In myocardial infarction patients with cardiogenic shock and multivessel disease, culprit lesion–only and multivessel percutaneous coronary interventions (PCI) had similar mortality rates at 1 year.

At 30 days, culprit lesion–only PCI was associated with fewer cases of death or renal replacement therapy than immediate multivessel PCI.

However, not all the news was good for culprit lesion–only PCI: At 1 year, it was associated with a higher frequency of rehospitalization for heart failure and of repeat vascularization, according to Holger Thiele, MD, of the Heart Center Leipzig at the University of Leipzig (Germany) and his colleagues.

These results from the Culprit Only Lesion PCI versus Multivessel PCI in Cardiogenic Shock (CULPRIT-SHOCK) study were presented at the annual congress of the European Society of Cardiology and published simultaneously in the New England Journal of Medicine.

The 30-day results from the study, published in the journal last year, were enough to convince the creators of the European revascularization guidelines to downgrade immediate multivessel PCI in cardiogenic shock to a class III B recommendation, which indicates that it is not effective and may cause harm.

However, the results also caused controversy because complete revascularization via immediate multivessel PCI in cardiogenic shock patients might lead to long-term benefits. In fact, evidence from nonrandomized trials and a registry study had suggested that immediate multivessel PCI may reduce mortality at 1 year.

But the new 1-year data don’t support that hypothesis of long-term benefit, Dr. Thiele and his colleagues found.

The CULPRIT-SHOCK trial randomized 684 patients at 83 centers to culprit lesion–only PCI or multivessel PCI. At 30 days, death or renal replacement therapy occurred at a lower frequency in the culprit lesion–only group (45.9% vs. 55.4%; relative risk, 0.83; P = .01).

At 1 year, all-cause mortality was 50.0% in the group that underwent culprit lesion–only PCI, compared with 56.9% in the group that underwent multivessel PCI, a result that was not statistically significant (RR, 0.88; 95% CI, 0.76-1.01). There was also no significant difference in death from cardiovascular causes, 46.2% in culprit lesion–only patients, compared with 52.8% in multivessel patients (RR, 0.88; 95% CI, 0.75-1.02).

Mortality rates between baseline and 1 year were similar in the intention-to-treat, per-protocol, and as-treated populations.

The researchers conducted a post hoc analysis of the original primary endpoint – death or renal replacement therapy – at 1 year, and they found results similar to those seen at 30 days: 52.0% in the culprit lesion–only group and 59.5% in the multivessel group (RR, 0.87; 95% CI, 0.76-0.99).

Some results favored multivessel PCI: 32.3% of the culprit lesion–only group underwent repeat revascularization, compared with 9.4% of multivessel PCI (RR, 3.44; 95% CI, 2.39-4.95). Rehospitalizations for congestive heart failure were rare, but occurred in 5.2% of the culprit lesion–only group, compared with 1.2% of the multivessel group (RR, 4.46; 95% CI, 1.53-13.04).

The study was funded by the European Union Seventh Framework Programme, the German Heart Research Foundation, and the German Centre for Cardiovascular Research. Dr. Thiele had no relevant conflicts of interest.

SOURCE: Thiele H et al. N Engl J Med. 2018 Aug 25. doi: 10.1056/NEJMoa1808788.

In myocardial infarction patients with cardiogenic shock and multivessel disease, culprit lesion–only and multivessel percutaneous coronary interventions (PCI) had similar mortality rates at 1 year.

At 30 days, culprit lesion–only PCI was associated with fewer cases of death or renal replacement therapy than immediate multivessel PCI.

However, not all the news was good for culprit lesion–only PCI: At 1 year, it was associated with a higher frequency of rehospitalization for heart failure and of repeat vascularization, according to Holger Thiele, MD, of the Heart Center Leipzig at the University of Leipzig (Germany) and his colleagues.

These results from the Culprit Only Lesion PCI versus Multivessel PCI in Cardiogenic Shock (CULPRIT-SHOCK) study were presented at the annual congress of the European Society of Cardiology and published simultaneously in the New England Journal of Medicine.

The 30-day results from the study, published in the journal last year, were enough to convince the creators of the European revascularization guidelines to downgrade immediate multivessel PCI in cardiogenic shock to a class III B recommendation, which indicates that it is not effective and may cause harm.

However, the results also caused controversy because complete revascularization via immediate multivessel PCI in cardiogenic shock patients might lead to long-term benefits. In fact, evidence from nonrandomized trials and a registry study had suggested that immediate multivessel PCI may reduce mortality at 1 year.

But the new 1-year data don’t support that hypothesis of long-term benefit, Dr. Thiele and his colleagues found.

The CULPRIT-SHOCK trial randomized 684 patients at 83 centers to culprit lesion–only PCI or multivessel PCI. At 30 days, death or renal replacement therapy occurred at a lower frequency in the culprit lesion–only group (45.9% vs. 55.4%; relative risk, 0.83; P = .01).

At 1 year, all-cause mortality was 50.0% in the group that underwent culprit lesion–only PCI, compared with 56.9% in the group that underwent multivessel PCI, a result that was not statistically significant (RR, 0.88; 95% CI, 0.76-1.01). There was also no significant difference in death from cardiovascular causes, 46.2% in culprit lesion–only patients, compared with 52.8% in multivessel patients (RR, 0.88; 95% CI, 0.75-1.02).

Mortality rates between baseline and 1 year were similar in the intention-to-treat, per-protocol, and as-treated populations.

The researchers conducted a post hoc analysis of the original primary endpoint – death or renal replacement therapy – at 1 year, and they found results similar to those seen at 30 days: 52.0% in the culprit lesion–only group and 59.5% in the multivessel group (RR, 0.87; 95% CI, 0.76-0.99).

Some results favored multivessel PCI: 32.3% of the culprit lesion–only group underwent repeat revascularization, compared with 9.4% of multivessel PCI (RR, 3.44; 95% CI, 2.39-4.95). Rehospitalizations for congestive heart failure were rare, but occurred in 5.2% of the culprit lesion–only group, compared with 1.2% of the multivessel group (RR, 4.46; 95% CI, 1.53-13.04).

The study was funded by the European Union Seventh Framework Programme, the German Heart Research Foundation, and the German Centre for Cardiovascular Research. Dr. Thiele had no relevant conflicts of interest.

SOURCE: Thiele H et al. N Engl J Med. 2018 Aug 25. doi: 10.1056/NEJMoa1808788.

In myocardial infarction patients with cardiogenic shock and multivessel disease, culprit lesion–only and multivessel percutaneous coronary interventions (PCI) had similar mortality rates at 1 year.

At 30 days, culprit lesion–only PCI was associated with fewer cases of death or renal replacement therapy than immediate multivessel PCI.

However, not all the news was good for culprit lesion–only PCI: At 1 year, it was associated with a higher frequency of rehospitalization for heart failure and of repeat vascularization, according to Holger Thiele, MD, of the Heart Center Leipzig at the University of Leipzig (Germany) and his colleagues.

These results from the Culprit Only Lesion PCI versus Multivessel PCI in Cardiogenic Shock (CULPRIT-SHOCK) study were presented at the annual congress of the European Society of Cardiology and published simultaneously in the New England Journal of Medicine.

The 30-day results from the study, published in the journal last year, were enough to convince the creators of the European revascularization guidelines to downgrade immediate multivessel PCI in cardiogenic shock to a class III B recommendation, which indicates that it is not effective and may cause harm.

However, the results also caused controversy because complete revascularization via immediate multivessel PCI in cardiogenic shock patients might lead to long-term benefits. In fact, evidence from nonrandomized trials and a registry study had suggested that immediate multivessel PCI may reduce mortality at 1 year.

But the new 1-year data don’t support that hypothesis of long-term benefit, Dr. Thiele and his colleagues found.

The CULPRIT-SHOCK trial randomized 684 patients at 83 centers to culprit lesion–only PCI or multivessel PCI. At 30 days, death or renal replacement therapy occurred at a lower frequency in the culprit lesion–only group (45.9% vs. 55.4%; relative risk, 0.83; P = .01).

At 1 year, all-cause mortality was 50.0% in the group that underwent culprit lesion–only PCI, compared with 56.9% in the group that underwent multivessel PCI, a result that was not statistically significant (RR, 0.88; 95% CI, 0.76-1.01). There was also no significant difference in death from cardiovascular causes, 46.2% in culprit lesion–only patients, compared with 52.8% in multivessel patients (RR, 0.88; 95% CI, 0.75-1.02).

Mortality rates between baseline and 1 year were similar in the intention-to-treat, per-protocol, and as-treated populations.

The researchers conducted a post hoc analysis of the original primary endpoint – death or renal replacement therapy – at 1 year, and they found results similar to those seen at 30 days: 52.0% in the culprit lesion–only group and 59.5% in the multivessel group (RR, 0.87; 95% CI, 0.76-0.99).

Some results favored multivessel PCI: 32.3% of the culprit lesion–only group underwent repeat revascularization, compared with 9.4% of multivessel PCI (RR, 3.44; 95% CI, 2.39-4.95). Rehospitalizations for congestive heart failure were rare, but occurred in 5.2% of the culprit lesion–only group, compared with 1.2% of the multivessel group (RR, 4.46; 95% CI, 1.53-13.04).

The study was funded by the European Union Seventh Framework Programme, the German Heart Research Foundation, and the German Centre for Cardiovascular Research. Dr. Thiele had no relevant conflicts of interest.

SOURCE: Thiele H et al. N Engl J Med. 2018 Aug 25. doi: 10.1056/NEJMoa1808788.

ORLANDO – In 42 states, emergency medical technicians aren’t allowed to administer glucagon to patients with severe hypoglycemia, and that’s a problem, according to investigators from the Joslin Diabetes Center, Boston.

Paramedics can administer the drug, but they’re only about a quarter of medical first-responders, so in many parts of the country, ambulance crews show up with only EMTs [emergency medical technicians] on board, and patients have to wait for the ED to get glucagon.

The delay increases the risk of coma, brain damage, and death. Just like in stroke, time is key with severe hypoglycemia. “The minutes really add up,” said lead investigator Nicole Wagner, a one-time researcher at Joslin and now a medical student at Thomas Jefferson Medical College, Philadelphia.

“Increasing the availability of glucagon in the prehospital setting will likely result in reduced cost burden and adverse consequences of severe hypoglycemia. All emergency persons should have access to glucagon along with the training to administer it,” she and her team concluded at the 2018 American Diabetes Association scientific sessions meeting.

The situation is puzzling because glucagon has a good safety profile – the main concern is nausea – and families of diabetics, at least at Joslin, are taught all the time how to mix and inject it.

[email protected]

SOURCE: Wagner NE et al. 2018 American Diabetes Association scientific sessions abstract 387-P

ORLANDO – In 42 states, emergency medical technicians aren’t allowed to administer glucagon to patients with severe hypoglycemia, and that’s a problem, according to investigators from the Joslin Diabetes Center, Boston.

Paramedics can administer the drug, but they’re only about a quarter of medical first-responders, so in many parts of the country, ambulance crews show up with only EMTs [emergency medical technicians] on board, and patients have to wait for the ED to get glucagon.

The delay increases the risk of coma, brain damage, and death. Just like in stroke, time is key with severe hypoglycemia. “The minutes really add up,” said lead investigator Nicole Wagner, a one-time researcher at Joslin and now a medical student at Thomas Jefferson Medical College, Philadelphia.

“Increasing the availability of glucagon in the prehospital setting will likely result in reduced cost burden and adverse consequences of severe hypoglycemia. All emergency persons should have access to glucagon along with the training to administer it,” she and her team concluded at the 2018 American Diabetes Association scientific sessions meeting.

The situation is puzzling because glucagon has a good safety profile – the main concern is nausea – and families of diabetics, at least at Joslin, are taught all the time how to mix and inject it.

[email protected]

SOURCE: Wagner NE et al. 2018 American Diabetes Association scientific sessions abstract 387-P

ORLANDO – In 42 states, emergency medical technicians aren’t allowed to administer glucagon to patients with severe hypoglycemia, and that’s a problem, according to investigators from the Joslin Diabetes Center, Boston.

Paramedics can administer the drug, but they’re only about a quarter of medical first-responders, so in many parts of the country, ambulance crews show up with only EMTs [emergency medical technicians] on board, and patients have to wait for the ED to get glucagon.

The delay increases the risk of coma, brain damage, and death. Just like in stroke, time is key with severe hypoglycemia. “The minutes really add up,” said lead investigator Nicole Wagner, a one-time researcher at Joslin and now a medical student at Thomas Jefferson Medical College, Philadelphia.

“Increasing the availability of glucagon in the prehospital setting will likely result in reduced cost burden and adverse consequences of severe hypoglycemia. All emergency persons should have access to glucagon along with the training to administer it,” she and her team concluded at the 2018 American Diabetes Association scientific sessions meeting.

The situation is puzzling because glucagon has a good safety profile – the main concern is nausea – and families of diabetics, at least at Joslin, are taught all the time how to mix and inject it.

[email protected]

SOURCE: Wagner NE et al. 2018 American Diabetes Association scientific sessions abstract 387-P

MUNICH – The use of coronary computed tomographic angiography (CTA) in patients with stable chest pain reduced the risk of nonfatal heart attack or cardiovascular death by 41% over 5 years.

Although the absolute numbers were small – 48 clinical events in the intervention group and 81 among patients who had standard care – the difference was significant and wasn’t associated with any increase in invasive coronary procedures, David E. Newby, MD, said at the annual congress of the European Society of Cardiology.

The study, presented August 25, was published simultaneously in the New England Journal of Medicine (NEJM 2018; DOI: 10.1056/NEJMoa1805971

The data suggest that 63 patients with stable chest pain would need to undergo CTA to prevent one fatal or nonfatal myocardial infarction over 5 years, said Dr. Newby, the BHF John Wheatley professor of cardiology at the University of Edinburgh, Scotland.

