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EMPEROR-Preserved spouts torrent of reports on empagliflozin treatment of HFpEF
The featured report from the 6,000-patient EMPEROR-Preserved trial at the virtual annual congress of the European Society of Cardiology drew lots of attention for its headline finding: the first unequivocal demonstration that a medication, empagliflozin, can significantly reduce the rate of cardiovascular death and hospitalization for heart failure in patients with heart failure with preserved ejection fraction (HFpEF, a left ventricular ejection fraction of more than 40%), with the details simultaneously published online.
But at the same time, the EMPEROR-Preserved investigators released four additional reports with a lot more outcome analyses that also deserve some attention.
The puzzling neutral effect on renal events
Perhaps the most surprising and complicated set of findings among the main EMPEROR-Preserved outcomes involved renal outcomes.
The trial’s primary outcome was the combined rate of cardiovascular death or hospitalization for heart failure (HHF), and the results showed that treatment with empagliflozin (Jardiance) for a median of 26 months on top of standard treatment for patients with HFpEF led to a significant 21% relative risk reduction, compared with placebo-treated patients.
The trial had two prespecified secondary outcomes. One was the total number of HHF, which dropped by a significant 27%, compared with placebo. The second was the mean change in slope of estimated glomerular filtration rate (eGFR) on an annualized basis, and the empagliflozin regimen reduced the cumulative annual deficit, compared with placebo by an average of 1.36 mL/min per 1.73 m2, a significant difference.
This preservation of renal function was consistent with results from many prior studies of empagliflozin and all of the other U.S.-approved agents from the sodium-glucose cotransporter 2 inhibitor class. Preservation of renal function and a reduction in renal events has become a hallmark property of all agents in the SGLT2 inhibitor class both in patients with type 2 diabetes, as well as in those without diabetes but with heart failure with reduced ejection fraction (HFrEF) or with chronic kidney disease.
EMPEROR-Preserved threw a wrench into what had been an unbroken history of renal protection by SGLT2 inhibitors. That happened when a prespecified endpoint of the study – a composite renal outcome defined as time to first occurrence of chronic dialysis, renal transplantation, a sustained reduction of at least 40% in eGFR, or a sustained drop in eGFR of more than 10 or 15 mL/min per 1.73 m2 from baseline – yielded an unexpected neutral finding.
For this composite renal outcome, EMPEROR-Preserved showed a nonsignificant 5% reduction, compared with placebo, a result that both differed from what had been seen in essentially all the other SGLT2 inhibitor trials that had looked at this, but which also seemed at odds with the observed significant preservation of renal function that seemed substantial enough to produce a clinically meaningful benefit.
Renal effects blunted in HFpEF
The immediate upshot was a letter published by several EMPEROR-Preserved investigators that spelled out this discrepancy and came to the jolting conclusion that “eGFR slope analysis has limitations as a surrogate for predicting the effect of drugs on renal outcomes in patients with heart failure.”
The same authors, along with some additional associates, also published a second letter that noted a further unexpected twist with the renal outcome: “In prior large-scale clinical trials, the effect of SGLT2 inhibitors on heart failure and renal outcomes had consistently tracked together,” they noted, but in this case it didn’t, a discordance they said was “extraordinarily puzzling”.
This led the study’s leaders to reanalyze the renal outcomes using a different definition, one that Milton Packer, MD, who helped design the trial and oversaw several of its analyses, called “a more conventional definition of renal events,” during his presentation of these findings at the congress. The researchers swapped out a 40% drop from baseline eGFR as an event and replaced it with a 50% decline, a change designed to screen out less severe, and often transient, reductions in kidney function that have less lasting impact on health. They also added an additional component to the composite endpoint, renal death. A revised analysis using this new renal composite outcome appeared in the European Journal of Heart Failure letter.
This change cut the total number of renal events tallied in the trial nearly in half, down to 112, and showed a more robust decline in renal events with empagliflozin treatment compared with the initial analysis, although the drop remained nonsignificant. The revised analysis also showed that the overall, nonsignificant 22% relative reduction in renal events in patients on empagliflozin, compared with placebo, dwindled down to completely nonexistent in the tertile of patients with a left ventricular ejection fraction of 60% or greater. In this tertile the hazard ratio actually showed a nonsignificant point estimate of a 24% increased rate of renal events on empagliflozin, with the caveat that this subgroup now included a total of just 40 total events between the two treatment arms. (Each of the two other tertiles also had roughly the same number of total events.)
