SAN ANTONIO – Partial-breast irradiation misses the statistical bar for being as efficacious as whole-breast irradiation in treating residual disease after lumpectomy, but absolute differences in long-term outcomes are minuscule, suggests a phase 3, randomized, controlled trial conducted by NRG Oncology.

MDedge/Susan London

At a median follow-up of 10.2 years, the trial was unable to refute the hypothesis that the partial technique was inferior in terms of ipsilateral breast tumor recurrences; however, the difference between techniques in this outcome was an absolute 0.7%, lead investigator Frank Vicini, MD, principal investigator at the MHP Radiation Oncology Institute/21st Century Oncology in Pontiac, Mich., reported in a session and press conference at the San Antonio Breast Cancer Symposium. The difference in recurrence-free interval was significant but likewise small, at 1.6%, and other efficacy outcomes were similar.

Meanwhile, the groups had low, statistically indistinguishable rates of grade 3-5 toxicities and second cancers. The investigators are still analyzing quality of life and cosmesis outcomes.

“This was the largest trial ever looking at partial-breast [irradiation] in a very diverse group of patients. Even though we weren’t able to demonstrate equivalence, it’s nice to see that in this large population of patients with extended follow-up, the differences are quite small,” Dr. Vicini said. “Because the differences for both ipsilateral breast tumor recurrence and recurrence-free interval were very small, partial-breast irradiation may be an acceptable alternative to whole-breast irradiation for a proportion of women who are undergoing breast-conserving surgery.”
 

Implications for practice and research

SABCS codirector and press conference moderator Virginia Kaklamani, MD, leader of the breast cancer program at UT Health San Antonio, asked how the findings have influenced his practice.

“This trial is over 15 years old now, and a lot of these techniques have been refined. But we are offering partial-breast irradiation to our patients,” Dr. Vicini replied. “There are a lot of competing ways to do radiation now; probably the biggest competing way is to do 3 weeks of whole-breast irradiation. But for those patients who have transportation issues and more elderly patients, we try to offer partial-breast irradiation, within the guidelines of ASTRO [American Society for Therapeutic Radiology and Oncology].”

Some of the women enrolled had risk factors that fall outside those guidelines, for example, higher-grade tumors or axillary node involvement, he acknowledged. “We tried to do exploratory analyses to look at whether certain patients did better with whole-breast irradiation or not, and we weren’t able to really pick out any group of patients that had better or worse outcome based on those criteria,” he said. “We have yet to look at the quality indices for radiation therapy, in other words, how much the breast actually needs to be treated. But at the present time, I would just suggest sticking with the ASTRO guidelines.”

It is noteworthy that likely the most important endpoints, disease-free and overall survival, did not differ between groups, according to Dr. Vicini. “Certainly, a recurrence is still an important event for a patient, so our goal is to always limit that as much as possible,” he said. “But putting it into perspective, does a 0.7% higher risk of recurrence [matter] when you know the survival rates are the same? That’s what patients and doctors need to take into consideration. This is a pretty dramatic difference in treatment [duration], 6 weeks, down to 1 week or less. There have been many studies looking at quality of life and, as you can imagine, quality of life is better” with the shorter therapy.

The trial’s results can also inform statistical planning of future trials, according to Dr. Kaklamani. “It’s important when we design the trials to look at clinically meaningful differences because we don’t want to harm our patients, but at the same time, we are also harming them by giving them more treatment. So if you are designing a trial where a 0.7% difference is statistically significant, you probably would have been able to get away with many fewer patients and a difference of 1.5% or 2% not being significant, and I think everybody would be happy with that.”
 

Study details

Dr. Vicini and colleagues enrolled in their trial 4,216 women with stage 0-II breast cancer who had undergone lumpectomy. They were randomized to whole-breast irradiation (5-6 weeks of radiation therapy at that time) or partial-breast irradiation using one of three techniques (3D conformal external beam radiation completed in 5 days, interstitial brachytherapy completed in 5 days, or device-based brachytherapy).

The hazard ratio for ipsilateral breast tumor recurrence (invasive or DCIS) as a first recurrence with partial-breast irradiation versus whole-breast irradiation was 1.22, with the upper bound of the 90% confidence interval (0.94-1.58) falling just outside the predefined range to declare the two modalities equivalent (0.667-1.5), Dr. Vicini reported. However, the absolute difference in the 10-year cumulative incidence of ipsilateral breast tumor recurrences was merely 0.7% (4.6% vs. 3.9%).

The 10-year recurrence-free interval was inferior with partial-breast irradiation (hazard ratio, 1.33; P = .02), but the absolute difference was again small at 1.6% (91.8% vs 93.4%). The partial- and whole-breast irradiation groups were statistically indistinguishable on distant disease-free interval (96.7% vs 97.1%; HR, 1.31; P = .15) and overall survival (90.6% vs. 91.3%; HR, 1.10; P = .35).

Dr. Vicini disclosed that he is a research advisor for ImpediMed. The study was sponsored by the National Cancer Institute.

SOURCE: Vicini FA et al. SABCS 2018, Abstract GS4-04,

SAN ANTONIO – Partial-breast irradiation misses the statistical bar for being as efficacious as whole-breast irradiation in treating residual disease after lumpectomy, but absolute differences in long-term outcomes are minuscule, suggests a phase 3, randomized, controlled trial conducted by NRG Oncology.

MDedge/Susan London

At a median follow-up of 10.2 years, the trial was unable to refute the hypothesis that the partial technique was inferior in terms of ipsilateral breast tumor recurrences; however, the difference between techniques in this outcome was an absolute 0.7%, lead investigator Frank Vicini, MD, principal investigator at the MHP Radiation Oncology Institute/21st Century Oncology in Pontiac, Mich., reported in a session and press conference at the San Antonio Breast Cancer Symposium. The difference in recurrence-free interval was significant but likewise small, at 1.6%, and other efficacy outcomes were similar.

Meanwhile, the groups had low, statistically indistinguishable rates of grade 3-5 toxicities and second cancers. The investigators are still analyzing quality of life and cosmesis outcomes.

“This was the largest trial ever looking at partial-breast [irradiation] in a very diverse group of patients. Even though we weren’t able to demonstrate equivalence, it’s nice to see that in this large population of patients with extended follow-up, the differences are quite small,” Dr. Vicini said. “Because the differences for both ipsilateral breast tumor recurrence and recurrence-free interval were very small, partial-breast irradiation may be an acceptable alternative to whole-breast irradiation for a proportion of women who are undergoing breast-conserving surgery.”
 

Implications for practice and research

SABCS codirector and press conference moderator Virginia Kaklamani, MD, leader of the breast cancer program at UT Health San Antonio, asked how the findings have influenced his practice.

“This trial is over 15 years old now, and a lot of these techniques have been refined. But we are offering partial-breast irradiation to our patients,” Dr. Vicini replied. “There are a lot of competing ways to do radiation now; probably the biggest competing way is to do 3 weeks of whole-breast irradiation. But for those patients who have transportation issues and more elderly patients, we try to offer partial-breast irradiation, within the guidelines of ASTRO [American Society for Therapeutic Radiology and Oncology].”

Some of the women enrolled had risk factors that fall outside those guidelines, for example, higher-grade tumors or axillary node involvement, he acknowledged. “We tried to do exploratory analyses to look at whether certain patients did better with whole-breast irradiation or not, and we weren’t able to really pick out any group of patients that had better or worse outcome based on those criteria,” he said. “We have yet to look at the quality indices for radiation therapy, in other words, how much the breast actually needs to be treated. But at the present time, I would just suggest sticking with the ASTRO guidelines.”

It is noteworthy that likely the most important endpoints, disease-free and overall survival, did not differ between groups, according to Dr. Vicini. “Certainly, a recurrence is still an important event for a patient, so our goal is to always limit that as much as possible,” he said. “But putting it into perspective, does a 0.7% higher risk of recurrence [matter] when you know the survival rates are the same? That’s what patients and doctors need to take into consideration. This is a pretty dramatic difference in treatment [duration], 6 weeks, down to 1 week or less. There have been many studies looking at quality of life and, as you can imagine, quality of life is better” with the shorter therapy.

The trial’s results can also inform statistical planning of future trials, according to Dr. Kaklamani. “It’s important when we design the trials to look at clinically meaningful differences because we don’t want to harm our patients, but at the same time, we are also harming them by giving them more treatment. So if you are designing a trial where a 0.7% difference is statistically significant, you probably would have been able to get away with many fewer patients and a difference of 1.5% or 2% not being significant, and I think everybody would be happy with that.”
 

Study details

Dr. Vicini and colleagues enrolled in their trial 4,216 women with stage 0-II breast cancer who had undergone lumpectomy. They were randomized to whole-breast irradiation (5-6 weeks of radiation therapy at that time) or partial-breast irradiation using one of three techniques (3D conformal external beam radiation completed in 5 days, interstitial brachytherapy completed in 5 days, or device-based brachytherapy).

The hazard ratio for ipsilateral breast tumor recurrence (invasive or DCIS) as a first recurrence with partial-breast irradiation versus whole-breast irradiation was 1.22, with the upper bound of the 90% confidence interval (0.94-1.58) falling just outside the predefined range to declare the two modalities equivalent (0.667-1.5), Dr. Vicini reported. However, the absolute difference in the 10-year cumulative incidence of ipsilateral breast tumor recurrences was merely 0.7% (4.6% vs. 3.9%).

The 10-year recurrence-free interval was inferior with partial-breast irradiation (hazard ratio, 1.33; P = .02), but the absolute difference was again small at 1.6% (91.8% vs 93.4%). The partial- and whole-breast irradiation groups were statistically indistinguishable on distant disease-free interval (96.7% vs 97.1%; HR, 1.31; P = .15) and overall survival (90.6% vs. 91.3%; HR, 1.10; P = .35).

Dr. Vicini disclosed that he is a research advisor for ImpediMed. The study was sponsored by the National Cancer Institute.

SOURCE: Vicini FA et al. SABCS 2018, Abstract GS4-04,

SAN ANTONIO – Partial-breast irradiation misses the statistical bar for being as efficacious as whole-breast irradiation in treating residual disease after lumpectomy, but absolute differences in long-term outcomes are minuscule, suggests a phase 3, randomized, controlled trial conducted by NRG Oncology.

MDedge/Susan London

At a median follow-up of 10.2 years, the trial was unable to refute the hypothesis that the partial technique was inferior in terms of ipsilateral breast tumor recurrences; however, the difference between techniques in this outcome was an absolute 0.7%, lead investigator Frank Vicini, MD, principal investigator at the MHP Radiation Oncology Institute/21st Century Oncology in Pontiac, Mich., reported in a session and press conference at the San Antonio Breast Cancer Symposium. The difference in recurrence-free interval was significant but likewise small, at 1.6%, and other efficacy outcomes were similar.

Meanwhile, the groups had low, statistically indistinguishable rates of grade 3-5 toxicities and second cancers. The investigators are still analyzing quality of life and cosmesis outcomes.

“This was the largest trial ever looking at partial-breast [irradiation] in a very diverse group of patients. Even though we weren’t able to demonstrate equivalence, it’s nice to see that in this large population of patients with extended follow-up, the differences are quite small,” Dr. Vicini said. “Because the differences for both ipsilateral breast tumor recurrence and recurrence-free interval were very small, partial-breast irradiation may be an acceptable alternative to whole-breast irradiation for a proportion of women who are undergoing breast-conserving surgery.”
 

Implications for practice and research

SABCS codirector and press conference moderator Virginia Kaklamani, MD, leader of the breast cancer program at UT Health San Antonio, asked how the findings have influenced his practice.

“This trial is over 15 years old now, and a lot of these techniques have been refined. But we are offering partial-breast irradiation to our patients,” Dr. Vicini replied. “There are a lot of competing ways to do radiation now; probably the biggest competing way is to do 3 weeks of whole-breast irradiation. But for those patients who have transportation issues and more elderly patients, we try to offer partial-breast irradiation, within the guidelines of ASTRO [American Society for Therapeutic Radiology and Oncology].”