He presented 5-year results of the SCOT-HEART study, an open-label trial that randomized 4,146 patients with stable chest pain to standard care plus CTA, or standard care alone. The primary endpoint was nonfatal myocardial infarction or death from coronary heart disease at 5 years. The 3-year results were previously reported.

“This is one of the most impactful studies in cardiovascular medicine. It’s a groundbreaking trial,” commented Todd C. Villines, MD, a designated discussant for the report at the meeting. SCOT-HEART “looked at the additive value of CTA compared with usual care using functional testing with an exercise stress test. It showed that when you visualize coronary atherosclerosis [with CTA] and change medical management based on whether or not plaque is present it drove a significant decrease in MIs,” noted Dr. Villines, a cardiologist affiliated with Georgetown University Medical School in Washington, and immediate past president of the Society of Cardiovascular CT.

Patients were recruited from 12 cardiology centers across Scotland and followed for a mean of 4.8 years, amassing 20,254 patient-years of follow-up. They were a mean of 57 years old; 41% had nonanginal chest pain, 35% typical angina, and 24% atypical angina About half were current or former smokers, a third had hypertension, and half had hypercholesterolemia. Resting EEG was normal in 85%.

Patients who underwent CTA were more likely to start preventive therapies (19% vs. 14.7%; odds ratio, 1.4) and antianginal therapies (13% vs. 10.7%; hazard ratio, 1.27). And although there were more revascularizations in that group early on, the numbers were similar by the end of follow-up (13.5% vs. 13%). After 12 months, CTA patients were 30% less likely to undergo invasive coronary angiography (HR, 0.70) and 41% less likely to undergo a coronary revascularization (HR, 0.59).

“This would be consistent with both the emergence of unrecognized disease and nonfatal myocardial infarction in the standard-care group and the reduction in disease progression in the CTA group owing to the implementation of lifestyle modifications and preventive therapies,” Dr. Newby and colleagues wrote in the NEJM paper.

The composite clinical endpoint occurred in 2.3% of the CTA group and 3.9% of the standard care group – a significant risk differential of 41% (HR, 0.59). The primary driver of this benefit was a significantly lower rate of nonfatal myocardial infarction (HR, 0.60) among CTA patients.

There was no evidence of a subgroup effect, Dr. Newby noted. Among the 48 CTA patients who experienced a clinical event, 22 had obstructive disease, 17 had nonobstructive disease, and three had normal coronary arteries (six patients assigned to the procedure didn’t return for it).

There was a slightly higher event rate among patients with possible angina than among those with nonanginal pain (3.1% vs. 1.8%), but the 5-year difference between the treatment groups was not significantly different.

“Our findings suggest that the use of CTA resulted in more correct diagnoses of coronary heart disease than standard care alone, which, in turn, led to the use of appropriate therapies and this change in management resulted in fewer clinical events in the CTA group than in the standard-care group,” Dr. Newby noted. “Patients who receive a correct diagnosis are also more likely to receive appropriate preventive therapies and may have greater motivation to implement healthy lifestyle modification.”

“The SCOT-HEART data solidify coronary CTA as the best first-line test for patients without established coronary disease,” especially now that a report documented that clinicians worldwide are performing coronary CTA using lower levels of radiation exposure to patients, commented Dr. Villines in an interview. During the same session where Dr. Newby reported the SCOT-HEART results, an international team of researchers reported results of a survey of CTA methods used at 61 centers in 32 countries, including several U.S. sites. The results from the survey showed that in 2017 patients undergoing coronary CTA received a median radiation dose of 2.7 mSv and a median dose-length product of 195 mGy*cm, both representing a 78% relative reduction compared with the median doses received during CTA when a similar survey ran in 2007 (Eur Heart J. 2018 Aug 25; doi:10.1093/eurheartj/ehy546).

In contrast, for patients with established coronary artery disease functional tests using stress imaging remain best, Dr. Villines said. “What SCOT-HEART said was that when you use coronary CTA in a population without established coronary disease you can identify not only whether the patient has obstructive disease but do they have coronary atherosclerosis, and that is prognostic and valuable. You miss that with functional testing.”

The Chief Scientist Office of the Scottish Government funded the study. Dr. Newby has received grants from Seimens. Dr. Villines had no relevant commercial disclosures.

Updated 8/27/18: Mitchel L. Zoler contributed commentary by Dr. Todd C. Villines, and additional data and discussion from the presentation, to this article.

[email protected]

SOURCE: Newby DE et al. NEJM 2018; DOI: 10.1056/NEJMoa1805971.

MUNICH – The use of coronary computed tomographic angiography (CTA) in patients with stable chest pain reduced the risk of nonfatal heart attack or cardiovascular death by 41% over 5 years.

Although the absolute numbers were small – 48 clinical events in the intervention group and 81 among patients who had standard care – the difference was significant and wasn’t associated with any increase in invasive coronary procedures, David E. Newby, MD, said at the annual congress of the European Society of Cardiology.

The study, presented August 25, was published simultaneously in the New England Journal of Medicine (NEJM 2018; DOI: 10.1056/NEJMoa1805971

The data suggest that 63 patients with stable chest pain would need to undergo CTA to prevent one fatal or nonfatal myocardial infarction over 5 years, said Dr. Newby, the BHF John Wheatley professor of cardiology at the University of Edinburgh, Scotland.

He presented 5-year results of the SCOT-HEART study, an open-label trial that randomized 4,146 patients with stable chest pain to standard care plus CTA, or standard care alone. The primary endpoint was nonfatal myocardial infarction or death from coronary heart disease at 5 years. The 3-year results were previously reported.

“This is one of the most impactful studies in cardiovascular medicine. It’s a groundbreaking trial,” commented Todd C. Villines, MD, a designated discussant for the report at the meeting. SCOT-HEART “looked at the additive value of CTA compared with usual care using functional testing with an exercise stress test. It showed that when you visualize coronary atherosclerosis [with CTA] and change medical management based on whether or not plaque is present it drove a significant decrease in MIs,” noted Dr. Villines, a cardiologist affiliated with Georgetown University Medical School in Washington, and immediate past president of the Society of Cardiovascular CT.

Patients were recruited from 12 cardiology centers across Scotland and followed for a mean of 4.8 years, amassing 20,254 patient-years of follow-up. They were a mean of 57 years old; 41% had nonanginal chest pain, 35% typical angina, and 24% atypical angina About half were current or former smokers, a third had hypertension, and half had hypercholesterolemia. Resting EEG was normal in 85%.

Patients who underwent CTA were more likely to start preventive therapies (19% vs. 14.7%; odds ratio, 1.4) and antianginal therapies (13% vs. 10.7%; hazard ratio, 1.27). And although there were more revascularizations in that group early on, the numbers were similar by the end of follow-up (13.5% vs. 13%). After 12 months, CTA patients were 30% less likely to undergo invasive coronary angiography (HR, 0.70) and 41% less likely to undergo a coronary revascularization (HR, 0.59).

“This would be consistent with both the emergence of unrecognized disease and nonfatal myocardial infarction in the standard-care group and the reduction in disease progression in the CTA group owing to the implementation of lifestyle modifications and preventive therapies,” Dr. Newby and colleagues wrote in the NEJM paper.

The composite clinical endpoint occurred in 2.3% of the CTA group and 3.9% of the standard care group – a significant risk differential of 41% (HR, 0.59). The primary driver of this benefit was a significantly lower rate of nonfatal myocardial infarction (HR, 0.60) among CTA patients.

There was no evidence of a subgroup effect, Dr. Newby noted. Among the 48 CTA patients who experienced a clinical event, 22 had obstructive disease, 17 had nonobstructive disease, and three had normal coronary arteries (six patients assigned to the procedure didn’t return for it).

There was a slightly higher event rate among patients with possible angina than among those with nonanginal pain (3.1% vs. 1.8%), but the 5-year difference between the treatment groups was not significantly different.

“Our findings suggest that the use of CTA resulted in more correct diagnoses of coronary heart disease than standard care alone, which, in turn, led to the use of appropriate therapies and this change in management resulted in fewer clinical events in the CTA group than in the standard-care group,” Dr. Newby noted. “Patients who receive a correct diagnosis are also more likely to receive appropriate preventive therapies and may have greater motivation to implement healthy lifestyle modification.”

“The SCOT-HEART data solidify coronary CTA as the best first-line test for patients without established coronary disease,” especially now that a report documented that clinicians worldwide are performing coronary CTA using lower levels of radiation exposure to patients, commented Dr. Villines in an interview. During the same session where Dr. Newby reported the SCOT-HEART results, an international team of researchers reported results of a survey of CTA methods used at 61 centers in 32 countries, including several U.S. sites. The results from the survey showed that in 2017 patients undergoing coronary CTA received a median radiation dose of 2.7 mSv and a median dose-length product of 195 mGy*cm, both representing a 78% relative reduction compared with the median doses received during CTA when a similar survey ran in 2007 (Eur Heart J. 2018 Aug 25; doi:10.1093/eurheartj/ehy546).

In contrast, for patients with established coronary artery disease functional tests using stress imaging remain best, Dr. Villines said. “What SCOT-HEART said was that when you use coronary CTA in a population without established coronary disease you can identify not only whether the patient has obstructive disease but do they have coronary atherosclerosis, and that is prognostic and valuable. You miss that with functional testing.”

The Chief Scientist Office of the Scottish Government funded the study. Dr. Newby has received grants from Seimens. Dr. Villines had no relevant commercial disclosures.

Updated 8/27/18: Mitchel L. Zoler contributed commentary by Dr. Todd C. Villines, and additional data and discussion from the presentation, to this article.

[email protected]

SOURCE: Newby DE et al. NEJM 2018; DOI: 10.1056/NEJMoa1805971.

MUNICH – The use of coronary computed tomographic angiography (CTA) in patients with stable chest pain reduced the risk of nonfatal heart attack or cardiovascular death by 41% over 5 years.

Although the absolute numbers were small – 48 clinical events in the intervention group and 81 among patients who had standard care – the difference was significant and wasn’t associated with any increase in invasive coronary procedures, David E. Newby, MD, said at the annual congress of the European Society of Cardiology.

The study, presented August 25, was published simultaneously in the New England Journal of Medicine (NEJM 2018; DOI: 10.1056/NEJMoa1805971

The data suggest that 63 patients with stable chest pain would need to undergo CTA to prevent one fatal or nonfatal myocardial infarction over 5 years, said Dr. Newby, the BHF John Wheatley professor of cardiology at the University of Edinburgh, Scotland.

He presented 5-year results of the SCOT-HEART study, an open-label trial that randomized 4,146 patients with stable chest pain to standard care plus CTA, or standard care alone. The primary endpoint was nonfatal myocardial infarction or death from coronary heart disease at 5 years. The 3-year results were previously reported.

“This is one of the most impactful studies in cardiovascular medicine. It’s a groundbreaking trial,” commented Todd C. Villines, MD, a designated discussant for the report at the meeting. SCOT-HEART “looked at the additive value of CTA compared with usual care using functional testing with an exercise stress test. It showed that when you visualize coronary atherosclerosis [with CTA] and change medical management based on whether or not plaque is present it drove a significant decrease in MIs,” noted Dr. Villines, a cardiologist affiliated with Georgetown University Medical School in Washington, and immediate past president of the Society of Cardiovascular CT.

Patients were recruited from 12 cardiology centers across Scotland and followed for a mean of 4.8 years, amassing 20,254 patient-years of follow-up. They were a mean of 57 years old; 41% had nonanginal chest pain, 35% typical angina, and 24% atypical angina About half were current or former smokers, a third had hypertension, and half had hypercholesterolemia. Resting EEG was normal in 85%.

Patients who underwent CTA were more likely to start preventive therapies (19% vs. 14.7%; odds ratio, 1.4) and antianginal therapies (13% vs. 10.7%; hazard ratio, 1.27). And although there were more revascularizations in that group early on, the numbers were similar by the end of follow-up (13.5% vs. 13%). After 12 months, CTA patients were 30% less likely to undergo invasive coronary angiography (HR, 0.70) and 41% less likely to undergo a coronary revascularization (HR, 0.59).

“This would be consistent with both the emergence of unrecognized disease and nonfatal myocardial infarction in the standard-care group and the reduction in disease progression in the CTA group owing to the implementation of lifestyle modifications and preventive therapies,” Dr. Newby and colleagues wrote in the NEJM paper.

The composite clinical endpoint occurred in 2.3% of the CTA group and 3.9% of the standard care group – a significant risk differential of 41% (HR, 0.59). The primary driver of this benefit was a significantly lower rate of nonfatal myocardial infarction (HR, 0.60) among CTA patients.

There was no evidence of a subgroup effect, Dr. Newby noted. Among the 48 CTA patients who experienced a clinical event, 22 had obstructive disease, 17 had nonobstructive disease, and three had normal coronary arteries (six patients assigned to the procedure didn’t return for it).

There was a slightly higher event rate among patients with possible angina than among those with nonanginal pain (3.1% vs. 1.8%), but the 5-year difference between the treatment groups was not significantly different.

“Our findings suggest that the use of CTA resulted in more correct diagnoses of coronary heart disease than standard care alone, which, in turn, led to the use of appropriate therapies and this change in management resulted in fewer clinical events in the CTA group than in the standard-care group,” Dr. Newby noted. “Patients who receive a correct diagnosis are also more likely to receive appropriate preventive therapies and may have greater motivation to implement healthy lifestyle modification.”

“The SCOT-HEART data solidify coronary CTA as the best first-line test for patients without established coronary disease,” especially now that a report documented that clinicians worldwide are performing coronary CTA using lower levels of radiation exposure to patients, commented Dr. Villines in an interview. During the same session where Dr. Newby reported the SCOT-HEART results, an international team of researchers reported results of a survey of CTA methods used at 61 centers in 32 countries, including several U.S. sites. The results from the survey showed that in 2017 patients undergoing coronary CTA received a median radiation dose of 2.7 mSv and a median dose-length product of 195 mGy*cm, both representing a 78% relative reduction compared with the median doses received during CTA when a similar survey ran in 2007 (Eur Heart J. 2018 Aug 25; doi:10.1093/eurheartj/ehy546).

