related toxicity or other drug intolerance on a prior eltrombopag study. Patients who discontinued a previous study due to toxicity were only eligible if they had received a placebo.
The patients’ median time from diagnosis to enrollment in EXTEND was 58.8 months (range, 9-552). Their median age was 50 (range, 18-86), and 67% were female.
Most patients (70%) had a baseline platelet count below 30×109/L. Thirty-three percent of patients were using concomitant ITP medications, 53% had received at least 3 prior ITP treatments, and 38% had undergone splenectomy.
Treatment
Eltrombopag was started at a dose of 50 mg/day and titrated to 25-75 mg/day or less often based on platelet counts. Maintenance dosing continued after minimization of concomitant ITP medication and optimization of eltrombopag dosing.
The overall median duration of eltrombopag exposure was 2.37 years (range, 2 days to 8.76 years), and the mean average daily dose was 50.2 mg/day (range, 1-75).
One hundred and thirty-five patients (45%) completed the study, and 75 patients (25%) were treated for 4 or more years. The most common reasons for study withdrawal included AEs (n=41), patient decision (n=39), lack of efficacy (n=32), and “other” reasons (n=39).
Safety
AEs leading to study withdrawal (occurring at least twice) included hepatobiliary AEs (n=7), cataracts (n=4), deep vein thrombosis (n=3), cerebral infarction (n=2), headache (n=2), and myelofibrosis (n=2).
The overall incidence of AEs was 92%. The most frequent AEs were headache (28%), nasopharyngitis (25%), and upper respiratory tract infection (23%).
Twenty-six percent of patients had grade 3 AEs, 6% had grade 4 AEs, and 32% had serious AEs. Serious AEs included cataracts (5%), pneumonia (3%), anemia (2%), ALT increase (2%), epistaxis (1%), AST increase, (1%), bilirubin increase (1%), and deep vein thrombosis (1%).
Three percent of patients reported a malignancy while on study, including basal cell carcinoma, intramucosal adenocarcinoma, breast cancer, metastases to the lung, ovarian cancer, squamous cell carcinoma, transitional cell carcinoma, lymphoma, unclassifiable B-cell lymphoma (low grade), and Hodgkin lymphoma.
Efficacy
In all, 85.8% (259/302) of patients had a response to eltrombopag, which was defined as achieving a platelet count of at least 50×109/L at least once without rescue therapy.
Fifty-two percent (133/257) of patients achieved a continuous response lasting at least 25 weeks.
Thirty-four percent (34/101) of patients who were on concomitant ITP medication discontinued at least 1 medication. Thirty-nine percent (39/101) reduced or permanently stopped at least 1 ITP medication without receiving rescue therapy.
Fifty-seven percent of patients (171/302) had bleeding symptoms at baseline. This decreased to 16% (13/80) at 1 year.
“The EXTEND data published in Blood validate [eltrombopag] as an important oral treatment option that, by often increasing platelet counts, significantly decreased bleeding rates and reduced the need for concurrent therapies in certain patients with chronic/persistent immune thrombocytopenia,” said study author James Bussel, MD, of Weill Cornell Medicine in New York, New York.
“With this information, physicians can better optimize long-term disease management for appropriate patients living with this chronic disease.” 
Eltrombopag can provide long-term disease control for chronic/persistent immune thrombocytopenia (ITP), according to research published in Blood.
In the EXTEND study, investigators evaluated patients exposed to eltrombopag for a median of 2.4 years.
Most patients achieved a response to the drug, and more than half of them maintained that response for at least 25 weeks.
More than a third of patients were able to discontinue at least 1 concomitant ITP medication.
Most adverse events (AEs) were grade 1 or 2. However, 32% of patients had serious AEs, and 14% of patients withdrew from the study due to AEs.
This research was sponsored by GlaxoSmithKline, the company that previously owned eltrombopag. Now, the drug is a product of Novartis.
Patients
EXTEND is an open-label extension study of 4 trials (TRA100773A, TRA100773B, TRA102537/RAISE, and TRA108057/REPEAT), which enrolled 302 adults with chronic/persistent ITP.
