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FDA opens the door to biosimilar insulin
The Food and Drug Administration published Feb. 21 in the Federal Register a final rule that transitions insulin and other products from regulation as a drug to a biologic. This will provide manufacturers access to the biosimilars approval pathway and is expected to bring more competition to the insulin market. The move comes as insulin manufacturers continue to get increased scrutiny over the significantly increased pricing of their products in recent years.
The transition was required under a provision of the Biologics Price Competition and Innovation Act of 2009.
The move is expected to have no impact on the distribution of insulin and other products affected by the transition.
“In general, prescribers should continue to prescribe and order insulin and other biological products the same way they did before the transition,” the FDA said in an FAQ on the transition for physicians and other health care workers. “In general, pharmacists should continue to dispense and counsel about insulin and other biological products the same way they did before the transition. Prescribers and pharmacists should ensure their patients understand there are no changes to the product and they should continue to use the product the same way as before the transition.”
Other products affected by the transition include human growth hormone (somatropin), pancrelipase, chorionic gonadotropin, follitropin alfa, and menotropins. Information on all the transitioning products will move from the Orange Book (which lists FDA-approved drug products with therapeutic equivalent evaluations) to the Purple Book (which lists FDA-licensed biological products with reference product exclusivity data and biosimilar/interchangeability evaluations).
The FDA in the FAQ reiterated its commitment to reviewing any applications for these transition products within 12 months of submission.
The Food and Drug Administration published Feb. 21 in the Federal Register a final rule that transitions insulin and other products from regulation as a drug to a biologic. This will provide manufacturers access to the biosimilars approval pathway and is expected to bring more competition to the insulin market. The move comes as insulin manufacturers continue to get increased scrutiny over the significantly increased pricing of their products in recent years.
The transition was required under a provision of the Biologics Price Competition and Innovation Act of 2009.
The move is expected to have no impact on the distribution of insulin and other products affected by the transition.
“In general, prescribers should continue to prescribe and order insulin and other biological products the same way they did before the transition,” the FDA said in an FAQ on the transition for physicians and other health care workers. “In general, pharmacists should continue to dispense and counsel about insulin and other biological products the same way they did before the transition. Prescribers and pharmacists should ensure their patients understand there are no changes to the product and they should continue to use the product the same way as before the transition.”
Other products affected by the transition include human growth hormone (somatropin), pancrelipase, chorionic gonadotropin, follitropin alfa, and menotropins. Information on all the transitioning products will move from the Orange Book (which lists FDA-approved drug products with therapeutic equivalent evaluations) to the Purple Book (which lists FDA-licensed biological products with reference product exclusivity data and biosimilar/interchangeability evaluations).
The FDA in the FAQ reiterated its commitment to reviewing any applications for these transition products within 12 months of submission.
The Food and Drug Administration published Feb. 21 in the Federal Register a final rule that transitions insulin and other products from regulation as a drug to a biologic. This will provide manufacturers access to the biosimilars approval pathway and is expected to bring more competition to the insulin market. The move comes as insulin manufacturers continue to get increased scrutiny over the significantly increased pricing of their products in recent years.
The transition was required under a provision of the Biologics Price Competition and Innovation Act of 2009.
The move is expected to have no impact on the distribution of insulin and other products affected by the transition.
“In general, prescribers should continue to prescribe and order insulin and other biological products the same way they did before the transition,” the FDA said in an FAQ on the transition for physicians and other health care workers. “In general, pharmacists should continue to dispense and counsel about insulin and other biological products the same way they did before the transition. Prescribers and pharmacists should ensure their patients understand there are no changes to the product and they should continue to use the product the same way as before the transition.”
Other products affected by the transition include human growth hormone (somatropin), pancrelipase, chorionic gonadotropin, follitropin alfa, and menotropins. Information on all the transitioning products will move from the Orange Book (which lists FDA-approved drug products with therapeutic equivalent evaluations) to the Purple Book (which lists FDA-licensed biological products with reference product exclusivity data and biosimilar/interchangeability evaluations).
The FDA in the FAQ reiterated its commitment to reviewing any applications for these transition products within 12 months of submission.
First clinical evidence of neuroprotection in acute stroke?
LOS ANGELES – A new potential neuroprotectant agent has been found to be beneficial for patients with acute ischemic stroke undergoing endovascular thrombectomy in a large placebo-controlled trial, but only for those patients who did not also receive thrombolysis.
There was no difference between groups on the primary outcome in the main analysis of the trial, lead author Michael Hill, MD, reported.
However, “In our study, we found a dramatic interaction of nerinetide with alteplase. There was a large benefit of nerinetide in patients not given thrombolysis, but in patients who received alteplase, this benefit was completely obliterated,” Dr. Hill said in an interview.
“In patients not treated with thrombolysis, we found a large effect size with a 9.5% absolute improvement in patients having an independent outcome (modified Rankin Score [mRS] 0-2) and a number need to treat of 10 to 11,” he said. “We also found a mortality benefit and a reduction in the size of strokes, with all other secondary outcomes going in the right direction.
“The drug works really well in patients who do not get thrombolysis, but it doesn’t work at all in patients who have had thrombolysis. The thrombolytic appears to break the peptide down so it is inactive,” he added.
“This is the first evidence that neuroprotection is possible in human stroke. This has never been shown before,” Dr. Hill noted. “Many previous clinical trials of potential neuroprotectants have been negative. We think this is a major breakthrough. This is pretty exciting stuff with really tantalizing results.”
Dr. Hill, professor of neurology at the University of Calgary (Alta.), presented results of the ESCAPE-NA1 trial on Feb. 20 at the International Stroke Conference (ISC) 2020. The trial was also simultaneously published online (Lancet. 2020 Feb 20; doi: 10.1016/S0140-6736(20)30258-0).
Endogenous nitric oxide
The new agent – known as NA1 or nerinetide – is a 20-amino-acid peptide with a novel mechanism of action; it inhibits signaling that leads to neuronal excitotoxicity. “It reduces endogenous nitric oxide generated inside the cell during ischemia, which is one of the main biochemical processes contributing to cell death,” Dr. Hill explained. In a primate model of ischemia reperfusion that was published in Nature in 2012, it was highly protective, he added.
The drug is given just once at the time of thrombectomy. It is short lived in the blood but detectable in the brain for up to 24 hours, he said.
The trial included 1,105 patients who had experienced acute ischemic stroke due to large-vessel occlusion within a 12-hour treatment window and for whom imaging results suitable for thrombectomy were available. The patients were randomly assigned to receive either intravenous nerinetide in a single dose of 2.6 mg/kg or saline placebo at the time of thrombectomy.
Patients were stratified by intravenous alteplase treatment and by declared endovascular device choice.
The primary outcome was a favorable functional outcome 90 days after randomization, defined as an mRS score of 0-2. In the main analysis of the whole population, this favorable outcome was achieved for 61.4% of the group that received nerinetide and for 59.2% of the placebo group, a nonsignificant difference. Secondary outcomes were also similar between the two groups.
But an exploratory analysis showed evidence that nerinetide’s treatment effect was modified by alteplase treatment. Among the patients who did not receive alteplase, use of nerinetide was associated with improved outcomes, whereas no benefit was found in the alteplase stratum. The difference in absolute risk slightly but not significantly favored placebo.
In the stratum that did not receive alteplase (40% of the trial population), the favorable mRS outcome was achieved by 59.3% of patients who received nerinetide, compared with 49.8% of those given placebo – a significant difference (adjusted risk ratio, 1.18; 95% confidence interval, 1.01-1.38).
There was also a 7.5% absolute risk reduction in mortality at 90 days post treatment with nerinetide for the patients who did not receive thrombolysis. This resulted in an approximate halving of the hazard of death (adjusted hazard ratio, 0.56).
In addition, infarct size was reduced in those patients who received nerinetide but not thrombolysis.
Among the patients who received alteplase, the proportion of patients who achieved an mRS of 0-2 was similar between groups, as were median infarct volumes.
The observed treatment effect modification by alteplase was supported by reductions in peak plasma nerinetide concentrations in the alteplase stratum, the researchers reported.
They said that the combination of the clinical results in the no-thrombolytic stratum and subsequent tests documenting that nerinetide is broken down by plasmin (which is generated by alteplase) “provide evidence that the clinical observation of effect modification is not a chance finding.” But they added: “This novel observation will require additional confirmation, and we cannot draw a definitive conclusion on treatment effect in this study.”
“Shaking up the field”
There is still more work to do, Dr. Hill said. “We don’t fully understand the pharmacology, and we will certainly have to do another trial, but we believe this agent is going to shake the field up. This is a totally new drug, and we have to think carefully about where it could fit in.”
“The obvious first group is those patients who do not receive thrombolysis. This is a large group, as most patients do not present in time for thrombolysis. Then we can work on the biochemistry and see if we can develop a version of nerinetide that is resistant to breakdown by thrombolysis,” he said.
Another possibility would be to withhold thrombolysis and give nerinetide instead. “It may be that thrombolysis is not needed if patients are receiving thrombectomy – this is being suggested now in initial studies,” Hill stated.
They also chose a very select group of patients – those undergoing thrombectomy, who represent only 10% to 15% of stroke patients. “We have to work out how to expand that population,” he said.
Hill noted that there have been many examples in the past of potential neuroprotectant agents that have worked in animal models of ischemia-reperfusion but that failed in humans with acute stroke.
“Until recently, we have not had a reliable ischemia-reperfusion model in humans, but now with endovascular therapy, we have a situation where the blood flow is reliably restored, which is an ideal situation to test new neuroprotectant agents. That may be another factor that has contributed to our positive findings,” he said.
In an accompanying comment in The Lancet, Graeme J. Hankey, MD, of the University of Western Australia, Perth, noted that although endovascular thrombectomy after use of intravenous alteplase improves reperfusion and clinical outcomes for a fifth of patients with ischemic stroke caused by large-artery occlusion, half of patients do not recover an independent lifestyle. Cytoprotection aims to augment the resilience of neurons, neurovascular units, and white matter during ischemia until perfusion is restored (Lancet. 2020 Feb 20; doi: 10.1016/S0140-6736(20)30316-0).
Dr. Hankey also pointed out that numerous cytoprotection strategies have been reported to reduce brain infarction in preclinical models of ischemic stroke but have not been found to improve clinical outcomes in clinical trials involving patients with ischemic stroke.
The advent of thrombectomy provides an opportunity to reassess cytoprotection as an adjunctive therapy for patients with types of temporary brain ischemia that align more closely with successful preclinical models of ischemia, cytoprotection, and reperfusion, he added.
On the results of the current study and the benefit in the no-thrombolysis group, Dr. Hankey stated: “Although this result might be a chance finding or confounded by the indication for alteplase, complementary pharmacokinetic data in a small number of patients treated with nerinetide showed that alteplase lowered plasma concentrations of nerinetide, probably by converting plasminogen to plasmin, which cleaves peptide bonds not only in fibrin but also in the eicosapeptide nerinetide.”
He said the ESCAPE-NA1 trial “informs the study of cytoprotection as an adjunct therapy to reperfusion in acute ischemic stroke” and suggested that researchers who have reported encouraging results of other cytoprotective therapies for ischemic stroke should test their compounds for interactions with concurrent thrombolytic therapies.
The ESCAPE-NA1 trial was sponsored by NoNO, the company developing nerinetide. Dr. Hill has received grants from NoNO for the conduct of the study, is named on a U.S. patent for systems and methods for assisting in decision making and triaging for acute stroke patients, and owns stock in Calgary Scientific. Other coauthors are employees of NoNO or have stock options in the company. Dr. Hankey has received personal honoraria from the American Heart Association, AC Immune, Bayer, Bristol-Myers Squibb, and Medscape outside the area of work that he commented on.
This article first appeared on Medscape.com.
LOS ANGELES – A new potential neuroprotectant agent has been found to be beneficial for patients with acute ischemic stroke undergoing endovascular thrombectomy in a large placebo-controlled trial, but only for those patients who did not also receive thrombolysis.
There was no difference between groups on the primary outcome in the main analysis of the trial, lead author Michael Hill, MD, reported.
However, “In our study, we found a dramatic interaction of nerinetide with alteplase. There was a large benefit of nerinetide in patients not given thrombolysis, but in patients who received alteplase, this benefit was completely obliterated,” Dr. Hill said in an interview.
“In patients not treated with thrombolysis, we found a large effect size with a 9.5% absolute improvement in patients having an independent outcome (modified Rankin Score [mRS] 0-2) and a number need to treat of 10 to 11,” he said. “We also found a mortality benefit and a reduction in the size of strokes, with all other secondary outcomes going in the right direction.
“The drug works really well in patients who do not get thrombolysis, but it doesn’t work at all in patients who have had thrombolysis. The thrombolytic appears to break the peptide down so it is inactive,” he added.
“This is the first evidence that neuroprotection is possible in human stroke. This has never been shown before,” Dr. Hill noted. “Many previous clinical trials of potential neuroprotectants have been negative. We think this is a major breakthrough. This is pretty exciting stuff with really tantalizing results.”
Dr. Hill, professor of neurology at the University of Calgary (Alta.), presented results of the ESCAPE-NA1 trial on Feb. 20 at the International Stroke Conference (ISC) 2020. The trial was also simultaneously published online (Lancet. 2020 Feb 20; doi: 10.1016/S0140-6736(20)30258-0).
Endogenous nitric oxide
The new agent – known as NA1 or nerinetide – is a 20-amino-acid peptide with a novel mechanism of action; it inhibits signaling that leads to neuronal excitotoxicity. “It reduces endogenous nitric oxide generated inside the cell during ischemia, which is one of the main biochemical processes contributing to cell death,” Dr. Hill explained. In a primate model of ischemia reperfusion that was published in Nature in 2012, it was highly protective, he added.
The drug is given just once at the time of thrombectomy. It is short lived in the blood but detectable in the brain for up to 24 hours, he said.
The trial included 1,105 patients who had experienced acute ischemic stroke due to large-vessel occlusion within a 12-hour treatment window and for whom imaging results suitable for thrombectomy were available. The patients were randomly assigned to receive either intravenous nerinetide in a single dose of 2.6 mg/kg or saline placebo at the time of thrombectomy.
Patients were stratified by intravenous alteplase treatment and by declared endovascular device choice.
The primary outcome was a favorable functional outcome 90 days after randomization, defined as an mRS score of 0-2. In the main analysis of the whole population, this favorable outcome was achieved for 61.4% of the group that received nerinetide and for 59.2% of the placebo group, a nonsignificant difference. Secondary outcomes were also similar between the two groups.
But an exploratory analysis showed evidence that nerinetide’s treatment effect was modified by alteplase treatment. Among the patients who did not receive alteplase, use of nerinetide was associated with improved outcomes, whereas no benefit was found in the alteplase stratum. The difference in absolute risk slightly but not significantly favored placebo.
In the stratum that did not receive alteplase (40% of the trial population), the favorable mRS outcome was achieved by 59.3% of patients who received nerinetide, compared with 49.8% of those given placebo – a significant difference (adjusted risk ratio, 1.18; 95% confidence interval, 1.01-1.38).
There was also a 7.5% absolute risk reduction in mortality at 90 days post treatment with nerinetide for the patients who did not receive thrombolysis. This resulted in an approximate halving of the hazard of death (adjusted hazard ratio, 0.56).