Some of the women enrolled had risk factors that fall outside those guidelines, for example, higher-grade tumors or axillary node involvement, he acknowledged. “We tried to do exploratory analyses to look at whether certain patients did better with whole-breast irradiation or not, and we weren’t able to really pick out any group of patients that had better or worse outcome based on those criteria,” he said. “We have yet to look at the quality indices for radiation therapy, in other words, how much the breast actually needs to be treated. But at the present time, I would just suggest sticking with the ASTRO guidelines.”

It is noteworthy that likely the most important endpoints, disease-free and overall survival, did not differ between groups, according to Dr. Vicini. “Certainly, a recurrence is still an important event for a patient, so our goal is to always limit that as much as possible,” he said. “But putting it into perspective, does a 0.7% higher risk of recurrence [matter] when you know the survival rates are the same? That’s what patients and doctors need to take into consideration. This is a pretty dramatic difference in treatment [duration], 6 weeks, down to 1 week or less. There have been many studies looking at quality of life and, as you can imagine, quality of life is better” with the shorter therapy.

The trial’s results can also inform statistical planning of future trials, according to Dr. Kaklamani. “It’s important when we design the trials to look at clinically meaningful differences because we don’t want to harm our patients, but at the same time, we are also harming them by giving them more treatment. So if you are designing a trial where a 0.7% difference is statistically significant, you probably would have been able to get away with many fewer patients and a difference of 1.5% or 2% not being significant, and I think everybody would be happy with that.”
 

Study details

Dr. Vicini and colleagues enrolled in their trial 4,216 women with stage 0-II breast cancer who had undergone lumpectomy. They were randomized to whole-breast irradiation (5-6 weeks of radiation therapy at that time) or partial-breast irradiation using one of three techniques (3D conformal external beam radiation completed in 5 days, interstitial brachytherapy completed in 5 days, or device-based brachytherapy).

The hazard ratio for ipsilateral breast tumor recurrence (invasive or DCIS) as a first recurrence with partial-breast irradiation versus whole-breast irradiation was 1.22, with the upper bound of the 90% confidence interval (0.94-1.58) falling just outside the predefined range to declare the two modalities equivalent (0.667-1.5), Dr. Vicini reported. However, the absolute difference in the 10-year cumulative incidence of ipsilateral breast tumor recurrences was merely 0.7% (4.6% vs. 3.9%).

The 10-year recurrence-free interval was inferior with partial-breast irradiation (hazard ratio, 1.33; P = .02), but the absolute difference was again small at 1.6% (91.8% vs 93.4%). The partial- and whole-breast irradiation groups were statistically indistinguishable on distant disease-free interval (96.7% vs 97.1%; HR, 1.31; P = .15) and overall survival (90.6% vs. 91.3%; HR, 1.10; P = .35).

Dr. Vicini disclosed that he is a research advisor for ImpediMed. The study was sponsored by the National Cancer Institute.

SOURCE: Vicini FA et al. SABCS 2018, Abstract GS4-04,

BETHESDA, MD. – The risk of brain damage from sickle cell disease (SCD) merits more attention, even with progress made in recent decades to prevent strokes, according to Lori Jordan, MD, PhD, of Vanderbilt University, Nashville, Tenn.

“Whether we can see it or not, the same injury we’ve been talking about in the kidney and the liver and other places is occurring in the brain” with sickle cell disease, Dr. Jordan said at Sickle Cell in Focus, a conference held by the National Institutes of Health.

The concern about long-term brain injury reflects major shifts in SCD treatment. Improved medical care has transformed SCD from a disease that often resulted in an early death to more of a chronic condition, Dr. Jordan said, citing research that shows a survival rate of roughly 99% to age 18 years (Br J Haematol. 2016 Jun;173[6]:927-37).

One of the major success stories in SCD treatment also has been using primary prevention steps to cut the risk of overt stroke at least 10-fold, Dr. Jordan said. Primary prevention includes annual scans with transcranial Doppler ultrasound to identify children with SCD at high risk of stroke.

“What’s not changing is that there is silent injury that accumulates” and can cause lifelong harm, she said. “We want to protect our patients long term so that they can have a successful adult life, not just a successful childhood.”

Research done by one of Dr. Jordan’s colleagues at Vanderbilt, Michael R. DeBaun, MD, showed that regular blood-transfusion therapy significantly reduced the incidence of the recurrence of brain infarct in children with sickle cell anemia. (N Engl J Med. 2014 Aug 21;371[8]:699-710).


But the lessons from the work of Dr. DeBaun and his colleagues with their Silent Cerebral Infarct Multi-Center Clinical (SIT) Trial have not yet been fully adopted, Dr. Jordan said. That’s partly due to the inconvenience and cost of routinely administered blood transfusions to prevent silent cerebral infarcts, which, when used long term, cause side effects, she said.

Dr. Jordan said there’s growing interest in identifying patients at high risk for stroke and moving them toward stem cell transplant, though studies are ongoing. She urged greater attention to the high lifetime costs of strokes and other cerebrovascular complications, particularly in children and young adults.

While some of the brain infarcts are small and don’t result in focal weakness of the body, these “silent infarcts” do produce cognitive effects that reduce function, school performance, employment, and quality of life, she said.

“The injury to the brain is present, whether we can see it or not,” Dr. Jordan said. “In these precious patients, slow cognitive decline isn’t acceptable, frankly.”

Dr. Jordan reported having received funding from the American Heart Association and the National Institutes of Health for stroke prevention studies in SCD.

BETHESDA, MD. – The risk of brain damage from sickle cell disease (SCD) merits more attention, even with progress made in recent decades to prevent strokes, according to Lori Jordan, MD, PhD, of Vanderbilt University, Nashville, Tenn.

“Whether we can see it or not, the same injury we’ve been talking about in the kidney and the liver and other places is occurring in the brain” with sickle cell disease, Dr. Jordan said at Sickle Cell in Focus, a conference held by the National Institutes of Health.

The concern about long-term brain injury reflects major shifts in SCD treatment. Improved medical care has transformed SCD from a disease that often resulted in an early death to more of a chronic condition, Dr. Jordan said, citing research that shows a survival rate of roughly 99% to age 18 years (Br J Haematol. 2016 Jun;173[6]:927-37).

One of the major success stories in SCD treatment also has been using primary prevention steps to cut the risk of overt stroke at least 10-fold, Dr. Jordan said. Primary prevention includes annual scans with transcranial Doppler ultrasound to identify children with SCD at high risk of stroke.

“What’s not changing is that there is silent injury that accumulates” and can cause lifelong harm, she said. “We want to protect our patients long term so that they can have a successful adult life, not just a successful childhood.”

Research done by one of Dr. Jordan’s colleagues at Vanderbilt, Michael R. DeBaun, MD, showed that regular blood-transfusion therapy significantly reduced the incidence of the recurrence of brain infarct in children with sickle cell anemia. (N Engl J Med. 2014 Aug 21;371[8]:699-710).


But the lessons from the work of Dr. DeBaun and his colleagues with their Silent Cerebral Infarct Multi-Center Clinical (SIT) Trial have not yet been fully adopted, Dr. Jordan said. That’s partly due to the inconvenience and cost of routinely administered blood transfusions to prevent silent cerebral infarcts, which, when used long term, cause side effects, she said.

Dr. Jordan said there’s growing interest in identifying patients at high risk for stroke and moving them toward stem cell transplant, though studies are ongoing. She urged greater attention to the high lifetime costs of strokes and other cerebrovascular complications, particularly in children and young adults.

While some of the brain infarcts are small and don’t result in focal weakness of the body, these “silent infarcts” do produce cognitive effects that reduce function, school performance, employment, and quality of life, she said.

“The injury to the brain is present, whether we can see it or not,” Dr. Jordan said. “In these precious patients, slow cognitive decline isn’t acceptable, frankly.”

Dr. Jordan reported having received funding from the American Heart Association and the National Institutes of Health for stroke prevention studies in SCD.

BETHESDA, MD. – The risk of brain damage from sickle cell disease (SCD) merits more attention, even with progress made in recent decades to prevent strokes, according to Lori Jordan, MD, PhD, of Vanderbilt University, Nashville, Tenn.

“Whether we can see it or not, the same injury we’ve been talking about in the kidney and the liver and other places is occurring in the brain” with sickle cell disease, Dr. Jordan said at Sickle Cell in Focus, a conference held by the National Institutes of Health.

The concern about long-term brain injury reflects major shifts in SCD treatment. Improved medical care has transformed SCD from a disease that often resulted in an early death to more of a chronic condition, Dr. Jordan said, citing research that shows a survival rate of roughly 99% to age 18 years (Br J Haematol. 2016 Jun;173[6]:927-37).

One of the major success stories in SCD treatment also has been using primary prevention steps to cut the risk of overt stroke at least 10-fold, Dr. Jordan said. Primary prevention includes annual scans with transcranial Doppler ultrasound to identify children with SCD at high risk of stroke.

“What’s not changing is that there is silent injury that accumulates” and can cause lifelong harm, she said. “We want to protect our patients long term so that they can have a successful adult life, not just a successful childhood.”

Research done by one of Dr. Jordan’s colleagues at Vanderbilt, Michael R. DeBaun, MD, showed that regular blood-transfusion therapy significantly reduced the incidence of the recurrence of brain infarct in children with sickle cell anemia. (N Engl J Med. 2014 Aug 21;371[8]:699-710).


But the lessons from the work of Dr. DeBaun and his colleagues with their Silent Cerebral Infarct Multi-Center Clinical (SIT) Trial have not yet been fully adopted, Dr. Jordan said. That’s partly due to the inconvenience and cost of routinely administered blood transfusions to prevent silent cerebral infarcts, which, when used long term, cause side effects, she said.

Dr. Jordan said there’s growing interest in identifying patients at high risk for stroke and moving them toward stem cell transplant, though studies are ongoing. She urged greater attention to the high lifetime costs of strokes and other cerebrovascular complications, particularly in children and young adults.

While some of the brain infarcts are small and don’t result in focal weakness of the body, these “silent infarcts” do produce cognitive effects that reduce function, school performance, employment, and quality of life, she said.

“The injury to the brain is present, whether we can see it or not,” Dr. Jordan said. “In these precious patients, slow cognitive decline isn’t acceptable, frankly.”

Dr. Jordan reported having received funding from the American Heart Association and the National Institutes of Health for stroke prevention studies in SCD.

SAN DIEGO – A retrospective study and combined meta-analysis of patients undergoing transcatheter aortic valve replacement (TAVR) confirms the protective effect of the Sentinel cerebral embolic protection (CEP) device, regardless of the valve type used, on periprocedural stroke and mortality.

Jim Kling/MDedge News

“The only significant predictor for being stroke free was use of the protective device. If you look at different valve types, you have an effect with use of the protection device with each of them,” Julia Seeger, MD, said in an interview at the Transcatheter Cardiovascular Therapeutics annual meeting.The finding just reinforces a decision that the institution made several years ago, to uniformly use embolic protection in TAVR procedures. Asked if she was convinced by the latest data on the utility of the device, she replied “Yes, definitely.”

Use of the device adds only a couple of minutes to the procedure time, and there haven’t been any adverse events associated with it, and no additional imaging agent was required, said Dr. Seeger, an interventional cardiologist at the University of Ulm (Germany).

The studies included patients being treated with the Medtronic CoreValve/Evolut, the mechanically implantable Boston Scientific Lotus, and the balloon-expandable Edwards Sapien. Subanalyses for all three valve types showed strong trends for reduction of strokes and mortality. Sentinel is the only Food and Drug Administration–approved device for reduction of strokes during TAVR procedures.

The Sentinel and Clean-TAVI trials showed the efficacy of the Sentinel device in reducing the number and volume of periprocedural cerebral lesions, but there were insufficient randomized data to draw conclusions about its relative efficacy among valve types. Dr. Seeger’s team analyzed data from 984 consecutive TAVR patients. The Sentinel device was used in 548, and not used in 436 consecutive patients. Self-expandable valves were used significantly more often in patients who underwent the procedure with CEP (22% vs. 6.0%). In the study population, 590 balloon-expandable valves, 246 mechanically implantable valves, and 148 self-expandable valves were used.