Patients had completed the treatment and follow-up periods as defined in their previous study protocol and did not experience eltrombopag-related toxicity or other drug intolerance on a prior eltrombopag study. Patients who discontinued a previous study due to toxicity were only eligible if they had received a placebo.
The patients’ median time from diagnosis to enrollment in EXTEND was 58.8 months (range, 9-552). Their median age was 50 (range, 18-86), and 67% were female.
Most patients (70%) had a baseline platelet count below 30×109/L. Thirty-three percent of patients were using concomitant ITP medications, 53% had received at least 3 prior ITP treatments, and 38% had undergone splenectomy.
Treatment
Eltrombopag was started at a dose of 50 mg/day and titrated to 25-75 mg/day or less often based on platelet counts. Maintenance dosing continued after minimization of concomitant ITP medication and optimization of eltrombopag dosing.
The overall median duration of eltrombopag exposure was 2.37 years (range, 2 days to 8.76 years), and the mean average daily dose was 50.2 mg/day (range, 1-75).
One hundred and thirty-five patients (45%) completed the study, and 75 patients (25%) were treated for 4 or more years. The most common reasons for study withdrawal included AEs (n=41), patient decision (n=39), lack of efficacy (n=32), and “other” reasons (n=39).
Safety
AEs leading to study withdrawal (occurring at least twice) included hepatobiliary AEs (n=7), cataracts (n=4), deep vein thrombosis (n=3), cerebral infarction (n=2), headache (n=2), and myelofibrosis (n=2).
The overall incidence of AEs was 92%. The most frequent AEs were headache (28%), nasopharyngitis (25%), and upper respiratory tract infection (23%).
Twenty-six percent of patients had grade 3 AEs, 6% had grade 4 AEs, and 32% had serious AEs. Serious AEs included cataracts (5%), pneumonia (3%), anemia (2%), ALT increase (2%), epistaxis (1%), AST increase, (1%), bilirubin increase (1%), and deep vein thrombosis (1%).
Three percent of patients reported a malignancy while on study, including basal cell carcinoma, intramucosal adenocarcinoma, breast cancer, metastases to the lung, ovarian cancer, squamous cell carcinoma, transitional cell carcinoma, lymphoma, unclassifiable B-cell lymphoma (low grade), and Hodgkin lymphoma.
Efficacy
In all, 85.8% (259/302) of patients had a response to eltrombopag, which was defined as achieving a platelet count of at least 50×109/L at least once without rescue therapy.
Fifty-two percent (133/257) of patients achieved a continuous response lasting at least 25 weeks.
Thirty-four percent (34/101) of patients who were on concomitant ITP medication discontinued at least 1 medication. Thirty-nine percent (39/101) reduced or permanently stopped at least 1 ITP medication without receiving rescue therapy.
Fifty-seven percent of patients (171/302) had bleeding symptoms at baseline. This decreased to 16% (13/80) at 1 year.
“The EXTEND data published in Blood validate [eltrombopag] as an important oral treatment option that, by often increasing platelet counts, significantly decreased bleeding rates and reduced the need for concurrent therapies in certain patients with chronic/persistent immune thrombocytopenia,” said study author James Bussel, MD, of Weill Cornell Medicine in New York, New York.
“With this information, physicians can better optimize long-term disease management for appropriate patients living with this chronic disease.”
Eltrombopag can provide long-term disease control for chronic/persistent immune thrombocytopenia (ITP), according to research published in Blood.
In the EXTEND study, investigators evaluated patients exposed to eltrombopag for a median of 2.4 years.
Most patients achieved a response to the drug, and more than half of them maintained that response for at least 25 weeks.
More than a third of patients were able to discontinue at least 1 concomitant ITP medication.
Most adverse events (AEs) were grade 1 or 2. However, 32% of patients had serious AEs, and 14% of patients withdrew from the study due to AEs.
This research was sponsored by GlaxoSmithKline, the company that previously owned eltrombopag. Now, the drug is a product of Novartis.