In addition, infarct size was reduced in those patients who received nerinetide but not thrombolysis.
Among the patients who received alteplase, the proportion of patients who achieved an mRS of 0-2 was similar between groups, as were median infarct volumes.
The observed treatment effect modification by alteplase was supported by reductions in peak plasma nerinetide concentrations in the alteplase stratum, the researchers reported.
They said that the combination of the clinical results in the no-thrombolytic stratum and subsequent tests documenting that nerinetide is broken down by plasmin (which is generated by alteplase) “provide evidence that the clinical observation of effect modification is not a chance finding.” But they added: “This novel observation will require additional confirmation, and we cannot draw a definitive conclusion on treatment effect in this study.”
“Shaking up the field”
There is still more work to do, Dr. Hill said. “We don’t fully understand the pharmacology, and we will certainly have to do another trial, but we believe this agent is going to shake the field up. This is a totally new drug, and we have to think carefully about where it could fit in.”
“The obvious first group is those patients who do not receive thrombolysis. This is a large group, as most patients do not present in time for thrombolysis. Then we can work on the biochemistry and see if we can develop a version of nerinetide that is resistant to breakdown by thrombolysis,” he said.
Another possibility would be to withhold thrombolysis and give nerinetide instead. “It may be that thrombolysis is not needed if patients are receiving thrombectomy – this is being suggested now in initial studies,” Hill stated.
They also chose a very select group of patients – those undergoing thrombectomy, who represent only 10% to 15% of stroke patients. “We have to work out how to expand that population,” he said.
Hill noted that there have been many examples in the past of potential neuroprotectant agents that have worked in animal models of ischemia-reperfusion but that failed in humans with acute stroke.
“Until recently, we have not had a reliable ischemia-reperfusion model in humans, but now with endovascular therapy, we have a situation where the blood flow is reliably restored, which is an ideal situation to test new neuroprotectant agents. That may be another factor that has contributed to our positive findings,” he said.
In an accompanying comment in The Lancet, Graeme J. Hankey, MD, of the University of Western Australia, Perth, noted that although endovascular thrombectomy after use of intravenous alteplase improves reperfusion and clinical outcomes for a fifth of patients with ischemic stroke caused by large-artery occlusion, half of patients do not recover an independent lifestyle. Cytoprotection aims to augment the resilience of neurons, neurovascular units, and white matter during ischemia until perfusion is restored (Lancet. 2020 Feb 20; doi: 10.1016/S0140-6736(20)30316-0).
Dr. Hankey also pointed out that numerous cytoprotection strategies have been reported to reduce brain infarction in preclinical models of ischemic stroke but have not been found to improve clinical outcomes in clinical trials involving patients with ischemic stroke.
The advent of thrombectomy provides an opportunity to reassess cytoprotection as an adjunctive therapy for patients with types of temporary brain ischemia that align more closely with successful preclinical models of ischemia, cytoprotection, and reperfusion, he added.
On the results of the current study and the benefit in the no-thrombolysis group, Dr. Hankey stated: “Although this result might be a chance finding or confounded by the indication for alteplase, complementary pharmacokinetic data in a small number of patients treated with nerinetide showed that alteplase lowered plasma concentrations of nerinetide, probably by converting plasminogen to plasmin, which cleaves peptide bonds not only in fibrin but also in the eicosapeptide nerinetide.”
He said the ESCAPE-NA1 trial “informs the study of cytoprotection as an adjunct therapy to reperfusion in acute ischemic stroke” and suggested that researchers who have reported encouraging results of other cytoprotective therapies for ischemic stroke should test their compounds for interactions with concurrent thrombolytic therapies.
The ESCAPE-NA1 trial was sponsored by NoNO, the company developing nerinetide. Dr. Hill has received grants from NoNO for the conduct of the study, is named on a U.S. patent for systems and methods for assisting in decision making and triaging for acute stroke patients, and owns stock in Calgary Scientific. Other coauthors are employees of NoNO or have stock options in the company. Dr. Hankey has received personal honoraria from the American Heart Association, AC Immune, Bayer, Bristol-Myers Squibb, and Medscape outside the area of work that he commented on.
This article first appeared on Medscape.com.
LOS ANGELES – A new potential neuroprotectant agent has been found to be beneficial for patients with acute ischemic stroke undergoing endovascular thrombectomy in a large placebo-controlled trial, but only for those patients who did not also receive thrombolysis.
There was no difference between groups on the primary outcome in the main analysis of the trial, lead author Michael Hill, MD, reported.
However, “In our study, we found a dramatic interaction of nerinetide with alteplase. There was a large benefit of nerinetide in patients not given thrombolysis, but in patients who received alteplase, this benefit was completely obliterated,” Dr. Hill said in an interview.
“In patients not treated with thrombolysis, we found a large effect size with a 9.5% absolute improvement in patients having an independent outcome (modified Rankin Score [mRS] 0-2) and a number need to treat of 10 to 11,” he said. “We also found a mortality benefit and a reduction in the size of strokes, with all other secondary outcomes going in the right direction.
“The drug works really well in patients who do not get thrombolysis, but it doesn’t work at all in patients who have had thrombolysis. The thrombolytic appears to break the peptide down so it is inactive,” he added.
“This is the first evidence that neuroprotection is possible in human stroke. This has never been shown before,” Dr. Hill noted. “Many previous clinical trials of potential neuroprotectants have been negative. We think this is a major breakthrough. This is pretty exciting stuff with really tantalizing results.”
Dr. Hill, professor of neurology at the University of Calgary (Alta.), presented results of the ESCAPE-NA1 trial on Feb. 20 at the International Stroke Conference (ISC) 2020. The trial was also simultaneously published online (Lancet. 2020 Feb 20; doi: 10.1016/S0140-6736(20)30258-0).
Endogenous nitric oxide
The new agent – known as NA1 or nerinetide – is a 20-amino-acid peptide with a novel mechanism of action; it inhibits signaling that leads to neuronal excitotoxicity. “It reduces endogenous nitric oxide generated inside the cell during ischemia, which is one of the main biochemical processes contributing to cell death,” Dr. Hill explained. In a primate model of ischemia reperfusion that was published in Nature in 2012, it was highly protective, he added.
The drug is given just once at the time of thrombectomy. It is short lived in the blood but detectable in the brain for up to 24 hours, he said.
The trial included 1,105 patients who had experienced acute ischemic stroke due to large-vessel occlusion within a 12-hour treatment window and for whom imaging results suitable for thrombectomy were available. The patients were randomly assigned to receive either intravenous nerinetide in a single dose of 2.6 mg/kg or saline placebo at the time of thrombectomy.
Patients were stratified by intravenous alteplase treatment and by declared endovascular device choice.
The primary outcome was a favorable functional outcome 90 days after randomization, defined as an mRS score of 0-2. In the main analysis of the whole population, this favorable outcome was achieved for 61.4% of the group that received nerinetide and for 59.2% of the placebo group, a nonsignificant difference. Secondary outcomes were also similar between the two groups.
But an exploratory analysis showed evidence that nerinetide’s treatment effect was modified by alteplase treatment. Among the patients who did not receive alteplase, use of nerinetide was associated with improved outcomes, whereas no benefit was found in the alteplase stratum. The difference in absolute risk slightly but not significantly favored placebo.
In the stratum that did not receive alteplase (40% of the trial population), the favorable mRS outcome was achieved by 59.3% of patients who received nerinetide, compared with 49.8% of those given placebo – a significant difference (adjusted risk ratio, 1.18; 95% confidence interval, 1.01-1.38).
There was also a 7.5% absolute risk reduction in mortality at 90 days post treatment with nerinetide for the patients who did not receive thrombolysis. This resulted in an approximate halving of the hazard of death (adjusted hazard ratio, 0.56).
In addition, infarct size was reduced in those patients who received nerinetide but not thrombolysis.
Among the patients who received alteplase, the proportion of patients who achieved an mRS of 0-2 was similar between groups, as were median infarct volumes.
The observed treatment effect modification by alteplase was supported by reductions in peak plasma nerinetide concentrations in the alteplase stratum, the researchers reported.
They said that the combination of the clinical results in the no-thrombolytic stratum and subsequent tests documenting that nerinetide is broken down by plasmin (which is generated by alteplase) “provide evidence that the clinical observation of effect modification is not a chance finding.” But they added: “This novel observation will require additional confirmation, and we cannot draw a definitive conclusion on treatment effect in this study.”
“Shaking up the field”
There is still more work to do, Dr. Hill said. “We don’t fully understand the pharmacology, and we will certainly have to do another trial, but we believe this agent is going to shake the field up. This is a totally new drug, and we have to think carefully about where it could fit in.”
“The obvious first group is those patients who do not receive thrombolysis. This is a large group, as most patients do not present in time for thrombolysis. Then we can work on the biochemistry and see if we can develop a version of nerinetide that is resistant to breakdown by thrombolysis,” he said.
Another possibility would be to withhold thrombolysis and give nerinetide instead. “It may be that thrombolysis is not needed if patients are receiving thrombectomy – this is being suggested now in initial studies,” Hill stated.
They also chose a very select group of patients – those undergoing thrombectomy, who represent only 10% to 15% of stroke patients. “We have to work out how to expand that population,” he said.
Hill noted that there have been many examples in the past of potential neuroprotectant agents that have worked in animal models of ischemia-reperfusion but that failed in humans with acute stroke.
“Until recently, we have not had a reliable ischemia-reperfusion model in humans, but now with endovascular therapy, we have a situation where the blood flow is reliably restored, which is an ideal situation to test new neuroprotectant agents. That may be another factor that has contributed to our positive findings,” he said.
In an accompanying comment in The Lancet, Graeme J. Hankey, MD, of the University of Western Australia, Perth, noted that although endovascular thrombectomy after use of intravenous alteplase improves reperfusion and clinical outcomes for a fifth of patients with ischemic stroke caused by large-artery occlusion, half of patients do not recover an independent lifestyle. Cytoprotection aims to augment the resilience of neurons, neurovascular units, and white matter during ischemia until perfusion is restored (Lancet. 2020 Feb 20; doi: 10.1016/S0140-6736(20)30316-0).
Dr. Hankey also pointed out that numerous cytoprotection strategies have been reported to reduce brain infarction in preclinical models of ischemic stroke but have not been found to improve clinical outcomes in clinical trials involving patients with ischemic stroke.
The advent of thrombectomy provides an opportunity to reassess cytoprotection as an adjunctive therapy for patients with types of temporary brain ischemia that align more closely with successful preclinical models of ischemia, cytoprotection, and reperfusion, he added.
On the results of the current study and the benefit in the no-thrombolysis group, Dr. Hankey stated: “Although this result might be a chance finding or confounded by the indication for alteplase, complementary pharmacokinetic data in a small number of patients treated with nerinetide showed that alteplase lowered plasma concentrations of nerinetide, probably by converting plasminogen to plasmin, which cleaves peptide bonds not only in fibrin but also in the eicosapeptide nerinetide.”
He said the ESCAPE-NA1 trial “informs the study of cytoprotection as an adjunct therapy to reperfusion in acute ischemic stroke” and suggested that researchers who have reported encouraging results of other cytoprotective therapies for ischemic stroke should test their compounds for interactions with concurrent thrombolytic therapies.
The ESCAPE-NA1 trial was sponsored by NoNO, the company developing nerinetide. Dr. Hill has received grants from NoNO for the conduct of the study, is named on a U.S. patent for systems and methods for assisting in decision making and triaging for acute stroke patients, and owns stock in Calgary Scientific. Other coauthors are employees of NoNO or have stock options in the company. Dr. Hankey has received personal honoraria from the American Heart Association, AC Immune, Bayer, Bristol-Myers Squibb, and Medscape outside the area of work that he commented on.
This article first appeared on Medscape.com.
Tumor neoantigenicity metric improves prediction of response to immunotherapy
A new tumor neoantigenicity metric may improve prediction of response to immunotherapy in patients with melanoma, lung cancer, and kidney cancer, a retrospective analysis suggests.
The new metric, known as the Cauchy-Schwarz index of neoantigens (CSiN) score, incorporates both immunogenicity and clonality, according to lead study author Tianshi Lu, a PhD candidate at the University of Texas Southwestern Medical Center in Dallas, and colleagues.
“The major biological insight from this study is that the neoantigen clonal structure in each tumor specimen and the immunogenicity of the neoantigens (represented by the MHC-binding strength in our study) are predictive of response to checkpoint inhibitors and prognosis,” the investigators wrote in Science Immunology.
The study involved 2,479 patients with various cancers, including immunogenic types such as renal cell carcinoma (RCC), and nonimmunogenic types, such as pediatric acute lymphocytic leukemia.
The investigators first evaluated CSiN in relation to clinical outcome among patients with immunogenic cancers who received immunotherapy. Drawing data from multiple cohorts, the investigators found that patients who had better responses to therapy were significantly more likely to have above average CSiN scores than those who had worse responses.
In one cohort of patients with melanoma who received anti–CTLA-4 therapy, those with better responses were more likely to have high CSiN scores (P = .009). In another cohort of melanoma patients who received anti–CTLA-4 therapy, those with higher CSiN scores were more likely to achieve durable clinical benefit (response or stable disease for more than 6 months), compared with patients who had lower CSiN scores (P = .033).
Among patients with clear cell RCC treated with anti-PD-1/PD-L1 therapy, there was a significant positive association between higher CSiN scores and better response (P = .036). Among T effector-high patients with metastatic clear cell RCC, there was a significant association between higher CSiN scores and better response to atezolizumab (P = .028) but not sunitinib (P = .890).
In a cohort of patients with non–small cell lung cancer treated with checkpoint inhibitors, those with sustained responses were more likely to have higher CSiN scores than were patients with short-term progression (P = .015).
The investigators also compared the predictive power of CSiN with existing neoantigenicity metrics, ultimately concluding that CSiN was superior.
“Overall, the neoantigen load and neoantigen fitness models were not as strongly predictive of treatment response as CSiN,” the investigators wrote.
Again using data from patients with immunogenic cancers, the investigators looked for an association between CSiN score and overall survival. Indeed, patients with higher-than-average CSiN scores had significantly better survival than that of those with lower scores (P less than .001). This finding was maintained in a multivariate analysis that accounted for disease type, stage, sex, and age.
In contrast with the above findings, CSiN did not predict survival among patients with nonimmunogenic cancer types.
“Overall, our work offers a rigorous methodology of predicting response to immunotherapy and prognosis from routine patient samples and should be useful for personalizing medicine in the modern era of immunotherapy,” the investigators concluded.
The study was funded by the National Institutes of Health, the Cancer Prevention Research Institute of Texas, and the American Cancer Society. The investigators reported no conflicts of interest.
SOURCE: Lu et al. Sci Immunol. 2020 Feb 21. doi: 10.1126/sciimmunol.aaz3199.
A new tumor neoantigenicity metric may improve prediction of response to immunotherapy in patients with melanoma, lung cancer, and kidney cancer, a retrospective analysis suggests.
The new metric, known as the Cauchy-Schwarz index of neoantigens (CSiN) score, incorporates both immunogenicity and clonality, according to lead study author Tianshi Lu, a PhD candidate at the University of Texas Southwestern Medical Center in Dallas, and colleagues.