In the 72 hours after the procedure, mortality or stroke was lower in the CEP group (1.5% versus 4.4%, P less than .01), as was disabling stroke (0.6% versus 3.2%, P less than .01). When results were analyzed by valve types, the researchers found a relative risk reduction for all stroke of 76% with the use of CEP with balloon-expandable devices, 68% with mechanically expandable devices, and 57% with self-expandable devices.

The researchers also conducted a patient-level meta-analysis, incorporating data on 1,306 subjects with symptomatic severe aortic stenosis, including 363 from the Sentinel trial (243 with CEP), 100 patients from the CLEAN-TAVI trial (1:1 randomization to CEP), and 843 patients from the Sentinel-Ulm study (423 with CEP).

They matched patients for valve type, Society of Thoracic Surgeons’ risk score, atrial fibrillation, diabetes, sex, coronary artery disease, and peripheral vascular disease. The all-procedural stroke rate was 5.4% in patients who did not receive CEP, and 1.9% in those who did, for a risk reduction of 65%. Similarly, 72-hour mortality stroke risk was reduced by 66% with the CEP device. It occurred in 6.0% of non-CEP patients, compared to 2.1% of the CEP patients.

The meeting was sponsored by the Cardiovascular Research Foundation.

SAN DIEGO – A retrospective study and combined meta-analysis of patients undergoing transcatheter aortic valve replacement (TAVR) confirms the protective effect of the Sentinel cerebral embolic protection (CEP) device, regardless of the valve type used, on periprocedural stroke and mortality.

Jim Kling/MDedge News

“The only significant predictor for being stroke free was use of the protective device. If you look at different valve types, you have an effect with use of the protection device with each of them,” Julia Seeger, MD, said in an interview at the Transcatheter Cardiovascular Therapeutics annual meeting.The finding just reinforces a decision that the institution made several years ago, to uniformly use embolic protection in TAVR procedures. Asked if she was convinced by the latest data on the utility of the device, she replied “Yes, definitely.”

Use of the device adds only a couple of minutes to the procedure time, and there haven’t been any adverse events associated with it, and no additional imaging agent was required, said Dr. Seeger, an interventional cardiologist at the University of Ulm (Germany).

The studies included patients being treated with the Medtronic CoreValve/Evolut, the mechanically implantable Boston Scientific Lotus, and the balloon-expandable Edwards Sapien. Subanalyses for all three valve types showed strong trends for reduction of strokes and mortality. Sentinel is the only Food and Drug Administration–approved device for reduction of strokes during TAVR procedures.

The Sentinel and Clean-TAVI trials showed the efficacy of the Sentinel device in reducing the number and volume of periprocedural cerebral lesions, but there were insufficient randomized data to draw conclusions about its relative efficacy among valve types. Dr. Seeger’s team analyzed data from 984 consecutive TAVR patients. The Sentinel device was used in 548, and not used in 436 consecutive patients. Self-expandable valves were used significantly more often in patients who underwent the procedure with CEP (22% vs. 6.0%). In the study population, 590 balloon-expandable valves, 246 mechanically implantable valves, and 148 self-expandable valves were used.

In the 72 hours after the procedure, mortality or stroke was lower in the CEP group (1.5% versus 4.4%, P less than .01), as was disabling stroke (0.6% versus 3.2%, P less than .01). When results were analyzed by valve types, the researchers found a relative risk reduction for all stroke of 76% with the use of CEP with balloon-expandable devices, 68% with mechanically expandable devices, and 57% with self-expandable devices.

The researchers also conducted a patient-level meta-analysis, incorporating data on 1,306 subjects with symptomatic severe aortic stenosis, including 363 from the Sentinel trial (243 with CEP), 100 patients from the CLEAN-TAVI trial (1:1 randomization to CEP), and 843 patients from the Sentinel-Ulm study (423 with CEP).

They matched patients for valve type, Society of Thoracic Surgeons’ risk score, atrial fibrillation, diabetes, sex, coronary artery disease, and peripheral vascular disease. The all-procedural stroke rate was 5.4% in patients who did not receive CEP, and 1.9% in those who did, for a risk reduction of 65%. Similarly, 72-hour mortality stroke risk was reduced by 66% with the CEP device. It occurred in 6.0% of non-CEP patients, compared to 2.1% of the CEP patients.

The meeting was sponsored by the Cardiovascular Research Foundation.

SAN DIEGO – A retrospective study and combined meta-analysis of patients undergoing transcatheter aortic valve replacement (TAVR) confirms the protective effect of the Sentinel cerebral embolic protection (CEP) device, regardless of the valve type used, on periprocedural stroke and mortality.

Jim Kling/MDedge News

“The only significant predictor for being stroke free was use of the protective device. If you look at different valve types, you have an effect with use of the protection device with each of them,” Julia Seeger, MD, said in an interview at the Transcatheter Cardiovascular Therapeutics annual meeting.The finding just reinforces a decision that the institution made several years ago, to uniformly use embolic protection in TAVR procedures. Asked if she was convinced by the latest data on the utility of the device, she replied “Yes, definitely.”

Use of the device adds only a couple of minutes to the procedure time, and there haven’t been any adverse events associated with it, and no additional imaging agent was required, said Dr. Seeger, an interventional cardiologist at the University of Ulm (Germany).

The studies included patients being treated with the Medtronic CoreValve/Evolut, the mechanically implantable Boston Scientific Lotus, and the balloon-expandable Edwards Sapien. Subanalyses for all three valve types showed strong trends for reduction of strokes and mortality. Sentinel is the only Food and Drug Administration–approved device for reduction of strokes during TAVR procedures.

The Sentinel and Clean-TAVI trials showed the efficacy of the Sentinel device in reducing the number and volume of periprocedural cerebral lesions, but there were insufficient randomized data to draw conclusions about its relative efficacy among valve types. Dr. Seeger’s team analyzed data from 984 consecutive TAVR patients. The Sentinel device was used in 548, and not used in 436 consecutive patients. Self-expandable valves were used significantly more often in patients who underwent the procedure with CEP (22% vs. 6.0%). In the study population, 590 balloon-expandable valves, 246 mechanically implantable valves, and 148 self-expandable valves were used.

In the 72 hours after the procedure, mortality or stroke was lower in the CEP group (1.5% versus 4.4%, P less than .01), as was disabling stroke (0.6% versus 3.2%, P less than .01). When results were analyzed by valve types, the researchers found a relative risk reduction for all stroke of 76% with the use of CEP with balloon-expandable devices, 68% with mechanically expandable devices, and 57% with self-expandable devices.

The researchers also conducted a patient-level meta-analysis, incorporating data on 1,306 subjects with symptomatic severe aortic stenosis, including 363 from the Sentinel trial (243 with CEP), 100 patients from the CLEAN-TAVI trial (1:1 randomization to CEP), and 843 patients from the Sentinel-Ulm study (423 with CEP).

They matched patients for valve type, Society of Thoracic Surgeons’ risk score, atrial fibrillation, diabetes, sex, coronary artery disease, and peripheral vascular disease. The all-procedural stroke rate was 5.4% in patients who did not receive CEP, and 1.9% in those who did, for a risk reduction of 65%. Similarly, 72-hour mortality stroke risk was reduced by 66% with the CEP device. It occurred in 6.0% of non-CEP patients, compared to 2.1% of the CEP patients.

The meeting was sponsored by the Cardiovascular Research Foundation.

Epidermal nevi are a subset of cutaneous hamartomas resulting from somatic mutations of epidermal cells, presenting as keratinocyte or epidermal appendage overgrowths. The most common type appear in a linear distribution and are termed linear epidermal nevi or linear verrucous epidermal nevi.

There are variations of epidermal nevi (EN) that can be composed of superficial epidermal keratinocytes, sebaceous glands, apocrine or eccrine glands, hair follicles, or smooth muscle. For example, many consider a nevus sebaceous to be a type of epidermal nevus as well. The incidence of EN is approximately 1 in 1,000 newborns. Postzygotic cell mutations result in a mosaic distribution that follows embryonic migration patterns, appearing in a Blaschkoid distribution.

EN present most frequently as unilateral linear or whorled hyperpigmented coalescing papules. The lesions can be present at birth or during childhood, and after appearing, grow with the patient. Typically the lesions become more raised and verrucous around puberty. The differential diagnosis of linear EN include lichen striatus, warts, and incontinentia pigmenti. Lichen striatus can be differentiated because it presents later in life and self-resolves. Verrucae are the most commonly mistaken diagnosis for EN; warts do not usually persist in the same pattern over time with proportionate growth and typically respond to locally destructive treatments such as liquid nitrogen, unlike EN. Incontinentia pigmenti presents as vesicles initially and shows a quick evolution, differentiating it from EN. Inflammatory linear verrucous epidermal nevus (ILVEN) is a variant of linear EN that has associated chronic and intermittent erythema, scale, and pruritus. Lichen nitidus often has a pruritic presentation; however, it is flat topped and skin colored, helping differentiate it from linear EN.

There has been recent research advancing gene associations for linear EN displaying many lesions associated with mosaic mutations in oncogenes. Multiple genes have been identified with EN including RAS, FGFR3, and PIK3CA¹. FGFR3 and PIK3CA mutations are associated with 50% of keratinocytic nevi. Of the RAS family, the HRAS pathway has been most closely associated with nevus sebaceous. While KRAS and NRAS genes have been associated with EN, it is to a lesser degree. However, there are multiple recent case reports demonstrating a potential association of G12D mosaicism of the KRAS gene in EN with rhabdomyosarcoma and bladder cancers².

The diagnosis of epidermal nevus syndrome should be considered when there is a nevus with associated developmental abnormality of the central nervous system, eyes, or musculoskeletal systems. The most common systemic symptoms include delays in developmental milestones, seizure disorders, coloboma, strabismus, muscle weakness, and hemihypertrophy. To date, there are six specific epidermal nevus syndromes identified: sebaceous nevus syndrome, nevus comedonicus syndrome, Becker nevus syndrome, phakomatosis pigmentokeratotica, Proteus syndrome, congenital hemidysplasia with ichthyosiform nevus and limb defects, and cutaneous-skeletal hypophosphatemia syndrome³. In addition to the syndromes described, there are reports of associations between keratinocytic nevi and ILVEN with hypophosphatemic rickets and precocious puberty.
 

Linear EN are rarely associated with malignant transformation to basal cell carcinoma or squamous cell carcinoma, depending on the cell type involved. Given the low risk of malignancy, the lesions do not need to be removed routinely. For small lesions, monitoring often is the preferred management. However, lesions with functional significance, or causing strangulation or deformity, can be treated with surgical excision, curettage, or laser destruction

Dr. Kaushik is with the division of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego, and Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. There are no conflicts of interest or financial disclosures for Dr. Kaushik or Dr. Eichenfield. Email them at [email protected].

References

1. Pediatr Dermatol. 2004 Jul-Aug;21(4):432-9.

2. J Med Genet. 2010 Dec;47(12):859-62.

3. Pediatr Dermatol. 2018 Jan;35(1):21-9.

Epidermal nevi are a subset of cutaneous hamartomas resulting from somatic mutations of epidermal cells, presenting as keratinocyte or epidermal appendage overgrowths. The most common type appear in a linear distribution and are termed linear epidermal nevi or linear verrucous epidermal nevi.

There are variations of epidermal nevi (EN) that can be composed of superficial epidermal keratinocytes, sebaceous glands, apocrine or eccrine glands, hair follicles, or smooth muscle. For example, many consider a nevus sebaceous to be a type of epidermal nevus as well. The incidence of EN is approximately 1 in 1,000 newborns. Postzygotic cell mutations result in a mosaic distribution that follows embryonic migration patterns, appearing in a Blaschkoid distribution.

EN present most frequently as unilateral linear or whorled hyperpigmented coalescing papules. The lesions can be present at birth or during childhood, and after appearing, grow with the patient. Typically the lesions become more raised and verrucous around puberty. The differential diagnosis of linear EN include lichen striatus, warts, and incontinentia pigmenti. Lichen striatus can be differentiated because it presents later in life and self-resolves. Verrucae are the most commonly mistaken diagnosis for EN; warts do not usually persist in the same pattern over time with proportionate growth and typically respond to locally destructive treatments such as liquid nitrogen, unlike EN. Incontinentia pigmenti presents as vesicles initially and shows a quick evolution, differentiating it from EN. Inflammatory linear verrucous epidermal nevus (ILVEN) is a variant of linear EN that has associated chronic and intermittent erythema, scale, and pruritus. Lichen nitidus often has a pruritic presentation; however, it is flat topped and skin colored, helping differentiate it from linear EN.