Patients
EXTEND is an open-label extension study of 4 trials (TRA100773A, TRA100773B, TRA102537/RAISE, and TRA108057/REPEAT), which enrolled 302 adults with chronic/persistent ITP.
Patients had completed the treatment and follow-up periods as defined in their previous study protocol and did not experience eltrombopag-related toxicity or other drug intolerance on a prior eltrombopag study. Patients who discontinued a previous study due to toxicity were only eligible if they had received a placebo.
The patients’ median time from diagnosis to enrollment in EXTEND was 58.8 months (range, 9-552). Their median age was 50 (range, 18-86), and 67% were female.
Most patients (70%) had a baseline platelet count below 30×109/L. Thirty-three percent of patients were using concomitant ITP medications, 53% had received at least 3 prior ITP treatments, and 38% had undergone splenectomy.
Treatment
Eltrombopag was started at a dose of 50 mg/day and titrated to 25-75 mg/day or less often based on platelet counts. Maintenance dosing continued after minimization of concomitant ITP medication and optimization of eltrombopag dosing.
The overall median duration of eltrombopag exposure was 2.37 years (range, 2 days to 8.76 years), and the mean average daily dose was 50.2 mg/day (range, 1-75).
One hundred and thirty-five patients (45%) completed the study, and 75 patients (25%) were treated for 4 or more years. The most common reasons for study withdrawal included AEs (n=41), patient decision (n=39), lack of efficacy (n=32), and “other” reasons (n=39).
Safety
AEs leading to study withdrawal (occurring at least twice) included hepatobiliary AEs (n=7), cataracts (n=4), deep vein thrombosis (n=3), cerebral infarction (n=2), headache (n=2), and myelofibrosis (n=2).
The overall incidence of AEs was 92%. The most frequent AEs were headache (28%), nasopharyngitis (25%), and upper respiratory tract infection (23%).
Twenty-six percent of patients had grade 3 AEs, 6% had grade 4 AEs, and 32% had serious AEs. Serious AEs included cataracts (5%), pneumonia (3%), anemia (2%), ALT increase (2%), epistaxis (1%), AST increase, (1%), bilirubin increase (1%), and deep vein thrombosis (1%).
Three percent of patients reported a malignancy while on study, including basal cell carcinoma, intramucosal adenocarcinoma, breast cancer, metastases to the lung, ovarian cancer, squamous cell carcinoma, transitional cell carcinoma, lymphoma, unclassifiable B-cell lymphoma (low grade), and Hodgkin lymphoma.
Efficacy
In all, 85.8% (259/302) of patients had a response to eltrombopag, which was defined as achieving a platelet count of at least 50×109/L at least once without rescue therapy.
Fifty-two percent (133/257) of patients achieved a continuous response lasting at least 25 weeks.
Thirty-four percent (34/101) of patients who were on concomitant ITP medication discontinued at least 1 medication. Thirty-nine percent (39/101) reduced or permanently stopped at least 1 ITP medication without receiving rescue therapy.
Fifty-seven percent of patients (171/302) had bleeding symptoms at baseline. This decreased to 16% (13/80) at 1 year.
“The EXTEND data published in Blood validate [eltrombopag] as an important oral treatment option that, by often increasing platelet counts, significantly decreased bleeding rates and reduced the need for concurrent therapies in certain patients with chronic/persistent immune thrombocytopenia,” said study author James Bussel, MD, of Weill Cornell Medicine in New York, New York.
“With this information, physicians can better optimize long-term disease management for appropriate patients living with this chronic disease.”
What we don’t know about BIA-ALCL
Results of a systematic review suggest a need for more research and long-term follow-up of patients with breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL).
Although data suggest BIA-ALCL is likely associated with textured implants and may result from chronic inflammation, neither of these theories has been confirmed.
Furthermore, researchers have yet to establish optimal prognostic and treatment guidelines for BIA-ALCL.
Dino Ravnic, DO, of Penn State Health Milton S. Hershey Medical Center in Hershey, Pennsylvania, and his colleagues highlighted these areas of need in an article published in JAMA Surgery.
The team conducted a literature review to learn more about the development, risk factors, diagnosis, and treatment of BIA-ALCL. They reviewed data from 115 articles and 95 patients.