“The major biological insight from this study is that the neoantigen clonal structure in each tumor specimen and the immunogenicity of the neoantigens (represented by the MHC-binding strength in our study) are predictive of response to checkpoint inhibitors and prognosis,” the investigators wrote in Science Immunology.
The study involved 2,479 patients with various cancers, including immunogenic types such as renal cell carcinoma (RCC), and nonimmunogenic types, such as pediatric acute lymphocytic leukemia.
The investigators first evaluated CSiN in relation to clinical outcome among patients with immunogenic cancers who received immunotherapy. Drawing data from multiple cohorts, the investigators found that patients who had better responses to therapy were significantly more likely to have above average CSiN scores than those who had worse responses.
In one cohort of patients with melanoma who received anti–CTLA-4 therapy, those with better responses were more likely to have high CSiN scores (P = .009). In another cohort of melanoma patients who received anti–CTLA-4 therapy, those with higher CSiN scores were more likely to achieve durable clinical benefit (response or stable disease for more than 6 months), compared with patients who had lower CSiN scores (P = .033).
Among patients with clear cell RCC treated with anti-PD-1/PD-L1 therapy, there was a significant positive association between higher CSiN scores and better response (P = .036). Among T effector-high patients with metastatic clear cell RCC, there was a significant association between higher CSiN scores and better response to atezolizumab (P = .028) but not sunitinib (P = .890).
In a cohort of patients with non–small cell lung cancer treated with checkpoint inhibitors, those with sustained responses were more likely to have higher CSiN scores than were patients with short-term progression (P = .015).
The investigators also compared the predictive power of CSiN with existing neoantigenicity metrics, ultimately concluding that CSiN was superior.
“Overall, the neoantigen load and neoantigen fitness models were not as strongly predictive of treatment response as CSiN,” the investigators wrote.
Again using data from patients with immunogenic cancers, the investigators looked for an association between CSiN score and overall survival. Indeed, patients with higher-than-average CSiN scores had significantly better survival than that of those with lower scores (P less than .001). This finding was maintained in a multivariate analysis that accounted for disease type, stage, sex, and age.
In contrast with the above findings, CSiN did not predict survival among patients with nonimmunogenic cancer types.
“Overall, our work offers a rigorous methodology of predicting response to immunotherapy and prognosis from routine patient samples and should be useful for personalizing medicine in the modern era of immunotherapy,” the investigators concluded.
The study was funded by the National Institutes of Health, the Cancer Prevention Research Institute of Texas, and the American Cancer Society. The investigators reported no conflicts of interest.
SOURCE: Lu et al. Sci Immunol. 2020 Feb 21. doi: 10.1126/sciimmunol.aaz3199.
A new tumor neoantigenicity metric may improve prediction of response to immunotherapy in patients with melanoma, lung cancer, and kidney cancer, a retrospective analysis suggests.
The new metric, known as the Cauchy-Schwarz index of neoantigens (CSiN) score, incorporates both immunogenicity and clonality, according to lead study author Tianshi Lu, a PhD candidate at the University of Texas Southwestern Medical Center in Dallas, and colleagues.
“The major biological insight from this study is that the neoantigen clonal structure in each tumor specimen and the immunogenicity of the neoantigens (represented by the MHC-binding strength in our study) are predictive of response to checkpoint inhibitors and prognosis,” the investigators wrote in Science Immunology.
The study involved 2,479 patients with various cancers, including immunogenic types such as renal cell carcinoma (RCC), and nonimmunogenic types, such as pediatric acute lymphocytic leukemia.
The investigators first evaluated CSiN in relation to clinical outcome among patients with immunogenic cancers who received immunotherapy. Drawing data from multiple cohorts, the investigators found that patients who had better responses to therapy were significantly more likely to have above average CSiN scores than those who had worse responses.
In one cohort of patients with melanoma who received anti–CTLA-4 therapy, those with better responses were more likely to have high CSiN scores (P = .009). In another cohort of melanoma patients who received anti–CTLA-4 therapy, those with higher CSiN scores were more likely to achieve durable clinical benefit (response or stable disease for more than 6 months), compared with patients who had lower CSiN scores (P = .033).
Among patients with clear cell RCC treated with anti-PD-1/PD-L1 therapy, there was a significant positive association between higher CSiN scores and better response (P = .036). Among T effector-high patients with metastatic clear cell RCC, there was a significant association between higher CSiN scores and better response to atezolizumab (P = .028) but not sunitinib (P = .890).
In a cohort of patients with non–small cell lung cancer treated with checkpoint inhibitors, those with sustained responses were more likely to have higher CSiN scores than were patients with short-term progression (P = .015).
The investigators also compared the predictive power of CSiN with existing neoantigenicity metrics, ultimately concluding that CSiN was superior.
“Overall, the neoantigen load and neoantigen fitness models were not as strongly predictive of treatment response as CSiN,” the investigators wrote.
Again using data from patients with immunogenic cancers, the investigators looked for an association between CSiN score and overall survival. Indeed, patients with higher-than-average CSiN scores had significantly better survival than that of those with lower scores (P less than .001). This finding was maintained in a multivariate analysis that accounted for disease type, stage, sex, and age.
In contrast with the above findings, CSiN did not predict survival among patients with nonimmunogenic cancer types.
“Overall, our work offers a rigorous methodology of predicting response to immunotherapy and prognosis from routine patient samples and should be useful for personalizing medicine in the modern era of immunotherapy,” the investigators concluded.
The study was funded by the National Institutes of Health, the Cancer Prevention Research Institute of Texas, and the American Cancer Society. The investigators reported no conflicts of interest.
SOURCE: Lu et al. Sci Immunol. 2020 Feb 21. doi: 10.1126/sciimmunol.aaz3199.
FROM SCIENCE IMMUNOLOGY
New lipid-lowering drug earns FDA approval
The Food and Drug Administration has approved bempedoic acid (Nexletol) for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or established atherosclerotic cardiovascular disease (ASCVD) who require additional LDL cholesterol lowering.
The oral adenosine triphosphate–citrate lyase (ACL) inhibitor is indicated as an adjunct to diet and maximally tolerated statin therapy in these patients, and approved at the 180 mg once daily dose, the agency announced today.
The safety and efficacy of bempedoic acid were demonstrated over 52 weeks in two multicenter randomized, clinical trials involving 3,009 adults with HeFH or established ASCVD on maximally tolerated statin therapy.
The difference between bempedoic acid and placebo for the primary outcome of change in LDL cholesterol from baseline to week 12 was –18% in the first trial, CLEAR Harmony (95% confidence interval, –20% to –16%; P less than .001), and –17% in the second trial, CLEAR Wisdom (95% CI, –21% to –14%; P less than .001).
The label notes that the effect on cardiovascular morbidity and mortality has not been determined. The label also includes warnings stating that bempedoic acid may increase blood uric acid levels and is associated with an increased risk of tendon rupture or injury.
In clinical trials, 26% of bempedoic acid–treated patients with normal baseline uric acid values versus 9.5% of placebo-treated patients experienced hyperuricemia one or more times, and 3.5% of patients experienced clinically significant hyperuricemia reported as an adverse reaction versus 1.1% with placebo, according to the label. Gout was reported in 1.5% of patients treated with bempedoic acid and 0.4% of those treated with placebo.
Also in clinical trials, the risk of tendon rupture was 0.5% with bempedoic acid and 0% with placebo. Tendon rupture involved the rotator cuff, biceps tendon, or Achilles tendon, and occurred within weeks to months of starting the drug. Rupture may “occur more frequently in patients over 60 years of age, in those taking corticosteroid or fluoroquinolone drugs, in patients with renal failure, and in patients with previous tendon disorders,” the label states.
The label also advises that patients avoid concomitant use of bempedoic acid with simvastatin greater than 20 mg or pravastatin greater than 40 mg because it causes an increase in statin concentrations and may increase the risk of related myopathy.
A decision is expected shortly on a new drug application submitted by Esperion for an LDL cholesterol–lowering indication for bempedoic acid 180 mg/ezetimibe 10 mg combination tablet.
Full prescribing information is available online.
This article first appeared on Medscape.com.
The Food and Drug Administration has approved bempedoic acid (Nexletol) for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or established atherosclerotic cardiovascular disease (ASCVD) who require additional LDL cholesterol lowering.
The oral adenosine triphosphate–citrate lyase (ACL) inhibitor is indicated as an adjunct to diet and maximally tolerated statin therapy in these patients, and approved at the 180 mg once daily dose, the agency announced today.
The safety and efficacy of bempedoic acid were demonstrated over 52 weeks in two multicenter randomized, clinical trials involving 3,009 adults with HeFH or established ASCVD on maximally tolerated statin therapy.
The difference between bempedoic acid and placebo for the primary outcome of change in LDL cholesterol from baseline to week 12 was –18% in the first trial, CLEAR Harmony (95% confidence interval, –20% to –16%; P less than .001), and –17% in the second trial, CLEAR Wisdom (95% CI, –21% to –14%; P less than .001).
The label notes that the effect on cardiovascular morbidity and mortality has not been determined. The label also includes warnings stating that bempedoic acid may increase blood uric acid levels and is associated with an increased risk of tendon rupture or injury.
In clinical trials, 26% of bempedoic acid–treated patients with normal baseline uric acid values versus 9.5% of placebo-treated patients experienced hyperuricemia one or more times, and 3.5% of patients experienced clinically significant hyperuricemia reported as an adverse reaction versus 1.1% with placebo, according to the label. Gout was reported in 1.5% of patients treated with bempedoic acid and 0.4% of those treated with placebo.
Also in clinical trials, the risk of tendon rupture was 0.5% with bempedoic acid and 0% with placebo. Tendon rupture involved the rotator cuff, biceps tendon, or Achilles tendon, and occurred within weeks to months of starting the drug. Rupture may “occur more frequently in patients over 60 years of age, in those taking corticosteroid or fluoroquinolone drugs, in patients with renal failure, and in patients with previous tendon disorders,” the label states.
The label also advises that patients avoid concomitant use of bempedoic acid with simvastatin greater than 20 mg or pravastatin greater than 40 mg because it causes an increase in statin concentrations and may increase the risk of related myopathy.
A decision is expected shortly on a new drug application submitted by Esperion for an LDL cholesterol–lowering indication for bempedoic acid 180 mg/ezetimibe 10 mg combination tablet.
Full prescribing information is available online.
This article first appeared on Medscape.com.
The Food and Drug Administration has approved bempedoic acid (Nexletol) for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or established atherosclerotic cardiovascular disease (ASCVD) who require additional LDL cholesterol lowering.
The oral adenosine triphosphate–citrate lyase (ACL) inhibitor is indicated as an adjunct to diet and maximally tolerated statin therapy in these patients, and approved at the 180 mg once daily dose, the agency announced today.
The safety and efficacy of bempedoic acid were demonstrated over 52 weeks in two multicenter randomized, clinical trials involving 3,009 adults with HeFH or established ASCVD on maximally tolerated statin therapy.
The difference between bempedoic acid and placebo for the primary outcome of change in LDL cholesterol from baseline to week 12 was –18% in the first trial, CLEAR Harmony (95% confidence interval, –20% to –16%; P less than .001), and –17% in the second trial, CLEAR Wisdom (95% CI, –21% to –14%; P less than .001).
The label notes that the effect on cardiovascular morbidity and mortality has not been determined. The label also includes warnings stating that bempedoic acid may increase blood uric acid levels and is associated with an increased risk of tendon rupture or injury.
In clinical trials, 26% of bempedoic acid–treated patients with normal baseline uric acid values versus 9.5% of placebo-treated patients experienced hyperuricemia one or more times, and 3.5% of patients experienced clinically significant hyperuricemia reported as an adverse reaction versus 1.1% with placebo, according to the label. Gout was reported in 1.5% of patients treated with bempedoic acid and 0.4% of those treated with placebo.
Also in clinical trials, the risk of tendon rupture was 0.5% with bempedoic acid and 0% with placebo. Tendon rupture involved the rotator cuff, biceps tendon, or Achilles tendon, and occurred within weeks to months of starting the drug. Rupture may “occur more frequently in patients over 60 years of age, in those taking corticosteroid or fluoroquinolone drugs, in patients with renal failure, and in patients with previous tendon disorders,” the label states.
The label also advises that patients avoid concomitant use of bempedoic acid with simvastatin greater than 20 mg or pravastatin greater than 40 mg because it causes an increase in statin concentrations and may increase the risk of related myopathy.
A decision is expected shortly on a new drug application submitted by Esperion for an LDL cholesterol–lowering indication for bempedoic acid 180 mg/ezetimibe 10 mg combination tablet.
Full prescribing information is available online.
This article first appeared on Medscape.com.
Variants in common genes linked to endometrial cancer risk
The 24 single-nucleotide polymorphisms (SNPs) were detected in genes that function in transcriptional regulation, cell survival, and estrogen metabolism.
“Understanding genetic predisposition to endometrial cancer could facilitate personalized risk assessment with a view to targeted prevention and screening interventions,” wrote Cemsel Bafligil, of the University of Manchester (England) and her coinvestigators. The group’s findings were published in the Journal of Medical Genetics.
The researchers searched major databases for primary studies that evaluated associations between endometrial cancer and SNPs. After applying the search criteria, 453 eligible records were found, and 149 of these were included in the study.
The majority of records were genome-wide association studies, case-control studies, and meta-analyses. Various data, including study type, ethnicity, and endometrial cancer type, were extracted and included in the qualitative synthesis.
After analysis, the researchers identified 24 independent genetic variants associated with a higher risk of developing endometrial cancer, and SNPs in 6 genes – CYP19A1, SOX4, HNF1B, MYC, KLF, and EIF2AK – showed a strong association.
The researchers also estimated the predictive value of the identified SNPs using a theoretical polygenic risk score model. They found that women with genome-wide significant SNPs had double the risk of developing endometrial cancer (relative risk, 2.09), and women with all 24 SNPs had a three-fold greater risk of developing the disease (RR, 3.16).
“The importance of these variants and relevance of the proximate genes in a functional or biological context is challenging to evaluate,” the researchers noted.
They also acknowledged that a key limitation of this study was the ethnic homogeneity of the cohort, with most patients being of European descent. As a result, the findings may not be fully representative of other ethnic groups.
“The multiplicative effects of these SNPs could be used in a PRS [polygenic risk score] to allow personalised risk prediction models to be developed for targeted screening and prevention interventions for women at greatest risk of endometrial cancer,” the researchers concluded.
The National Institute for Health Research Manchester Biomedical Research Centre funded the study. The authors reported having no conflicts of interest.
SOURCE: Bafligil C et al. J Med Genet. 2020 Feb 17. doi: 10.1136/jmedgenet-2019-106529.
The 24 single-nucleotide polymorphisms (SNPs) were detected in genes that function in transcriptional regulation, cell survival, and estrogen metabolism.
“Understanding genetic predisposition to endometrial cancer could facilitate personalized risk assessment with a view to targeted prevention and screening interventions,” wrote Cemsel Bafligil, of the University of Manchester (England) and her coinvestigators. The group’s findings were published in the Journal of Medical Genetics.
The researchers searched major databases for primary studies that evaluated associations between endometrial cancer and SNPs. After applying the search criteria, 453 eligible records were found, and 149 of these were included in the study.