In contrast, for patients with established coronary artery disease functional tests using stress imaging remain best, Dr. Villines said. “What SCOT-HEART said was that when you use coronary CTA in a population without established coronary disease you can identify not only whether the patient has obstructive disease but do they have coronary atherosclerosis, and that is prognostic and valuable. You miss that with functional testing.”

The Chief Scientist Office of the Scottish Government funded the study. Dr. Newby has received grants from Seimens. Dr. Villines had no relevant commercial disclosures.

Updated 8/27/18: Mitchel L. Zoler contributed commentary by Dr. Todd C. Villines, and additional data and discussion from the presentation, to this article.

[email protected]

SOURCE: Newby DE et al. NEJM 2018; DOI: 10.1056/NEJMoa1805971.

Photo by Bill Branson

A low-intensity regimen could be an effective treatment option for elderly or unfit patients with newly diagnosed acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS), according to researchers.

The regimen—cladribine plus low-dose cytarabine alternating with decitabine—produced a response rate of 68%.

The median disease-free survival (DFS) was 10.8 months, and the median overall survival (OS) was 13.8 months.

The regimen was considered well tolerated, although all patients experienced myelosuppression, and three-quarters developed infections that may have been treatment-related.

Tapan M. Kadia, MD, of the University of Texas MD Anderson Cancer Center in Houston, and his colleagues reported these results in The Lancet Haematology.

This phase 2 trial enrolled 118 patients with previously untreated AML or high-risk MDS. Seventeen percent of patients had therapy-related AML, 25% had secondary AML (prior MDS or myeloproliferative neoplasm [MPN]), and 15% had treated secondary AML (received treatment for MDS/MPN).

Forty-one percent of patients had an adverse risk karyotype, and 27% had a complex karyotype. Patients had a range of mutations, but the most common were in RAS, TP53, DNMT3a, NPM1, and FLT3-ITD.

Most patients (n=116) were age 60 or older, with a median age of 69. However, there were 2 patients younger than age 60. Both had “extensive” exposure to anthracycline, and one had a prior myocardial infarction.

Treatment

Patients received cladribine plus low-dose cytarabine for two cycles, alternating with decitabine for two cycles, for up to 18 cycles (28 days each).

For cycle 1, patients received cladribine at 5 mg/m² (given intravenously over 1 to 2 hours) on days 1 to 5 and cytarabine at 20 mg (given subcutaneously) twice daily on days 1 to 10.

Patients who achieved remission went on to receive consolidation with cladribine at 5 mg/m² (given intravenously over 1 to 2 hours) on days 1 to 3 and cytarabine at 20 mg twice daily on days 1 to 10, alternating with decitabine at 20 mg/m² (intravenously) on days 1 to 5.

Efficacy

The objective response rate was 68%, the rate of complete response was 58%, and the rate of complete response with incomplete count recovery was 9%.

The median DFS was 10.8 months, and the median OS was 13.8 months. The 1-year OS rate was 64%, and the 2-year OS rate was 28%.

Outcomes were better in patients with a diploid karyotype than in those with adverse karyotypes or TP53 mutation. Among patients with a diploid karyotype (n=38), the response rate was 84%, and the median OS was 19.9 months.

Among patients with adverse karyotypes (n=48), the response rate was 50%, and the median OS was 10.5 months. In patients with TP53 mutation (n=20), the response rate was 40%, and the median OS was 8.9 months.

Of all responders (n=80), 23% went on to allogeneic stem cell transplant. There was no significant difference in OS between patients who received a transplant and those who did not. The median OS was 16.4 months and 15.9 months, respectively (P=0.18).

Safety

The researchers said this regimen was generally well tolerated, but all patients experienced myelosuppression.

The most common non-hematologic adverse events (AEs) considered at least possibly related to treatment included infection (n=88), elevated total bilirubin (n=26), rash (n=13), nausea (n=13), diarrhea (n=9), ALT/AST elevation (n=7), elevated creatinine (n=7), mucositis (n=7), and constipation (n=6).

Overall, grade 3/4 non-hematologic AEs tended to occur in few patients. The exception was infections. There were 77 grade 3 infections, and two grade 4 infections.

There were 9 grade 5 infections but no other fatal AEs considered at least possibly related to treatment.

One patient (1%) died within the first 4 weeks of treatment, and 8 (7%) died within the first 8 weeks. None of these patients had responded.

“Our findings suggest that the combination of cladribine and low-dose cytarabine alternating with decitabine is a highly active and well tolerated regimen for older patients with AML,” the researchers wrote.

The team also called for a phase 3 trial comparing this regimen to hypomethylating agents.

This study was sponsored by MD Anderson and supported, in part, by the National Institutes of Health.

Photo by Bill Branson

A low-intensity regimen could be an effective treatment option for elderly or unfit patients with newly diagnosed acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS), according to researchers.

The regimen—cladribine plus low-dose cytarabine alternating with decitabine—produced a response rate of 68%.

The median disease-free survival (DFS) was 10.8 months, and the median overall survival (OS) was 13.8 months.

The regimen was considered well tolerated, although all patients experienced myelosuppression, and three-quarters developed infections that may have been treatment-related.

Tapan M. Kadia, MD, of the University of Texas MD Anderson Cancer Center in Houston, and his colleagues reported these results in The Lancet Haematology.

This phase 2 trial enrolled 118 patients with previously untreated AML or high-risk MDS. Seventeen percent of patients had therapy-related AML, 25% had secondary AML (prior MDS or myeloproliferative neoplasm [MPN]), and 15% had treated secondary AML (received treatment for MDS/MPN).

Forty-one percent of patients had an adverse risk karyotype, and 27% had a complex karyotype. Patients had a range of mutations, but the most common were in RAS, TP53, DNMT3a, NPM1, and FLT3-ITD.

Most patients (n=116) were age 60 or older, with a median age of 69. However, there were 2 patients younger than age 60. Both had “extensive” exposure to anthracycline, and one had a prior myocardial infarction.

Treatment

Patients received cladribine plus low-dose cytarabine for two cycles, alternating with decitabine for two cycles, for up to 18 cycles (28 days each).

For cycle 1, patients received cladribine at 5 mg/m² (given intravenously over 1 to 2 hours) on days 1 to 5 and cytarabine at 20 mg (given subcutaneously) twice daily on days 1 to 10.

Patients who achieved remission went on to receive consolidation with cladribine at 5 mg/m² (given intravenously over 1 to 2 hours) on days 1 to 3 and cytarabine at 20 mg twice daily on days 1 to 10, alternating with decitabine at 20 mg/m² (intravenously) on days 1 to 5.

Efficacy

The objective response rate was 68%, the rate of complete response was 58%, and the rate of complete response with incomplete count recovery was 9%.

The median DFS was 10.8 months, and the median OS was 13.8 months. The 1-year OS rate was 64%, and the 2-year OS rate was 28%.

Outcomes were better in patients with a diploid karyotype than in those with adverse karyotypes or TP53 mutation. Among patients with a diploid karyotype (n=38), the response rate was 84%, and the median OS was 19.9 months.

Among patients with adverse karyotypes (n=48), the response rate was 50%, and the median OS was 10.5 months. In patients with TP53 mutation (n=20), the response rate was 40%, and the median OS was 8.9 months.

Of all responders (n=80), 23% went on to allogeneic stem cell transplant. There was no significant difference in OS between patients who received a transplant and those who did not. The median OS was 16.4 months and 15.9 months, respectively (P=0.18).

Safety

The researchers said this regimen was generally well tolerated, but all patients experienced myelosuppression.

The most common non-hematologic adverse events (AEs) considered at least possibly related to treatment included infection (n=88), elevated total bilirubin (n=26), rash (n=13), nausea (n=13), diarrhea (n=9), ALT/AST elevation (n=7), elevated creatinine (n=7), mucositis (n=7), and constipation (n=6).

Overall, grade 3/4 non-hematologic AEs tended to occur in few patients. The exception was infections. There were 77 grade 3 infections, and two grade 4 infections.

There were 9 grade 5 infections but no other fatal AEs considered at least possibly related to treatment.

One patient (1%) died within the first 4 weeks of treatment, and 8 (7%) died within the first 8 weeks. None of these patients had responded.

“Our findings suggest that the combination of cladribine and low-dose cytarabine alternating with decitabine is a highly active and well tolerated regimen for older patients with AML,” the researchers wrote.

The team also called for a phase 3 trial comparing this regimen to hypomethylating agents.

This study was sponsored by MD Anderson and supported, in part, by the National Institutes of Health.

Photo by Bill Branson

A low-intensity regimen could be an effective treatment option for elderly or unfit patients with newly diagnosed acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS), according to researchers.

The regimen—cladribine plus low-dose cytarabine alternating with decitabine—produced a response rate of 68%.

The median disease-free survival (DFS) was 10.8 months, and the median overall survival (OS) was 13.8 months.

The regimen was considered well tolerated, although all patients experienced myelosuppression, and three-quarters developed infections that may have been treatment-related.

Tapan M. Kadia, MD, of the University of Texas MD Anderson Cancer Center in Houston, and his colleagues reported these results in The Lancet Haematology.

This phase 2 trial enrolled 118 patients with previously untreated AML or high-risk MDS. Seventeen percent of patients had therapy-related AML, 25% had secondary AML (prior MDS or myeloproliferative neoplasm [MPN]), and 15% had treated secondary AML (received treatment for MDS/MPN).

Forty-one percent of patients had an adverse risk karyotype, and 27% had a complex karyotype. Patients had a range of mutations, but the most common were in RAS, TP53, DNMT3a, NPM1, and FLT3-ITD.

Most patients (n=116) were age 60 or older, with a median age of 69. However, there were 2 patients younger than age 60. Both had “extensive” exposure to anthracycline, and one had a prior myocardial infarction.

Treatment

Patients received cladribine plus low-dose cytarabine for two cycles, alternating with decitabine for two cycles, for up to 18 cycles (28 days each).

For cycle 1, patients received cladribine at 5 mg/m² (given intravenously over 1 to 2 hours) on days 1 to 5 and cytarabine at 20 mg (given subcutaneously) twice daily on days 1 to 10.

Patients who achieved remission went on to receive consolidation with cladribine at 5 mg/m² (given intravenously over 1 to 2 hours) on days 1 to 3 and cytarabine at 20 mg twice daily on days 1 to 10, alternating with decitabine at 20 mg/m² (intravenously) on days 1 to 5.

Efficacy

The objective response rate was 68%, the rate of complete response was 58%, and the rate of complete response with incomplete count recovery was 9%.

The median DFS was 10.8 months, and the median OS was 13.8 months. The 1-year OS rate was 64%, and the 2-year OS rate was 28%.

Outcomes were better in patients with a diploid karyotype than in those with adverse karyotypes or TP53 mutation. Among patients with a diploid karyotype (n=38), the response rate was 84%, and the median OS was 19.9 months.

Among patients with adverse karyotypes (n=48), the response rate was 50%, and the median OS was 10.5 months. In patients with TP53 mutation (n=20), the response rate was 40%, and the median OS was 8.9 months.

Of all responders (n=80), 23% went on to allogeneic stem cell transplant. There was no significant difference in OS between patients who received a transplant and those who did not. The median OS was 16.4 months and 15.9 months, respectively (P=0.18).

Safety

The researchers said this regimen was generally well tolerated, but all patients experienced myelosuppression.

The most common non-hematologic adverse events (AEs) considered at least possibly related to treatment included infection (n=88), elevated total bilirubin (n=26), rash (n=13), nausea (n=13), diarrhea (n=9), ALT/AST elevation (n=7), elevated creatinine (n=7), mucositis (n=7), and constipation (n=6).

Overall, grade 3/4 non-hematologic AEs tended to occur in few patients. The exception was infections. There were 77 grade 3 infections, and two grade 4 infections.

There were 9 grade 5 infections but no other fatal AEs considered at least possibly related to treatment.

One patient (1%) died within the first 4 weeks of treatment, and 8 (7%) died within the first 8 weeks. None of these patients had responded.

“Our findings suggest that the combination of cladribine and low-dose cytarabine alternating with decitabine is a highly active and well tolerated regimen for older patients with AML,” the researchers wrote.

The team also called for a phase 3 trial comparing this regimen to hypomethylating agents.

This study was sponsored by MD Anderson and supported, in part, by the National Institutes of Health.

Unlike some children who wanted be firefighters or astronauts when they grew up, ever since Raj Sehgal, MD, FHM, was a boy, he dreamed of being a doctor.

Since earning his medical degree, Dr. Sehgal has kept himself involved in a wide variety of projects, driven by the desire to diversify his expertise.

Currently a clinical associate professor of medicine in the division of general and hospital medicine at the South Texas Veterans Health Care System, San Antonio, and University of Texas Health San Antonio, Dr. Sehgal has found his place as an educator as well as a clinician, earning the Division of Hospital Medicine Teaching Award in 2016.

As a member of the The Hospitalist’s volunteer editorial advisory board, Dr. Sehgal enjoys helping to educate and inform fellow hospitalists. He spoke with The Hospitalist to tell us more about himself.
 

How did you get into medicine?

I don’t know how old I was when I decided I was going to be a doctor, but it was at a very young age and I never really wavered in that desire. I guess I also would have wanted to be a baseball player or a musician, but I never had the talents for those, so it was doctor. That’s always what I was thinking of doing, straight through high school and college, and then after college I took a year off and joined AmeriCorps. I spent a year there and then went to medical school in Dallas at UT Southwestern. After medical school, I thought I should go somewhere as different from Dallas as possible, so I went to Portland, Ore., for my residency and then a fellowship in general internal medicine.