The researchers noted that the incidence of BIA-ALCL is unknown. The Association of Breast Surgery estimates an incidence of 1 in 300,000 breast implants, while the Australian Therapeutic Goods Administration estimates BIA-ALCL could affect between 1 in 1000 and 1 in 10,000 women with breast implants.
“We’re seeing that this cancer is likely very underreported, and, as more information on this type of cancer comes to light, the number of cases is likely to increase in the coming years,” Dr Ravnic said.
He and his colleagues noted that almost all documented cases of BIA-ALCL have been associated with textured implants. These implants rose in popularity in the 1990s, and the first case of BIA-ALCL was documented in 1997.
The researchers said that because they could find no incidents of BIA-ALCL prior to the introduction of textured implants, this suggests a causal relationship, but more research is needed to confirm this theory.
“We’re still exploring the exact causes, but according to current knowledge, this cancer only really started to appear after textured implants came on the market in the 1990s,” Dr Ravnic said.
“All manufacturers of textured implants have had cases linked to this type of lymphoma, and we haven’t seen cases linked to smooth implants. But, in many of these cases, the implant was removed without testing the surrounding fluid and tissue for lymphoma cells, so it’s difficult to definitively correlate the two.”
The researchers also said the evidence suggests BIA-ALCL may occur as a result of inflammation surrounding the breast implant, and tissue that grows into pores in the textured implant may prolong inflammation.
Chronic inflammation may lead to malignant transformation of T cells that are anaplastic lymphoma kinase-negative and CD30-positive.
The data also suggest BIA-ALCL tends to develop slowly. The mean time to BIA-ALCL presentation in the 95 patients analyzed was about 10 years after the patients received their implants.
The researchers said treatment of BIA-ALCL must include removal of the implant and surrounding capsule. However, patients with advanced disease—including a tumor mass (stage II), lymph node involvement (stage II/III), or distant disease (stage IV)—may require chemotherapy, radiotherapy, or both. Brentuximab vedotin has also been used.
Overall, the patients included in this review appeared to have a good prognosis, with only 5 patients experiencing disease recurrence and dying of BIA-ALCL.
However, the researchers noted that it was difficult to calculate the mean overall survival and disease-free survival of these patients due to a lack of data and inadequate follow-up.
Results of a systematic review suggest a need for more research and long-term follow-up of patients with breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL).
Although data suggest BIA-ALCL is likely associated with textured implants and may result from chronic inflammation, neither of these theories has been confirmed.
Furthermore, researchers have yet to establish optimal prognostic and treatment guidelines for BIA-ALCL.
Dino Ravnic, DO, of Penn State Health Milton S. Hershey Medical Center in Hershey, Pennsylvania, and his colleagues highlighted these areas of need in an article published in JAMA Surgery.
The team conducted a literature review to learn more about the development, risk factors, diagnosis, and treatment of BIA-ALCL. They reviewed data from 115 articles and 95 patients.
The researchers noted that the incidence of BIA-ALCL is unknown. The Association of Breast Surgery estimates an incidence of 1 in 300,000 breast implants, while the Australian Therapeutic Goods Administration estimates BIA-ALCL could affect between 1 in 1000 and 1 in 10,000 women with breast implants.
“We’re seeing that this cancer is likely very underreported, and, as more information on this type of cancer comes to light, the number of cases is likely to increase in the coming years,” Dr Ravnic said.
He and his colleagues noted that almost all documented cases of BIA-ALCL have been associated with textured implants. These implants rose in popularity in the 1990s, and the first case of BIA-ALCL was documented in 1997.
The researchers said that because they could find no incidents of BIA-ALCL prior to the introduction of textured implants, this suggests a causal relationship, but more research is needed to confirm this theory.
“We’re still exploring the exact causes, but according to current knowledge, this cancer only really started to appear after textured implants came on the market in the 1990s,” Dr Ravnic said.
“All manufacturers of textured implants have had cases linked to this type of lymphoma, and we haven’t seen cases linked to smooth implants. But, in many of these cases, the implant was removed without testing the surrounding fluid and tissue for lymphoma cells, so it’s difficult to definitively correlate the two.”