The majority of records were genome-wide association studies, case-control studies, and meta-analyses. Various data, including study type, ethnicity, and endometrial cancer type, were extracted and included in the qualitative synthesis.
After analysis, the researchers identified 24 independent genetic variants associated with a higher risk of developing endometrial cancer, and SNPs in 6 genes – CYP19A1, SOX4, HNF1B, MYC, KLF, and EIF2AK – showed a strong association.
The researchers also estimated the predictive value of the identified SNPs using a theoretical polygenic risk score model. They found that women with genome-wide significant SNPs had double the risk of developing endometrial cancer (relative risk, 2.09), and women with all 24 SNPs had a three-fold greater risk of developing the disease (RR, 3.16).
“The importance of these variants and relevance of the proximate genes in a functional or biological context is challenging to evaluate,” the researchers noted.
They also acknowledged that a key limitation of this study was the ethnic homogeneity of the cohort, with most patients being of European descent. As a result, the findings may not be fully representative of other ethnic groups.
“The multiplicative effects of these SNPs could be used in a PRS [polygenic risk score] to allow personalised risk prediction models to be developed for targeted screening and prevention interventions for women at greatest risk of endometrial cancer,” the researchers concluded.
The National Institute for Health Research Manchester Biomedical Research Centre funded the study. The authors reported having no conflicts of interest.
SOURCE: Bafligil C et al. J Med Genet. 2020 Feb 17. doi: 10.1136/jmedgenet-2019-106529.
The 24 single-nucleotide polymorphisms (SNPs) were detected in genes that function in transcriptional regulation, cell survival, and estrogen metabolism.
“Understanding genetic predisposition to endometrial cancer could facilitate personalized risk assessment with a view to targeted prevention and screening interventions,” wrote Cemsel Bafligil, of the University of Manchester (England) and her coinvestigators. The group’s findings were published in the Journal of Medical Genetics.
The researchers searched major databases for primary studies that evaluated associations between endometrial cancer and SNPs. After applying the search criteria, 453 eligible records were found, and 149 of these were included in the study.
The majority of records were genome-wide association studies, case-control studies, and meta-analyses. Various data, including study type, ethnicity, and endometrial cancer type, were extracted and included in the qualitative synthesis.
After analysis, the researchers identified 24 independent genetic variants associated with a higher risk of developing endometrial cancer, and SNPs in 6 genes – CYP19A1, SOX4, HNF1B, MYC, KLF, and EIF2AK – showed a strong association.
The researchers also estimated the predictive value of the identified SNPs using a theoretical polygenic risk score model. They found that women with genome-wide significant SNPs had double the risk of developing endometrial cancer (relative risk, 2.09), and women with all 24 SNPs had a three-fold greater risk of developing the disease (RR, 3.16).
“The importance of these variants and relevance of the proximate genes in a functional or biological context is challenging to evaluate,” the researchers noted.
They also acknowledged that a key limitation of this study was the ethnic homogeneity of the cohort, with most patients being of European descent. As a result, the findings may not be fully representative of other ethnic groups.
“The multiplicative effects of these SNPs could be used in a PRS [polygenic risk score] to allow personalised risk prediction models to be developed for targeted screening and prevention interventions for women at greatest risk of endometrial cancer,” the researchers concluded.
The National Institute for Health Research Manchester Biomedical Research Centre funded the study. The authors reported having no conflicts of interest.
SOURCE: Bafligil C et al. J Med Genet. 2020 Feb 17. doi: 10.1136/jmedgenet-2019-106529.
FROM THE JOURNAL OF MEDICAL GENETICS
Higher endovascular thrombectomy volumes yield better stroke outcomes
LOS ANGELES – Higher case volumes matter for getting better outcomes in acute ischemic stroke patients treated with endovascular thrombectomy, according to data from more than 13,000 Medicare patients treated during 2016 and 2017.
That’s hardly surprising, given that it’s consistent with what’s already been reported for several other types of endovascular and transcatheter procedures: The more cases a center or individual proceduralist performs, the better their patients do. Routine use of endovascular thrombectomy to treat selected acute ischemic stroke patients is a new-enough paradigm that until now few reports have come out that looked at this issue (Stroke. 2019 May;50[5]:1178-83).
The new analysis of Medicare data “is one of the first contemporary studies of the volume-outcome relationship in endovascular thrombectomy,” Laura K. Stein, MD, said at the International Stroke Conference sponsored by the American Heart Association. The analysis showed that, when the researchers adjusted the Medicare data to better reflect overall case volumes (Medicare patients represent just 59% of all endovascular thrombectomies performed on U.S. acute ischemic stroke patients), the minimum case number for a stroke center to have statistically better in-hospital survival than lower volume centers was 24 cases/year, and 29 cases/year to have a statistically significant higher rate of “good” outcomes than lower-volume centers, reported Dr. Stein, a stroke neurologist with the Mount Sinai Health System in New York. For individual proceduralists, the minimum, adjusted case number to have statistically better acute patient survival was 4 cases/year, and 19 cases/year to have a statistically better rate of good outcomes.
For this analysis, good outcomes were defined as cases when patients left the hospital following their acute care and returned home with either self care or a home health care service, and also patients discharged to rehabilitation. “Bad” outcomes for this analysis were discharges to a skilled nursing facility or hospice, as well as patients who died during their acute hospitalization.
The analyses also showed no plateau to the volume effect for any of the four parameters examined: in-hospital mortality by center and by proceduralist, and the rates of good outcomes by center and by proceduralist. For each of these measures, as case volume increased above the minimum number needed to produce statistically better outcomes, the rate of good outcomes continued to steadily rise and acute mortality continued to steadily fall.
The study run by Dr. Stein and associates used data collected by the Center for Medicare & Medicaid Services on 13,311 Medicare patients who underwent endovascular thrombectomy for acute ischemic stroke at any of 641 U.S. hospitals and received treatment from any of 2,754 thrombectomy proceduralists. Outcomes rated as good occurred in 56% of the patients. The statistical adjustments that the researchers applied to calculate the incremental effect of increasing case volume took into account the variables of patient age, sex, and comorbidities measured by the Charlson Comorbidity Index.
The analysis also showed that, during this 2-year period, the average number of endovascular thrombectomy cases among Medicare patients was just under 21 cases per center, with a range of 1-160 cases; for individual proceduralists, the average was just under 5 cases, with a range of 1-82 cases.
The 19 case/year volume minimum that the analysis identified for an individual proceduralist to have a statistically significant higher rate of good outcomes, compared with lower-volume proceduralists, came close to the 15 cases/year minimum set by the Joint Commission in 2019 for individual operators at centers seeking accreditation from the Joint Commission as either a Thrombectomy-Capable Stroke Center or a Comprehensive Stroke Center. The CMS has not yet set thrombectomy case-load requirements for centers or operators to qualify for Medicare reimbursements, although CMS has set such standards for other endovascular procedures, such as transcatheter aortic valve replacement. When setting such standards, CMS has cited its need to balance the better outcomes produced by higher-volume centers against a societal interest in facilitating access to vital medical services, a balance that Dr. Stein also highlighted in her talk.
“We want to optimize access as well as outcomes for every patient,” she said. “These data support certification volume standards,” but they are “in no way an argument for limiting access based on volume.”
Dr. Stein had no disclosures.
SOURCE: Stein LK et al. ISC 2020, Abstract LB11.
The results reported by Dr. Stein raise issues about balancing the access to certain therapies with the outcomes of those therapies. Having procedures like endovascular thrombectomy for acute ischemic stroke done primarily at high-volume centers might improve procedural outcomes, but having more centers offering this treatment across wider geographical areas would make this treatment more broadly available to more people.
For endovascular thrombectomy, center volume and experience may be much more important than proceduralist volume because having a smoothly functioning system in place is so important for rapid stroke assessment and treatment. It’s also important for programs to provide experienced and comprehensive postthrombectomy care. Success in endovascular thrombectomy involves much more than just taking a clot out. It means quickly and smoothly moving patients through the steps that precede thrombectomy and then following the intervention with a range of services that optimize recovery.
Ashutosh P. Jadhav, MD, PhD , is director of the comprehensive stroke center at the University of Pittsburgh. He had no relevant disclosures. He made these comments in an interview.
The results reported by Dr. Stein raise issues about balancing the access to certain therapies with the outcomes of those therapies. Having procedures like endovascular thrombectomy for acute ischemic stroke done primarily at high-volume centers might improve procedural outcomes, but having more centers offering this treatment across wider geographical areas would make this treatment more broadly available to more people.
For endovascular thrombectomy, center volume and experience may be much more important than proceduralist volume because having a smoothly functioning system in place is so important for rapid stroke assessment and treatment. It’s also important for programs to provide experienced and comprehensive postthrombectomy care. Success in endovascular thrombectomy involves much more than just taking a clot out. It means quickly and smoothly moving patients through the steps that precede thrombectomy and then following the intervention with a range of services that optimize recovery.
Ashutosh P. Jadhav, MD, PhD , is director of the comprehensive stroke center at the University of Pittsburgh. He had no relevant disclosures. He made these comments in an interview.
The results reported by Dr. Stein raise issues about balancing the access to certain therapies with the outcomes of those therapies. Having procedures like endovascular thrombectomy for acute ischemic stroke done primarily at high-volume centers might improve procedural outcomes, but having more centers offering this treatment across wider geographical areas would make this treatment more broadly available to more people.
For endovascular thrombectomy, center volume and experience may be much more important than proceduralist volume because having a smoothly functioning system in place is so important for rapid stroke assessment and treatment. It’s also important for programs to provide experienced and comprehensive postthrombectomy care. Success in endovascular thrombectomy involves much more than just taking a clot out. It means quickly and smoothly moving patients through the steps that precede thrombectomy and then following the intervention with a range of services that optimize recovery.
Ashutosh P. Jadhav, MD, PhD , is director of the comprehensive stroke center at the University of Pittsburgh. He had no relevant disclosures. He made these comments in an interview.
LOS ANGELES – Higher case volumes matter for getting better outcomes in acute ischemic stroke patients treated with endovascular thrombectomy, according to data from more than 13,000 Medicare patients treated during 2016 and 2017.
That’s hardly surprising, given that it’s consistent with what’s already been reported for several other types of endovascular and transcatheter procedures: The more cases a center or individual proceduralist performs, the better their patients do. Routine use of endovascular thrombectomy to treat selected acute ischemic stroke patients is a new-enough paradigm that until now few reports have come out that looked at this issue (Stroke. 2019 May;50[5]:1178-83).
The new analysis of Medicare data “is one of the first contemporary studies of the volume-outcome relationship in endovascular thrombectomy,” Laura K. Stein, MD, said at the International Stroke Conference sponsored by the American Heart Association. The analysis showed that, when the researchers adjusted the Medicare data to better reflect overall case volumes (Medicare patients represent just 59% of all endovascular thrombectomies performed on U.S. acute ischemic stroke patients), the minimum case number for a stroke center to have statistically better in-hospital survival than lower volume centers was 24 cases/year, and 29 cases/year to have a statistically significant higher rate of “good” outcomes than lower-volume centers, reported Dr. Stein, a stroke neurologist with the Mount Sinai Health System in New York. For individual proceduralists, the minimum, adjusted case number to have statistically better acute patient survival was 4 cases/year, and 19 cases/year to have a statistically better rate of good outcomes.
For this analysis, good outcomes were defined as cases when patients left the hospital following their acute care and returned home with either self care or a home health care service, and also patients discharged to rehabilitation. “Bad” outcomes for this analysis were discharges to a skilled nursing facility or hospice, as well as patients who died during their acute hospitalization.
The analyses also showed no plateau to the volume effect for any of the four parameters examined: in-hospital mortality by center and by proceduralist, and the rates of good outcomes by center and by proceduralist. For each of these measures, as case volume increased above the minimum number needed to produce statistically better outcomes, the rate of good outcomes continued to steadily rise and acute mortality continued to steadily fall.
The study run by Dr. Stein and associates used data collected by the Center for Medicare & Medicaid Services on 13,311 Medicare patients who underwent endovascular thrombectomy for acute ischemic stroke at any of 641 U.S. hospitals and received treatment from any of 2,754 thrombectomy proceduralists. Outcomes rated as good occurred in 56% of the patients. The statistical adjustments that the researchers applied to calculate the incremental effect of increasing case volume took into account the variables of patient age, sex, and comorbidities measured by the Charlson Comorbidity Index.
The analysis also showed that, during this 2-year period, the average number of endovascular thrombectomy cases among Medicare patients was just under 21 cases per center, with a range of 1-160 cases; for individual proceduralists, the average was just under 5 cases, with a range of 1-82 cases.
The 19 case/year volume minimum that the analysis identified for an individual proceduralist to have a statistically significant higher rate of good outcomes, compared with lower-volume proceduralists, came close to the 15 cases/year minimum set by the Joint Commission in 2019 for individual operators at centers seeking accreditation from the Joint Commission as either a Thrombectomy-Capable Stroke Center or a Comprehensive Stroke Center. The CMS has not yet set thrombectomy case-load requirements for centers or operators to qualify for Medicare reimbursements, although CMS has set such standards for other endovascular procedures, such as transcatheter aortic valve replacement. When setting such standards, CMS has cited its need to balance the better outcomes produced by higher-volume centers against a societal interest in facilitating access to vital medical services, a balance that Dr. Stein also highlighted in her talk.
“We want to optimize access as well as outcomes for every patient,” she said. “These data support certification volume standards,” but they are “in no way an argument for limiting access based on volume.”
Dr. Stein had no disclosures.
SOURCE: Stein LK et al. ISC 2020, Abstract LB11.
LOS ANGELES – Higher case volumes matter for getting better outcomes in acute ischemic stroke patients treated with endovascular thrombectomy, according to data from more than 13,000 Medicare patients treated during 2016 and 2017.
That’s hardly surprising, given that it’s consistent with what’s already been reported for several other types of endovascular and transcatheter procedures: The more cases a center or individual proceduralist performs, the better their patients do. Routine use of endovascular thrombectomy to treat selected acute ischemic stroke patients is a new-enough paradigm that until now few reports have come out that looked at this issue (Stroke. 2019 May;50[5]:1178-83).
The new analysis of Medicare data “is one of the first contemporary studies of the volume-outcome relationship in endovascular thrombectomy,” Laura K. Stein, MD, said at the International Stroke Conference sponsored by the American Heart Association. The analysis showed that, when the researchers adjusted the Medicare data to better reflect overall case volumes (Medicare patients represent just 59% of all endovascular thrombectomies performed on U.S. acute ischemic stroke patients), the minimum case number for a stroke center to have statistically better in-hospital survival than lower volume centers was 24 cases/year, and 29 cases/year to have a statistically significant higher rate of “good” outcomes than lower-volume centers, reported Dr. Stein, a stroke neurologist with the Mount Sinai Health System in New York. For individual proceduralists, the minimum, adjusted case number to have statistically better acute patient survival was 4 cases/year, and 19 cases/year to have a statistically better rate of good outcomes.
For this analysis, good outcomes were defined as cases when patients left the hospital following their acute care and returned home with either self care or a home health care service, and also patients discharged to rehabilitation. “Bad” outcomes for this analysis were discharges to a skilled nursing facility or hospice, as well as patients who died during their acute hospitalization.