The biggest effect on renal-event reduction was in the tertile of patients with an ejection fraction of 41%-49%, in which empagliflozin treatment was linked with a significant 59% cut in renal events, compared with placebo. The analysis also showed significant heterogeneity in thus outcome between this subgroup and the other two tertiles that had higher ejection fractions and showed reduced rates of protection by empagliflozin against renal events.
This apparent blunting of a renal effect despite preservation of renal function seemed to mimic the blunting of the primary cardiovascular outcome effect that also appeared in patients with ejection fractions in the 60%-65% range or above.
“If we knew what blunted the effect of empagliflozin on heart failure outcomes at higher ejection fraction levels, we think the same explanation may also apply to the blunting of effect on renal outcomes, but right now we do not know the answer to either question,” Dr. Packer said in an interview. He’s suggested that one possibility is that many of the enrolled patients identified as having HFpEF, but with these high ejection fractions may have not actually had HFpEF, and their signs and symptoms may have instead resulted from atrial fibrillation.
“Many patients with an ejection fraction of 60%-65% and above had atrial fibrillation,” he noted, with a prevalence at enrollment in this subgroup of about 50%. Atrial fibrillation can cause dyspnea, a hallmark symptom leading to diagnosis of heart failure, and it also increases levels of N-terminal of the prohormone brain natriuretic peptide, a metric that served as a gatekeeper for entry into the trial. “Essentially, we are saying that many of the criteria that we specified to ensure that patients had heart failure probably did not work very well in patients with an ejection fraction of 65% or greater,” said Dr. Packer, a cardiologist at Baylor University Medical Center in Dallas. “We need to figure out who these patients are.”
Some experts not involved with the study voiced skepticism that the renal findings reflected a real issue.
“I’m quite optimistic that in the long-term the effect on eGFR will translate into renal protection,” said Rudolf A. de Boer, MD, PhD, a professor of translational cardiology at University Medical Center Groningen (the Netherlands), and designated discussant at the congress for the presentation by Dr. Packer.
John J.V. McMurray, MD, a professor of cardiology and a heart failure specialist at Glasgow University, speculated that the unexpected renal outcomes data may relate to the initial decline in renal function produced by treatment with SGLT2 inhibitors despite their longer-term enhancement of renal protection.
“If you use a treatment that protects the kidneys in the long-term but causes an initial dip in eGFR, more patients receiving that treatment will have an early ‘event,’ ” he noted in an interview. He also cautioned about the dangers of subgroup analyses that dice the study population into small cohorts.
“Trials are powered to look at the effect of treatment in the overall population. Everything else is exploratory, underpowered, and subject to the play of chance,” Dr. McMurray stressed.
Counting additional cardiovascular disease events allows more analyses
A third auxiliary report from the EMPEROR-Preserved investigators performed several prespecified analyses that depended on adding additional cardiovascular disease endpoints to the core tallies of cardiovascular death or HHF – such as emergent, urgent, and outpatient events that reflected worsening heart failure – and also included information on diuretic and vasopressor use because of worsening heart failure. The increased event numbers allowed the researchers to perform 30 additional analyses included in this report, according to the count kept by Dr. Packer who was the lead author.
He highlighted several of the additional results in this paper that documented benefits from empagliflozin treatment, compared with placebo:
- A significant 29% reduction in the need for admission to a cardiac care unit or intensive care unit during an HHF.
- A nonsignificant 33% reduction in the need for intravenous vasopressors or positive inotropic drugs during HHF.
- A significantly increased rate of patients achieving a higher New York Heart Association functional class. For example, after the first year of treatment patients who received empagliflozin had a 37% higher rate of functional class improvement, compared with patients who received placebo.
Dr. McMurray had his own list of key takeaways from this paper, including:
- Among patients who needed hospitalization, “those treated with empagliflozin were less sick than those in the placebo group.”
- In addition to reducing HHF empagliflozin treatment also reduced episodes of outpatient worsening as reflected by their receipt of intensified diuretic treatment, which occurred a significant 27% less often, compared with patients on placebo.
- Treatment with empagliflozin also linked with a significant 39% relative reduction in emergency or urgent-care visits that required intravenous therapy.
Empagliflozin’s performance relative to sacubitril/valsartan
The fourth additional report focused on a post hoc, cross-trial comparison of the results from EMPEROR-Preserved and from another recent trial that, like EMPEROR-Preserved, assessed in patients with HFpEF a drug previously proven to work quite well in patients with HFrEF. The comparator drug was sacubitril/valsartan (Entresto), which underwent testing in patients with HFpEF in the PARAGON-HF trial.