The researchers also said the evidence suggests BIA-ALCL may occur as a result of inflammation surrounding the breast implant, and tissue that grows into pores in the textured implant may prolong inflammation.
Chronic inflammation may lead to malignant transformation of T cells that are anaplastic lymphoma kinase-negative and CD30-positive.
The data also suggest BIA-ALCL tends to develop slowly. The mean time to BIA-ALCL presentation in the 95 patients analyzed was about 10 years after the patients received their implants.
The researchers said treatment of BIA-ALCL must include removal of the implant and surrounding capsule. However, patients with advanced disease—including a tumor mass (stage II), lymph node involvement (stage II/III), or distant disease (stage IV)—may require chemotherapy, radiotherapy, or both. Brentuximab vedotin has also been used.
Overall, the patients included in this review appeared to have a good prognosis, with only 5 patients experiencing disease recurrence and dying of BIA-ALCL.
However, the researchers noted that it was difficult to calculate the mean overall survival and disease-free survival of these patients due to a lack of data and inadequate follow-up.
Results of a systematic review suggest a need for more research and long-term follow-up of patients with breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL).
Although data suggest BIA-ALCL is likely associated with textured implants and may result from chronic inflammation, neither of these theories has been confirmed.
Furthermore, researchers have yet to establish optimal prognostic and treatment guidelines for BIA-ALCL.
Dino Ravnic, DO, of Penn State Health Milton S. Hershey Medical Center in Hershey, Pennsylvania, and his colleagues highlighted these areas of need in an article published in JAMA Surgery.
The team conducted a literature review to learn more about the development, risk factors, diagnosis, and treatment of BIA-ALCL. They reviewed data from 115 articles and 95 patients.
The researchers noted that the incidence of BIA-ALCL is unknown. The Association of Breast Surgery estimates an incidence of 1 in 300,000 breast implants, while the Australian Therapeutic Goods Administration estimates BIA-ALCL could affect between 1 in 1000 and 1 in 10,000 women with breast implants.
“We’re seeing that this cancer is likely very underreported, and, as more information on this type of cancer comes to light, the number of cases is likely to increase in the coming years,” Dr Ravnic said.
He and his colleagues noted that almost all documented cases of BIA-ALCL have been associated with textured implants. These implants rose in popularity in the 1990s, and the first case of BIA-ALCL was documented in 1997.
The researchers said that because they could find no incidents of BIA-ALCL prior to the introduction of textured implants, this suggests a causal relationship, but more research is needed to confirm this theory.
“We’re still exploring the exact causes, but according to current knowledge, this cancer only really started to appear after textured implants came on the market in the 1990s,” Dr Ravnic said.
“All manufacturers of textured implants have had cases linked to this type of lymphoma, and we haven’t seen cases linked to smooth implants. But, in many of these cases, the implant was removed without testing the surrounding fluid and tissue for lymphoma cells, so it’s difficult to definitively correlate the two.”
The researchers also said the evidence suggests BIA-ALCL may occur as a result of inflammation surrounding the breast implant, and tissue that grows into pores in the textured implant may prolong inflammation.
Chronic inflammation may lead to malignant transformation of T cells that are anaplastic lymphoma kinase-negative and CD30-positive.
The data also suggest BIA-ALCL tends to develop slowly. The mean time to BIA-ALCL presentation in the 95 patients analyzed was about 10 years after the patients received their implants.
The researchers said treatment of BIA-ALCL must include removal of the implant and surrounding capsule. However, patients with advanced disease—including a tumor mass (stage II), lymph node involvement (stage II/III), or distant disease (stage IV)—may require chemotherapy, radiotherapy, or both. Brentuximab vedotin has also been used.
Overall, the patients included in this review appeared to have a good prognosis, with only 5 patients experiencing disease recurrence and dying of BIA-ALCL.
However, the researchers noted that it was difficult to calculate the mean overall survival and disease-free survival of these patients due to a lack of data and inadequate follow-up.