How did you end up in hospital medicine?

When I was doing my residency, I always enjoyed being a generalist. A lot of different areas of medicine interested me, but I like the breadth of things you encounter as a generalist, so I could never picture myself being a subspecialist, doing the same things every day, seeing the same things. I knew I wanted to keep practicing general internal medicine, so I took a fellowship where I was working both inpatient and outpatient, and when I was looking for a job, I sought out things that involved some inpatient and some outpatient work. It turned out hospital medicine was the best fit.

What would you say is your favorite part of hospital medicine?

My favorite part of the job is getting to teach, working with medical students and residents. I also like the variety of what I do as a hospitalist, so I’m about 50% clinical and the rest of the time I perform a variety of tasks, both administrative and educational.

What about your least favorite part of hospitalist work?

Sometimes, particularly if you’re doing clinical, educational, and administrative work, it can be a little overwhelming to try and do a little bit of everything. I think generally that’s a good thing, but sometimes it can feel like a little too much.

What is some of the best advice you have received regarding how to handle the stresses of hospital medicine?

Feel free to say no to things. When hospitalists are starting their careers, and particularly when they are new to a job and trying to express their desire to get involved, sometimes they can have too much thrown at them at once. People can get overloaded very quickly, so I think feeling like you’re able to say no to some requests, or to take some time to think before you accept an additional role. The other piece of advice I remember from my fellowship, is that, when you do something, make it count twice. For example, if you’re involved in a project, you get the practical clinical or educational benefits of whatever the project was. But also think about how you might write about your experience for research purposes, such as for a poster, article, or other presentation.

What is the worst advice you have been given?

I think it’s not necessarily bad advice, but I guess it’s advice that I haven’t really followed. Since I work in academic medicine, I’ve found that the people in academics fall into one of two categories: There are the people who find their niche and remain on that path, and they’re very clear about it and don’t really stray from it; and there are people who don’t find that niche right away. I think the advice I received when starting out was to try to find that niche, and if you’re building an academic career it is very helpful to have these things in which you have become the expert. But I’ve just tried to go where the job takes me. I don’t necessarily have a single academic niche or something that I spend all my time doing, but I do have my hand in a lot of different things. To me, that’s a lot more interesting because it adds to the variety of what you’re doing. Every day is a little different.

What else do you do professionally outside of hospital medicine?

I actually practice a little outpatient medicine. When I first started here, I wanted to keep some outpatient experience, and so I actually created my own clinic. It’s a procedure clinic where I do paracentesis on people who have cirrhosis. Then on the educational side, I sit on the admission committees for the medical school here, so I get to look through the applicants and choose who we interview, and then once we interview candidates, I help choose how we rank students for admission.

Where do you see yourself in the next 10 years?

I’ve never been one who looks at a particular job and says ‘Okay, I want to be the dean or have this position.’ I guess I just hope I’m better at the things I’m currently doing. I hope in 10 years that I’m a better teacher, that I’ll have learned more strategies to help more people, and that I have a better handle on the administrative side of the work. I hope I’ve progressed to a point in my career where I’m doing an even better job than I am now.

What are your goals as a member of the editorial board?

I have an interest not only in medicine but also in writing; I’ve gotten to do some writing both medical and nonmedical in the past. I’ve published a few articles in The Hospitalist, and hopefully, I can do more of that because writing is just another part of education.

Unlike some children who wanted be firefighters or astronauts when they grew up, ever since Raj Sehgal, MD, FHM, was a boy, he dreamed of being a doctor.

Since earning his medical degree, Dr. Sehgal has kept himself involved in a wide variety of projects, driven by the desire to diversify his expertise.

Currently a clinical associate professor of medicine in the division of general and hospital medicine at the South Texas Veterans Health Care System, San Antonio, and University of Texas Health San Antonio, Dr. Sehgal has found his place as an educator as well as a clinician, earning the Division of Hospital Medicine Teaching Award in 2016.

As a member of the The Hospitalist’s volunteer editorial advisory board, Dr. Sehgal enjoys helping to educate and inform fellow hospitalists. He spoke with The Hospitalist to tell us more about himself.
 

How did you get into medicine?

I don’t know how old I was when I decided I was going to be a doctor, but it was at a very young age and I never really wavered in that desire. I guess I also would have wanted to be a baseball player or a musician, but I never had the talents for those, so it was doctor. That’s always what I was thinking of doing, straight through high school and college, and then after college I took a year off and joined AmeriCorps. I spent a year there and then went to medical school in Dallas at UT Southwestern. After medical school, I thought I should go somewhere as different from Dallas as possible, so I went to Portland, Ore., for my residency and then a fellowship in general internal medicine.

How did you end up in hospital medicine?

When I was doing my residency, I always enjoyed being a generalist. A lot of different areas of medicine interested me, but I like the breadth of things you encounter as a generalist, so I could never picture myself being a subspecialist, doing the same things every day, seeing the same things. I knew I wanted to keep practicing general internal medicine, so I took a fellowship where I was working both inpatient and outpatient, and when I was looking for a job, I sought out things that involved some inpatient and some outpatient work. It turned out hospital medicine was the best fit.

What would you say is your favorite part of hospital medicine?

My favorite part of the job is getting to teach, working with medical students and residents. I also like the variety of what I do as a hospitalist, so I’m about 50% clinical and the rest of the time I perform a variety of tasks, both administrative and educational.

What about your least favorite part of hospitalist work?

Sometimes, particularly if you’re doing clinical, educational, and administrative work, it can be a little overwhelming to try and do a little bit of everything. I think generally that’s a good thing, but sometimes it can feel like a little too much.

What is some of the best advice you have received regarding how to handle the stresses of hospital medicine?

Feel free to say no to things. When hospitalists are starting their careers, and particularly when they are new to a job and trying to express their desire to get involved, sometimes they can have too much thrown at them at once. People can get overloaded very quickly, so I think feeling like you’re able to say no to some requests, or to take some time to think before you accept an additional role. The other piece of advice I remember from my fellowship, is that, when you do something, make it count twice. For example, if you’re involved in a project, you get the practical clinical or educational benefits of whatever the project was. But also think about how you might write about your experience for research purposes, such as for a poster, article, or other presentation.

What is the worst advice you have been given?

I think it’s not necessarily bad advice, but I guess it’s advice that I haven’t really followed. Since I work in academic medicine, I’ve found that the people in academics fall into one of two categories: There are the people who find their niche and remain on that path, and they’re very clear about it and don’t really stray from it; and there are people who don’t find that niche right away. I think the advice I received when starting out was to try to find that niche, and if you’re building an academic career it is very helpful to have these things in which you have become the expert. But I’ve just tried to go where the job takes me. I don’t necessarily have a single academic niche or something that I spend all my time doing, but I do have my hand in a lot of different things. To me, that’s a lot more interesting because it adds to the variety of what you’re doing. Every day is a little different.

What else do you do professionally outside of hospital medicine?

I actually practice a little outpatient medicine. When I first started here, I wanted to keep some outpatient experience, and so I actually created my own clinic. It’s a procedure clinic where I do paracentesis on people who have cirrhosis. Then on the educational side, I sit on the admission committees for the medical school here, so I get to look through the applicants and choose who we interview, and then once we interview candidates, I help choose how we rank students for admission.

Where do you see yourself in the next 10 years?

I’ve never been one who looks at a particular job and says ‘Okay, I want to be the dean or have this position.’ I guess I just hope I’m better at the things I’m currently doing. I hope in 10 years that I’m a better teacher, that I’ll have learned more strategies to help more people, and that I have a better handle on the administrative side of the work. I hope I’ve progressed to a point in my career where I’m doing an even better job than I am now.

What are your goals as a member of the editorial board?

I have an interest not only in medicine but also in writing; I’ve gotten to do some writing both medical and nonmedical in the past. I’ve published a few articles in The Hospitalist, and hopefully, I can do more of that because writing is just another part of education.

Unlike some children who wanted be firefighters or astronauts when they grew up, ever since Raj Sehgal, MD, FHM, was a boy, he dreamed of being a doctor.

Since earning his medical degree, Dr. Sehgal has kept himself involved in a wide variety of projects, driven by the desire to diversify his expertise.

Currently a clinical associate professor of medicine in the division of general and hospital medicine at the South Texas Veterans Health Care System, San Antonio, and University of Texas Health San Antonio, Dr. Sehgal has found his place as an educator as well as a clinician, earning the Division of Hospital Medicine Teaching Award in 2016.

As a member of the The Hospitalist’s volunteer editorial advisory board, Dr. Sehgal enjoys helping to educate and inform fellow hospitalists. He spoke with The Hospitalist to tell us more about himself.
 

How did you get into medicine?

I don’t know how old I was when I decided I was going to be a doctor, but it was at a very young age and I never really wavered in that desire. I guess I also would have wanted to be a baseball player or a musician, but I never had the talents for those, so it was doctor. That’s always what I was thinking of doing, straight through high school and college, and then after college I took a year off and joined AmeriCorps. I spent a year there and then went to medical school in Dallas at UT Southwestern. After medical school, I thought I should go somewhere as different from Dallas as possible, so I went to Portland, Ore., for my residency and then a fellowship in general internal medicine.

How did you end up in hospital medicine?

When I was doing my residency, I always enjoyed being a generalist. A lot of different areas of medicine interested me, but I like the breadth of things you encounter as a generalist, so I could never picture myself being a subspecialist, doing the same things every day, seeing the same things. I knew I wanted to keep practicing general internal medicine, so I took a fellowship where I was working both inpatient and outpatient, and when I was looking for a job, I sought out things that involved some inpatient and some outpatient work. It turned out hospital medicine was the best fit.

What would you say is your favorite part of hospital medicine?

My favorite part of the job is getting to teach, working with medical students and residents. I also like the variety of what I do as a hospitalist, so I’m about 50% clinical and the rest of the time I perform a variety of tasks, both administrative and educational.

What about your least favorite part of hospitalist work?

Sometimes, particularly if you’re doing clinical, educational, and administrative work, it can be a little overwhelming to try and do a little bit of everything. I think generally that’s a good thing, but sometimes it can feel like a little too much.

What is some of the best advice you have received regarding how to handle the stresses of hospital medicine?

Feel free to say no to things. When hospitalists are starting their careers, and particularly when they are new to a job and trying to express their desire to get involved, sometimes they can have too much thrown at them at once. People can get overloaded very quickly, so I think feeling like you’re able to say no to some requests, or to take some time to think before you accept an additional role. The other piece of advice I remember from my fellowship, is that, when you do something, make it count twice. For example, if you’re involved in a project, you get the practical clinical or educational benefits of whatever the project was. But also think about how you might write about your experience for research purposes, such as for a poster, article, or other presentation.

What is the worst advice you have been given?

I think it’s not necessarily bad advice, but I guess it’s advice that I haven’t really followed. Since I work in academic medicine, I’ve found that the people in academics fall into one of two categories: There are the people who find their niche and remain on that path, and they’re very clear about it and don’t really stray from it; and there are people who don’t find that niche right away. I think the advice I received when starting out was to try to find that niche, and if you’re building an academic career it is very helpful to have these things in which you have become the expert. But I’ve just tried to go where the job takes me. I don’t necessarily have a single academic niche or something that I spend all my time doing, but I do have my hand in a lot of different things. To me, that’s a lot more interesting because it adds to the variety of what you’re doing. Every day is a little different.

What else do you do professionally outside of hospital medicine?

I actually practice a little outpatient medicine. When I first started here, I wanted to keep some outpatient experience, and so I actually created my own clinic. It’s a procedure clinic where I do paracentesis on people who have cirrhosis. Then on the educational side, I sit on the admission committees for the medical school here, so I get to look through the applicants and choose who we interview, and then once we interview candidates, I help choose how we rank students for admission.

Where do you see yourself in the next 10 years?

I’ve never been one who looks at a particular job and says ‘Okay, I want to be the dean or have this position.’ I guess I just hope I’m better at the things I’m currently doing. I hope in 10 years that I’m a better teacher, that I’ll have learned more strategies to help more people, and that I have a better handle on the administrative side of the work. I hope I’ve progressed to a point in my career where I’m doing an even better job than I am now.

What are your goals as a member of the editorial board?

I have an interest not only in medicine but also in writing; I’ve gotten to do some writing both medical and nonmedical in the past. I’ve published a few articles in The Hospitalist, and hopefully, I can do more of that because writing is just another part of education.

NEW ORLEANS – Neil M. Resnick, MD, has devoted more than 30 years of his career to refining the diagnosis and management of geriatric urinary incontinence. He has found it to be a deeply rewarding area of his medical practice. And he wants primary care physicians to share the joy.

Once you get the hang of it, you’re going to love it,” he promised at the annual meeting of the American College of Physicians.

“There is so much you have to offer, and it’s going to make you one happy, fulfilled, non–burned-out physician,” added Dr. Resnick, professor of medicine and chief of the division of geriatric medicine at the University of Pittsburgh.

He insisted that geriatric urinary incontinence belongs squarely in the province of primary care physicians, not just urologic surgeons. That’s because the condition is typically caused or exacerbated by medical diseases and drugs.

“These are things for which we are the experts, because they are conditions outside the bladder that our surgical colleagues aren’t always expert in,” the internist emphasized.

The seven reversible causes of geriatric urinary incontinence, which are categorized as transient urinary incontinence, can easily be remembered by busy primary care practitioners with the aid of a mnemonic of Dr. Resnick’s own devising: DIAPERS. It stands for Delirium, Infection, Atrophic urethritis/vaginitis, Pharmaceuticals, Excess urine output, Restricted mobility, and Stool impaction.

“Treatable causes of urinary incontinence are much more common in older people than in the young,” Dr. Resnick said. “If you just pay attention to these, and you can’t even spell ‘bladder,’ you can cure one-third of older patients. It’s pretty dramatic. And it improves the incontinence in all of the people in whom it’s still persistent, and that means improved responsiveness to further treatment addressing the urinary tract, improvement of other problems related to the incontinence, better quality of life, and it just makes patients better overall. This is really the joy and glory of geriatrics.”