The primary outcome of PARAGON-HF, which randomized 4,822 patients, was reduction in cardiovascular death and in total HHF. This dropped by a relative 13%, compared with placebo, during a median of 35 months, a between-group difference that came close to but did not achieve significance (P = .06). Despite this limitation, the Food and Drug Administration in February 2021 loosened the indication for using sacubitril/valsartan in patients with heart failure and a “below normal” ejection fraction, a category that can include many patients considered to have HFpEF.
Although the researchers who ran this analysis, including Dr. Packer, who was the first author, admitted that “comparison of effect sizes across trials is fraught with difficulties,” they nonetheless concluded from their analysis that “for all outcomes that included HHF the effect size was larger for empagliflozin than for sacubitril/valsartan.”
Dr. McMurray, a lead instigator for PARAGON-HF, said there was little to take away from this analysis.
“The patient populations were different, and sacubitril/valsartan was compared against an active therapy, valsartan,” while in EMPEROR-Preserved empagliflozin compared against placebo. “Most of us believe that sacubitril/valsartan and SGLT2 inhibitors work in different but complementary ways, and their benefits are additive. You would want patients with HFpEF or HFrEF to take both,” he said in an interview.
Dr. Packer agreed with that approach and added that he would probably also prescribe a third agent, spironolactone, to many patients with HFpEF.
EMPEROR-Preserved was sponsored by Boehringer Ingelheim and Eli Lilly, which jointly market empagliflozin (Jardiance). PARAGON-HF was sponsored by Novartis, which markets sacubitril/valsartan (Entresto). Dr. Packer has received consulting fees from Boehringer Ingelheim and from numerous other companies. Dr. de Boer has research contracts with Boehringer Ingelheim as well as from Abbott, AstraZeneca, Cardior, Ionis, Novo Nordisk, and Roche, and he has been a consultant to Novartis as well as to Abbott, AstraZeneca, Gayer, and Roche. Dr. McMurray led trials of sacubitril/valsartan sponsored by Novartis, and his institution has received compensation for his participation in studies sponsored by Abbvie, AstraZeneca, Cardurion, DalCor, GlaxoSmithKline, Pfizer, and Theracos.
The featured report from the 6,000-patient EMPEROR-Preserved trial at the virtual annual congress of the European Society of Cardiology drew lots of attention for its headline finding: the first unequivocal demonstration that a medication, empagliflozin, can significantly reduce the rate of cardiovascular death and hospitalization for heart failure in patients with heart failure with preserved ejection fraction (HFpEF, a left ventricular ejection fraction of more than 40%), with the details simultaneously published online.
But at the same time, the EMPEROR-Preserved investigators released four additional reports with a lot more outcome analyses that also deserve some attention.
The puzzling neutral effect on renal events
Perhaps the most surprising and complicated set of findings among the main EMPEROR-Preserved outcomes involved renal outcomes.
The trial’s primary outcome was the combined rate of cardiovascular death or hospitalization for heart failure (HHF), and the results showed that treatment with empagliflozin (Jardiance) for a median of 26 months on top of standard treatment for patients with HFpEF led to a significant 21% relative risk reduction, compared with placebo-treated patients.
The trial had two prespecified secondary outcomes. One was the total number of HHF, which dropped by a significant 27%, compared with placebo. The second was the mean change in slope of estimated glomerular filtration rate (eGFR) on an annualized basis, and the empagliflozin regimen reduced the cumulative annual deficit, compared with placebo by an average of 1.36 mL/min per 1.73 m2, a significant difference.
This preservation of renal function was consistent with results from many prior studies of empagliflozin and all of the other U.S.-approved agents from the sodium-glucose cotransporter 2 inhibitor class. Preservation of renal function and a reduction in renal events has become a hallmark property of all agents in the SGLT2 inhibitor class both in patients with type 2 diabetes, as well as in those without diabetes but with heart failure with reduced ejection fraction (HFrEF) or with chronic kidney disease.
EMPEROR-Preserved threw a wrench into what had been an unbroken history of renal protection by SGLT2 inhibitors. That happened when a prespecified endpoint of the study – a composite renal outcome defined as time to first occurrence of chronic dialysis, renal transplantation, a sustained reduction of at least 40% in eGFR, or a sustained drop in eGFR of more than 10 or 15 mL/min per 1.73 m2 from baseline – yielded an unexpected neutral finding.