There has been recent research advancing gene associations for linear EN displaying many lesions associated with mosaic mutations in oncogenes. Multiple genes have been identified with EN including RAS, FGFR3, and PIK3CA¹. FGFR3 and PIK3CA mutations are associated with 50% of keratinocytic nevi. Of the RAS family, the HRAS pathway has been most closely associated with nevus sebaceous. While KRAS and NRAS genes have been associated with EN, it is to a lesser degree. However, there are multiple recent case reports demonstrating a potential association of G12D mosaicism of the KRAS gene in EN with rhabdomyosarcoma and bladder cancers².

The diagnosis of epidermal nevus syndrome should be considered when there is a nevus with associated developmental abnormality of the central nervous system, eyes, or musculoskeletal systems. The most common systemic symptoms include delays in developmental milestones, seizure disorders, coloboma, strabismus, muscle weakness, and hemihypertrophy. To date, there are six specific epidermal nevus syndromes identified: sebaceous nevus syndrome, nevus comedonicus syndrome, Becker nevus syndrome, phakomatosis pigmentokeratotica, Proteus syndrome, congenital hemidysplasia with ichthyosiform nevus and limb defects, and cutaneous-skeletal hypophosphatemia syndrome³. In addition to the syndromes described, there are reports of associations between keratinocytic nevi and ILVEN with hypophosphatemic rickets and precocious puberty.
 

Linear EN are rarely associated with malignant transformation to basal cell carcinoma or squamous cell carcinoma, depending on the cell type involved. Given the low risk of malignancy, the lesions do not need to be removed routinely. For small lesions, monitoring often is the preferred management. However, lesions with functional significance, or causing strangulation or deformity, can be treated with surgical excision, curettage, or laser destruction

Dr. Kaushik is with the division of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego, and Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. There are no conflicts of interest or financial disclosures for Dr. Kaushik or Dr. Eichenfield. Email them at [email protected].

References

1. Pediatr Dermatol. 2004 Jul-Aug;21(4):432-9.

2. J Med Genet. 2010 Dec;47(12):859-62.

3. Pediatr Dermatol. 2018 Jan;35(1):21-9.

Epidermal nevi are a subset of cutaneous hamartomas resulting from somatic mutations of epidermal cells, presenting as keratinocyte or epidermal appendage overgrowths. The most common type appear in a linear distribution and are termed linear epidermal nevi or linear verrucous epidermal nevi.

There are variations of epidermal nevi (EN) that can be composed of superficial epidermal keratinocytes, sebaceous glands, apocrine or eccrine glands, hair follicles, or smooth muscle. For example, many consider a nevus sebaceous to be a type of epidermal nevus as well. The incidence of EN is approximately 1 in 1,000 newborns. Postzygotic cell mutations result in a mosaic distribution that follows embryonic migration patterns, appearing in a Blaschkoid distribution.

EN present most frequently as unilateral linear or whorled hyperpigmented coalescing papules. The lesions can be present at birth or during childhood, and after appearing, grow with the patient. Typically the lesions become more raised and verrucous around puberty. The differential diagnosis of linear EN include lichen striatus, warts, and incontinentia pigmenti. Lichen striatus can be differentiated because it presents later in life and self-resolves. Verrucae are the most commonly mistaken diagnosis for EN; warts do not usually persist in the same pattern over time with proportionate growth and typically respond to locally destructive treatments such as liquid nitrogen, unlike EN. Incontinentia pigmenti presents as vesicles initially and shows a quick evolution, differentiating it from EN. Inflammatory linear verrucous epidermal nevus (ILVEN) is a variant of linear EN that has associated chronic and intermittent erythema, scale, and pruritus. Lichen nitidus often has a pruritic presentation; however, it is flat topped and skin colored, helping differentiate it from linear EN.

There has been recent research advancing gene associations for linear EN displaying many lesions associated with mosaic mutations in oncogenes. Multiple genes have been identified with EN including RAS, FGFR3, and PIK3CA¹. FGFR3 and PIK3CA mutations are associated with 50% of keratinocytic nevi. Of the RAS family, the HRAS pathway has been most closely associated with nevus sebaceous. While KRAS and NRAS genes have been associated with EN, it is to a lesser degree. However, there are multiple recent case reports demonstrating a potential association of G12D mosaicism of the KRAS gene in EN with rhabdomyosarcoma and bladder cancers².

The diagnosis of epidermal nevus syndrome should be considered when there is a nevus with associated developmental abnormality of the central nervous system, eyes, or musculoskeletal systems. The most common systemic symptoms include delays in developmental milestones, seizure disorders, coloboma, strabismus, muscle weakness, and hemihypertrophy. To date, there are six specific epidermal nevus syndromes identified: sebaceous nevus syndrome, nevus comedonicus syndrome, Becker nevus syndrome, phakomatosis pigmentokeratotica, Proteus syndrome, congenital hemidysplasia with ichthyosiform nevus and limb defects, and cutaneous-skeletal hypophosphatemia syndrome³. In addition to the syndromes described, there are reports of associations between keratinocytic nevi and ILVEN with hypophosphatemic rickets and precocious puberty.
 

Linear EN are rarely associated with malignant transformation to basal cell carcinoma or squamous cell carcinoma, depending on the cell type involved. Given the low risk of malignancy, the lesions do not need to be removed routinely. For small lesions, monitoring often is the preferred management. However, lesions with functional significance, or causing strangulation or deformity, can be treated with surgical excision, curettage, or laser destruction

Dr. Kaushik is with the division of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego, and Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. There are no conflicts of interest or financial disclosures for Dr. Kaushik or Dr. Eichenfield. Email them at [email protected].

References

1. Pediatr Dermatol. 2004 Jul-Aug;21(4):432-9.

2. J Med Genet. 2010 Dec;47(12):859-62.

3. Pediatr Dermatol. 2018 Jan;35(1):21-9.

Medical science’s broad knowledge of endometriosis notwithstanding, “many questions remain unanswered” about the management of a condition that is often refractory to established therapies, observed Sawsan As-Sanie, MD, MPH, at the 2018 Pelvic Anatomy and Gynecologic Surgery Symposium meeting in Las Vegas, Nevada. Dr. As-Sanie is Associate Professor and Director, Minimally Invasive Gynecologic Surgery Fellowship, Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor. How, then, should clinicians approach the challenge of caring for women with this enigmatic disease in the larger context of chronic pelvic pain, in which, as Dr. As-Sanie said, “one size never fits all”?

Complex correlation between endometriosis and CPP

Despite high prevalence and negative impact on the health and quality of life of women who suffer from endometriosis, Dr. As-Sanie emphasized, it remains unclear why only some women with endometriosis develop chronic pelvic pain (CPP) and why there is little, if any, correlation between disease severity and the intensity of pain.

The clinical approach to endometriosis and CPP can be frustrating for several reasons: there is minimal relationship between extent or location of disease with pain symptoms; there is no consistent relationship among inflammatory markers, nerve-fiber density, and pain symptoms; and pain can recur after medical and surgical therapy—often without evidence of recurrent endometriosis. Furthermore, the differential diagnosis of CPP is broad, and also includes adenomyosis, adhesions, chronic pelvic inflammatory disease, uterine fibroids, pelvic congestion, ovarian remnant, and residual ovarian syndrome. Chronic overlapping pain conditions are prevalent, too, including interstitial cystitis, irritable bowel syndrome, and vulvodynia, to name a few.¹

_

CPP is not just a pain disorder

Dr. As-Sanie said that understanding of CPP must extend to include fatigue, memory difficulties, poor sleep, and heightened sensitivity to multiple sensory stimuli (e.g., sound and light).² So what, she asked, do we know about endometriosis, chronic pelvic pain, and the brain? We know that CPP, with and without endometriosis, is associated with increased pain sensitivity and altered central nervous system structure and function.^3-5 Central amplification of pain can lead to chronic pain independent of nociceptive signals, including multifocal, widespread pain; higher lifetime history of pain throughout the body; and pain triggered or exacerbated by stressors. And CPP brings with it other, potentially debilitating problems, including elevated distress, decreased activity, isolation, poor sleep, and maladaptive illness behaviors.

Finding, then addressing, the culprit

Identifying the underlying cause(s) of CPP in the individual woman should guide clinical care. This includes the decision to proceed with, or avoid, surgery. Remember: Patients with centralized pain respond differently to therapy; surgery is less likely to help relieve the pain.

Dr. As-Sanie offered several fundamental guidelines for managing CPP:

• Treat early, to prevent transition from acute to chronic pain; treatment delay increases connectivity between pain regulatory regions.
• Hysterectomy is not definitive therapy for all women with endometriosis or CPP.⁶
• Take a multisystem approach, comprising medical, behavioral, and interventional strategies.
• If an organ- or disease-based diagnostic and treatment approach does not work, reconsider the diagnosis; re-evaluate comorbid psychosocial variables; and consider treating centralized pain.
• Choice of treatment should include consideration of cost and adverse-effect profile.
• If one modality is ineffective, try another.

Continue to: What are the levels of evidence for centralized pain treatment?

Available pharmacotherapeutic agents have modest benefit, possibly because the population of pain patients is heterogeneous, with various underlying mechanisms of pain. And, Dr. As-Sanie pointed out, clinical tools do not currently exist to pre-emptively select the right medicine for individual patients.

Evidence is strong, Dr. As-Sanie noted, for dual reuptake-inhibitor antidepressants, such as tricyclic compounds (amitriptyline, cyclobenzaprine) and serotonin–norepinephrine reuptake inhibitors, and for anticonvulsants with analgesic properties (pregabalin, gabapentin). Evidence is “modest,” Dr. As-Sanie said, for tramadol, gamma hydroxybutyrate, and low-dose naltrexone, and “weak” for cannabinoids, human growth hormone, 5-hydroxytryptamine, tropisetron, and S-adenosyl-L-methionine. There is no evidence for using opioids, corticosteroids, nonsteroidal anti-inflammatory drugs, benzodiazepine and non–benzodiazepine hypnotics, or guaifenesin.⁷

When surgery or pharmacotherapy alone fail to yield the necessary outcome, consider adjunctive nonpharmacotherapy.⁸ For example, there is strong evidence for patient education, aerobic exercise, and cognitive behavior therapy; modest evidence for acupressure, acupuncture, strength training, hypnotherapy, biofeedback, trigger-point injection, and neuromodulation; but only weak evidence for chiropractic, manual and massage therapy, electrotherapy, and ultrasound. ⁷

_

With CPP, “one size never fits all”

Dr. As-Sanie concluded with a reminder that CPP can be the product of any of a range of underlying contributory causes. Pathology might stand foremost as you search for the source of pain and an effective treatment, but keep in mind that genetics, environment, co-existing pain conditions, the patient’s ability to cope, and her resilience and social support might play a role.

Medical science’s broad knowledge of endometriosis notwithstanding, “many questions remain unanswered” about the management of a condition that is often refractory to established therapies, observed Sawsan As-Sanie, MD, MPH, at the 2018 Pelvic Anatomy and Gynecologic Surgery Symposium meeting in Las Vegas, Nevada. Dr. As-Sanie is Associate Professor and Director, Minimally Invasive Gynecologic Surgery Fellowship, Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor. How, then, should clinicians approach the challenge of caring for women with this enigmatic disease in the larger context of chronic pelvic pain, in which, as Dr. As-Sanie said, “one size never fits all”?

Complex correlation between endometriosis and CPP

Despite high prevalence and negative impact on the health and quality of life of women who suffer from endometriosis, Dr. As-Sanie emphasized, it remains unclear why only some women with endometriosis develop chronic pelvic pain (CPP) and why there is little, if any, correlation between disease severity and the intensity of pain.