He emphasized that urinary incontinence is never normal, no matter how advanced the patient’s age. The basic geriatric principle is that aging reduces resilience. Bladder sensation and contractility decrease with age. The prostate enlarges. Sphincter strength and urethral length decrease in older women. Involuntary bladder contractions occur in half of all elderly individuals. Nocturnal urine excretion increases. Postvoid urine volume creeps up to 50-100 mL. These are normal changes, but they predispose to tipping over into urinary incontinence in the setting of any additional challenges created by DIAPERS.

The scope of the problem

More than one-third of elderly individuals experience urinary incontinence with daily to weekly frequency. The associated morbidity includes cellulitis, perineal rashes, pressure ulcers, falls, fractures, anxiety, depression, and sexual dysfunction. The economic cost of geriatric urinary incontinence is believed to exceed that of coronary artery bypass surgery and renal dialysis combined.

“The morbidity is huge and the costs are astonishing,” the geriatrician declared.

Fewer than one-fifth and perhaps as few as one-tenth of affected patients actually require surgery.

Less than 20% of elderly patients with urinary incontinence volunteer that information to their primary care physician because of the stigma involved. So, it’s important to ask about it, he noted.
 

The lowdown on DIAPERS

• Delirium. “The last thing you want to do is refer a patient with urinary incontinence and delirium to a urologist for cystoscopy or urodynamic testing,” according to Dr. Resnick. “It misses the point: The problem is their brain is not working. If you address the causes of delirium, once the delirium subsides, the incontinence will abate.” However, addressing the cause of the acute confusional state can be challenging, he conceded, because delirium can result from virtually any drug or disease anywhere in the body.
• Infection. Acute urinary tract infection (UTI) is the cause of about only 3% of geriatric urinary incontinence. But when present, it’s simple enough to diagnosis and treat. Far more common is asymptomatic bacteriuria, which is present in about 20% of elderly men and 40% of elderly women but does not cause incontinence.
• “The key symptom is dysuria: If the patient [with bacteriuria] has new-onset urinary incontinence or worsened urinary incontinence that’s happened for only the last couple days, that’s an acute UTI that needs to be treated,” Dr. Resnick advised. “Other than that, don’t treat. All you’ll do is select for more virulent organisms, so when the patient does get an acute UTI, it’s tougher to treat.”
• Atrophic vaginitis/urethritis. A common condition when endogenous estrogen goes down. It is characterized by vaginal and urethral erosions and tissue friability. When an affected woman urinates, the acid urine gains exposure to the underlying subendothelial tissue, causing inflammation and irritation that prevent the urethra from closing properly. This condition, frequently mistaken for a UTI, responds well to low-dose topical estrogen in the form of either an easily implantable ring that lasts for 3 months or a topical estrogen cream applied once daily, after establishing the absence of breast or uterine cancer.
• “It takes weeks to months for this condition to remit,” he said. “So, if they’re doing cream, they do it every day for a month. Then every month, they pull back by one day. Eventually, they get to the point where they can be maintained with once- or twice-weekly application.”
• Pharmaceuticals. The list of potential offenders is lengthy. Dr. Resnick focused on six types of medications that are most often linked to increased risk of geriatric urinary incontinence. Those six include long-acting sedative hypnotics, including diazepam (Valium); loop diuretics; and anticholinergic agents, including sedating antihistamines, antipsychotics, tricyclic antidepressants, and tiotropium bromide (Spiriva).
• They also include adrenergic agents, with alpha-adrenergic blockers causing or contributing to urinary incontinence in women and alpha-adrenergic agonists – present in a vast number of OTC cold, sleep, and cough medications – being responsible for problems in men; drugs causing fluid accumulation, including the dihydropyridine calcium channel blockers, NSAIDs, some Parkinson’s agents, and gabapentin/pregabalin; and ACE inhibitors because of their side effect of cough.
• “The most common problem drugs in my practice are calcium channel blockers and gabapentin or pregabalin,” according to the geriatrician.
• Excess urine output. Older people have smaller bladders. Dr. Resnick loathes the popular advice to drink 8 glasses of water per day. Every time that so-called health tip appears in the mass media, he sees a flurry of patients with new-onset geriatric urinary incontinence. Other causes of excess urine output include alcohol, caffeine, metabolic disorders including hyperglycemia, and peripheral edema attributable to heart failure or venous insufficiency.
• Restricted mobility. This often results from overlooked correctable conditions that bedevil older people, including poorly fitting shoes, calluses, bunions, and deformed toenails, as well as readily treatable disorders including depression, orthostatic or postprandial hypotension, and arthritis pain.
• Stool impaction. “The clinical key is new onset of double incontinence associated with bladder distension. One gloved finger will disimpact and cure both,” Dr. Resnick said.
• In patients whose urinary incontinence persists after systematic attention to the DIAPERS details, there are only four possible mechanisms, according to Dr. Resnick: an overactive detrusor or stress incontinence, which can be categorized as storage problems, or an underactive detrusor or a urethral obstruction, which can be considered emptying problems.

Dr. Resnick reported having no financial conflicts of interest regarding his presentation.

[email protected]

NEW ORLEANS – Neil M. Resnick, MD, has devoted more than 30 years of his career to refining the diagnosis and management of geriatric urinary incontinence. He has found it to be a deeply rewarding area of his medical practice. And he wants primary care physicians to share the joy.

Once you get the hang of it, you’re going to love it,” he promised at the annual meeting of the American College of Physicians.

“There is so much you have to offer, and it’s going to make you one happy, fulfilled, non–burned-out physician,” added Dr. Resnick, professor of medicine and chief of the division of geriatric medicine at the University of Pittsburgh.

He insisted that geriatric urinary incontinence belongs squarely in the province of primary care physicians, not just urologic surgeons. That’s because the condition is typically caused or exacerbated by medical diseases and drugs.

“These are things for which we are the experts, because they are conditions outside the bladder that our surgical colleagues aren’t always expert in,” the internist emphasized.

The seven reversible causes of geriatric urinary incontinence, which are categorized as transient urinary incontinence, can easily be remembered by busy primary care practitioners with the aid of a mnemonic of Dr. Resnick’s own devising: DIAPERS. It stands for Delirium, Infection, Atrophic urethritis/vaginitis, Pharmaceuticals, Excess urine output, Restricted mobility, and Stool impaction.

“Treatable causes of urinary incontinence are much more common in older people than in the young,” Dr. Resnick said. “If you just pay attention to these, and you can’t even spell ‘bladder,’ you can cure one-third of older patients. It’s pretty dramatic. And it improves the incontinence in all of the people in whom it’s still persistent, and that means improved responsiveness to further treatment addressing the urinary tract, improvement of other problems related to the incontinence, better quality of life, and it just makes patients better overall. This is really the joy and glory of geriatrics.”

He emphasized that urinary incontinence is never normal, no matter how advanced the patient’s age. The basic geriatric principle is that aging reduces resilience. Bladder sensation and contractility decrease with age. The prostate enlarges. Sphincter strength and urethral length decrease in older women. Involuntary bladder contractions occur in half of all elderly individuals. Nocturnal urine excretion increases. Postvoid urine volume creeps up to 50-100 mL. These are normal changes, but they predispose to tipping over into urinary incontinence in the setting of any additional challenges created by DIAPERS.

The scope of the problem

More than one-third of elderly individuals experience urinary incontinence with daily to weekly frequency. The associated morbidity includes cellulitis, perineal rashes, pressure ulcers, falls, fractures, anxiety, depression, and sexual dysfunction. The economic cost of geriatric urinary incontinence is believed to exceed that of coronary artery bypass surgery and renal dialysis combined.

“The morbidity is huge and the costs are astonishing,” the geriatrician declared.

Fewer than one-fifth and perhaps as few as one-tenth of affected patients actually require surgery.

Less than 20% of elderly patients with urinary incontinence volunteer that information to their primary care physician because of the stigma involved. So, it’s important to ask about it, he noted.
 

The lowdown on DIAPERS

• Delirium. “The last thing you want to do is refer a patient with urinary incontinence and delirium to a urologist for cystoscopy or urodynamic testing,” according to Dr. Resnick. “It misses the point: The problem is their brain is not working. If you address the causes of delirium, once the delirium subsides, the incontinence will abate.” However, addressing the cause of the acute confusional state can be challenging, he conceded, because delirium can result from virtually any drug or disease anywhere in the body.
• Infection. Acute urinary tract infection (UTI) is the cause of about only 3% of geriatric urinary incontinence. But when present, it’s simple enough to diagnosis and treat. Far more common is asymptomatic bacteriuria, which is present in about 20% of elderly men and 40% of elderly women but does not cause incontinence.
• “The key symptom is dysuria: If the patient [with bacteriuria] has new-onset urinary incontinence or worsened urinary incontinence that’s happened for only the last couple days, that’s an acute UTI that needs to be treated,” Dr. Resnick advised. “Other than that, don’t treat. All you’ll do is select for more virulent organisms, so when the patient does get an acute UTI, it’s tougher to treat.”
• Atrophic vaginitis/urethritis. A common condition when endogenous estrogen goes down. It is characterized by vaginal and urethral erosions and tissue friability. When an affected woman urinates, the acid urine gains exposure to the underlying subendothelial tissue, causing inflammation and irritation that prevent the urethra from closing properly. This condition, frequently mistaken for a UTI, responds well to low-dose topical estrogen in the form of either an easily implantable ring that lasts for 3 months or a topical estrogen cream applied once daily, after establishing the absence of breast or uterine cancer.
• “It takes weeks to months for this condition to remit,” he said. “So, if they’re doing cream, they do it every day for a month. Then every month, they pull back by one day. Eventually, they get to the point where they can be maintained with once- or twice-weekly application.”
• Pharmaceuticals. The list of potential offenders is lengthy. Dr. Resnick focused on six types of medications that are most often linked to increased risk of geriatric urinary incontinence. Those six include long-acting sedative hypnotics, including diazepam (Valium); loop diuretics; and anticholinergic agents, including sedating antihistamines, antipsychotics, tricyclic antidepressants, and tiotropium bromide (Spiriva).
• They also include adrenergic agents, with alpha-adrenergic blockers causing or contributing to urinary incontinence in women and alpha-adrenergic agonists – present in a vast number of OTC cold, sleep, and cough medications – being responsible for problems in men; drugs causing fluid accumulation, including the dihydropyridine calcium channel blockers, NSAIDs, some Parkinson’s agents, and gabapentin/pregabalin; and ACE inhibitors because of their side effect of cough.
• “The most common problem drugs in my practice are calcium channel blockers and gabapentin or pregabalin,” according to the geriatrician.
• Excess urine output. Older people have smaller bladders. Dr. Resnick loathes the popular advice to drink 8 glasses of water per day. Every time that so-called health tip appears in the mass media, he sees a flurry of patients with new-onset geriatric urinary incontinence. Other causes of excess urine output include alcohol, caffeine, metabolic disorders including hyperglycemia, and peripheral edema attributable to heart failure or venous insufficiency.
• Restricted mobility. This often results from overlooked correctable conditions that bedevil older people, including poorly fitting shoes, calluses, bunions, and deformed toenails, as well as readily treatable disorders including depression, orthostatic or postprandial hypotension, and arthritis pain.
• Stool impaction. “The clinical key is new onset of double incontinence associated with bladder distension. One gloved finger will disimpact and cure both,” Dr. Resnick said.
• In patients whose urinary incontinence persists after systematic attention to the DIAPERS details, there are only four possible mechanisms, according to Dr. Resnick: an overactive detrusor or stress incontinence, which can be categorized as storage problems, or an underactive detrusor or a urethral obstruction, which can be considered emptying problems.

Dr. Resnick reported having no financial conflicts of interest regarding his presentation.

[email protected]

NEW ORLEANS – Neil M. Resnick, MD, has devoted more than 30 years of his career to refining the diagnosis and management of geriatric urinary incontinence. He has found it to be a deeply rewarding area of his medical practice. And he wants primary care physicians to share the joy.

Once you get the hang of it, you’re going to love it,” he promised at the annual meeting of the American College of Physicians.

“There is so much you have to offer, and it’s going to make you one happy, fulfilled, non–burned-out physician,” added Dr. Resnick, professor of medicine and chief of the division of geriatric medicine at the University of Pittsburgh.

He insisted that geriatric urinary incontinence belongs squarely in the province of primary care physicians, not just urologic surgeons. That’s because the condition is typically caused or exacerbated by medical diseases and drugs.

“These are things for which we are the experts, because they are conditions outside the bladder that our surgical colleagues aren’t always expert in,” the internist emphasized.

The seven reversible causes of geriatric urinary incontinence, which are categorized as transient urinary incontinence, can easily be remembered by busy primary care practitioners with the aid of a mnemonic of Dr. Resnick’s own devising: DIAPERS. It stands for Delirium, Infection, Atrophic urethritis/vaginitis, Pharmaceuticals, Excess urine output, Restricted mobility, and Stool impaction.

“Treatable causes of urinary incontinence are much more common in older people than in the young,” Dr. Resnick said. “If you just pay attention to these, and you can’t even spell ‘bladder,’ you can cure one-third of older patients. It’s pretty dramatic. And it improves the incontinence in all of the people in whom it’s still persistent, and that means improved responsiveness to further treatment addressing the urinary tract, improvement of other problems related to the incontinence, better quality of life, and it just makes patients better overall. This is really the joy and glory of geriatrics.”