For this composite renal outcome, EMPEROR-Preserved showed a nonsignificant 5% reduction, compared with placebo, a result that both differed from what had been seen in essentially all the other SGLT2 inhibitor trials that had looked at this, but which also seemed at odds with the observed significant preservation of renal function that seemed substantial enough to produce a clinically meaningful benefit.
Renal effects blunted in HFpEF
The immediate upshot was a letter published by several EMPEROR-Preserved investigators that spelled out this discrepancy and came to the jolting conclusion that “eGFR slope analysis has limitations as a surrogate for predicting the effect of drugs on renal outcomes in patients with heart failure.”
The same authors, along with some additional associates, also published a second letter that noted a further unexpected twist with the renal outcome: “In prior large-scale clinical trials, the effect of SGLT2 inhibitors on heart failure and renal outcomes had consistently tracked together,” they noted, but in this case it didn’t, a discordance they said was “extraordinarily puzzling”.
This led the study’s leaders to reanalyze the renal outcomes using a different definition, one that Milton Packer, MD, who helped design the trial and oversaw several of its analyses, called “a more conventional definition of renal events,” during his presentation of these findings at the congress. The researchers swapped out a 40% drop from baseline eGFR as an event and replaced it with a 50% decline, a change designed to screen out less severe, and often transient, reductions in kidney function that have less lasting impact on health. They also added an additional component to the composite endpoint, renal death. A revised analysis using this new renal composite outcome appeared in the European Journal of Heart Failure letter.
This change cut the total number of renal events tallied in the trial nearly in half, down to 112, and showed a more robust decline in renal events with empagliflozin treatment compared with the initial analysis, although the drop remained nonsignificant. The revised analysis also showed that the overall, nonsignificant 22% relative reduction in renal events in patients on empagliflozin, compared with placebo, dwindled down to completely nonexistent in the tertile of patients with a left ventricular ejection fraction of 60% or greater. In this tertile the hazard ratio actually showed a nonsignificant point estimate of a 24% increased rate of renal events on empagliflozin, with the caveat that this subgroup now included a total of just 40 total events between the two treatment arms. (Each of the two other tertiles also had roughly the same number of total events.)
The biggest effect on renal-event reduction was in the tertile of patients with an ejection fraction of 41%-49%, in which empagliflozin treatment was linked with a significant 59% cut in renal events, compared with placebo. The analysis also showed significant heterogeneity in thus outcome between this subgroup and the other two tertiles that had higher ejection fractions and showed reduced rates of protection by empagliflozin against renal events.
This apparent blunting of a renal effect despite preservation of renal function seemed to mimic the blunting of the primary cardiovascular outcome effect that also appeared in patients with ejection fractions in the 60%-65% range or above.
“If we knew what blunted the effect of empagliflozin on heart failure outcomes at higher ejection fraction levels, we think the same explanation may also apply to the blunting of effect on renal outcomes, but right now we do not know the answer to either question,” Dr. Packer said in an interview. He’s suggested that one possibility is that many of the enrolled patients identified as having HFpEF, but with these high ejection fractions may have not actually had HFpEF, and their signs and symptoms may have instead resulted from atrial fibrillation.
“Many patients with an ejection fraction of 60%-65% and above had atrial fibrillation,” he noted, with a prevalence at enrollment in this subgroup of about 50%. Atrial fibrillation can cause dyspnea, a hallmark symptom leading to diagnosis of heart failure, and it also increases levels of N-terminal of the prohormone brain natriuretic peptide, a metric that served as a gatekeeper for entry into the trial. “Essentially, we are saying that many of the criteria that we specified to ensure that patients had heart failure probably did not work very well in patients with an ejection fraction of 65% or greater,” said Dr. Packer, a cardiologist at Baylor University Medical Center in Dallas. “We need to figure out who these patients are.”
Some experts not involved with the study voiced skepticism that the renal findings reflected a real issue.
“I’m quite optimistic that in the long-term the effect on eGFR will translate into renal protection,” said Rudolf A. de Boer, MD, PhD, a professor of translational cardiology at University Medical Center Groningen (the Netherlands), and designated discussant at the congress for the presentation by Dr. Packer.
John J.V. McMurray, MD, a professor of cardiology and a heart failure specialist at Glasgow University, speculated that the unexpected renal outcomes data may relate to the initial decline in renal function produced by treatment with SGLT2 inhibitors despite their longer-term enhancement of renal protection.