The clinical approach to endometriosis and CPP can be frustrating for several reasons: there is minimal relationship between extent or location of disease with pain symptoms; there is no consistent relationship among inflammatory markers, nerve-fiber density, and pain symptoms; and pain can recur after medical and surgical therapy—often without evidence of recurrent endometriosis. Furthermore, the differential diagnosis of CPP is broad, and also includes adenomyosis, adhesions, chronic pelvic inflammatory disease, uterine fibroids, pelvic congestion, ovarian remnant, and residual ovarian syndrome. Chronic overlapping pain conditions are prevalent, too, including interstitial cystitis, irritable bowel syndrome, and vulvodynia, to name a few.¹

_

CPP is not just a pain disorder

Dr. As-Sanie said that understanding of CPP must extend to include fatigue, memory difficulties, poor sleep, and heightened sensitivity to multiple sensory stimuli (e.g., sound and light).² So what, she asked, do we know about endometriosis, chronic pelvic pain, and the brain? We know that CPP, with and without endometriosis, is associated with increased pain sensitivity and altered central nervous system structure and function.^3-5 Central amplification of pain can lead to chronic pain independent of nociceptive signals, including multifocal, widespread pain; higher lifetime history of pain throughout the body; and pain triggered or exacerbated by stressors. And CPP brings with it other, potentially debilitating problems, including elevated distress, decreased activity, isolation, poor sleep, and maladaptive illness behaviors.

Finding, then addressing, the culprit

Identifying the underlying cause(s) of CPP in the individual woman should guide clinical care. This includes the decision to proceed with, or avoid, surgery. Remember: Patients with centralized pain respond differently to therapy; surgery is less likely to help relieve the pain.

Dr. As-Sanie offered several fundamental guidelines for managing CPP:

• Treat early, to prevent transition from acute to chronic pain; treatment delay increases connectivity between pain regulatory regions.
• Hysterectomy is not definitive therapy for all women with endometriosis or CPP.⁶
• Take a multisystem approach, comprising medical, behavioral, and interventional strategies.
• If an organ- or disease-based diagnostic and treatment approach does not work, reconsider the diagnosis; re-evaluate comorbid psychosocial variables; and consider treating centralized pain.
• Choice of treatment should include consideration of cost and adverse-effect profile.
• If one modality is ineffective, try another.

Continue to: What are the levels of evidence for centralized pain treatment?

Available pharmacotherapeutic agents have modest benefit, possibly because the population of pain patients is heterogeneous, with various underlying mechanisms of pain. And, Dr. As-Sanie pointed out, clinical tools do not currently exist to pre-emptively select the right medicine for individual patients.

Evidence is strong, Dr. As-Sanie noted, for dual reuptake-inhibitor antidepressants, such as tricyclic compounds (amitriptyline, cyclobenzaprine) and serotonin–norepinephrine reuptake inhibitors, and for anticonvulsants with analgesic properties (pregabalin, gabapentin). Evidence is “modest,” Dr. As-Sanie said, for tramadol, gamma hydroxybutyrate, and low-dose naltrexone, and “weak” for cannabinoids, human growth hormone, 5-hydroxytryptamine, tropisetron, and S-adenosyl-L-methionine. There is no evidence for using opioids, corticosteroids, nonsteroidal anti-inflammatory drugs, benzodiazepine and non–benzodiazepine hypnotics, or guaifenesin.⁷

When surgery or pharmacotherapy alone fail to yield the necessary outcome, consider adjunctive nonpharmacotherapy.⁸ For example, there is strong evidence for patient education, aerobic exercise, and cognitive behavior therapy; modest evidence for acupressure, acupuncture, strength training, hypnotherapy, biofeedback, trigger-point injection, and neuromodulation; but only weak evidence for chiropractic, manual and massage therapy, electrotherapy, and ultrasound. ⁷

_

With CPP, “one size never fits all”

Dr. As-Sanie concluded with a reminder that CPP can be the product of any of a range of underlying contributory causes. Pathology might stand foremost as you search for the source of pain and an effective treatment, but keep in mind that genetics, environment, co-existing pain conditions, the patient’s ability to cope, and her resilience and social support might play a role.

Medical science’s broad knowledge of endometriosis notwithstanding, “many questions remain unanswered” about the management of a condition that is often refractory to established therapies, observed Sawsan As-Sanie, MD, MPH, at the 2018 Pelvic Anatomy and Gynecologic Surgery Symposium meeting in Las Vegas, Nevada. Dr. As-Sanie is Associate Professor and Director, Minimally Invasive Gynecologic Surgery Fellowship, Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor. How, then, should clinicians approach the challenge of caring for women with this enigmatic disease in the larger context of chronic pelvic pain, in which, as Dr. As-Sanie said, “one size never fits all”?

Complex correlation between endometriosis and CPP

Despite high prevalence and negative impact on the health and quality of life of women who suffer from endometriosis, Dr. As-Sanie emphasized, it remains unclear why only some women with endometriosis develop chronic pelvic pain (CPP) and why there is little, if any, correlation between disease severity and the intensity of pain.

The clinical approach to endometriosis and CPP can be frustrating for several reasons: there is minimal relationship between extent or location of disease with pain symptoms; there is no consistent relationship among inflammatory markers, nerve-fiber density, and pain symptoms; and pain can recur after medical and surgical therapy—often without evidence of recurrent endometriosis. Furthermore, the differential diagnosis of CPP is broad, and also includes adenomyosis, adhesions, chronic pelvic inflammatory disease, uterine fibroids, pelvic congestion, ovarian remnant, and residual ovarian syndrome. Chronic overlapping pain conditions are prevalent, too, including interstitial cystitis, irritable bowel syndrome, and vulvodynia, to name a few.¹

_

CPP is not just a pain disorder

Dr. As-Sanie said that understanding of CPP must extend to include fatigue, memory difficulties, poor sleep, and heightened sensitivity to multiple sensory stimuli (e.g., sound and light).² So what, she asked, do we know about endometriosis, chronic pelvic pain, and the brain? We know that CPP, with and without endometriosis, is associated with increased pain sensitivity and altered central nervous system structure and function.^3-5 Central amplification of pain can lead to chronic pain independent of nociceptive signals, including multifocal, widespread pain; higher lifetime history of pain throughout the body; and pain triggered or exacerbated by stressors. And CPP brings with it other, potentially debilitating problems, including elevated distress, decreased activity, isolation, poor sleep, and maladaptive illness behaviors.

Finding, then addressing, the culprit

Identifying the underlying cause(s) of CPP in the individual woman should guide clinical care. This includes the decision to proceed with, or avoid, surgery. Remember: Patients with centralized pain respond differently to therapy; surgery is less likely to help relieve the pain.

Dr. As-Sanie offered several fundamental guidelines for managing CPP:

• Treat early, to prevent transition from acute to chronic pain; treatment delay increases connectivity between pain regulatory regions.
• Hysterectomy is not definitive therapy for all women with endometriosis or CPP.⁶
• Take a multisystem approach, comprising medical, behavioral, and interventional strategies.
• If an organ- or disease-based diagnostic and treatment approach does not work, reconsider the diagnosis; re-evaluate comorbid psychosocial variables; and consider treating centralized pain.
• Choice of treatment should include consideration of cost and adverse-effect profile.
• If one modality is ineffective, try another.

Continue to: What are the levels of evidence for centralized pain treatment?

Available pharmacotherapeutic agents have modest benefit, possibly because the population of pain patients is heterogeneous, with various underlying mechanisms of pain. And, Dr. As-Sanie pointed out, clinical tools do not currently exist to pre-emptively select the right medicine for individual patients.

Evidence is strong, Dr. As-Sanie noted, for dual reuptake-inhibitor antidepressants, such as tricyclic compounds (amitriptyline, cyclobenzaprine) and serotonin–norepinephrine reuptake inhibitors, and for anticonvulsants with analgesic properties (pregabalin, gabapentin). Evidence is “modest,” Dr. As-Sanie said, for tramadol, gamma hydroxybutyrate, and low-dose naltrexone, and “weak” for cannabinoids, human growth hormone, 5-hydroxytryptamine, tropisetron, and S-adenosyl-L-methionine. There is no evidence for using opioids, corticosteroids, nonsteroidal anti-inflammatory drugs, benzodiazepine and non–benzodiazepine hypnotics, or guaifenesin.⁷

When surgery or pharmacotherapy alone fail to yield the necessary outcome, consider adjunctive nonpharmacotherapy.⁸ For example, there is strong evidence for patient education, aerobic exercise, and cognitive behavior therapy; modest evidence for acupressure, acupuncture, strength training, hypnotherapy, biofeedback, trigger-point injection, and neuromodulation; but only weak evidence for chiropractic, manual and massage therapy, electrotherapy, and ultrasound. ⁷

_

With CPP, “one size never fits all”

Dr. As-Sanie concluded with a reminder that CPP can be the product of any of a range of underlying contributory causes. Pathology might stand foremost as you search for the source of pain and an effective treatment, but keep in mind that genetics, environment, co-existing pain conditions, the patient’s ability to cope, and her resilience and social support might play a role.

Children and young people who received antipsychotic doses higher than 50-mg chlorpromazine equivalents had an 80% increased risk of death at follow-up, compared with a control group, according to a study of young Medicaid enrollees who recently had begun medication.

“The study findings seem to reinforce existing guidelines for improving the outcomes of antipsychotic therapy in children and youths,” wrote lead author Wayne A. Ray, PhD, of the department of health policy at the Vanderbilt University in Nashville, Tenn., and his coauthors. Those guidelines include using “psychosocial interventions when possible, cardiometabolic assessment before treatment and monitoring after treatment, and limiting therapy to the lowest dose and shortest duration possible,” they wrote.

The study, published online in JAMA Psychiatry, analyzed children and young adults from Tennessee, aged 5-24 years, who were new medication users, and had been enrolled in Medicaid between 1999 and 2014.

They were split into three groups: a control group (189,361) with users primarily taking attention-deficit/hyperactivity disorder medications and antidepressants; a group (28,377) with users who received antipsychotic doses of 50 mg or less chlorpromazine equivalents; and a group (30,120) with users who received doses higher than 50-mg chlorpromazine equivalents.

At follow-up, the incidence of death in the higher-dose group was 146.2 per 100,000 person-years (95% confidence interval, 107.3-199.4 per 100,000 person-years), compared with 49.5 in the lower-dose group (95% CI, 24.8-99.0) and 54.5 in the control group (95% CI, 42.9-69.2). This difference was attributed to unexpected deaths, which accounted for 52.5% of deaths in the higher-dose group. No increased risk of death was noted for injuries or suicides. “The elevated risk persisted for unexpected deaths not due to overdose, with a 4.3-fold increased risk of death from cardiovascular or metabolic causes,” Dr. Ray and his coauthors wrote.

The authors shared potential limitations of their study, including a relatively small number of deaths during follow-up and subsequent statistical adjustment during analysis. They also recognized that their data did not factor in important characteristics such as body mass index and family history, and that a “single-state Medicaid cohort may limit the study’s generalizability.”

Nonetheless, they emphasized Medicaid’s relevance as coverage provider for an estimated 39% of U.S. children, along with noting that this was a first step toward better understanding the consequences of prescribing antipsychotics in younger populations.

“Further studies are needed that compare antipsychotic users and controls within more narrow comorbidity ranges or in analyses that include richer clinical data,” they wrote.

The study was supported by grants from the National Heart, Lung, and Blood Institute, and the National Institute for Child Health and Human Development. No conflicts of interest were reported.

SOURCE: Ray WA et al. JAMA Psychiatry. 2018 Dec 12. doi: 10.1001/jamapsychiatry.2018.3421.

Children and young people who received antipsychotic doses higher than 50-mg chlorpromazine equivalents had an 80% increased risk of death at follow-up, compared with a control group, according to a study of young Medicaid enrollees who recently had begun medication.

“The study findings seem to reinforce existing guidelines for improving the outcomes of antipsychotic therapy in children and youths,” wrote lead author Wayne A. Ray, PhD, of the department of health policy at the Vanderbilt University in Nashville, Tenn., and his coauthors. Those guidelines include using “psychosocial interventions when possible, cardiometabolic assessment before treatment and monitoring after treatment, and limiting therapy to the lowest dose and shortest duration possible,” they wrote.

The study, published online in JAMA Psychiatry, analyzed children and young adults from Tennessee, aged 5-24 years, who were new medication users, and had been enrolled in Medicaid between 1999 and 2014.