The analyses also showed no plateau to the volume effect for any of the four parameters examined: in-hospital mortality by center and by proceduralist, and the rates of good outcomes by center and by proceduralist. For each of these measures, as case volume increased above the minimum number needed to produce statistically better outcomes, the rate of good outcomes continued to steadily rise and acute mortality continued to steadily fall.
The study run by Dr. Stein and associates used data collected by the Center for Medicare & Medicaid Services on 13,311 Medicare patients who underwent endovascular thrombectomy for acute ischemic stroke at any of 641 U.S. hospitals and received treatment from any of 2,754 thrombectomy proceduralists. Outcomes rated as good occurred in 56% of the patients. The statistical adjustments that the researchers applied to calculate the incremental effect of increasing case volume took into account the variables of patient age, sex, and comorbidities measured by the Charlson Comorbidity Index.
The analysis also showed that, during this 2-year period, the average number of endovascular thrombectomy cases among Medicare patients was just under 21 cases per center, with a range of 1-160 cases; for individual proceduralists, the average was just under 5 cases, with a range of 1-82 cases.
The 19 case/year volume minimum that the analysis identified for an individual proceduralist to have a statistically significant higher rate of good outcomes, compared with lower-volume proceduralists, came close to the 15 cases/year minimum set by the Joint Commission in 2019 for individual operators at centers seeking accreditation from the Joint Commission as either a Thrombectomy-Capable Stroke Center or a Comprehensive Stroke Center. The CMS has not yet set thrombectomy case-load requirements for centers or operators to qualify for Medicare reimbursements, although CMS has set such standards for other endovascular procedures, such as transcatheter aortic valve replacement. When setting such standards, CMS has cited its need to balance the better outcomes produced by higher-volume centers against a societal interest in facilitating access to vital medical services, a balance that Dr. Stein also highlighted in her talk.
“We want to optimize access as well as outcomes for every patient,” she said. “These data support certification volume standards,” but they are “in no way an argument for limiting access based on volume.”
Dr. Stein had no disclosures.
SOURCE: Stein LK et al. ISC 2020, Abstract LB11.
REPORTING FROM ISC 2020
Late effects in young cancer survivors underscore importance of high-risk screening
according to data from the Childhood Cancer Survivor Study.
At a median follow-up of 21 years, the SMR for all-cause mortality was 5.9 among survivors aged 15-20 years and 6.2 among diagnosis-matched children under 15 years, compared with expected rates at the same ages in the general population. For health-related causes – excluding primary cancer recurrence or progression but including late effects of cancer therapy – the SMRs were 4.8 in the older group and 6.8 in the younger group.
Eugene Suh, MD, of Loyola University Chicago Medical Center, Maywood, Ill., and colleagues reported these results in Lancet Oncology.
The difference between the older and younger survivors (n = 5,804 in each group) was most evident at least 20 years after cancer diagnosis, the authors noted.
For both groups, but more so for childhood cancer survivors, the risk of developing any chronic health condition and any grade 3-5 health condition was greater than for siblings of the same age who did not have cancer (hazard ratios, 4.2 for adolescents/young adults and 5.6 for childhood survivors). The same was true for grade 3-5 cardiac conditions (HRs, 4.3 and 5.6, respectively), endocrine conditions (HRs, 3.9 and 6.4, respectively), and musculoskeletal conditions (HRs, 6.5 and 8.0, respectively).
These findings, which confirm those of previous studies suggesting that younger children might be more vulnerable to the adverse effects of cancer treatment, “underscore that focused efforts are needed to ensure early-adolescent and young adult cancer survivors are receiving recommended risk-based care, with a focus on high-risk cancer screening, to reduce morbidity and premature mortality,” the researchers concluded, noting that “studies to date indicate that adherence to such high-risk screening is poor.”
In a related editorial, Päivi Lähteenmäki, MD, PhD, of University of Turku (Finland) and Turku University Hospital, wrote that these findings warrant long-term follow-up of adolescent and young adult cancer survivors. She also argued that the results “might not be fully generalizable to patients treated today who might be on different treatment regimens to those treated in previous decades” and that “[m]ore prospectively collected objective data focusing on survivors ... are needed.”
Accurate characterization of patients at high risk who would benefit from a tailored screening program is most important, and identifying underlying genetic or molecular factors that confer higher risk for late sequelae would be useful for “planning approaches to survivorship,” Dr. Lähteenmäki added.
This study was funded by the National Cancer Institute and American Lebanese-Syrian Associated Charities. Dr. Suh and Dr. Lähteenmäki reported having no competing interests.
SOURCES: Suh E et al. Lancet Oncology. 2020 Feb 14. doi: 10.1016/S1470-2045(19)30800-9;Lähteenmäki P. Lancet Oncol. 2020 Feb 14. doi: 10.106/S1470-2045(19)30858-7.
according to data from the Childhood Cancer Survivor Study.
At a median follow-up of 21 years, the SMR for all-cause mortality was 5.9 among survivors aged 15-20 years and 6.2 among diagnosis-matched children under 15 years, compared with expected rates at the same ages in the general population. For health-related causes – excluding primary cancer recurrence or progression but including late effects of cancer therapy – the SMRs were 4.8 in the older group and 6.8 in the younger group.
Eugene Suh, MD, of Loyola University Chicago Medical Center, Maywood, Ill., and colleagues reported these results in Lancet Oncology.
The difference between the older and younger survivors (n = 5,804 in each group) was most evident at least 20 years after cancer diagnosis, the authors noted.
For both groups, but more so for childhood cancer survivors, the risk of developing any chronic health condition and any grade 3-5 health condition was greater than for siblings of the same age who did not have cancer (hazard ratios, 4.2 for adolescents/young adults and 5.6 for childhood survivors). The same was true for grade 3-5 cardiac conditions (HRs, 4.3 and 5.6, respectively), endocrine conditions (HRs, 3.9 and 6.4, respectively), and musculoskeletal conditions (HRs, 6.5 and 8.0, respectively).
These findings, which confirm those of previous studies suggesting that younger children might be more vulnerable to the adverse effects of cancer treatment, “underscore that focused efforts are needed to ensure early-adolescent and young adult cancer survivors are receiving recommended risk-based care, with a focus on high-risk cancer screening, to reduce morbidity and premature mortality,” the researchers concluded, noting that “studies to date indicate that adherence to such high-risk screening is poor.”
In a related editorial, Päivi Lähteenmäki, MD, PhD, of University of Turku (Finland) and Turku University Hospital, wrote that these findings warrant long-term follow-up of adolescent and young adult cancer survivors. She also argued that the results “might not be fully generalizable to patients treated today who might be on different treatment regimens to those treated in previous decades” and that “[m]ore prospectively collected objective data focusing on survivors ... are needed.”
Accurate characterization of patients at high risk who would benefit from a tailored screening program is most important, and identifying underlying genetic or molecular factors that confer higher risk for late sequelae would be useful for “planning approaches to survivorship,” Dr. Lähteenmäki added.
This study was funded by the National Cancer Institute and American Lebanese-Syrian Associated Charities. Dr. Suh and Dr. Lähteenmäki reported having no competing interests.
SOURCES: Suh E et al. Lancet Oncology. 2020 Feb 14. doi: 10.1016/S1470-2045(19)30800-9;Lähteenmäki P. Lancet Oncol. 2020 Feb 14. doi: 10.106/S1470-2045(19)30858-7.
according to data from the Childhood Cancer Survivor Study.
At a median follow-up of 21 years, the SMR for all-cause mortality was 5.9 among survivors aged 15-20 years and 6.2 among diagnosis-matched children under 15 years, compared with expected rates at the same ages in the general population. For health-related causes – excluding primary cancer recurrence or progression but including late effects of cancer therapy – the SMRs were 4.8 in the older group and 6.8 in the younger group.
Eugene Suh, MD, of Loyola University Chicago Medical Center, Maywood, Ill., and colleagues reported these results in Lancet Oncology.
The difference between the older and younger survivors (n = 5,804 in each group) was most evident at least 20 years after cancer diagnosis, the authors noted.
For both groups, but more so for childhood cancer survivors, the risk of developing any chronic health condition and any grade 3-5 health condition was greater than for siblings of the same age who did not have cancer (hazard ratios, 4.2 for adolescents/young adults and 5.6 for childhood survivors). The same was true for grade 3-5 cardiac conditions (HRs, 4.3 and 5.6, respectively), endocrine conditions (HRs, 3.9 and 6.4, respectively), and musculoskeletal conditions (HRs, 6.5 and 8.0, respectively).
These findings, which confirm those of previous studies suggesting that younger children might be more vulnerable to the adverse effects of cancer treatment, “underscore that focused efforts are needed to ensure early-adolescent and young adult cancer survivors are receiving recommended risk-based care, with a focus on high-risk cancer screening, to reduce morbidity and premature mortality,” the researchers concluded, noting that “studies to date indicate that adherence to such high-risk screening is poor.”
In a related editorial, Päivi Lähteenmäki, MD, PhD, of University of Turku (Finland) and Turku University Hospital, wrote that these findings warrant long-term follow-up of adolescent and young adult cancer survivors. She also argued that the results “might not be fully generalizable to patients treated today who might be on different treatment regimens to those treated in previous decades” and that “[m]ore prospectively collected objective data focusing on survivors ... are needed.”
Accurate characterization of patients at high risk who would benefit from a tailored screening program is most important, and identifying underlying genetic or molecular factors that confer higher risk for late sequelae would be useful for “planning approaches to survivorship,” Dr. Lähteenmäki added.
This study was funded by the National Cancer Institute and American Lebanese-Syrian Associated Charities. Dr. Suh and Dr. Lähteenmäki reported having no competing interests.
SOURCES: Suh E et al. Lancet Oncology. 2020 Feb 14. doi: 10.1016/S1470-2045(19)30800-9;Lähteenmäki P. Lancet Oncol. 2020 Feb 14. doi: 10.106/S1470-2045(19)30858-7.
FROM LANCET ONCOLOGY
Medical malpractice insurance premiums likely to rise in 2020
For more than a decade, most physicians have paid a steady amount for medical liability insurance. But that price stability appears to be ending, according to a recent analysis.
In 2019, more than 25% of medical liability insurance premiums rose for internists, ob.gyns., and surgeons, a review by the Medical Liability Monitor (MLM) found. The MLM survey, published annually, analyzes premium data from major malpractice insurers based on mature, claims-made policies with $1 million/$3 million limits for internists, general surgeons, and ob.gyns.
The increases mark a shift in the long-stable market and suggest rising premiums in the future, said Michael Matray, editor for the Medical Liability Monitor.
“It’s my impression that rates will increase again in [2020]. It’s almost a foregone conclusion,” he said in an interview. “We can expect more firming within the market.”
Most of the premium increases in 2019 were small – between 0.1% and 10%, Mr. Matray said. At the same time, close to 70% of premium rates were flat in 2019 and about 5% of premium rates decreased, according to the survey, released in late 2019.
Comparatively, about 58% of premium rates were flat from 2007 to 2014, about 30% of rates went down during that time frame, and 12% of rates went up. From 2015 to 2018, nearly 76% of rates were steady, 10% went down, and 15% of rates increased, according to the latest analysis. 2019 was the first time since 2006 that more than 25% of premium rates rose, the survey noted.
“This is a normal cycle for the insurance industry – years of feast, followed by years of famine. Eventually companies reach a point where they feel enough pain and one response is to raise rates,” said Alyssa Gittleman, a coauthor of the survey and senior associate in the insurance research department at Conning, an investment management firm for the insurance industry.
“We could also point out many of the rate increases reported in the survey came from the larger [medical professional liability] companies. These companies are well capitalized, and the fact that they are raising rates could be a bellwether that a hard market is coming. However, as we said in the survey, it will probably take another 12-24 months before we know for certain,” she added.
Location, location, location
Physicians continue to pay vastly different premiums depending on where they practice. Ob.gyns. in eastern New York for example, paid about $201,000 in 2019, while their Minnesota colleagues paid about $16,500. Internists in southern Florida, meanwhile, paid about $49,000 in 2019, while their counterparts in northern California paid about $4,100. General surgeons in southern Florida paid about $195,000 for malpractice insurance, while some Wisconsin general surgeons paid about $11,000.
“Medical malpractice rates are determined locally, that’s why we don’t give state averages or national averages [in the survey],” Mr. Matray said. “It’s all determined by malpractice claims history within that territory and how aggressive the plaintiffs bar is in those areas.”
Two states – Arizona and Pennsylvania – experienced exceptional rate decreases in 2019. In Arizona, The Doctors Company lowered their rates by more than 60% for internists, general surgeons, and ob.gyns. In Pennsylvania, which operates a patient compensation fund, The Doctors Company decreased its rates between 20% and 46% for each of the three specialties. The insurer reported it made the decreases to align its rates with other insurers in those states, according to the survey. The Doctors Company did not respond to messages seeking comment for this article.
When individual companies greatly increase or greatly decrease rates in a given state, it’s generally to bring their rates in line with those of larger companies in the market, said Bill Burns, a coauthor of the MLM report and a vice president in the insurance research department at Conning. In 2018, The Doctors Company held about 2% of the market in Arizona, and the company held about 1% of the Pennsylvania market, he noted.
“These decreases, which get them in line with the larger writers, should tighten up the range of rates in those states,” Mr. Burns said in an interview. “To sell the product, they’re going to have be close to the competition.”
For a clear picture of the overall premium landscape, the survey authors analyzed the data both with and without the exceptional rate decreases in Arizona and Pennsylvania. Regionally – excluding the exceptional decreases – the average premium rate increase was 2% in the Midwest, 1.4% in the Northeast, 1.1% in the South, and 0.3% in the West.
For all three specialties surveyed, premiums rose slightly in 2019, with surgeons experiencing the largest increase. Internists saw a nearly 1% average rate increase, ob.gyns. experienced a 0.5% rise, and surgeons experienced a 2.3% rate increase, the survey found. For doctors in the seven states that have patient compensation funds, internists experienced a nearly 2.1% average rate increase, ob.gyns. saw a 1.4% rise, and surgeons experienced a 2.1% rate increase. (These data sets exclude the exceptional rate decreases in Arizona and Pennsylvania.)
The change in rates for general surgery could mean more claims are being filed against surgeons or that the cost of claims are rising, Mr. Burns said.
“The differences are not terribly significant, but suggest something is happening with general surgery,” he said.
Why are rates on the rise?
A number of factors are behind the changing medical liability insurance market, said Brian Atchinson, president and CEO for the Medical Professional Liability Association (MPL Association), a trade association for medical liability insurers.
While the frequency of claims against physicians has remained flat for an extended period of time, the cost of managing those claims has continued to increase, he said.
“Medical liability insurers insuring physicians and other clinicians, they need to defend every claim that they believe warrants defense,” Mr. Atchinson said in an interview. “When the medical treatment provided is within the appropriate standards, even though there may be claims or lawsuits, every one of those [cases] can be very expensive to defend.”
Other contributers to the increasing rates include the trend of high-dollar settlements and judgments, particularly in the hospital space, Mr. Atchinson noted. Such large payouts are generally tied to hospital and health system claims, but they still affect the broader medical liability insurance marketplace, he said.