“If you use a treatment that protects the kidneys in the long-term but causes an initial dip in eGFR, more patients receiving that treatment will have an early ‘event,’ ” he noted in an interview. He also cautioned about the dangers of subgroup analyses that dice the study population into small cohorts.
“Trials are powered to look at the effect of treatment in the overall population. Everything else is exploratory, underpowered, and subject to the play of chance,” Dr. McMurray stressed.
Counting additional cardiovascular disease events allows more analyses
A third auxiliary report from the EMPEROR-Preserved investigators performed several prespecified analyses that depended on adding additional cardiovascular disease endpoints to the core tallies of cardiovascular death or HHF – such as emergent, urgent, and outpatient events that reflected worsening heart failure – and also included information on diuretic and vasopressor use because of worsening heart failure. The increased event numbers allowed the researchers to perform 30 additional analyses included in this report, according to the count kept by Dr. Packer who was the lead author.
He highlighted several of the additional results in this paper that documented benefits from empagliflozin treatment, compared with placebo:
- A significant 29% reduction in the need for admission to a cardiac care unit or intensive care unit during an HHF.
- A nonsignificant 33% reduction in the need for intravenous vasopressors or positive inotropic drugs during HHF.
- A significantly increased rate of patients achieving a higher New York Heart Association functional class. For example, after the first year of treatment patients who received empagliflozin had a 37% higher rate of functional class improvement, compared with patients who received placebo.
Dr. McMurray had his own list of key takeaways from this paper, including:
- Among patients who needed hospitalization, “those treated with empagliflozin were less sick than those in the placebo group.”
- In addition to reducing HHF empagliflozin treatment also reduced episodes of outpatient worsening as reflected by their receipt of intensified diuretic treatment, which occurred a significant 27% less often, compared with patients on placebo.
- Treatment with empagliflozin also linked with a significant 39% relative reduction in emergency or urgent-care visits that required intravenous therapy.
Empagliflozin’s performance relative to sacubitril/valsartan
The fourth additional report focused on a post hoc, cross-trial comparison of the results from EMPEROR-Preserved and from another recent trial that, like EMPEROR-Preserved, assessed in patients with HFpEF a drug previously proven to work quite well in patients with HFrEF. The comparator drug was sacubitril/valsartan (Entresto), which underwent testing in patients with HFpEF in the PARAGON-HF trial.
The primary outcome of PARAGON-HF, which randomized 4,822 patients, was reduction in cardiovascular death and in total HHF. This dropped by a relative 13%, compared with placebo, during a median of 35 months, a between-group difference that came close to but did not achieve significance (P = .06). Despite this limitation, the Food and Drug Administration in February 2021 loosened the indication for using sacubitril/valsartan in patients with heart failure and a “below normal” ejection fraction, a category that can include many patients considered to have HFpEF.
Although the researchers who ran this analysis, including Dr. Packer, who was the first author, admitted that “comparison of effect sizes across trials is fraught with difficulties,” they nonetheless concluded from their analysis that “for all outcomes that included HHF the effect size was larger for empagliflozin than for sacubitril/valsartan.”
Dr. McMurray, a lead instigator for PARAGON-HF, said there was little to take away from this analysis.
“The patient populations were different, and sacubitril/valsartan was compared against an active therapy, valsartan,” while in EMPEROR-Preserved empagliflozin compared against placebo. “Most of us believe that sacubitril/valsartan and SGLT2 inhibitors work in different but complementary ways, and their benefits are additive. You would want patients with HFpEF or HFrEF to take both,” he said in an interview.
Dr. Packer agreed with that approach and added that he would probably also prescribe a third agent, spironolactone, to many patients with HFpEF.
EMPEROR-Preserved was sponsored by Boehringer Ingelheim and Eli Lilly, which jointly market empagliflozin (Jardiance). PARAGON-HF was sponsored by Novartis, which markets sacubitril/valsartan (Entresto). Dr. Packer has received consulting fees from Boehringer Ingelheim and from numerous other companies. Dr. de Boer has research contracts with Boehringer Ingelheim as well as from Abbott, AstraZeneca, Cardior, Ionis, Novo Nordisk, and Roche, and he has been a consultant to Novartis as well as to Abbott, AstraZeneca, Gayer, and Roche. Dr. McMurray led trials of sacubitril/valsartan sponsored by Novartis, and his institution has received compensation for his participation in studies sponsored by Abbvie, AstraZeneca, Cardurion, DalCor, GlaxoSmithKline, Pfizer, and Theracos.