He emphasized that urinary incontinence is never normal, no matter how advanced the patient’s age. The basic geriatric principle is that aging reduces resilience. Bladder sensation and contractility decrease with age. The prostate enlarges. Sphincter strength and urethral length decrease in older women. Involuntary bladder contractions occur in half of all elderly individuals. Nocturnal urine excretion increases. Postvoid urine volume creeps up to 50-100 mL. These are normal changes, but they predispose to tipping over into urinary incontinence in the setting of any additional challenges created by DIAPERS.

The scope of the problem

More than one-third of elderly individuals experience urinary incontinence with daily to weekly frequency. The associated morbidity includes cellulitis, perineal rashes, pressure ulcers, falls, fractures, anxiety, depression, and sexual dysfunction. The economic cost of geriatric urinary incontinence is believed to exceed that of coronary artery bypass surgery and renal dialysis combined.

“The morbidity is huge and the costs are astonishing,” the geriatrician declared.

Fewer than one-fifth and perhaps as few as one-tenth of affected patients actually require surgery.

Less than 20% of elderly patients with urinary incontinence volunteer that information to their primary care physician because of the stigma involved. So, it’s important to ask about it, he noted.
 

The lowdown on DIAPERS

• Delirium. “The last thing you want to do is refer a patient with urinary incontinence and delirium to a urologist for cystoscopy or urodynamic testing,” according to Dr. Resnick. “It misses the point: The problem is their brain is not working. If you address the causes of delirium, once the delirium subsides, the incontinence will abate.” However, addressing the cause of the acute confusional state can be challenging, he conceded, because delirium can result from virtually any drug or disease anywhere in the body.
• Infection. Acute urinary tract infection (UTI) is the cause of about only 3% of geriatric urinary incontinence. But when present, it’s simple enough to diagnosis and treat. Far more common is asymptomatic bacteriuria, which is present in about 20% of elderly men and 40% of elderly women but does not cause incontinence.
• “The key symptom is dysuria: If the patient [with bacteriuria] has new-onset urinary incontinence or worsened urinary incontinence that’s happened for only the last couple days, that’s an acute UTI that needs to be treated,” Dr. Resnick advised. “Other than that, don’t treat. All you’ll do is select for more virulent organisms, so when the patient does get an acute UTI, it’s tougher to treat.”
• Atrophic vaginitis/urethritis. A common condition when endogenous estrogen goes down. It is characterized by vaginal and urethral erosions and tissue friability. When an affected woman urinates, the acid urine gains exposure to the underlying subendothelial tissue, causing inflammation and irritation that prevent the urethra from closing properly. This condition, frequently mistaken for a UTI, responds well to low-dose topical estrogen in the form of either an easily implantable ring that lasts for 3 months or a topical estrogen cream applied once daily, after establishing the absence of breast or uterine cancer.
• “It takes weeks to months for this condition to remit,” he said. “So, if they’re doing cream, they do it every day for a month. Then every month, they pull back by one day. Eventually, they get to the point where they can be maintained with once- or twice-weekly application.”
• Pharmaceuticals. The list of potential offenders is lengthy. Dr. Resnick focused on six types of medications that are most often linked to increased risk of geriatric urinary incontinence. Those six include long-acting sedative hypnotics, including diazepam (Valium); loop diuretics; and anticholinergic agents, including sedating antihistamines, antipsychotics, tricyclic antidepressants, and tiotropium bromide (Spiriva).
• They also include adrenergic agents, with alpha-adrenergic blockers causing or contributing to urinary incontinence in women and alpha-adrenergic agonists – present in a vast number of OTC cold, sleep, and cough medications – being responsible for problems in men; drugs causing fluid accumulation, including the dihydropyridine calcium channel blockers, NSAIDs, some Parkinson’s agents, and gabapentin/pregabalin; and ACE inhibitors because of their side effect of cough.
• “The most common problem drugs in my practice are calcium channel blockers and gabapentin or pregabalin,” according to the geriatrician.
• Excess urine output. Older people have smaller bladders. Dr. Resnick loathes the popular advice to drink 8 glasses of water per day. Every time that so-called health tip appears in the mass media, he sees a flurry of patients with new-onset geriatric urinary incontinence. Other causes of excess urine output include alcohol, caffeine, metabolic disorders including hyperglycemia, and peripheral edema attributable to heart failure or venous insufficiency.
• Restricted mobility. This often results from overlooked correctable conditions that bedevil older people, including poorly fitting shoes, calluses, bunions, and deformed toenails, as well as readily treatable disorders including depression, orthostatic or postprandial hypotension, and arthritis pain.
• Stool impaction. “The clinical key is new onset of double incontinence associated with bladder distension. One gloved finger will disimpact and cure both,” Dr. Resnick said.
• In patients whose urinary incontinence persists after systematic attention to the DIAPERS details, there are only four possible mechanisms, according to Dr. Resnick: an overactive detrusor or stress incontinence, which can be categorized as storage problems, or an underactive detrusor or a urethral obstruction, which can be considered emptying problems.

Dr. Resnick reported having no financial conflicts of interest regarding his presentation.

[email protected]

The Food and Drug Administration has granted priority review to elotuzumab (Empliciti) for treatment of patients with relapsed/refractory multiple myeloma.

Bristol-Myers Squibb is seeking approval for elotuzumab in combination with pomalidomide and low-dose dexamethasone to treat patients with relapsed/refractory multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.

Elotuzumab is already approved for use in combination with lenalidomide and dexamethasone to treat multiple myeloma patients who have received between one and three prior therapies.

The elotuzumab application is supported by data from ELOQUENT-3, a randomized, phase 2 study that evaluated the addition of elotuzumab to pomalidomide and low-dose dexamethasone in patients with relapsed/refractory multiple myeloma.

Researchers presented findings from this study at the annual congress of the European Hematology Association in June 2018.

The overall response rate was 53% in the elotuzumab, pomalidomide, and low-dose dexamethasone (EPd) arm and 26% in the pomalidomide and low-dose dexamethasone (Pd) arm. The median progression-free survival was 10.3 months in the EPd arm and 4.7 months in the Pd arm (hazard ratio, 0.54; P = .0078), the researchers reported.

The researchers also reported that adverse events in the EPd arm were consistent with expectations based on previous results with elotuzumab and pomalidomide regimens.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions. The priority review typically shortens the time to an approval decision by a few months. The agency is expected to make a decision on elotuzumab by Dec. 27, 2018.

Bristol-Myers Squibb and AbbVie are codeveloping elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.

The Food and Drug Administration has granted priority review to elotuzumab (Empliciti) for treatment of patients with relapsed/refractory multiple myeloma.

Bristol-Myers Squibb is seeking approval for elotuzumab in combination with pomalidomide and low-dose dexamethasone to treat patients with relapsed/refractory multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.

Elotuzumab is already approved for use in combination with lenalidomide and dexamethasone to treat multiple myeloma patients who have received between one and three prior therapies.

The elotuzumab application is supported by data from ELOQUENT-3, a randomized, phase 2 study that evaluated the addition of elotuzumab to pomalidomide and low-dose dexamethasone in patients with relapsed/refractory multiple myeloma.

Researchers presented findings from this study at the annual congress of the European Hematology Association in June 2018.

The overall response rate was 53% in the elotuzumab, pomalidomide, and low-dose dexamethasone (EPd) arm and 26% in the pomalidomide and low-dose dexamethasone (Pd) arm. The median progression-free survival was 10.3 months in the EPd arm and 4.7 months in the Pd arm (hazard ratio, 0.54; P = .0078), the researchers reported.

The researchers also reported that adverse events in the EPd arm were consistent with expectations based on previous results with elotuzumab and pomalidomide regimens.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions. The priority review typically shortens the time to an approval decision by a few months. The agency is expected to make a decision on elotuzumab by Dec. 27, 2018.

Bristol-Myers Squibb and AbbVie are codeveloping elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.

The Food and Drug Administration has granted priority review to elotuzumab (Empliciti) for treatment of patients with relapsed/refractory multiple myeloma.

Bristol-Myers Squibb is seeking approval for elotuzumab in combination with pomalidomide and low-dose dexamethasone to treat patients with relapsed/refractory multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.

Elotuzumab is already approved for use in combination with lenalidomide and dexamethasone to treat multiple myeloma patients who have received between one and three prior therapies.

The elotuzumab application is supported by data from ELOQUENT-3, a randomized, phase 2 study that evaluated the addition of elotuzumab to pomalidomide and low-dose dexamethasone in patients with relapsed/refractory multiple myeloma.

Researchers presented findings from this study at the annual congress of the European Hematology Association in June 2018.

The overall response rate was 53% in the elotuzumab, pomalidomide, and low-dose dexamethasone (EPd) arm and 26% in the pomalidomide and low-dose dexamethasone (Pd) arm. The median progression-free survival was 10.3 months in the EPd arm and 4.7 months in the Pd arm (hazard ratio, 0.54; P = .0078), the researchers reported.

The researchers also reported that adverse events in the EPd arm were consistent with expectations based on previous results with elotuzumab and pomalidomide regimens.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions. The priority review typically shortens the time to an approval decision by a few months. The agency is expected to make a decision on elotuzumab by Dec. 27, 2018.

Bristol-Myers Squibb and AbbVie are codeveloping elotuzumab, with Bristol-Myers Squibb solely responsible for commercial activities.

Among scenarios where immune checkpoint inhibitors (ICIs) might be combined, particular caution is needed in the setting of brain metastases, according to authors of a recent clinical review.

While evidence to date is mixed, some studies do suggest that adding ICIs to high-dose stereotactic intracranial radiotherapy for brain metastases might increase the risk of treatment-related brain necrosis, the authors said.

By contrast, the balance of evidence suggests ICIs can be safely combined with palliative radiotherapy without site-specific increases in adverse events, they added.

Likewise, in patients with non–small-cell lung cancer, ICIs do not appear to increase incidence of grade 3 or greater pneumonitis when given after definitive chemoradiotherapy, in both retrospective and prospective investigations.

Nevertheless, the addition of ICIs to radiotherapy requires careful further study because of the potential for increased type or severity of toxicities, including the immune-related adverse events associated with ICIs, wrote corresponding author Jay S. Loeffler, MD, of Massachusetts General Hospital, Boston, and his colleagues.

“Caution is warranted when combining radiotherapy and ICI, especially with intracranial radiotherapy,” the researchers wrote. Their report is in Nature Reviews Clinical Oncology.

Some studies have indicated a higher rate of treatment-associated brain necrosis when ICIs are combined with intracranial radiotherapy, while others have shown no such trend, the authors said.

In one single-institution experience involving 180 patients with brain metastases undergoing stereotactic radiotherapy, incidence of treatment-associated brain necrosis was significantly higher in patients receiving an ICI, with an odds ratio of 2.4 (95% confidence interval, 1.06-5.44; P = .03).

Similarly, a retrospective single institution 480-patient study showed an incidence of treatment-associated brain necrosis of 20% for ICIs plus stereotactic radiotherapy versus 7% for radiotherapy alone (P less than .001), but substantial differences in baseline characteristics between groups limited the strength of the study’s conclusions, according to the researchers.

Increased risk is primarily in the form of asymptomatic or minimally symptomatic episodes in some series, the authors noted. A retrospective, 54-patient report showed a rate of treatment-associated brain necrosis of 30% when ICIs were combined with stereotactic radiotherapy, versus 21% for radiotherapy alone (P = .08), but the incidence of symptomatic cases was 15% in both groups, they noted.

“Intriguingly, the findings of several studies have demonstrated an association between [treatment-associated brain necrosis] and improved survival outcomes in patients with melanoma brain metastases that is similar to the independent observations of an analogous relationship between risk of [immune-related adverse events] in general and responsiveness to ICI,” the researchers wrote.

Most of the Food and Drug Administration–approved indications for ICIs are in the metastatic setting, where palliative radiotherapy is frequently important, the authors noted.

In two retrospective studies of patients with metastatic cancers receiving palliative radiotherapy with ICIs, there was a lack of clear association between the irradiated site and specific immune-related adverse events; that lack of association suggests that any toxicities arising from interactions between palliative radiotherapy and ICIs are mainly systemic, rather than local, the authors wrote.

Several retrospective series in advanced-stage melanoma patients have suggested that palliative radiotherapy plus ICIs is safe and does not significantly increase incidence of immune-related adverse events. However, findings from one series showed a correlation between both the ICI and radiotherapy dose given and the incidence of immune-related adverse events.

Prospective studies will be essential to optimize the balance between disease control and risk of morbidity associated with ICIs and radiotherapy combinations, the authors concluded.

The researchers declared no competing interests related to their review article.

SOURCE: Hwang WL, et al. Nat Rev Clin Oncol. 2018 Aug;15(8):477-494.

Among scenarios where immune checkpoint inhibitors (ICIs) might be combined, particular caution is needed in the setting of brain metastases, according to authors of a recent clinical review.

While evidence to date is mixed, some studies do suggest that adding ICIs to high-dose stereotactic intracranial radiotherapy for brain metastases might increase the risk of treatment-related brain necrosis, the authors said.

By contrast, the balance of evidence suggests ICIs can be safely combined with palliative radiotherapy without site-specific increases in adverse events, they added.

Likewise, in patients with non–small-cell lung cancer, ICIs do not appear to increase incidence of grade 3 or greater pneumonitis when given after definitive chemoradiotherapy, in both retrospective and prospective investigations.

Nevertheless, the addition of ICIs to radiotherapy requires careful further study because of the potential for increased type or severity of toxicities, including the immune-related adverse events associated with ICIs, wrote corresponding author Jay S. Loeffler, MD, of Massachusetts General Hospital, Boston, and his colleagues.

“Caution is warranted when combining radiotherapy and ICI, especially with intracranial radiotherapy,” the researchers wrote. Their report is in Nature Reviews Clinical Oncology.

Some studies have indicated a higher rate of treatment-associated brain necrosis when ICIs are combined with intracranial radiotherapy, while others have shown no such trend, the authors said.