They were split into three groups: a control group (189,361) with users primarily taking attention-deficit/hyperactivity disorder medications and antidepressants; a group (28,377) with users who received antipsychotic doses of 50 mg or less chlorpromazine equivalents; and a group (30,120) with users who received doses higher than 50-mg chlorpromazine equivalents.

At follow-up, the incidence of death in the higher-dose group was 146.2 per 100,000 person-years (95% confidence interval, 107.3-199.4 per 100,000 person-years), compared with 49.5 in the lower-dose group (95% CI, 24.8-99.0) and 54.5 in the control group (95% CI, 42.9-69.2). This difference was attributed to unexpected deaths, which accounted for 52.5% of deaths in the higher-dose group. No increased risk of death was noted for injuries or suicides. “The elevated risk persisted for unexpected deaths not due to overdose, with a 4.3-fold increased risk of death from cardiovascular or metabolic causes,” Dr. Ray and his coauthors wrote.

The authors shared potential limitations of their study, including a relatively small number of deaths during follow-up and subsequent statistical adjustment during analysis. They also recognized that their data did not factor in important characteristics such as body mass index and family history, and that a “single-state Medicaid cohort may limit the study’s generalizability.”

Nonetheless, they emphasized Medicaid’s relevance as coverage provider for an estimated 39% of U.S. children, along with noting that this was a first step toward better understanding the consequences of prescribing antipsychotics in younger populations.

“Further studies are needed that compare antipsychotic users and controls within more narrow comorbidity ranges or in analyses that include richer clinical data,” they wrote.

The study was supported by grants from the National Heart, Lung, and Blood Institute, and the National Institute for Child Health and Human Development. No conflicts of interest were reported.

SOURCE: Ray WA et al. JAMA Psychiatry. 2018 Dec 12. doi: 10.1001/jamapsychiatry.2018.3421.

Children and young people who received antipsychotic doses higher than 50-mg chlorpromazine equivalents had an 80% increased risk of death at follow-up, compared with a control group, according to a study of young Medicaid enrollees who recently had begun medication.

“The study findings seem to reinforce existing guidelines for improving the outcomes of antipsychotic therapy in children and youths,” wrote lead author Wayne A. Ray, PhD, of the department of health policy at the Vanderbilt University in Nashville, Tenn., and his coauthors. Those guidelines include using “psychosocial interventions when possible, cardiometabolic assessment before treatment and monitoring after treatment, and limiting therapy to the lowest dose and shortest duration possible,” they wrote.

The study, published online in JAMA Psychiatry, analyzed children and young adults from Tennessee, aged 5-24 years, who were new medication users, and had been enrolled in Medicaid between 1999 and 2014.

They were split into three groups: a control group (189,361) with users primarily taking attention-deficit/hyperactivity disorder medications and antidepressants; a group (28,377) with users who received antipsychotic doses of 50 mg or less chlorpromazine equivalents; and a group (30,120) with users who received doses higher than 50-mg chlorpromazine equivalents.

At follow-up, the incidence of death in the higher-dose group was 146.2 per 100,000 person-years (95% confidence interval, 107.3-199.4 per 100,000 person-years), compared with 49.5 in the lower-dose group (95% CI, 24.8-99.0) and 54.5 in the control group (95% CI, 42.9-69.2). This difference was attributed to unexpected deaths, which accounted for 52.5% of deaths in the higher-dose group. No increased risk of death was noted for injuries or suicides. “The elevated risk persisted for unexpected deaths not due to overdose, with a 4.3-fold increased risk of death from cardiovascular or metabolic causes,” Dr. Ray and his coauthors wrote.

The authors shared potential limitations of their study, including a relatively small number of deaths during follow-up and subsequent statistical adjustment during analysis. They also recognized that their data did not factor in important characteristics such as body mass index and family history, and that a “single-state Medicaid cohort may limit the study’s generalizability.”

Nonetheless, they emphasized Medicaid’s relevance as coverage provider for an estimated 39% of U.S. children, along with noting that this was a first step toward better understanding the consequences of prescribing antipsychotics in younger populations.

“Further studies are needed that compare antipsychotic users and controls within more narrow comorbidity ranges or in analyses that include richer clinical data,” they wrote.

The study was supported by grants from the National Heart, Lung, and Blood Institute, and the National Institute for Child Health and Human Development. No conflicts of interest were reported.

SOURCE: Ray WA et al. JAMA Psychiatry. 2018 Dec 12. doi: 10.1001/jamapsychiatry.2018.3421.

Severe sleep-disordered breathing was significantly associated with more aggressive skin cancer in a study of 443 adults.

Dlumen/Thinkstock

Sleep-disordered breathing (SDB) has been associated with increased cancer risk and mortality, but no large studies have examined the association in specific cancers, wrote Miguel Angel Martinez-Garcia, MD, of La Fe University and Polytechnic Hospital, Valencia, Spain, and his colleagues.

The researchers conducted a sleep study of 443 adults with melanoma within 6 months of their diagnoses. The findings were published in the journal CHEST®. Overall, patients with more severe sleep apnea were nearly twice as likely to have aggressive type melanoma, compared with those with less severe sleep apnea.

Sleep apnea was defined via the Apnea Hypopnea Index (AHI) and the desaturation indices (DI). Aggressive melanoma was defined as a Breslow index greater than 1 mm, compared with 1 mm or less.

Patients with AHI greater than 15.6 events per hour or in the DI4% tertile (more than 9.3 desaturations per hour) were approximately twice as likely (1.94 and 1.93 times, respectively) to have a more aggressive melanoma as were those with less severe sleep apnea, after adjustment for age, gender, body mass index, and melanoma location.

The average age of the patients was 60 years, 51% were male, and the average time between the melanoma diagnosis and the sleep study was 82 days. Sleep symptoms were not significantly different between the patients with aggressive or less aggressive melanoma. However, in addition to more severe sleep apnea, those with aggressive melanoma were significantly more likely to be older, male, and have a higher BMI than were those with less aggressive disease.

“Among the most salient findings were the dependence of the association between SDB and the markers of melanoma aggressiveness on both age and the actual indicators of tumor aggressiveness,” the researchers noted. The association was significant in patients younger than 55 years only if their Breslow index was greater than 2 mm, the researchers said.

The study findings were limited by the absence of full overnight polysomnography to assess SDB because not all participating centers had access to that option, the researchers noted. However, the results support an independent link between sleep apnea and common measures of aggressive melanoma, especially in younger patients, they said. “Future prospective studies are needed to confirm whether the presence and treatment of SDB and its evolution over time are also associated with poor melanoma outcomes, including death, the pathophysiological mechanisms underlying this association,” they added.

The study was supported in part by Fondo de Investigation Sanitaria, SEPAR, Red Respira, and Sociedad Valenciana de Neumología. The researchers had no financial conflicts to disclose

SOURCE: Martinez-Garcia M et al. CHEST. 2018; doi: 10.1016/j.chest.2018.07.015.

Severe sleep-disordered breathing was significantly associated with more aggressive skin cancer in a study of 443 adults.

Dlumen/Thinkstock

Sleep-disordered breathing (SDB) has been associated with increased cancer risk and mortality, but no large studies have examined the association in specific cancers, wrote Miguel Angel Martinez-Garcia, MD, of La Fe University and Polytechnic Hospital, Valencia, Spain, and his colleagues.

The researchers conducted a sleep study of 443 adults with melanoma within 6 months of their diagnoses. The findings were published in the journal CHEST®. Overall, patients with more severe sleep apnea were nearly twice as likely to have aggressive type melanoma, compared with those with less severe sleep apnea.

Sleep apnea was defined via the Apnea Hypopnea Index (AHI) and the desaturation indices (DI). Aggressive melanoma was defined as a Breslow index greater than 1 mm, compared with 1 mm or less.

Patients with AHI greater than 15.6 events per hour or in the DI4% tertile (more than 9.3 desaturations per hour) were approximately twice as likely (1.94 and 1.93 times, respectively) to have a more aggressive melanoma as were those with less severe sleep apnea, after adjustment for age, gender, body mass index, and melanoma location.

The average age of the patients was 60 years, 51% were male, and the average time between the melanoma diagnosis and the sleep study was 82 days. Sleep symptoms were not significantly different between the patients with aggressive or less aggressive melanoma. However, in addition to more severe sleep apnea, those with aggressive melanoma were significantly more likely to be older, male, and have a higher BMI than were those with less aggressive disease.

“Among the most salient findings were the dependence of the association between SDB and the markers of melanoma aggressiveness on both age and the actual indicators of tumor aggressiveness,” the researchers noted. The association was significant in patients younger than 55 years only if their Breslow index was greater than 2 mm, the researchers said.

The study findings were limited by the absence of full overnight polysomnography to assess SDB because not all participating centers had access to that option, the researchers noted. However, the results support an independent link between sleep apnea and common measures of aggressive melanoma, especially in younger patients, they said. “Future prospective studies are needed to confirm whether the presence and treatment of SDB and its evolution over time are also associated with poor melanoma outcomes, including death, the pathophysiological mechanisms underlying this association,” they added.

The study was supported in part by Fondo de Investigation Sanitaria, SEPAR, Red Respira, and Sociedad Valenciana de Neumología. The researchers had no financial conflicts to disclose

SOURCE: Martinez-Garcia M et al. CHEST. 2018; doi: 10.1016/j.chest.2018.07.015.

Severe sleep-disordered breathing was significantly associated with more aggressive skin cancer in a study of 443 adults.

Dlumen/Thinkstock

Sleep-disordered breathing (SDB) has been associated with increased cancer risk and mortality, but no large studies have examined the association in specific cancers, wrote Miguel Angel Martinez-Garcia, MD, of La Fe University and Polytechnic Hospital, Valencia, Spain, and his colleagues.

The researchers conducted a sleep study of 443 adults with melanoma within 6 months of their diagnoses. The findings were published in the journal CHEST®. Overall, patients with more severe sleep apnea were nearly twice as likely to have aggressive type melanoma, compared with those with less severe sleep apnea.

Sleep apnea was defined via the Apnea Hypopnea Index (AHI) and the desaturation indices (DI). Aggressive melanoma was defined as a Breslow index greater than 1 mm, compared with 1 mm or less.

Patients with AHI greater than 15.6 events per hour or in the DI4% tertile (more than 9.3 desaturations per hour) were approximately twice as likely (1.94 and 1.93 times, respectively) to have a more aggressive melanoma as were those with less severe sleep apnea, after adjustment for age, gender, body mass index, and melanoma location.

The average age of the patients was 60 years, 51% were male, and the average time between the melanoma diagnosis and the sleep study was 82 days. Sleep symptoms were not significantly different between the patients with aggressive or less aggressive melanoma. However, in addition to more severe sleep apnea, those with aggressive melanoma were significantly more likely to be older, male, and have a higher BMI than were those with less aggressive disease.

“Among the most salient findings were the dependence of the association between SDB and the markers of melanoma aggressiveness on both age and the actual indicators of tumor aggressiveness,” the researchers noted. The association was significant in patients younger than 55 years only if their Breslow index was greater than 2 mm, the researchers said.

The study findings were limited by the absence of full overnight polysomnography to assess SDB because not all participating centers had access to that option, the researchers noted. However, the results support an independent link between sleep apnea and common measures of aggressive melanoma, especially in younger patients, they said. “Future prospective studies are needed to confirm whether the presence and treatment of SDB and its evolution over time are also associated with poor melanoma outcomes, including death, the pathophysiological mechanisms underlying this association,” they added.

The study was supported in part by Fondo de Investigation Sanitaria, SEPAR, Red Respira, and Sociedad Valenciana de Neumología. The researchers had no financial conflicts to disclose

SOURCE: Martinez-Garcia M et al. CHEST. 2018; doi: 10.1016/j.chest.2018.07.015.

The symptoms of burnout include emotional exhaustion, depersonalization, and reduced personal efficacy, and burnout is a widespread problem among hospitalists; recent data suggest that half of physicians are experiencing at least one such symptom.

Health care leaders are increasingly concerned that these levels of physician burnout pose a threat to patient quality and safety. “As a result, some health care systems are shifting emphasis from the Triple Aim – population health, reduced costs, and patient satisfaction – to the Quadruple Aim, which incorporates health care provider wellness,” according to a recent abstract.