The featured report from the 6,000-patient EMPEROR-Preserved trial at the virtual annual congress of the European Society of Cardiology drew lots of attention for its headline finding: the first unequivocal demonstration that a medication, empagliflozin, can significantly reduce the rate of cardiovascular death and hospitalization for heart failure in patients with heart failure with preserved ejection fraction (HFpEF, a left ventricular ejection fraction of more than 40%), with the details simultaneously published online.
But at the same time, the EMPEROR-Preserved investigators released four additional reports with a lot more outcome analyses that also deserve some attention.
The puzzling neutral effect on renal events
Perhaps the most surprising and complicated set of findings among the main EMPEROR-Preserved outcomes involved renal outcomes.
The trial’s primary outcome was the combined rate of cardiovascular death or hospitalization for heart failure (HHF), and the results showed that treatment with empagliflozin (Jardiance) for a median of 26 months on top of standard treatment for patients with HFpEF led to a significant 21% relative risk reduction, compared with placebo-treated patients.
The trial had two prespecified secondary outcomes. One was the total number of HHF, which dropped by a significant 27%, compared with placebo. The second was the mean change in slope of estimated glomerular filtration rate (eGFR) on an annualized basis, and the empagliflozin regimen reduced the cumulative annual deficit, compared with placebo by an average of 1.36 mL/min per 1.73 m2, a significant difference.
This preservation of renal function was consistent with results from many prior studies of empagliflozin and all of the other U.S.-approved agents from the sodium-glucose cotransporter 2 inhibitor class. Preservation of renal function and a reduction in renal events has become a hallmark property of all agents in the SGLT2 inhibitor class both in patients with type 2 diabetes, as well as in those without diabetes but with heart failure with reduced ejection fraction (HFrEF) or with chronic kidney disease.
EMPEROR-Preserved threw a wrench into what had been an unbroken history of renal protection by SGLT2 inhibitors. That happened when a prespecified endpoint of the study – a composite renal outcome defined as time to first occurrence of chronic dialysis, renal transplantation, a sustained reduction of at least 40% in eGFR, or a sustained drop in eGFR of more than 10 or 15 mL/min per 1.73 m2 from baseline – yielded an unexpected neutral finding.
For this composite renal outcome, EMPEROR-Preserved showed a nonsignificant 5% reduction, compared with placebo, a result that both differed from what had been seen in essentially all the other SGLT2 inhibitor trials that had looked at this, but which also seemed at odds with the observed significant preservation of renal function that seemed substantial enough to produce a clinically meaningful benefit.
Renal effects blunted in HFpEF
The immediate upshot was a letter published by several EMPEROR-Preserved investigators that spelled out this discrepancy and came to the jolting conclusion that “eGFR slope analysis has limitations as a surrogate for predicting the effect of drugs on renal outcomes in patients with heart failure.”
The same authors, along with some additional associates, also published a second letter that noted a further unexpected twist with the renal outcome: “In prior large-scale clinical trials, the effect of SGLT2 inhibitors on heart failure and renal outcomes had consistently tracked together,” they noted, but in this case it didn’t, a discordance they said was “extraordinarily puzzling”.
This led the study’s leaders to reanalyze the renal outcomes using a different definition, one that Milton Packer, MD, who helped design the trial and oversaw several of its analyses, called “a more conventional definition of renal events,” during his presentation of these findings at the congress. The researchers swapped out a 40% drop from baseline eGFR as an event and replaced it with a 50% decline, a change designed to screen out less severe, and often transient, reductions in kidney function that have less lasting impact on health. They also added an additional component to the composite endpoint, renal death. A revised analysis using this new renal composite outcome appeared in the European Journal of Heart Failure letter.
This change cut the total number of renal events tallied in the trial nearly in half, down to 112, and showed a more robust decline in renal events with empagliflozin treatment compared with the initial analysis, although the drop remained nonsignificant. The revised analysis also showed that the overall, nonsignificant 22% relative reduction in renal events in patients on empagliflozin, compared with placebo, dwindled down to completely nonexistent in the tertile of patients with a left ventricular ejection fraction of 60% or greater. In this tertile the hazard ratio actually showed a nonsignificant point estimate of a 24% increased rate of renal events on empagliflozin, with the caveat that this subgroup now included a total of just 40 total events between the two treatment arms. (Each of the two other tertiles also had roughly the same number of total events.)