Additionally, a growing number of medical liability tort reform measures enacted over the last 20 years are being eliminated, Mr. Atchinson said. In June 2019, the Kansas Supreme Court for instance, struck down the state’s cap on damages for noneconomic injuries in medical liability cases. In a 2017 ruling, the Pennsylvania Supreme Court changed the state’s statue of limitations for medical malpractice wrongful death claims from 2 years from the time of the patient’s injury to 2 years from the time of the patient’s death.
When legislatures change state laws and courts invalidate protections against nonmeritorious lawsuits, the actions can have serious consequences for physicians and companies operating in those states, Mr. Atchinson said.
“These [changes] will all ultimately work their way into the rates that physicians are paying,” he said.
For more than a decade, most physicians have paid a steady amount for medical liability insurance. But that price stability appears to be ending, according to a recent analysis.
In 2019, more than 25% of medical liability insurance premiums rose for internists, ob.gyns., and surgeons, a review by the Medical Liability Monitor (MLM) found. The MLM survey, published annually, analyzes premium data from major malpractice insurers based on mature, claims-made policies with $1 million/$3 million limits for internists, general surgeons, and ob.gyns.
The increases mark a shift in the long-stable market and suggest rising premiums in the future, said Michael Matray, editor for the Medical Liability Monitor.
“It’s my impression that rates will increase again in [2020]. It’s almost a foregone conclusion,” he said in an interview. “We can expect more firming within the market.”
Most of the premium increases in 2019 were small – between 0.1% and 10%, Mr. Matray said. At the same time, close to 70% of premium rates were flat in 2019 and about 5% of premium rates decreased, according to the survey, released in late 2019.
Comparatively, about 58% of premium rates were flat from 2007 to 2014, about 30% of rates went down during that time frame, and 12% of rates went up. From 2015 to 2018, nearly 76% of rates were steady, 10% went down, and 15% of rates increased, according to the latest analysis. 2019 was the first time since 2006 that more than 25% of premium rates rose, the survey noted.
“This is a normal cycle for the insurance industry – years of feast, followed by years of famine. Eventually companies reach a point where they feel enough pain and one response is to raise rates,” said Alyssa Gittleman, a coauthor of the survey and senior associate in the insurance research department at Conning, an investment management firm for the insurance industry.
“We could also point out many of the rate increases reported in the survey came from the larger [medical professional liability] companies. These companies are well capitalized, and the fact that they are raising rates could be a bellwether that a hard market is coming. However, as we said in the survey, it will probably take another 12-24 months before we know for certain,” she added.
Location, location, location
Physicians continue to pay vastly different premiums depending on where they practice. Ob.gyns. in eastern New York for example, paid about $201,000 in 2019, while their Minnesota colleagues paid about $16,500. Internists in southern Florida, meanwhile, paid about $49,000 in 2019, while their counterparts in northern California paid about $4,100. General surgeons in southern Florida paid about $195,000 for malpractice insurance, while some Wisconsin general surgeons paid about $11,000.
“Medical malpractice rates are determined locally, that’s why we don’t give state averages or national averages [in the survey],” Mr. Matray said. “It’s all determined by malpractice claims history within that territory and how aggressive the plaintiffs bar is in those areas.”
Two states – Arizona and Pennsylvania – experienced exceptional rate decreases in 2019. In Arizona, The Doctors Company lowered their rates by more than 60% for internists, general surgeons, and ob.gyns. In Pennsylvania, which operates a patient compensation fund, The Doctors Company decreased its rates between 20% and 46% for each of the three specialties. The insurer reported it made the decreases to align its rates with other insurers in those states, according to the survey. The Doctors Company did not respond to messages seeking comment for this article.
When individual companies greatly increase or greatly decrease rates in a given state, it’s generally to bring their rates in line with those of larger companies in the market, said Bill Burns, a coauthor of the MLM report and a vice president in the insurance research department at Conning. In 2018, The Doctors Company held about 2% of the market in Arizona, and the company held about 1% of the Pennsylvania market, he noted.
“These decreases, which get them in line with the larger writers, should tighten up the range of rates in those states,” Mr. Burns said in an interview. “To sell the product, they’re going to have be close to the competition.”
For a clear picture of the overall premium landscape, the survey authors analyzed the data both with and without the exceptional rate decreases in Arizona and Pennsylvania. Regionally – excluding the exceptional decreases – the average premium rate increase was 2% in the Midwest, 1.4% in the Northeast, 1.1% in the South, and 0.3% in the West.
For all three specialties surveyed, premiums rose slightly in 2019, with surgeons experiencing the largest increase. Internists saw a nearly 1% average rate increase, ob.gyns. experienced a 0.5% rise, and surgeons experienced a 2.3% rate increase, the survey found. For doctors in the seven states that have patient compensation funds, internists experienced a nearly 2.1% average rate increase, ob.gyns. saw a 1.4% rise, and surgeons experienced a 2.1% rate increase. (These data sets exclude the exceptional rate decreases in Arizona and Pennsylvania.)
The change in rates for general surgery could mean more claims are being filed against surgeons or that the cost of claims are rising, Mr. Burns said.
“The differences are not terribly significant, but suggest something is happening with general surgery,” he said.
Why are rates on the rise?
A number of factors are behind the changing medical liability insurance market, said Brian Atchinson, president and CEO for the Medical Professional Liability Association (MPL Association), a trade association for medical liability insurers.
While the frequency of claims against physicians has remained flat for an extended period of time, the cost of managing those claims has continued to increase, he said.
“Medical liability insurers insuring physicians and other clinicians, they need to defend every claim that they believe warrants defense,” Mr. Atchinson said in an interview. “When the medical treatment provided is within the appropriate standards, even though there may be claims or lawsuits, every one of those [cases] can be very expensive to defend.”
Other contributers to the increasing rates include the trend of high-dollar settlements and judgments, particularly in the hospital space, Mr. Atchinson noted. Such large payouts are generally tied to hospital and health system claims, but they still affect the broader medical liability insurance marketplace, he said.
Additionally, a growing number of medical liability tort reform measures enacted over the last 20 years are being eliminated, Mr. Atchinson said. In June 2019, the Kansas Supreme Court for instance, struck down the state’s cap on damages for noneconomic injuries in medical liability cases. In a 2017 ruling, the Pennsylvania Supreme Court changed the state’s statue of limitations for medical malpractice wrongful death claims from 2 years from the time of the patient’s injury to 2 years from the time of the patient’s death.
When legislatures change state laws and courts invalidate protections against nonmeritorious lawsuits, the actions can have serious consequences for physicians and companies operating in those states, Mr. Atchinson said.
“These [changes] will all ultimately work their way into the rates that physicians are paying,” he said.
For more than a decade, most physicians have paid a steady amount for medical liability insurance. But that price stability appears to be ending, according to a recent analysis.
In 2019, more than 25% of medical liability insurance premiums rose for internists, ob.gyns., and surgeons, a review by the Medical Liability Monitor (MLM) found. The MLM survey, published annually, analyzes premium data from major malpractice insurers based on mature, claims-made policies with $1 million/$3 million limits for internists, general surgeons, and ob.gyns.
The increases mark a shift in the long-stable market and suggest rising premiums in the future, said Michael Matray, editor for the Medical Liability Monitor.
“It’s my impression that rates will increase again in [2020]. It’s almost a foregone conclusion,” he said in an interview. “We can expect more firming within the market.”
Most of the premium increases in 2019 were small – between 0.1% and 10%, Mr. Matray said. At the same time, close to 70% of premium rates were flat in 2019 and about 5% of premium rates decreased, according to the survey, released in late 2019.
Comparatively, about 58% of premium rates were flat from 2007 to 2014, about 30% of rates went down during that time frame, and 12% of rates went up. From 2015 to 2018, nearly 76% of rates were steady, 10% went down, and 15% of rates increased, according to the latest analysis. 2019 was the first time since 2006 that more than 25% of premium rates rose, the survey noted.
“This is a normal cycle for the insurance industry – years of feast, followed by years of famine. Eventually companies reach a point where they feel enough pain and one response is to raise rates,” said Alyssa Gittleman, a coauthor of the survey and senior associate in the insurance research department at Conning, an investment management firm for the insurance industry.
“We could also point out many of the rate increases reported in the survey came from the larger [medical professional liability] companies. These companies are well capitalized, and the fact that they are raising rates could be a bellwether that a hard market is coming. However, as we said in the survey, it will probably take another 12-24 months before we know for certain,” she added.
Location, location, location
Physicians continue to pay vastly different premiums depending on where they practice. Ob.gyns. in eastern New York for example, paid about $201,000 in 2019, while their Minnesota colleagues paid about $16,500. Internists in southern Florida, meanwhile, paid about $49,000 in 2019, while their counterparts in northern California paid about $4,100. General surgeons in southern Florida paid about $195,000 for malpractice insurance, while some Wisconsin general surgeons paid about $11,000.
“Medical malpractice rates are determined locally, that’s why we don’t give state averages or national averages [in the survey],” Mr. Matray said. “It’s all determined by malpractice claims history within that territory and how aggressive the plaintiffs bar is in those areas.”
Two states – Arizona and Pennsylvania – experienced exceptional rate decreases in 2019. In Arizona, The Doctors Company lowered their rates by more than 60% for internists, general surgeons, and ob.gyns. In Pennsylvania, which operates a patient compensation fund, The Doctors Company decreased its rates between 20% and 46% for each of the three specialties. The insurer reported it made the decreases to align its rates with other insurers in those states, according to the survey. The Doctors Company did not respond to messages seeking comment for this article.
When individual companies greatly increase or greatly decrease rates in a given state, it’s generally to bring their rates in line with those of larger companies in the market, said Bill Burns, a coauthor of the MLM report and a vice president in the insurance research department at Conning. In 2018, The Doctors Company held about 2% of the market in Arizona, and the company held about 1% of the Pennsylvania market, he noted.
“These decreases, which get them in line with the larger writers, should tighten up the range of rates in those states,” Mr. Burns said in an interview. “To sell the product, they’re going to have be close to the competition.”
For a clear picture of the overall premium landscape, the survey authors analyzed the data both with and without the exceptional rate decreases in Arizona and Pennsylvania. Regionally – excluding the exceptional decreases – the average premium rate increase was 2% in the Midwest, 1.4% in the Northeast, 1.1% in the South, and 0.3% in the West.
For all three specialties surveyed, premiums rose slightly in 2019, with surgeons experiencing the largest increase. Internists saw a nearly 1% average rate increase, ob.gyns. experienced a 0.5% rise, and surgeons experienced a 2.3% rate increase, the survey found. For doctors in the seven states that have patient compensation funds, internists experienced a nearly 2.1% average rate increase, ob.gyns. saw a 1.4% rise, and surgeons experienced a 2.1% rate increase. (These data sets exclude the exceptional rate decreases in Arizona and Pennsylvania.)
The change in rates for general surgery could mean more claims are being filed against surgeons or that the cost of claims are rising, Mr. Burns said.
“The differences are not terribly significant, but suggest something is happening with general surgery,” he said.
Why are rates on the rise?
A number of factors are behind the changing medical liability insurance market, said Brian Atchinson, president and CEO for the Medical Professional Liability Association (MPL Association), a trade association for medical liability insurers.
While the frequency of claims against physicians has remained flat for an extended period of time, the cost of managing those claims has continued to increase, he said.
“Medical liability insurers insuring physicians and other clinicians, they need to defend every claim that they believe warrants defense,” Mr. Atchinson said in an interview. “When the medical treatment provided is within the appropriate standards, even though there may be claims or lawsuits, every one of those [cases] can be very expensive to defend.”
Other contributers to the increasing rates include the trend of high-dollar settlements and judgments, particularly in the hospital space, Mr. Atchinson noted. Such large payouts are generally tied to hospital and health system claims, but they still affect the broader medical liability insurance marketplace, he said.
Additionally, a growing number of medical liability tort reform measures enacted over the last 20 years are being eliminated, Mr. Atchinson said. In June 2019, the Kansas Supreme Court for instance, struck down the state’s cap on damages for noneconomic injuries in medical liability cases. In a 2017 ruling, the Pennsylvania Supreme Court changed the state’s statue of limitations for medical malpractice wrongful death claims from 2 years from the time of the patient’s injury to 2 years from the time of the patient’s death.
When legislatures change state laws and courts invalidate protections against nonmeritorious lawsuits, the actions can have serious consequences for physicians and companies operating in those states, Mr. Atchinson said.
“These [changes] will all ultimately work their way into the rates that physicians are paying,” he said.
Resident experience with hysterectomy is on the decline
The total number of hysterectomies performed during residency training has declined significantly since 2008, despite an increase in laparoscopic hysterectomies performed, according to a new analysis of data from graduating ob.gyn. residents that has implications for the structure of resident education.
The investigators abstracted case log data from the Accreditation Council for Graduate Medical Education (ACGME) database to assess trends in residents’ operative experience and found decreases in abdominal and vaginal cases but an increase in experience with laparoscopic hysterectomy.
(from 85 cases to 37), and the median number of vaginal hysterectomies decreased by 36% (from 31 to 20 cases).
Laparoscopic hysterectomy increased by 115% from a median of 20 procedures in 2008-2009 to 43 in 2017-2018. Even so, the median total number of hysterectomies per resident decreased by 6%, from 112 to 105 procedures during those two time periods. (Data on total hysterectomy and laparoscopic hysterectomy were not collected by ACGME until 2008.)
While the absolute decrease in the total number of hysterectomies is “relatively small,” the trend “raises questions about what the appropriate number of hysterectomies per graduating resident should be,” Gregory M. Gressel, MD, MSc, of the Montefiore Medical Center, New York, and coauthors wrote in Obstetrics & Gynecology.
“These data point,” they wrote, “to the necessity of maximizing surgical exposure in the face of a declining availability of procedures and the importance of reflecting on which (and how many) procedures an obstetrics and gynecology resident needs to complete before entering clinical practice.”
The training numbers parallel an increased use of laparoscopic hysterectomy in the United States and other countries, as well as a well-documented decline in the total number of hysterectomies performed in the United States, the latter of which is driven largely by the availability and increasing use of alternatives to the procedure (such as hormone therapy, endometrial ablation, and uterine artery embolization).
Hysterectomy still is a “core procedure of gynecologic surgery,” however, and is “at the heart of surgical training in obstetrics and gynecology,” as surgical techniques developed from learning hysterectomy “are applied broadly in the pelvis,” Saketh R. Guntupalli, MD, wrote in an accompanying editorial.
Dr. Guntupalli, of the University of Colorado at Aurora, Denver, was involved in a survey of fellowship program directors, published in 2015, that found only 20% of first-year fellows were able to independently perform a vaginal hysterectomy and 46% to independently perform an abdominal hysterectomy (Obstet Gynecol. 2015;126:559-68).
This and other research suggest that fellowship training is “used to address deficiencies in residency training rather than to develop new, specialized surgical skills,” he wrote. Given a dearth of fellowship positions in ob.gyn., “it is impossible to adequately use those avenues to train the number of competent surgeons necessary to address the surgical needs of women’s health in the United States.”
To address such concerns, some residency programs have instituted resident tracking to direct more hysterectomy cases toward those residents who plan to pursue surgical subspecialties. The Cleveland Clinic, Dr. Guntupalli noted, has tried the latter approach “with success.”