The authors began their own attempt to address the problem when Penn State Health in Dauphin County, Pa., built a stand-alone children’s hospital and experienced bed demands that exceeded bed availability, creating decreased organizational efficiency, high stress, and elevated physician burnout.

The LEAN principles offer a process-focused, customer-centered methodology that improves efficiency and quality. “We redesigned our service line using LEAN principles, such as ‘staff to demand’ and ‘standardize work,’ ” the authors wrote. “To ‘staff to demand,’ we hired three additional FTE [full-time equivalent employees]. This allowed creation of two rounding teams ([up] from one) and reduced our patient-to-attending ratio from 15:1 to 8:1. Workflow was resequenced and standardized, which enabled teams to see discharges at the start of rounds. We also provided in-house evening and overnight resident supervision. Our model permitted flexibility in physicians’ schedules, deemphasized reliance on RVUs, and heightened purpose and efficiency in work as determinants of providers’ value-adding capacity.”

As a result, both service line and hospital efficiency improved and faculty stress decreased in their hospital. “Mean stress scores decreased from 23 (preintervention) to 15 over the first 2 years, and has remained steady for a period of 3 years. Our divisional work-life balance measurement 2 years after the intervention was 85%, well above the reported average of 41%. We have maintained a low physician turnover rate at 3.5% over the last 3 years.”
 

Reference

Keefer L et al. LEAN in: Our secrets to decreasing provider stress, maximizing efficiency on a pediatric hospitalist service [abstract]. Accessed April 6, 2018.


 

The symptoms of burnout include emotional exhaustion, depersonalization, and reduced personal efficacy, and burnout is a widespread problem among hospitalists; recent data suggest that half of physicians are experiencing at least one such symptom.

Health care leaders are increasingly concerned that these levels of physician burnout pose a threat to patient quality and safety. “As a result, some health care systems are shifting emphasis from the Triple Aim – population health, reduced costs, and patient satisfaction – to the Quadruple Aim, which incorporates health care provider wellness,” according to a recent abstract.

The authors began their own attempt to address the problem when Penn State Health in Dauphin County, Pa., built a stand-alone children’s hospital and experienced bed demands that exceeded bed availability, creating decreased organizational efficiency, high stress, and elevated physician burnout.

The LEAN principles offer a process-focused, customer-centered methodology that improves efficiency and quality. “We redesigned our service line using LEAN principles, such as ‘staff to demand’ and ‘standardize work,’ ” the authors wrote. “To ‘staff to demand,’ we hired three additional FTE [full-time equivalent employees]. This allowed creation of two rounding teams ([up] from one) and reduced our patient-to-attending ratio from 15:1 to 8:1. Workflow was resequenced and standardized, which enabled teams to see discharges at the start of rounds. We also provided in-house evening and overnight resident supervision. Our model permitted flexibility in physicians’ schedules, deemphasized reliance on RVUs, and heightened purpose and efficiency in work as determinants of providers’ value-adding capacity.”

As a result, both service line and hospital efficiency improved and faculty stress decreased in their hospital. “Mean stress scores decreased from 23 (preintervention) to 15 over the first 2 years, and has remained steady for a period of 3 years. Our divisional work-life balance measurement 2 years after the intervention was 85%, well above the reported average of 41%. We have maintained a low physician turnover rate at 3.5% over the last 3 years.”
 

Reference

Keefer L et al. LEAN in: Our secrets to decreasing provider stress, maximizing efficiency on a pediatric hospitalist service [abstract]. Accessed April 6, 2018.


 

The symptoms of burnout include emotional exhaustion, depersonalization, and reduced personal efficacy, and burnout is a widespread problem among hospitalists; recent data suggest that half of physicians are experiencing at least one such symptom.

Health care leaders are increasingly concerned that these levels of physician burnout pose a threat to patient quality and safety. “As a result, some health care systems are shifting emphasis from the Triple Aim – population health, reduced costs, and patient satisfaction – to the Quadruple Aim, which incorporates health care provider wellness,” according to a recent abstract.

The authors began their own attempt to address the problem when Penn State Health in Dauphin County, Pa., built a stand-alone children’s hospital and experienced bed demands that exceeded bed availability, creating decreased organizational efficiency, high stress, and elevated physician burnout.

The LEAN principles offer a process-focused, customer-centered methodology that improves efficiency and quality. “We redesigned our service line using LEAN principles, such as ‘staff to demand’ and ‘standardize work,’ ” the authors wrote. “To ‘staff to demand,’ we hired three additional FTE [full-time equivalent employees]. This allowed creation of two rounding teams ([up] from one) and reduced our patient-to-attending ratio from 15:1 to 8:1. Workflow was resequenced and standardized, which enabled teams to see discharges at the start of rounds. We also provided in-house evening and overnight resident supervision. Our model permitted flexibility in physicians’ schedules, deemphasized reliance on RVUs, and heightened purpose and efficiency in work as determinants of providers’ value-adding capacity.”

As a result, both service line and hospital efficiency improved and faculty stress decreased in their hospital. “Mean stress scores decreased from 23 (preintervention) to 15 over the first 2 years, and has remained steady for a period of 3 years. Our divisional work-life balance measurement 2 years after the intervention was 85%, well above the reported average of 41%. We have maintained a low physician turnover rate at 3.5% over the last 3 years.”
 

Reference

Keefer L et al. LEAN in: Our secrets to decreasing provider stress, maximizing efficiency on a pediatric hospitalist service [abstract]. Accessed April 6, 2018.


 

The Internet has been a transformative means of transmitting information. Alas, the information is often not vetted, so the effects on science, truth, and health literacy have been mixed. Unfortunately, Facebook spawned a billion dollar industry that transmits gossip. Twitter distributes information based on celebrity rather than intelligence or expertise.

Listservs and Google groups have allowed small communities to form unrestricted by the physical locations of the members. A listserv for pediatric hospitalists, with 3,800 members, provides quick access to a vast body of knowledge, an extensive array of experience, and insightful clinical wisdom. Discussions on this listserv resource have inspired several of my columns, including this one. The professionalism of the listserv members ensures the accuracy of the messages. Because many of the members work nights, it is possible to post a question and receive five consults from peers, even at 1 a.m. When I first started office practice in rural areas, all I had available was my memory, Rudolph’s Pediatrics textbook, and The Harriet Lane Handbook.

Misinformation has led to vaccine hesitancy and the reemergence of diseases such as measles that had been essentially eliminated. Because people haven’t seen these diseases, they are prone to believing any critique about the risk of vaccines. More recently, parents have been refusing the vitamin K shot that is provided to all newborns to prevent hemorrhagic disease of the newborn, now called vitamin K deficiency bleeding. The incidence of this bleeding disorder is relatively rare. However, when it occurs, the results can be disastrous, with life-threatening gastrointestinal bleeds and disabling brain hemorrhages. As with vaccine hesitancy, the corruption of scientific knowledge has led to bad outcomes that once were nearly eliminated by modern health care.

Part of being a professional is communicating in a manner that helps parents understand small risks. I compare newborn vitamin K deficiency to the risk of driving the newborn around for the first 30 days of life without a car seat. The vast majority of people will not have an accident in that time and their babies will be fine. But emergency department doctors would see so many preventable cases of injury that they would strongly advocate for car seats. I also note that if the baby has a stroke due to vitamin K deficiency, we can’t catch it early and fix it.

eldemir/iStock/Getty Images

Physicians themselves have contributed to this diminished credibility of scientists. Recommendations have been published and later withdrawn in areas such as dietary cholesterol, salt, and saturated fats, estrogen replacement therapy, and screening for prostate and breast cancers. In modern America, even small inconsistencies and errors get blown up into conspiracy plots.

The era of expecting patients to blindly follow a doctor’s orders has long since passed. Parents will search the Internet for answers. The modern physician needs to guide them to good ones.

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].

References

1. Pediatrics. 2016 Aug. doi: 10.1542/peds.2016-2146.

2. “Doubt is Their Product,” by David Michaels, Oxford University Press, 2008, and “Merchants of Doubt,” by Naomi Oreskes and Erik M. Conway, Bloomsbury Press, 2011.

The Internet has been a transformative means of transmitting information. Alas, the information is often not vetted, so the effects on science, truth, and health literacy have been mixed. Unfortunately, Facebook spawned a billion dollar industry that transmits gossip. Twitter distributes information based on celebrity rather than intelligence or expertise.

Listservs and Google groups have allowed small communities to form unrestricted by the physical locations of the members. A listserv for pediatric hospitalists, with 3,800 members, provides quick access to a vast body of knowledge, an extensive array of experience, and insightful clinical wisdom. Discussions on this listserv resource have inspired several of my columns, including this one. The professionalism of the listserv members ensures the accuracy of the messages. Because many of the members work nights, it is possible to post a question and receive five consults from peers, even at 1 a.m. When I first started office practice in rural areas, all I had available was my memory, Rudolph’s Pediatrics textbook, and The Harriet Lane Handbook.

Misinformation has led to vaccine hesitancy and the reemergence of diseases such as measles that had been essentially eliminated. Because people haven’t seen these diseases, they are prone to believing any critique about the risk of vaccines. More recently, parents have been refusing the vitamin K shot that is provided to all newborns to prevent hemorrhagic disease of the newborn, now called vitamin K deficiency bleeding. The incidence of this bleeding disorder is relatively rare. However, when it occurs, the results can be disastrous, with life-threatening gastrointestinal bleeds and disabling brain hemorrhages. As with vaccine hesitancy, the corruption of scientific knowledge has led to bad outcomes that once were nearly eliminated by modern health care.

Part of being a professional is communicating in a manner that helps parents understand small risks. I compare newborn vitamin K deficiency to the risk of driving the newborn around for the first 30 days of life without a car seat. The vast majority of people will not have an accident in that time and their babies will be fine. But emergency department doctors would see so many preventable cases of injury that they would strongly advocate for car seats. I also note that if the baby has a stroke due to vitamin K deficiency, we can’t catch it early and fix it.

eldemir/iStock/Getty Images

Physicians themselves have contributed to this diminished credibility of scientists. Recommendations have been published and later withdrawn in areas such as dietary cholesterol, salt, and saturated fats, estrogen replacement therapy, and screening for prostate and breast cancers. In modern America, even small inconsistencies and errors get blown up into conspiracy plots.

The era of expecting patients to blindly follow a doctor’s orders has long since passed. Parents will search the Internet for answers. The modern physician needs to guide them to good ones.

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].

References

1. Pediatrics. 2016 Aug. doi: 10.1542/peds.2016-2146.

2. “Doubt is Their Product,” by David Michaels, Oxford University Press, 2008, and “Merchants of Doubt,” by Naomi Oreskes and Erik M. Conway, Bloomsbury Press, 2011.

The Internet has been a transformative means of transmitting information. Alas, the information is often not vetted, so the effects on science, truth, and health literacy have been mixed. Unfortunately, Facebook spawned a billion dollar industry that transmits gossip. Twitter distributes information based on celebrity rather than intelligence or expertise.

Listservs and Google groups have allowed small communities to form unrestricted by the physical locations of the members. A listserv for pediatric hospitalists, with 3,800 members, provides quick access to a vast body of knowledge, an extensive array of experience, and insightful clinical wisdom. Discussions on this listserv resource have inspired several of my columns, including this one. The professionalism of the listserv members ensures the accuracy of the messages. Because many of the members work nights, it is possible to post a question and receive five consults from peers, even at 1 a.m. When I first started office practice in rural areas, all I had available was my memory, Rudolph’s Pediatrics textbook, and The Harriet Lane Handbook.

Misinformation has led to vaccine hesitancy and the reemergence of diseases such as measles that had been essentially eliminated. Because people haven’t seen these diseases, they are prone to believing any critique about the risk of vaccines. More recently, parents have been refusing the vitamin K shot that is provided to all newborns to prevent hemorrhagic disease of the newborn, now called vitamin K deficiency bleeding. The incidence of this bleeding disorder is relatively rare. However, when it occurs, the results can be disastrous, with life-threatening gastrointestinal bleeds and disabling brain hemorrhages. As with vaccine hesitancy, the corruption of scientific knowledge has led to bad outcomes that once were nearly eliminated by modern health care.