The biggest effect on renal-event reduction was in the tertile of patients with an ejection fraction of 41%-49%, in which empagliflozin treatment was linked with a significant 59% cut in renal events, compared with placebo. The analysis also showed significant heterogeneity in thus outcome between this subgroup and the other two tertiles that had higher ejection fractions and showed reduced rates of protection by empagliflozin against renal events.
This apparent blunting of a renal effect despite preservation of renal function seemed to mimic the blunting of the primary cardiovascular outcome effect that also appeared in patients with ejection fractions in the 60%-65% range or above.
“If we knew what blunted the effect of empagliflozin on heart failure outcomes at higher ejection fraction levels, we think the same explanation may also apply to the blunting of effect on renal outcomes, but right now we do not know the answer to either question,” Dr. Packer said in an interview. He’s suggested that one possibility is that many of the enrolled patients identified as having HFpEF, but with these high ejection fractions may have not actually had HFpEF, and their signs and symptoms may have instead resulted from atrial fibrillation.
“Many patients with an ejection fraction of 60%-65% and above had atrial fibrillation,” he noted, with a prevalence at enrollment in this subgroup of about 50%. Atrial fibrillation can cause dyspnea, a hallmark symptom leading to diagnosis of heart failure, and it also increases levels of N-terminal of the prohormone brain natriuretic peptide, a metric that served as a gatekeeper for entry into the trial. “Essentially, we are saying that many of the criteria that we specified to ensure that patients had heart failure probably did not work very well in patients with an ejection fraction of 65% or greater,” said Dr. Packer, a cardiologist at Baylor University Medical Center in Dallas. “We need to figure out who these patients are.”
Some experts not involved with the study voiced skepticism that the renal findings reflected a real issue.
“I’m quite optimistic that in the long-term the effect on eGFR will translate into renal protection,” said Rudolf A. de Boer, MD, PhD, a professor of translational cardiology at University Medical Center Groningen (the Netherlands), and designated discussant at the congress for the presentation by Dr. Packer.
John J.V. McMurray, MD, a professor of cardiology and a heart failure specialist at Glasgow University, speculated that the unexpected renal outcomes data may relate to the initial decline in renal function produced by treatment with SGLT2 inhibitors despite their longer-term enhancement of renal protection.
“If you use a treatment that protects the kidneys in the long-term but causes an initial dip in eGFR, more patients receiving that treatment will have an early ‘event,’ ” he noted in an interview. He also cautioned about the dangers of subgroup analyses that dice the study population into small cohorts.
“Trials are powered to look at the effect of treatment in the overall population. Everything else is exploratory, underpowered, and subject to the play of chance,” Dr. McMurray stressed.
Counting additional cardiovascular disease events allows more analyses
A third auxiliary report from the EMPEROR-Preserved investigators performed several prespecified analyses that depended on adding additional cardiovascular disease endpoints to the core tallies of cardiovascular death or HHF – such as emergent, urgent, and outpatient events that reflected worsening heart failure – and also included information on diuretic and vasopressor use because of worsening heart failure. The increased event numbers allowed the researchers to perform 30 additional analyses included in this report, according to the count kept by Dr. Packer who was the lead author.
He highlighted several of the additional results in this paper that documented benefits from empagliflozin treatment, compared with placebo:
- A significant 29% reduction in the need for admission to a cardiac care unit or intensive care unit during an HHF.
- A nonsignificant 33% reduction in the need for intravenous vasopressors or positive inotropic drugs during HHF.
- A significantly increased rate of patients achieving a higher New York Heart Association functional class. For example, after the first year of treatment patients who received empagliflozin had a 37% higher rate of functional class improvement, compared with patients who received placebo.
Dr. McMurray had his own list of key takeaways from this paper, including:
- Among patients who needed hospitalization, “those treated with empagliflozin were less sick than those in the placebo group.”
- In addition to reducing HHF empagliflozin treatment also reduced episodes of outpatient worsening as reflected by their receipt of intensified diuretic treatment, which occurred a significant 27% less often, compared with patients on placebo.
- Treatment with empagliflozin also linked with a significant 39% relative reduction in emergency or urgent-care visits that required intravenous therapy.
Empagliflozin’s performance relative to sacubitril/valsartan
The fourth additional report focused on a post hoc, cross-trial comparison of the results from EMPEROR-Preserved and from another recent trial that, like EMPEROR-Preserved, assessed in patients with HFpEF a drug previously proven to work quite well in patients with HFrEF. The comparator drug was sacubitril/valsartan (Entresto), which underwent testing in patients with HFpEF in the PARAGON-HF trial.