An increase in the number of accredited training programs and a decrease in the number of residents per program also might help to improve surgical exposure for residents, Dr. Gressel and associates wrote. Over the 16-year study period, the number of graduating residents increased significantly (by 12 per year) and the number of residency programs decreased significantly (0.52 fewer programs per year).
Additionally, Dr. Guntupalli wrote, regulatory bodies may need to reevaluate how competencies are assessed, and whether minimal numbers of cases “continue to carry the same weight as they did in previous generations.”
In the study, one coauthor is a full-time employee of ACGME, and another receives funds as a director for the American Board of Obstetrics and Gynecology. The remaining authors had no relevant financial disclosures. There was no outside funding for the study. Dr. Guntupalli said he had no conflicts of interest.
SOURCES: Gressel GM et al. Obstet Gynecol. 2020 Feb;135(2):268-73; Guntupalli SR. Obstet Gynecol 2020 Feb;135(2):266-7.
This excellent paper by Dr. Gressel and coauthors shows decreasing numbers of hysterectomies – especially open and vaginal approaches – being performed by ob.gyn. residents. Considering also the 2015 publication by Guntupalli et al. showing the low numbers of incoming fellows able to perform hysterectomy, as well as Dr. Guntupalli’s editorial on this new research, we all must question how our patients will be able to undergo safe and effective surgery in the future.
Furthermore, it would truly be disheartening and disconcerting for a young physician to choose a residency with the desire of a specific track, only to lose that choice to a coresident.
In his presidential address to the AAGL some years ago, Javier Magrina, MD, of the Mayo Clinic in Phoenix, discussed separating the “O from the G” (J Minim Invasive Gynecol. 2014;21[4]:501-3). Among his points: From 1979 to 2006, there was a 46% decrease in the number of gynecologic operations (2,852,000 vs. 1,309,000), a 54% increase in the number of American College of Obstetricians and Gynecologists’ fellows (21,364 vs. 51,123), and an 81% decrease in the number of gynecologic operations performed per ACOG fellow (132 vs. 25).
In 1980, he pointed out, the total number of hysterectomy procedures performed in the United States was 647,000. In 2007, this total was 517,000. The total number of ACOG fellows in 1980 was 22,516, compared with 52,385 in 2007. And the total number of hysterectomies performed per ACOG fellow was 28, compared with 9.8 hysterectomies per fellow in 2007.
Dr. Magrina’s data goes hand in hand with Dr. Gressel’s new study. The surgical experience of the gynecologic surgeon certainly is on the wane. The result of this lack of experience is noted by Dr. Guntupalli in his 2015 publication. To us, it is readily apparent that Dr. Magrina is right: The only true solution is to finally realize that we must separate the O from the G.
Charles E. Miller, MD, is director of minimally invasive gynecologic surgery, and director of the AAGL fellowship in minimally invasive gynecologic surgery, at Advocate Lutheran General Hospital, Park Ridge, Ill. Kirsten Sasaki, MD, is associate director of the AAGL fellowship in minimally invasive gynecologic surgery at Advocate Lutheran. They have no other conflicts of interest.
This excellent paper by Dr. Gressel and coauthors shows decreasing numbers of hysterectomies – especially open and vaginal approaches – being performed by ob.gyn. residents. Considering also the 2015 publication by Guntupalli et al. showing the low numbers of incoming fellows able to perform hysterectomy, as well as Dr. Guntupalli’s editorial on this new research, we all must question how our patients will be able to undergo safe and effective surgery in the future.
Furthermore, it would truly be disheartening and disconcerting for a young physician to choose a residency with the desire of a specific track, only to lose that choice to a coresident.
In his presidential address to the AAGL some years ago, Javier Magrina, MD, of the Mayo Clinic in Phoenix, discussed separating the “O from the G” (J Minim Invasive Gynecol. 2014;21[4]:501-3). Among his points: From 1979 to 2006, there was a 46% decrease in the number of gynecologic operations (2,852,000 vs. 1,309,000), a 54% increase in the number of American College of Obstetricians and Gynecologists’ fellows (21,364 vs. 51,123), and an 81% decrease in the number of gynecologic operations performed per ACOG fellow (132 vs. 25).
In 1980, he pointed out, the total number of hysterectomy procedures performed in the United States was 647,000. In 2007, this total was 517,000. The total number of ACOG fellows in 1980 was 22,516, compared with 52,385 in 2007. And the total number of hysterectomies performed per ACOG fellow was 28, compared with 9.8 hysterectomies per fellow in 2007.
Dr. Magrina’s data goes hand in hand with Dr. Gressel’s new study. The surgical experience of the gynecologic surgeon certainly is on the wane. The result of this lack of experience is noted by Dr. Guntupalli in his 2015 publication. To us, it is readily apparent that Dr. Magrina is right: The only true solution is to finally realize that we must separate the O from the G.
Charles E. Miller, MD, is director of minimally invasive gynecologic surgery, and director of the AAGL fellowship in minimally invasive gynecologic surgery, at Advocate Lutheran General Hospital, Park Ridge, Ill. Kirsten Sasaki, MD, is associate director of the AAGL fellowship in minimally invasive gynecologic surgery at Advocate Lutheran. They have no other conflicts of interest.
This excellent paper by Dr. Gressel and coauthors shows decreasing numbers of hysterectomies – especially open and vaginal approaches – being performed by ob.gyn. residents. Considering also the 2015 publication by Guntupalli et al. showing the low numbers of incoming fellows able to perform hysterectomy, as well as Dr. Guntupalli’s editorial on this new research, we all must question how our patients will be able to undergo safe and effective surgery in the future.
Furthermore, it would truly be disheartening and disconcerting for a young physician to choose a residency with the desire of a specific track, only to lose that choice to a coresident.
In his presidential address to the AAGL some years ago, Javier Magrina, MD, of the Mayo Clinic in Phoenix, discussed separating the “O from the G” (J Minim Invasive Gynecol. 2014;21[4]:501-3). Among his points: From 1979 to 2006, there was a 46% decrease in the number of gynecologic operations (2,852,000 vs. 1,309,000), a 54% increase in the number of American College of Obstetricians and Gynecologists’ fellows (21,364 vs. 51,123), and an 81% decrease in the number of gynecologic operations performed per ACOG fellow (132 vs. 25).
In 1980, he pointed out, the total number of hysterectomy procedures performed in the United States was 647,000. In 2007, this total was 517,000. The total number of ACOG fellows in 1980 was 22,516, compared with 52,385 in 2007. And the total number of hysterectomies performed per ACOG fellow was 28, compared with 9.8 hysterectomies per fellow in 2007.
Dr. Magrina’s data goes hand in hand with Dr. Gressel’s new study. The surgical experience of the gynecologic surgeon certainly is on the wane. The result of this lack of experience is noted by Dr. Guntupalli in his 2015 publication. To us, it is readily apparent that Dr. Magrina is right: The only true solution is to finally realize that we must separate the O from the G.
Charles E. Miller, MD, is director of minimally invasive gynecologic surgery, and director of the AAGL fellowship in minimally invasive gynecologic surgery, at Advocate Lutheran General Hospital, Park Ridge, Ill. Kirsten Sasaki, MD, is associate director of the AAGL fellowship in minimally invasive gynecologic surgery at Advocate Lutheran. They have no other conflicts of interest.
The total number of hysterectomies performed during residency training has declined significantly since 2008, despite an increase in laparoscopic hysterectomies performed, according to a new analysis of data from graduating ob.gyn. residents that has implications for the structure of resident education.
The investigators abstracted case log data from the Accreditation Council for Graduate Medical Education (ACGME) database to assess trends in residents’ operative experience and found decreases in abdominal and vaginal cases but an increase in experience with laparoscopic hysterectomy.
(from 85 cases to 37), and the median number of vaginal hysterectomies decreased by 36% (from 31 to 20 cases).
Laparoscopic hysterectomy increased by 115% from a median of 20 procedures in 2008-2009 to 43 in 2017-2018. Even so, the median total number of hysterectomies per resident decreased by 6%, from 112 to 105 procedures during those two time periods. (Data on total hysterectomy and laparoscopic hysterectomy were not collected by ACGME until 2008.)
While the absolute decrease in the total number of hysterectomies is “relatively small,” the trend “raises questions about what the appropriate number of hysterectomies per graduating resident should be,” Gregory M. Gressel, MD, MSc, of the Montefiore Medical Center, New York, and coauthors wrote in Obstetrics & Gynecology.
“These data point,” they wrote, “to the necessity of maximizing surgical exposure in the face of a declining availability of procedures and the importance of reflecting on which (and how many) procedures an obstetrics and gynecology resident needs to complete before entering clinical practice.”
The training numbers parallel an increased use of laparoscopic hysterectomy in the United States and other countries, as well as a well-documented decline in the total number of hysterectomies performed in the United States, the latter of which is driven largely by the availability and increasing use of alternatives to the procedure (such as hormone therapy, endometrial ablation, and uterine artery embolization).
Hysterectomy still is a “core procedure of gynecologic surgery,” however, and is “at the heart of surgical training in obstetrics and gynecology,” as surgical techniques developed from learning hysterectomy “are applied broadly in the pelvis,” Saketh R. Guntupalli, MD, wrote in an accompanying editorial.
Dr. Guntupalli, of the University of Colorado at Aurora, Denver, was involved in a survey of fellowship program directors, published in 2015, that found only 20% of first-year fellows were able to independently perform a vaginal hysterectomy and 46% to independently perform an abdominal hysterectomy (Obstet Gynecol. 2015;126:559-68).
This and other research suggest that fellowship training is “used to address deficiencies in residency training rather than to develop new, specialized surgical skills,” he wrote. Given a dearth of fellowship positions in ob.gyn., “it is impossible to adequately use those avenues to train the number of competent surgeons necessary to address the surgical needs of women’s health in the United States.”
To address such concerns, some residency programs have instituted resident tracking to direct more hysterectomy cases toward those residents who plan to pursue surgical subspecialties. The Cleveland Clinic, Dr. Guntupalli noted, has tried the latter approach “with success.”
An increase in the number of accredited training programs and a decrease in the number of residents per program also might help to improve surgical exposure for residents, Dr. Gressel and associates wrote. Over the 16-year study period, the number of graduating residents increased significantly (by 12 per year) and the number of residency programs decreased significantly (0.52 fewer programs per year).
Additionally, Dr. Guntupalli wrote, regulatory bodies may need to reevaluate how competencies are assessed, and whether minimal numbers of cases “continue to carry the same weight as they did in previous generations.”
In the study, one coauthor is a full-time employee of ACGME, and another receives funds as a director for the American Board of Obstetrics and Gynecology. The remaining authors had no relevant financial disclosures. There was no outside funding for the study. Dr. Guntupalli said he had no conflicts of interest.
SOURCES: Gressel GM et al. Obstet Gynecol. 2020 Feb;135(2):268-73; Guntupalli SR. Obstet Gynecol 2020 Feb;135(2):266-7.
The total number of hysterectomies performed during residency training has declined significantly since 2008, despite an increase in laparoscopic hysterectomies performed, according to a new analysis of data from graduating ob.gyn. residents that has implications for the structure of resident education.
The investigators abstracted case log data from the Accreditation Council for Graduate Medical Education (ACGME) database to assess trends in residents’ operative experience and found decreases in abdominal and vaginal cases but an increase in experience with laparoscopic hysterectomy.
(from 85 cases to 37), and the median number of vaginal hysterectomies decreased by 36% (from 31 to 20 cases).
Laparoscopic hysterectomy increased by 115% from a median of 20 procedures in 2008-2009 to 43 in 2017-2018. Even so, the median total number of hysterectomies per resident decreased by 6%, from 112 to 105 procedures during those two time periods. (Data on total hysterectomy and laparoscopic hysterectomy were not collected by ACGME until 2008.)
While the absolute decrease in the total number of hysterectomies is “relatively small,” the trend “raises questions about what the appropriate number of hysterectomies per graduating resident should be,” Gregory M. Gressel, MD, MSc, of the Montefiore Medical Center, New York, and coauthors wrote in Obstetrics & Gynecology.
“These data point,” they wrote, “to the necessity of maximizing surgical exposure in the face of a declining availability of procedures and the importance of reflecting on which (and how many) procedures an obstetrics and gynecology resident needs to complete before entering clinical practice.”
The training numbers parallel an increased use of laparoscopic hysterectomy in the United States and other countries, as well as a well-documented decline in the total number of hysterectomies performed in the United States, the latter of which is driven largely by the availability and increasing use of alternatives to the procedure (such as hormone therapy, endometrial ablation, and uterine artery embolization).
Hysterectomy still is a “core procedure of gynecologic surgery,” however, and is “at the heart of surgical training in obstetrics and gynecology,” as surgical techniques developed from learning hysterectomy “are applied broadly in the pelvis,” Saketh R. Guntupalli, MD, wrote in an accompanying editorial.
Dr. Guntupalli, of the University of Colorado at Aurora, Denver, was involved in a survey of fellowship program directors, published in 2015, that found only 20% of first-year fellows were able to independently perform a vaginal hysterectomy and 46% to independently perform an abdominal hysterectomy (Obstet Gynecol. 2015;126:559-68).
This and other research suggest that fellowship training is “used to address deficiencies in residency training rather than to develop new, specialized surgical skills,” he wrote. Given a dearth of fellowship positions in ob.gyn., “it is impossible to adequately use those avenues to train the number of competent surgeons necessary to address the surgical needs of women’s health in the United States.”
To address such concerns, some residency programs have instituted resident tracking to direct more hysterectomy cases toward those residents who plan to pursue surgical subspecialties. The Cleveland Clinic, Dr. Guntupalli noted, has tried the latter approach “with success.”
An increase in the number of accredited training programs and a decrease in the number of residents per program also might help to improve surgical exposure for residents, Dr. Gressel and associates wrote. Over the 16-year study period, the number of graduating residents increased significantly (by 12 per year) and the number of residency programs decreased significantly (0.52 fewer programs per year).
Additionally, Dr. Guntupalli wrote, regulatory bodies may need to reevaluate how competencies are assessed, and whether minimal numbers of cases “continue to carry the same weight as they did in previous generations.”
In the study, one coauthor is a full-time employee of ACGME, and another receives funds as a director for the American Board of Obstetrics and Gynecology. The remaining authors had no relevant financial disclosures. There was no outside funding for the study. Dr. Guntupalli said he had no conflicts of interest.
SOURCES: Gressel GM et al. Obstet Gynecol. 2020 Feb;135(2):268-73; Guntupalli SR. Obstet Gynecol 2020 Feb;135(2):266-7.
FROM OBSTETRICS & GYNECOLOGY
Adolescent obesity linked with midlife cancer risk
Obesity during adolescence is associated with increased midlife cancer risk, according to findings from a large population-based cohort of Israeli teens examined between 1967 and 2010.
The association, which was stronger in individuals in the later period of the cohort than in those in the earlier years, suggests that the burden of obesity-related cancers might increase over time, given the increasing prevalence of adolescent obesity, wrote Ariel Furer, MD, of Israel Defense Forces Medical Corps, Ramat Gan, and colleagues. Their report is in The Lancet.
Obesity is a known causal factor for several types of cancer, but most studies have looked at middle-age or older individuals and had relatively short follow-up, and period effects are rarely assessed, the investigators said, noting that “the attributable burden of obesity-related cancer was previously calculated with an unverified assumption that the association remained unchanged over time.