Part of being a professional is communicating in a manner that helps parents understand small risks. I compare newborn vitamin K deficiency to the risk of driving the newborn around for the first 30 days of life without a car seat. The vast majority of people will not have an accident in that time and their babies will be fine. But emergency department doctors would see so many preventable cases of injury that they would strongly advocate for car seats. I also note that if the baby has a stroke due to vitamin K deficiency, we can’t catch it early and fix it.

eldemir/iStock/Getty Images

Physicians themselves have contributed to this diminished credibility of scientists. Recommendations have been published and later withdrawn in areas such as dietary cholesterol, salt, and saturated fats, estrogen replacement therapy, and screening for prostate and breast cancers. In modern America, even small inconsistencies and errors get blown up into conspiracy plots.

The era of expecting patients to blindly follow a doctor’s orders has long since passed. Parents will search the Internet for answers. The modern physician needs to guide them to good ones.

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].

References

1. Pediatrics. 2016 Aug. doi: 10.1542/peds.2016-2146.

2. “Doubt is Their Product,” by David Michaels, Oxford University Press, 2008, and “Merchants of Doubt,” by Naomi Oreskes and Erik M. Conway, Bloomsbury Press, 2011.

SAN DIEGO – Patients with newly diagnosed multiple myeloma who were ineligible for transplant had a 44% reduction in the risk of disease progression or death when they were treated with the anti-CD38 monoclonal antibody daratumumab (Darzalex) added to lenalidomide (Revlimid) and dexamethasone, compared with lenalidomide-dexamethasone alone, an interim analysis from the MAIA trial showed.

Among 737 patients in a phase 3 trial, median progression-free survival – the primary endpoint – had not been reached after a median follow-up of 28 months for patients randomized to daratumumab, lenalidomide, and dexamethasone (DRd), versus 31.9 months for patients randomized to lenalidomide and dexamethasone (Rd).

The 30-month PFS rate in the DRd arm was 71%, compared with 56% for the Rd arm. This difference translated into a hazard ratio (HR) for progression of 0.56 (P less than .0001), reported Thierry Facon, MD, of Hôpital Claude Huriez and the University of Lille, France.

“These results support DRd as a new standard of care for elderly patients with myeloma who are ineligible for transplant,” he said at the annual meeting of the American Society of Hematology.

Dr. Facon and his colleagues had previously shown in the FIRST trial that in newly diagnosed transplant-ineligible patients, continuous treatment with lenalidomide and low-dose dexamethasone was associated with significant overall survival and PFS benefits, compared with melphalan-prednisone-thalidomide.

In the POLLUX trial, investigators reported that in patients with multiple myeloma that was refractory or had relapsed after at least one prior line of therapy, the DRd combination was associated with a 63% reduction in the risk for disease progression or death, compared with Rd alone.
 

MAIA details

The MAIA trial is a pivotal, phase 3 study pitting DRd against Rd in transplant-ineligible patients with newly diagnosed multiple myeloma.

Patients with untreated disease who had Eastern Cooperative Oncology Group (ECOG) status of 0-2 and creatinine clearance rates of at least 30 mL/min were enrolled. Patients were randomly assigned to either DRd, with intravenous daratumumab 16 mg/kg weekly for cycles 1 and 2, every other week for cycles 3 through 6, and every 4 weeks from cycle 7 until disease progression, plus lenalidomide 25 mg orally per day on days 1-21 until disease progression, and dexamethasone 40 mg orally or intravenously weekly until disease progression; or to the same regimen without daratumumab.

The median patient age was 73 years and 99% of all patients were aged 65 years or older. Demographic and clinical characteristics were well balanced between the treatment arms.

The primary endpoint of progression-free survival was superior with DRd.

DRd also was associated with a significantly higher overall response rate (93% vs. 81%), complete response rate (48% vs. 25%), very good partial response or better rate (79% vs. 53%), and minimal residual disease (MRD) negativity rate (24% vs. 7%; P less than .0001 for all comparisons).

The DRd combination was associated with infusion-related reactions in 41% of patients, but only 3% were grade 3 or 4 in severity.

Hematologic treatment-emergent adverse events (TEAE) grade 3 or greater that were more common with DRd included neutropenia (50% vs. 35%) and lymphopenia (15% vs. 11%). Conversely, thrombocytopenia (7% vs. 9%, grade 3 or 4) and anemia (12% vs. 20%) were more frequent with Rd.

Nonhematologic TEAEs that were more frequent with DRd included diarrhea, constipation, fatigue, peripheral edema, and pneumonia. Rates of asthenia, back pain, nausea, and deep vein thrombosis/pulmonary embolism were similar between the study arms.

Janssen funded the study. Dr. Facon reported speakers bureau and advisory board participation for Celgene, Janssen, and Takeda; and advisory board participation for Sanofi, Amgen, Karyopharm, and Oncopeptides.

SOURCE: Facon T et al. ASH 2018, Abstract LBA-2.

SAN DIEGO – Patients with newly diagnosed multiple myeloma who were ineligible for transplant had a 44% reduction in the risk of disease progression or death when they were treated with the anti-CD38 monoclonal antibody daratumumab (Darzalex) added to lenalidomide (Revlimid) and dexamethasone, compared with lenalidomide-dexamethasone alone, an interim analysis from the MAIA trial showed.

Among 737 patients in a phase 3 trial, median progression-free survival – the primary endpoint – had not been reached after a median follow-up of 28 months for patients randomized to daratumumab, lenalidomide, and dexamethasone (DRd), versus 31.9 months for patients randomized to lenalidomide and dexamethasone (Rd).

The 30-month PFS rate in the DRd arm was 71%, compared with 56% for the Rd arm. This difference translated into a hazard ratio (HR) for progression of 0.56 (P less than .0001), reported Thierry Facon, MD, of Hôpital Claude Huriez and the University of Lille, France.

“These results support DRd as a new standard of care for elderly patients with myeloma who are ineligible for transplant,” he said at the annual meeting of the American Society of Hematology.

Dr. Facon and his colleagues had previously shown in the FIRST trial that in newly diagnosed transplant-ineligible patients, continuous treatment with lenalidomide and low-dose dexamethasone was associated with significant overall survival and PFS benefits, compared with melphalan-prednisone-thalidomide.

In the POLLUX trial, investigators reported that in patients with multiple myeloma that was refractory or had relapsed after at least one prior line of therapy, the DRd combination was associated with a 63% reduction in the risk for disease progression or death, compared with Rd alone.
 

MAIA details

The MAIA trial is a pivotal, phase 3 study pitting DRd against Rd in transplant-ineligible patients with newly diagnosed multiple myeloma.

Patients with untreated disease who had Eastern Cooperative Oncology Group (ECOG) status of 0-2 and creatinine clearance rates of at least 30 mL/min were enrolled. Patients were randomly assigned to either DRd, with intravenous daratumumab 16 mg/kg weekly for cycles 1 and 2, every other week for cycles 3 through 6, and every 4 weeks from cycle 7 until disease progression, plus lenalidomide 25 mg orally per day on days 1-21 until disease progression, and dexamethasone 40 mg orally or intravenously weekly until disease progression; or to the same regimen without daratumumab.

The median patient age was 73 years and 99% of all patients were aged 65 years or older. Demographic and clinical characteristics were well balanced between the treatment arms.

The primary endpoint of progression-free survival was superior with DRd.

DRd also was associated with a significantly higher overall response rate (93% vs. 81%), complete response rate (48% vs. 25%), very good partial response or better rate (79% vs. 53%), and minimal residual disease (MRD) negativity rate (24% vs. 7%; P less than .0001 for all comparisons).

The DRd combination was associated with infusion-related reactions in 41% of patients, but only 3% were grade 3 or 4 in severity.

Hematologic treatment-emergent adverse events (TEAE) grade 3 or greater that were more common with DRd included neutropenia (50% vs. 35%) and lymphopenia (15% vs. 11%). Conversely, thrombocytopenia (7% vs. 9%, grade 3 or 4) and anemia (12% vs. 20%) were more frequent with Rd.

Nonhematologic TEAEs that were more frequent with DRd included diarrhea, constipation, fatigue, peripheral edema, and pneumonia. Rates of asthenia, back pain, nausea, and deep vein thrombosis/pulmonary embolism were similar between the study arms.

Janssen funded the study. Dr. Facon reported speakers bureau and advisory board participation for Celgene, Janssen, and Takeda; and advisory board participation for Sanofi, Amgen, Karyopharm, and Oncopeptides.

SOURCE: Facon T et al. ASH 2018, Abstract LBA-2.

SAN DIEGO – Patients with newly diagnosed multiple myeloma who were ineligible for transplant had a 44% reduction in the risk of disease progression or death when they were treated with the anti-CD38 monoclonal antibody daratumumab (Darzalex) added to lenalidomide (Revlimid) and dexamethasone, compared with lenalidomide-dexamethasone alone, an interim analysis from the MAIA trial showed.

Among 737 patients in a phase 3 trial, median progression-free survival – the primary endpoint – had not been reached after a median follow-up of 28 months for patients randomized to daratumumab, lenalidomide, and dexamethasone (DRd), versus 31.9 months for patients randomized to lenalidomide and dexamethasone (Rd).

The 30-month PFS rate in the DRd arm was 71%, compared with 56% for the Rd arm. This difference translated into a hazard ratio (HR) for progression of 0.56 (P less than .0001), reported Thierry Facon, MD, of Hôpital Claude Huriez and the University of Lille, France.

“These results support DRd as a new standard of care for elderly patients with myeloma who are ineligible for transplant,” he said at the annual meeting of the American Society of Hematology.

Dr. Facon and his colleagues had previously shown in the FIRST trial that in newly diagnosed transplant-ineligible patients, continuous treatment with lenalidomide and low-dose dexamethasone was associated with significant overall survival and PFS benefits, compared with melphalan-prednisone-thalidomide.

In the POLLUX trial, investigators reported that in patients with multiple myeloma that was refractory or had relapsed after at least one prior line of therapy, the DRd combination was associated with a 63% reduction in the risk for disease progression or death, compared with Rd alone.
 

MAIA details

The MAIA trial is a pivotal, phase 3 study pitting DRd against Rd in transplant-ineligible patients with newly diagnosed multiple myeloma.

Patients with untreated disease who had Eastern Cooperative Oncology Group (ECOG) status of 0-2 and creatinine clearance rates of at least 30 mL/min were enrolled. Patients were randomly assigned to either DRd, with intravenous daratumumab 16 mg/kg weekly for cycles 1 and 2, every other week for cycles 3 through 6, and every 4 weeks from cycle 7 until disease progression, plus lenalidomide 25 mg orally per day on days 1-21 until disease progression, and dexamethasone 40 mg orally or intravenously weekly until disease progression; or to the same regimen without daratumumab.

The median patient age was 73 years and 99% of all patients were aged 65 years or older. Demographic and clinical characteristics were well balanced between the treatment arms.

The primary endpoint of progression-free survival was superior with DRd.

DRd also was associated with a significantly higher overall response rate (93% vs. 81%), complete response rate (48% vs. 25%), very good partial response or better rate (79% vs. 53%), and minimal residual disease (MRD) negativity rate (24% vs. 7%; P less than .0001 for all comparisons).

The DRd combination was associated with infusion-related reactions in 41% of patients, but only 3% were grade 3 or 4 in severity.

Hematologic treatment-emergent adverse events (TEAE) grade 3 or greater that were more common with DRd included neutropenia (50% vs. 35%) and lymphopenia (15% vs. 11%). Conversely, thrombocytopenia (7% vs. 9%, grade 3 or 4) and anemia (12% vs. 20%) were more frequent with Rd.

Nonhematologic TEAEs that were more frequent with DRd included diarrhea, constipation, fatigue, peripheral edema, and pneumonia. Rates of asthenia, back pain, nausea, and deep vein thrombosis/pulmonary embolism were similar between the study arms.

Janssen funded the study. Dr. Facon reported speakers bureau and advisory board participation for Celgene, Janssen, and Takeda; and advisory board participation for Sanofi, Amgen, Karyopharm, and Oncopeptides.

SOURCE: Facon T et al. ASH 2018, Abstract LBA-2.