In one single-institution experience involving 180 patients with brain metastases undergoing stereotactic radiotherapy, incidence of treatment-associated brain necrosis was significantly higher in patients receiving an ICI, with an odds ratio of 2.4 (95% confidence interval, 1.06-5.44; P = .03).

Similarly, a retrospective single institution 480-patient study showed an incidence of treatment-associated brain necrosis of 20% for ICIs plus stereotactic radiotherapy versus 7% for radiotherapy alone (P less than .001), but substantial differences in baseline characteristics between groups limited the strength of the study’s conclusions, according to the researchers.

Increased risk is primarily in the form of asymptomatic or minimally symptomatic episodes in some series, the authors noted. A retrospective, 54-patient report showed a rate of treatment-associated brain necrosis of 30% when ICIs were combined with stereotactic radiotherapy, versus 21% for radiotherapy alone (P = .08), but the incidence of symptomatic cases was 15% in both groups, they noted.

“Intriguingly, the findings of several studies have demonstrated an association between [treatment-associated brain necrosis] and improved survival outcomes in patients with melanoma brain metastases that is similar to the independent observations of an analogous relationship between risk of [immune-related adverse events] in general and responsiveness to ICI,” the researchers wrote.

Most of the Food and Drug Administration–approved indications for ICIs are in the metastatic setting, where palliative radiotherapy is frequently important, the authors noted.

In two retrospective studies of patients with metastatic cancers receiving palliative radiotherapy with ICIs, there was a lack of clear association between the irradiated site and specific immune-related adverse events; that lack of association suggests that any toxicities arising from interactions between palliative radiotherapy and ICIs are mainly systemic, rather than local, the authors wrote.

Several retrospective series in advanced-stage melanoma patients have suggested that palliative radiotherapy plus ICIs is safe and does not significantly increase incidence of immune-related adverse events. However, findings from one series showed a correlation between both the ICI and radiotherapy dose given and the incidence of immune-related adverse events.

Prospective studies will be essential to optimize the balance between disease control and risk of morbidity associated with ICIs and radiotherapy combinations, the authors concluded.

The researchers declared no competing interests related to their review article.

SOURCE: Hwang WL, et al. Nat Rev Clin Oncol. 2018 Aug;15(8):477-494.

Among scenarios where immune checkpoint inhibitors (ICIs) might be combined, particular caution is needed in the setting of brain metastases, according to authors of a recent clinical review.

While evidence to date is mixed, some studies do suggest that adding ICIs to high-dose stereotactic intracranial radiotherapy for brain metastases might increase the risk of treatment-related brain necrosis, the authors said.

By contrast, the balance of evidence suggests ICIs can be safely combined with palliative radiotherapy without site-specific increases in adverse events, they added.

Likewise, in patients with non–small-cell lung cancer, ICIs do not appear to increase incidence of grade 3 or greater pneumonitis when given after definitive chemoradiotherapy, in both retrospective and prospective investigations.

Nevertheless, the addition of ICIs to radiotherapy requires careful further study because of the potential for increased type or severity of toxicities, including the immune-related adverse events associated with ICIs, wrote corresponding author Jay S. Loeffler, MD, of Massachusetts General Hospital, Boston, and his colleagues.

“Caution is warranted when combining radiotherapy and ICI, especially with intracranial radiotherapy,” the researchers wrote. Their report is in Nature Reviews Clinical Oncology.

Some studies have indicated a higher rate of treatment-associated brain necrosis when ICIs are combined with intracranial radiotherapy, while others have shown no such trend, the authors said.

In one single-institution experience involving 180 patients with brain metastases undergoing stereotactic radiotherapy, incidence of treatment-associated brain necrosis was significantly higher in patients receiving an ICI, with an odds ratio of 2.4 (95% confidence interval, 1.06-5.44; P = .03).

Similarly, a retrospective single institution 480-patient study showed an incidence of treatment-associated brain necrosis of 20% for ICIs plus stereotactic radiotherapy versus 7% for radiotherapy alone (P less than .001), but substantial differences in baseline characteristics between groups limited the strength of the study’s conclusions, according to the researchers.

Increased risk is primarily in the form of asymptomatic or minimally symptomatic episodes in some series, the authors noted. A retrospective, 54-patient report showed a rate of treatment-associated brain necrosis of 30% when ICIs were combined with stereotactic radiotherapy, versus 21% for radiotherapy alone (P = .08), but the incidence of symptomatic cases was 15% in both groups, they noted.

“Intriguingly, the findings of several studies have demonstrated an association between [treatment-associated brain necrosis] and improved survival outcomes in patients with melanoma brain metastases that is similar to the independent observations of an analogous relationship between risk of [immune-related adverse events] in general and responsiveness to ICI,” the researchers wrote.

Most of the Food and Drug Administration–approved indications for ICIs are in the metastatic setting, where palliative radiotherapy is frequently important, the authors noted.

In two retrospective studies of patients with metastatic cancers receiving palliative radiotherapy with ICIs, there was a lack of clear association between the irradiated site and specific immune-related adverse events; that lack of association suggests that any toxicities arising from interactions between palliative radiotherapy and ICIs are mainly systemic, rather than local, the authors wrote.

Several retrospective series in advanced-stage melanoma patients have suggested that palliative radiotherapy plus ICIs is safe and does not significantly increase incidence of immune-related adverse events. However, findings from one series showed a correlation between both the ICI and radiotherapy dose given and the incidence of immune-related adverse events.

Prospective studies will be essential to optimize the balance between disease control and risk of morbidity associated with ICIs and radiotherapy combinations, the authors concluded.

The researchers declared no competing interests related to their review article.

SOURCE: Hwang WL, et al. Nat Rev Clin Oncol. 2018 Aug;15(8):477-494.

CORONADO, CALIF. – Atraumatic embryo transfer is essential to success of in vitro fertilization (IVF), and ultrasound guidance maximizes the chance for this to occur, according to William Schoolcraft, MD, HCLD.

At a meeting on IVF and embryo transfer sponsored by the University of California, San Diego, Dr. Schoolcraft said that ultrasound-guided embryo transfer helps clinicians avoid difficult transfers, minimizes contamination with blood, facilitates proper placement of the catheter tip, and minimizes the stimulation of uterine contractions. “We know that contaminating the catheter either with blood or mucous or endometrial tissue lowers clinical pregnancy rates, compared to a clean catheter,” said Dr. Schoolcraft, founder and medical director of the Colorado Center for Reproductive Medicine, Denver.

“Ultrasound guidance can help you follow the contour of the cervix and avoid touching the fundus. Your catheter should be free of blood, mucous, or endometrial cells when the embryologist examines it,” he said. In his clinical opinion, it’s hard to argue against using ultrasound guidance for embryo transfer. “It’s also very popular with IVF patients, because they get to visualize the transfer and have some reassurance that the embryo is delivered to their uterus,” he said.

The potential benefit of using three-dimensional ultrasound for embryo transfer is less clear. “It does require more expensive equipment and it’s a little more skill dependent, but in a randomized trial it didn’t lead to any difference in outcomes,” Dr. Schoolcraft said. “I think if you’re good with two-dimensional ultrasound, three-dimensional ultrasound doesn’t seem to have much benefit in terms of pregnancy outcomes.”

In a study published in 2017, researchers from Barcelona analyzed 7,714 embryo transfers to determine the impact of maneuvers during embryo transfers on the pregnancy rate (Fertil Steril. 2017 Mar;107[3]:657-63.e1). Using the direct embryo transfer as a reference, each instrumentation needed to successfully deposit the embryos in the fundus served as an index of the difficulty of transfer. A difficult transfer occurred in 7.7% of cycles, and the researchers found that the clinical pregnancy rate decreased progressively with the use of additional maneuvers during embryo transfer. Specifically, the clinical pregnancy rate was 39.4% when no additional maneuvers were required, 36.9% when an outer catheter sheath was used (odds ratio, 0.89), 31.7% when a Wallace stylet was used (OR, 0.71), and 26.1% when a tenaculum was used (OR, 0.54). “I think without question, avoiding a difficult transfer is important and certainly a key to our success,” said Dr. Schoolcraft, who was not involved with the study.

The ideal depth of embryo transfer is “a bit complicated,” he said, but according to the best available evidence, a depth of 15-20 mm from the fundus by ultrasound guidance appears to optimize implantation by avoiding the lower cavity where implantation is compromised. This range of depth also avoids problems with upper cavity transfers, including trauma, contractions, and tubal pregnancy. “I think that transfers which are close to the fundus, and possibly in some cases touching the fundus, may lead to uterine contractions, plugging the catheter with endometrium and generating bleeding,” Dr. Schoolcraft said. He pointed out that during natural pregnancies, embryos implant in the upper fundus nearly 90% of the time, compared with 66% of the time during IVF pregnancies. “To mimic Mother Nature we don’t want to be too low, either,” he said. “We all know that placenta previa is increased with IVF. This may be due to placing the embryos too low.”

According to Dr. Schoolcraft, many published studies have found that significantly higher pregnancy rates occur with routine bladder distension prior to embryo transfer, probably because of the smooth and easy insertion of the embryo transfer. A Scandinavian meta-analysis found that the odds ratio favoring ultrasound guidance and a full bladder for ongoing pregnancy was 1.44 and clinical pregnancy was 1.55, which is similar to that seen during an earlier review from The Cochrane Collaborative, with an OR of 1.47 for ongoing pregnancy and OR 1.53 for live birth (Cochrane Database Syst Rev. 2016 Mar 17. doi: 10.1002/14651858.CD006107.pub4).

Dr. Schoolcraft reported having no financial disclosures.

[email protected]

CORONADO, CALIF. – Atraumatic embryo transfer is essential to success of in vitro fertilization (IVF), and ultrasound guidance maximizes the chance for this to occur, according to William Schoolcraft, MD, HCLD.

At a meeting on IVF and embryo transfer sponsored by the University of California, San Diego, Dr. Schoolcraft said that ultrasound-guided embryo transfer helps clinicians avoid difficult transfers, minimizes contamination with blood, facilitates proper placement of the catheter tip, and minimizes the stimulation of uterine contractions. “We know that contaminating the catheter either with blood or mucous or endometrial tissue lowers clinical pregnancy rates, compared to a clean catheter,” said Dr. Schoolcraft, founder and medical director of the Colorado Center for Reproductive Medicine, Denver.

“Ultrasound guidance can help you follow the contour of the cervix and avoid touching the fundus. Your catheter should be free of blood, mucous, or endometrial cells when the embryologist examines it,” he said. In his clinical opinion, it’s hard to argue against using ultrasound guidance for embryo transfer. “It’s also very popular with IVF patients, because they get to visualize the transfer and have some reassurance that the embryo is delivered to their uterus,” he said.

The potential benefit of using three-dimensional ultrasound for embryo transfer is less clear. “It does require more expensive equipment and it’s a little more skill dependent, but in a randomized trial it didn’t lead to any difference in outcomes,” Dr. Schoolcraft said. “I think if you’re good with two-dimensional ultrasound, three-dimensional ultrasound doesn’t seem to have much benefit in terms of pregnancy outcomes.”

In a study published in 2017, researchers from Barcelona analyzed 7,714 embryo transfers to determine the impact of maneuvers during embryo transfers on the pregnancy rate (Fertil Steril. 2017 Mar;107[3]:657-63.e1). Using the direct embryo transfer as a reference, each instrumentation needed to successfully deposit the embryos in the fundus served as an index of the difficulty of transfer. A difficult transfer occurred in 7.7% of cycles, and the researchers found that the clinical pregnancy rate decreased progressively with the use of additional maneuvers during embryo transfer. Specifically, the clinical pregnancy rate was 39.4% when no additional maneuvers were required, 36.9% when an outer catheter sheath was used (odds ratio, 0.89), 31.7% when a Wallace stylet was used (OR, 0.71), and 26.1% when a tenaculum was used (OR, 0.54). “I think without question, avoiding a difficult transfer is important and certainly a key to our success,” said Dr. Schoolcraft, who was not involved with the study.

The ideal depth of embryo transfer is “a bit complicated,” he said, but according to the best available evidence, a depth of 15-20 mm from the fundus by ultrasound guidance appears to optimize implantation by avoiding the lower cavity where implantation is compromised. This range of depth also avoids problems with upper cavity transfers, including trauma, contractions, and tubal pregnancy. “I think that transfers which are close to the fundus, and possibly in some cases touching the fundus, may lead to uterine contractions, plugging the catheter with endometrium and generating bleeding,” Dr. Schoolcraft said. He pointed out that during natural pregnancies, embryos implant in the upper fundus nearly 90% of the time, compared with 66% of the time during IVF pregnancies. “To mimic Mother Nature we don’t want to be too low, either,” he said. “We all know that placenta previa is increased with IVF. This may be due to placing the embryos too low.”

According to Dr. Schoolcraft, many published studies have found that significantly higher pregnancy rates occur with routine bladder distension prior to embryo transfer, probably because of the smooth and easy insertion of the embryo transfer. A Scandinavian meta-analysis found that the odds ratio favoring ultrasound guidance and a full bladder for ongoing pregnancy was 1.44 and clinical pregnancy was 1.55, which is similar to that seen during an earlier review from The Cochrane Collaborative, with an OR of 1.47 for ongoing pregnancy and OR 1.53 for live birth (Cochrane Database Syst Rev. 2016 Mar 17. doi: 10.1002/14651858.CD006107.pub4).

Dr. Schoolcraft reported having no financial disclosures.

[email protected]

CORONADO, CALIF. – Atraumatic embryo transfer is essential to success of in vitro fertilization (IVF), and ultrasound guidance maximizes the chance for this to occur, according to William Schoolcraft, MD, HCLD.

At a meeting on IVF and embryo transfer sponsored by the University of California, San Diego, Dr. Schoolcraft said that ultrasound-guided embryo transfer helps clinicians avoid difficult transfers, minimizes contamination with blood, facilitates proper placement of the catheter tip, and minimizes the stimulation of uterine contractions. “We know that contaminating the catheter either with blood or mucous or endometrial tissue lowers clinical pregnancy rates, compared to a clean catheter,” said Dr. Schoolcraft, founder and medical director of the Colorado Center for Reproductive Medicine, Denver.