“In contrast to this paucity of knowledge, the prevalence of youth obesity – particularly severe obesity – has increased worldwide, which parallels the rise in youth cancer incidence,” they wrote.
To address this paucity of data, the researchers reviewed medical and sociodemographic data for adolescents who were assessed at age 17 years for medical eligibility for mandatory military service, and linked that information with data from the National Cancer Registry to create a unified file. The primary study outcome was any cancer diagnosis between Jan. 1, 1967, and Dec. 31, 2012, and a secondary endpoint was all-cause mortality through Dec. 31, 2017, among those who developed cancer.
Among nearly 2.3 million participating adolescents who were evaluated for associations between body mass index at age 17 years and later cancer incidence, 1,370,020 were men with more than 29.5 million person-years of follow-up, and 928,110 were women with more than 18 million person-years of follow-up. The numbers of incident cancer cases in the men and women were 26,353 and 29,488, and the mean ages at diagnosis were 43.2 and 40.0 years, respectively, the investigators reported (Lancet. 2020 Feb 3. doi: 10.1016/S2213-8587(20)30019-X).
Adolescent obesity in men was significantly associated with midlife cancer incidence (hazard ratio, 1.26), but in women, no association was seen due to the previously reported inverse associations between obesity and cervical and breast cancers, they said.
However, when those cancers were excluded for women, the adjusted hazard ratio was similar to that for men (HR, 1.27).
Cancer incidence in both men and women increased gradually across BMI percentiles, and for both sexes, overweight BMI was associated with an increased cancer risk after 10 years of follow-up (HR, 1.14 for men, 1.22 for women after exclusion of cervical and breast cancer). Therefore, in some cases the increased cancer risk in those who were overweight as teens was evident before age 30 years, the authors noted.
Further, BMI was positively associated with greater mortality risk. For men, 5-year survival rates were 75.2% in those with adolescent BMI in the 5th-49th percentile, compared with 72.2% in those with BMI in the obesity range (95th percentile or greater), and the corresponding rates in women were 89.3% and 83.1% (HR, 1.33 and 1.89, respectively).
Of note, the investigators identified a period effect. That is, after stratification by enrollment period/cancer recording period (1967-1981/1982-1996 vs. 1982-1996/1997-2011), a stronger association was noted in individuals who entered the study during the later period, compared with those who entered in the early period (HR, 1.36 vs. 1.13; adjusted HR, 1.11 vs. 1.07 per 5 kg/m2). Possible mechanisms for this finding include environmental and nutritional factors, increased use of medical services, and changes in early cancer screening techniques, but further study is needed to verify the trend and “refine the exact nature of carcinogenic elements, compared with earlier periods,” they said.
Also of note, some cancers that were not associated with BMI in the early period, including stomach cancer, non-Hodgkin lymphoma, thyroid cancer, and colorectal and oral cavity cancers, became significantly associated with BMI in the late period.
“The projected population attributable risk percentage, using 2017 prevalence data of high BMI, was 5.1% for any cancer in men and 5.7% for cancers other than breast and cervical in women,” the researchers wrote, noting that this “is probably an underestimation, given the accentuation of the BMI-cancer association and the rapid increase in adolescent obesity prevalence within the past decade in Israel and worldwide.”
In an accompanying editorial, the journal editors noted that the findings by Dr. Furer and colleagues highlight the need to tackle obesity early in life and the need for obesity prevention strategies to reduce cancer incidence and mortality for those cancers that can be prevented by lifestyle modifications. They added, however, that care would be needed to avoid stigmatizing those with obesity, as obesity itself is a “multifactorial condition driven by social injustice and health inequalities” that most often affect those who are least able to implement lifestyle change (Lancet. 2020 Feb 3. doi: 10.106/S2213-8587(20)30031-0).
They also emphasized that the links between obesity and cancer, like those between obesity and other diseases such as diabetes, underscore the fact that noncommunicable diseases do not exist in isolation, and that tackling them requires bold action, a consolidated approach, and elimination of the environmental and social factors driving the epidemic.
The study was limited by a number of factors, including the lack of data on lifestyle factors, underrepresentation of some ethnicities, and lack of data on BMI and medical comorbidities at the time of cancer diagnosis. However, strengths of the study include the systematic data collection, narrow range of age at study entry, strict control of coexisting conditions, and high statistical power, which strengthen the generalizability of the results, the investigators said, concluding, therefore, that “[c]urrent trends of rising BMI among adolescents could constitute an important intervention target for cancer prevention.”
The authors reported having no disclosures.
SOURCE: Furer A et al. Lancet Diabetes Endocrinol. 2020 Feb 3. doi: 10.1016/S2213-8587(20)30019-X.
Obesity during adolescence is associated with increased midlife cancer risk, according to findings from a large population-based cohort of Israeli teens examined between 1967 and 2010.
The association, which was stronger in individuals in the later period of the cohort than in those in the earlier years, suggests that the burden of obesity-related cancers might increase over time, given the increasing prevalence of adolescent obesity, wrote Ariel Furer, MD, of Israel Defense Forces Medical Corps, Ramat Gan, and colleagues. Their report is in The Lancet.
Obesity is a known causal factor for several types of cancer, but most studies have looked at middle-age or older individuals and had relatively short follow-up, and period effects are rarely assessed, the investigators said, noting that “the attributable burden of obesity-related cancer was previously calculated with an unverified assumption that the association remained unchanged over time.
“In contrast to this paucity of knowledge, the prevalence of youth obesity – particularly severe obesity – has increased worldwide, which parallels the rise in youth cancer incidence,” they wrote.
To address this paucity of data, the researchers reviewed medical and sociodemographic data for adolescents who were assessed at age 17 years for medical eligibility for mandatory military service, and linked that information with data from the National Cancer Registry to create a unified file. The primary study outcome was any cancer diagnosis between Jan. 1, 1967, and Dec. 31, 2012, and a secondary endpoint was all-cause mortality through Dec. 31, 2017, among those who developed cancer.
Among nearly 2.3 million participating adolescents who were evaluated for associations between body mass index at age 17 years and later cancer incidence, 1,370,020 were men with more than 29.5 million person-years of follow-up, and 928,110 were women with more than 18 million person-years of follow-up. The numbers of incident cancer cases in the men and women were 26,353 and 29,488, and the mean ages at diagnosis were 43.2 and 40.0 years, respectively, the investigators reported (Lancet. 2020 Feb 3. doi: 10.1016/S2213-8587(20)30019-X).
Adolescent obesity in men was significantly associated with midlife cancer incidence (hazard ratio, 1.26), but in women, no association was seen due to the previously reported inverse associations between obesity and cervical and breast cancers, they said.
However, when those cancers were excluded for women, the adjusted hazard ratio was similar to that for men (HR, 1.27).
Cancer incidence in both men and women increased gradually across BMI percentiles, and for both sexes, overweight BMI was associated with an increased cancer risk after 10 years of follow-up (HR, 1.14 for men, 1.22 for women after exclusion of cervical and breast cancer). Therefore, in some cases the increased cancer risk in those who were overweight as teens was evident before age 30 years, the authors noted.
Further, BMI was positively associated with greater mortality risk. For men, 5-year survival rates were 75.2% in those with adolescent BMI in the 5th-49th percentile, compared with 72.2% in those with BMI in the obesity range (95th percentile or greater), and the corresponding rates in women were 89.3% and 83.1% (HR, 1.33 and 1.89, respectively).
Of note, the investigators identified a period effect. That is, after stratification by enrollment period/cancer recording period (1967-1981/1982-1996 vs. 1982-1996/1997-2011), a stronger association was noted in individuals who entered the study during the later period, compared with those who entered in the early period (HR, 1.36 vs. 1.13; adjusted HR, 1.11 vs. 1.07 per 5 kg/m2). Possible mechanisms for this finding include environmental and nutritional factors, increased use of medical services, and changes in early cancer screening techniques, but further study is needed to verify the trend and “refine the exact nature of carcinogenic elements, compared with earlier periods,” they said.
Also of note, some cancers that were not associated with BMI in the early period, including stomach cancer, non-Hodgkin lymphoma, thyroid cancer, and colorectal and oral cavity cancers, became significantly associated with BMI in the late period.
“The projected population attributable risk percentage, using 2017 prevalence data of high BMI, was 5.1% for any cancer in men and 5.7% for cancers other than breast and cervical in women,” the researchers wrote, noting that this “is probably an underestimation, given the accentuation of the BMI-cancer association and the rapid increase in adolescent obesity prevalence within the past decade in Israel and worldwide.”
In an accompanying editorial, the journal editors noted that the findings by Dr. Furer and colleagues highlight the need to tackle obesity early in life and the need for obesity prevention strategies to reduce cancer incidence and mortality for those cancers that can be prevented by lifestyle modifications. They added, however, that care would be needed to avoid stigmatizing those with obesity, as obesity itself is a “multifactorial condition driven by social injustice and health inequalities” that most often affect those who are least able to implement lifestyle change (Lancet. 2020 Feb 3. doi: 10.106/S2213-8587(20)30031-0).
They also emphasized that the links between obesity and cancer, like those between obesity and other diseases such as diabetes, underscore the fact that noncommunicable diseases do not exist in isolation, and that tackling them requires bold action, a consolidated approach, and elimination of the environmental and social factors driving the epidemic.
The study was limited by a number of factors, including the lack of data on lifestyle factors, underrepresentation of some ethnicities, and lack of data on BMI and medical comorbidities at the time of cancer diagnosis. However, strengths of the study include the systematic data collection, narrow range of age at study entry, strict control of coexisting conditions, and high statistical power, which strengthen the generalizability of the results, the investigators said, concluding, therefore, that “[c]urrent trends of rising BMI among adolescents could constitute an important intervention target for cancer prevention.”
The authors reported having no disclosures.
SOURCE: Furer A et al. Lancet Diabetes Endocrinol. 2020 Feb 3. doi: 10.1016/S2213-8587(20)30019-X.
Obesity during adolescence is associated with increased midlife cancer risk, according to findings from a large population-based cohort of Israeli teens examined between 1967 and 2010.
The association, which was stronger in individuals in the later period of the cohort than in those in the earlier years, suggests that the burden of obesity-related cancers might increase over time, given the increasing prevalence of adolescent obesity, wrote Ariel Furer, MD, of Israel Defense Forces Medical Corps, Ramat Gan, and colleagues. Their report is in The Lancet.
Obesity is a known causal factor for several types of cancer, but most studies have looked at middle-age or older individuals and had relatively short follow-up, and period effects are rarely assessed, the investigators said, noting that “the attributable burden of obesity-related cancer was previously calculated with an unverified assumption that the association remained unchanged over time.
“In contrast to this paucity of knowledge, the prevalence of youth obesity – particularly severe obesity – has increased worldwide, which parallels the rise in youth cancer incidence,” they wrote.
To address this paucity of data, the researchers reviewed medical and sociodemographic data for adolescents who were assessed at age 17 years for medical eligibility for mandatory military service, and linked that information with data from the National Cancer Registry to create a unified file. The primary study outcome was any cancer diagnosis between Jan. 1, 1967, and Dec. 31, 2012, and a secondary endpoint was all-cause mortality through Dec. 31, 2017, among those who developed cancer.
Among nearly 2.3 million participating adolescents who were evaluated for associations between body mass index at age 17 years and later cancer incidence, 1,370,020 were men with more than 29.5 million person-years of follow-up, and 928,110 were women with more than 18 million person-years of follow-up. The numbers of incident cancer cases in the men and women were 26,353 and 29,488, and the mean ages at diagnosis were 43.2 and 40.0 years, respectively, the investigators reported (Lancet. 2020 Feb 3. doi: 10.1016/S2213-8587(20)30019-X).
Adolescent obesity in men was significantly associated with midlife cancer incidence (hazard ratio, 1.26), but in women, no association was seen due to the previously reported inverse associations between obesity and cervical and breast cancers, they said.
However, when those cancers were excluded for women, the adjusted hazard ratio was similar to that for men (HR, 1.27).
Cancer incidence in both men and women increased gradually across BMI percentiles, and for both sexes, overweight BMI was associated with an increased cancer risk after 10 years of follow-up (HR, 1.14 for men, 1.22 for women after exclusion of cervical and breast cancer). Therefore, in some cases the increased cancer risk in those who were overweight as teens was evident before age 30 years, the authors noted.
Further, BMI was positively associated with greater mortality risk. For men, 5-year survival rates were 75.2% in those with adolescent BMI in the 5th-49th percentile, compared with 72.2% in those with BMI in the obesity range (95th percentile or greater), and the corresponding rates in women were 89.3% and 83.1% (HR, 1.33 and 1.89, respectively).
Of note, the investigators identified a period effect. That is, after stratification by enrollment period/cancer recording period (1967-1981/1982-1996 vs. 1982-1996/1997-2011), a stronger association was noted in individuals who entered the study during the later period, compared with those who entered in the early period (HR, 1.36 vs. 1.13; adjusted HR, 1.11 vs. 1.07 per 5 kg/m2). Possible mechanisms for this finding include environmental and nutritional factors, increased use of medical services, and changes in early cancer screening techniques, but further study is needed to verify the trend and “refine the exact nature of carcinogenic elements, compared with earlier periods,” they said.
Also of note, some cancers that were not associated with BMI in the early period, including stomach cancer, non-Hodgkin lymphoma, thyroid cancer, and colorectal and oral cavity cancers, became significantly associated with BMI in the late period.
“The projected population attributable risk percentage, using 2017 prevalence data of high BMI, was 5.1% for any cancer in men and 5.7% for cancers other than breast and cervical in women,” the researchers wrote, noting that this “is probably an underestimation, given the accentuation of the BMI-cancer association and the rapid increase in adolescent obesity prevalence within the past decade in Israel and worldwide.”
In an accompanying editorial, the journal editors noted that the findings by Dr. Furer and colleagues highlight the need to tackle obesity early in life and the need for obesity prevention strategies to reduce cancer incidence and mortality for those cancers that can be prevented by lifestyle modifications. They added, however, that care would be needed to avoid stigmatizing those with obesity, as obesity itself is a “multifactorial condition driven by social injustice and health inequalities” that most often affect those who are least able to implement lifestyle change (Lancet. 2020 Feb 3. doi: 10.106/S2213-8587(20)30031-0).
They also emphasized that the links between obesity and cancer, like those between obesity and other diseases such as diabetes, underscore the fact that noncommunicable diseases do not exist in isolation, and that tackling them requires bold action, a consolidated approach, and elimination of the environmental and social factors driving the epidemic.
The study was limited by a number of factors, including the lack of data on lifestyle factors, underrepresentation of some ethnicities, and lack of data on BMI and medical comorbidities at the time of cancer diagnosis. However, strengths of the study include the systematic data collection, narrow range of age at study entry, strict control of coexisting conditions, and high statistical power, which strengthen the generalizability of the results, the investigators said, concluding, therefore, that “[c]urrent trends of rising BMI among adolescents could constitute an important intervention target for cancer prevention.”
The authors reported having no disclosures.
SOURCE: Furer A et al. Lancet Diabetes Endocrinol. 2020 Feb 3. doi: 10.1016/S2213-8587(20)30019-X.
FROM THE LANCET