“Ultrasound guidance can help you follow the contour of the cervix and avoid touching the fundus. Your catheter should be free of blood, mucous, or endometrial cells when the embryologist examines it,” he said. In his clinical opinion, it’s hard to argue against using ultrasound guidance for embryo transfer. “It’s also very popular with IVF patients, because they get to visualize the transfer and have some reassurance that the embryo is delivered to their uterus,” he said.

The potential benefit of using three-dimensional ultrasound for embryo transfer is less clear. “It does require more expensive equipment and it’s a little more skill dependent, but in a randomized trial it didn’t lead to any difference in outcomes,” Dr. Schoolcraft said. “I think if you’re good with two-dimensional ultrasound, three-dimensional ultrasound doesn’t seem to have much benefit in terms of pregnancy outcomes.”

In a study published in 2017, researchers from Barcelona analyzed 7,714 embryo transfers to determine the impact of maneuvers during embryo transfers on the pregnancy rate (Fertil Steril. 2017 Mar;107[3]:657-63.e1). Using the direct embryo transfer as a reference, each instrumentation needed to successfully deposit the embryos in the fundus served as an index of the difficulty of transfer. A difficult transfer occurred in 7.7% of cycles, and the researchers found that the clinical pregnancy rate decreased progressively with the use of additional maneuvers during embryo transfer. Specifically, the clinical pregnancy rate was 39.4% when no additional maneuvers were required, 36.9% when an outer catheter sheath was used (odds ratio, 0.89), 31.7% when a Wallace stylet was used (OR, 0.71), and 26.1% when a tenaculum was used (OR, 0.54). “I think without question, avoiding a difficult transfer is important and certainly a key to our success,” said Dr. Schoolcraft, who was not involved with the study.

The ideal depth of embryo transfer is “a bit complicated,” he said, but according to the best available evidence, a depth of 15-20 mm from the fundus by ultrasound guidance appears to optimize implantation by avoiding the lower cavity where implantation is compromised. This range of depth also avoids problems with upper cavity transfers, including trauma, contractions, and tubal pregnancy. “I think that transfers which are close to the fundus, and possibly in some cases touching the fundus, may lead to uterine contractions, plugging the catheter with endometrium and generating bleeding,” Dr. Schoolcraft said. He pointed out that during natural pregnancies, embryos implant in the upper fundus nearly 90% of the time, compared with 66% of the time during IVF pregnancies. “To mimic Mother Nature we don’t want to be too low, either,” he said. “We all know that placenta previa is increased with IVF. This may be due to placing the embryos too low.”

According to Dr. Schoolcraft, many published studies have found that significantly higher pregnancy rates occur with routine bladder distension prior to embryo transfer, probably because of the smooth and easy insertion of the embryo transfer. A Scandinavian meta-analysis found that the odds ratio favoring ultrasound guidance and a full bladder for ongoing pregnancy was 1.44 and clinical pregnancy was 1.55, which is similar to that seen during an earlier review from The Cochrane Collaborative, with an OR of 1.47 for ongoing pregnancy and OR 1.53 for live birth (Cochrane Database Syst Rev. 2016 Mar 17. doi: 10.1002/14651858.CD006107.pub4).

Dr. Schoolcraft reported having no financial disclosures.

[email protected]

The latest seasonal influenza vaccine recommendations from the Advisory Committee on Immunization Practices provide several key updates that will impact clinical practice in the 2018-2019 influenza season.

CAP53/iStockphoto.com

Of note, live attenuated influenza vaccine (LAIV; FluMist Quadrivalent) is an option, following two seasons in which the committee recommended it not be used.

ACIP also updated its recommendations for individuals with a history of egg allergy, described the vaccine strains chosen for 2018-2019 season, and detailed the changes in age indications for Afluria Quadrivalent and Fluarix Quadrivalent that have been made since publication of its previous guidelines.

Published in MMWR Recommendations and Reports, the updated ACIP recommendations reflect discussions and decisions from the three public meetings of ACIP that have taken place since the last annual update.

All individuals 6 months of age and older who have no contraindications to influenza vaccine should receive routine annual influenza vaccine, ACIP also said in its report, reinforcing a key recommendation that has been in place since 2010.

“To avoid missed opportunities for vaccination, providers should offer vaccination during routine health care visits and hospitalizations,” wrote authors of the report, including lead author Lisa A. Grohskopf, MD, of the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta.

Dr. Grohskopf and coauthors made no specific recommendations on which vaccine to use. They said providers should choose licensed, age-appropriate recommended vaccines expected to be available for the 2018-2019 season, including inactivated influenza vaccines (IIV), a recombinant influenza vaccine (RIV4), and the LAIV option.

FluMist Quadrivalent, the one LAIV product expected to be available for the 2018-2019 season, is licensed for individuals aged 2-49 years.

In its deliberations over the updated LAIV recommendation, ACIP reviewed observational data from previous seasons suggesting that the vaccine was poorly effective, and significantly less effective than IIV, against influenza A(H1N1) pdm09 viruses.

The current formulation of FluMist includes a new H1N1pdm09-like vaccine virus. While no effectiveness estimates were available at the time of review, ACIP said it did consider manufacturer data on shedding and immunogenicity for the current vaccine in children between the ages of 24 months through less than 4 years.

“These data suggest that this new H1N1pdm09-like virus has improved replicative fitness over previous H1N1pdm09-like viruses included in LAIV,” Dr. Grohskopf and colleagues wrote.

Individuals with an egg allergy history also can receive any licensed, recommended, age-appropriate IIV, RIV, or LAIV vaccine, said ACIP. This updated recommendation was based in part on the committee’s review and discussion of three studies that showed no cases of anaphylaxis in egg-allergic children receiving LAIV.

The ACIP recommendation update also outlines the strains selected earlier this year for the 2018-2019 season. Trivalent influenza vaccines in the United States will include an A/Michigan/45/2015 (H1N1) pdm09–like virus, an A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus, and a B/Colorado/06/2017–like virus (Victoria lineage). Quadrivalent vaccines will include those strains plus a B/Phuket/3073/2013–like virus (Yamagata lineage).

The report also acknowledges the recent expansion of age indication for two vaccines that have occurred since the last ACIP recommendations.

Afluria Quadrivalent was previously licensed for individuals 18 years of age and older. In August 2017, the Food and Drug Administration approved expansion of the indication to individuals 5 years of age or older. In January 2018, FDA approved expansion of the Fluarix Quadrivalent indication, previously licensed for age 3 and older, to individuals 6 months and older.

Report coauthor Emmanuel B. Walter disclosed grants from Novavax and Merck. The remaining report authors reported no relevant financial disclosures.

SOURCE: Grohskopf LA et al. MMWR Recomm Rep. 2018 Aug 24;67(3):1-20.

The latest seasonal influenza vaccine recommendations from the Advisory Committee on Immunization Practices provide several key updates that will impact clinical practice in the 2018-2019 influenza season.

CAP53/iStockphoto.com

Of note, live attenuated influenza vaccine (LAIV; FluMist Quadrivalent) is an option, following two seasons in which the committee recommended it not be used.

ACIP also updated its recommendations for individuals with a history of egg allergy, described the vaccine strains chosen for 2018-2019 season, and detailed the changes in age indications for Afluria Quadrivalent and Fluarix Quadrivalent that have been made since publication of its previous guidelines.

Published in MMWR Recommendations and Reports, the updated ACIP recommendations reflect discussions and decisions from the three public meetings of ACIP that have taken place since the last annual update.

All individuals 6 months of age and older who have no contraindications to influenza vaccine should receive routine annual influenza vaccine, ACIP also said in its report, reinforcing a key recommendation that has been in place since 2010.

“To avoid missed opportunities for vaccination, providers should offer vaccination during routine health care visits and hospitalizations,” wrote authors of the report, including lead author Lisa A. Grohskopf, MD, of the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta.

Dr. Grohskopf and coauthors made no specific recommendations on which vaccine to use. They said providers should choose licensed, age-appropriate recommended vaccines expected to be available for the 2018-2019 season, including inactivated influenza vaccines (IIV), a recombinant influenza vaccine (RIV4), and the LAIV option.

FluMist Quadrivalent, the one LAIV product expected to be available for the 2018-2019 season, is licensed for individuals aged 2-49 years.

In its deliberations over the updated LAIV recommendation, ACIP reviewed observational data from previous seasons suggesting that the vaccine was poorly effective, and significantly less effective than IIV, against influenza A(H1N1) pdm09 viruses.

The current formulation of FluMist includes a new H1N1pdm09-like vaccine virus. While no effectiveness estimates were available at the time of review, ACIP said it did consider manufacturer data on shedding and immunogenicity for the current vaccine in children between the ages of 24 months through less than 4 years.

“These data suggest that this new H1N1pdm09-like virus has improved replicative fitness over previous H1N1pdm09-like viruses included in LAIV,” Dr. Grohskopf and colleagues wrote.

Individuals with an egg allergy history also can receive any licensed, recommended, age-appropriate IIV, RIV, or LAIV vaccine, said ACIP. This updated recommendation was based in part on the committee’s review and discussion of three studies that showed no cases of anaphylaxis in egg-allergic children receiving LAIV.

The ACIP recommendation update also outlines the strains selected earlier this year for the 2018-2019 season. Trivalent influenza vaccines in the United States will include an A/Michigan/45/2015 (H1N1) pdm09–like virus, an A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus, and a B/Colorado/06/2017–like virus (Victoria lineage). Quadrivalent vaccines will include those strains plus a B/Phuket/3073/2013–like virus (Yamagata lineage).

The report also acknowledges the recent expansion of age indication for two vaccines that have occurred since the last ACIP recommendations.

Afluria Quadrivalent was previously licensed for individuals 18 years of age and older. In August 2017, the Food and Drug Administration approved expansion of the indication to individuals 5 years of age or older. In January 2018, FDA approved expansion of the Fluarix Quadrivalent indication, previously licensed for age 3 and older, to individuals 6 months and older.

Report coauthor Emmanuel B. Walter disclosed grants from Novavax and Merck. The remaining report authors reported no relevant financial disclosures.

SOURCE: Grohskopf LA et al. MMWR Recomm Rep. 2018 Aug 24;67(3):1-20.

The latest seasonal influenza vaccine recommendations from the Advisory Committee on Immunization Practices provide several key updates that will impact clinical practice in the 2018-2019 influenza season.

CAP53/iStockphoto.com

Of note, live attenuated influenza vaccine (LAIV; FluMist Quadrivalent) is an option, following two seasons in which the committee recommended it not be used.

ACIP also updated its recommendations for individuals with a history of egg allergy, described the vaccine strains chosen for 2018-2019 season, and detailed the changes in age indications for Afluria Quadrivalent and Fluarix Quadrivalent that have been made since publication of its previous guidelines.

Published in MMWR Recommendations and Reports, the updated ACIP recommendations reflect discussions and decisions from the three public meetings of ACIP that have taken place since the last annual update.

All individuals 6 months of age and older who have no contraindications to influenza vaccine should receive routine annual influenza vaccine, ACIP also said in its report, reinforcing a key recommendation that has been in place since 2010.

“To avoid missed opportunities for vaccination, providers should offer vaccination during routine health care visits and hospitalizations,” wrote authors of the report, including lead author Lisa A. Grohskopf, MD, of the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta.

Dr. Grohskopf and coauthors made no specific recommendations on which vaccine to use. They said providers should choose licensed, age-appropriate recommended vaccines expected to be available for the 2018-2019 season, including inactivated influenza vaccines (IIV), a recombinant influenza vaccine (RIV4), and the LAIV option.

FluMist Quadrivalent, the one LAIV product expected to be available for the 2018-2019 season, is licensed for individuals aged 2-49 years.

In its deliberations over the updated LAIV recommendation, ACIP reviewed observational data from previous seasons suggesting that the vaccine was poorly effective, and significantly less effective than IIV, against influenza A(H1N1) pdm09 viruses.

The current formulation of FluMist includes a new H1N1pdm09-like vaccine virus. While no effectiveness estimates were available at the time of review, ACIP said it did consider manufacturer data on shedding and immunogenicity for the current vaccine in children between the ages of 24 months through less than 4 years.

“These data suggest that this new H1N1pdm09-like virus has improved replicative fitness over previous H1N1pdm09-like viruses included in LAIV,” Dr. Grohskopf and colleagues wrote.

Individuals with an egg allergy history also can receive any licensed, recommended, age-appropriate IIV, RIV, or LAIV vaccine, said ACIP. This updated recommendation was based in part on the committee’s review and discussion of three studies that showed no cases of anaphylaxis in egg-allergic children receiving LAIV.

The ACIP recommendation update also outlines the strains selected earlier this year for the 2018-2019 season. Trivalent influenza vaccines in the United States will include an A/Michigan/45/2015 (H1N1) pdm09–like virus, an A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus, and a B/Colorado/06/2017–like virus (Victoria lineage). Quadrivalent vaccines will include those strains plus a B/Phuket/3073/2013–like virus (Yamagata lineage).

The report also acknowledges the recent expansion of age indication for two vaccines that have occurred since the last ACIP recommendations.

Afluria Quadrivalent was previously licensed for individuals 18 years of age and older. In August 2017, the Food and Drug Administration approved expansion of the indication to individuals 5 years of age or older. In January 2018, FDA approved expansion of the Fluarix Quadrivalent indication, previously licensed for age 3 and older, to individuals 6 months and older.

Report coauthor Emmanuel B. Walter disclosed grants from Novavax and Merck. The remaining report authors reported no relevant financial disclosures.

SOURCE: Grohskopf LA et al. MMWR Recomm Rep. 2018 Aug 24;67(3):1-20.