The primary outcome of PARAGON-HF, which randomized 4,822 patients, was reduction in cardiovascular death and in total HHF. This dropped by a relative 13%, compared with placebo, during a median of 35 months, a between-group difference that came close to but did not achieve significance (P = .06). Despite this limitation, the Food and Drug Administration in February 2021 loosened the indication for using sacubitril/valsartan in patients with heart failure and a “below normal” ejection fraction, a category that can include many patients considered to have HFpEF.
Although the researchers who ran this analysis, including Dr. Packer, who was the first author, admitted that “comparison of effect sizes across trials is fraught with difficulties,” they nonetheless concluded from their analysis that “for all outcomes that included HHF the effect size was larger for empagliflozin than for sacubitril/valsartan.”
Dr. McMurray, a lead instigator for PARAGON-HF, said there was little to take away from this analysis.
“The patient populations were different, and sacubitril/valsartan was compared against an active therapy, valsartan,” while in EMPEROR-Preserved empagliflozin compared against placebo. “Most of us believe that sacubitril/valsartan and SGLT2 inhibitors work in different but complementary ways, and their benefits are additive. You would want patients with HFpEF or HFrEF to take both,” he said in an interview.
Dr. Packer agreed with that approach and added that he would probably also prescribe a third agent, spironolactone, to many patients with HFpEF.
EMPEROR-Preserved was sponsored by Boehringer Ingelheim and Eli Lilly, which jointly market empagliflozin (Jardiance). PARAGON-HF was sponsored by Novartis, which markets sacubitril/valsartan (Entresto). Dr. Packer has received consulting fees from Boehringer Ingelheim and from numerous other companies. Dr. de Boer has research contracts with Boehringer Ingelheim as well as from Abbott, AstraZeneca, Cardior, Ionis, Novo Nordisk, and Roche, and he has been a consultant to Novartis as well as to Abbott, AstraZeneca, Gayer, and Roche. Dr. McMurray led trials of sacubitril/valsartan sponsored by Novartis, and his institution has received compensation for his participation in studies sponsored by Abbvie, AstraZeneca, Cardurion, DalCor, GlaxoSmithKline, Pfizer, and Theracos.
FROM ESC 2021
Early end for trial of experimental oxygenation strategies in ARDS
Background: Both observational studies and clinical trials have found that a liberal oxygenation strategy in multiple inpatient settings may be harmful. Furthermore, a conservative strategy is what has been recommended in guidelines. Conversely, the relevance of this recent concept has been challenged in a large trial of a critically ill population (ICU-ROX).
Study design: Randomized clinical trial, unblinded.
Setting: Thirteen sites in France.
Synopsis: In a multicenter randomized clinical trial, investigators enrolled patients with ARDS to either a liberal oxygenation group (PaO2 target 90-105 mm Hg or SpO2 of 96% or greater) or a conservative oxygenation group (PaO2 target 55-70 mm Hg or SpO2 88%-92%). The trial was planned for inclusion of 850 patients, but the data and safety monitoring board decided to stop the trial after inclusion of 205 patients. Although the primary outcome (28-day all-cause mortality) was not significantly different between groups (34.3% vs 26.5%; absolute difference, 7.8%; 95% confidence interval, –4.8 to 20.6), the direction was signaling possible harm and there were five episodes of mesenteric ischemia in the conservative oxygenation group (none in the liberal oxygenation group).
Bottom line: A conservative oxygenation strategy cannot be currently recommended to patients with ARDS in the ICU. A minimum SpO2 of 90% was suggested in an accompanying editorial.
Editorial commentary: Interestingly, the supplemental results of the article show that prone positioning was used much less frequently in the conservative oxygenation group (34.3 vs 51.0%). If the impressive results of Guerin (2013) would be repeated in this population, this difference could help explain the higher observed mortality in the conservative oxygenation group. It is possible that, by aiming to be less aggressive in improving the PaO2, clinicians inadvertently withheld effective treatments for ARDS. The results of this trial bring up several interesting questions, but provide the bedside clinician with few answers. The complex interplay of treatment factors needs to be dissected in future trials.
Citation: Barrot L et al. Liberal or conservative oxygen therapy for acute respiratory distress syndrome. N Eng J Med. 2020;382:999-1008.
Dr. Saraiva is a hospitalist and assistant professor of medicine at UK HealthCare, Lexington, Ky.
Background: Both observational studies and clinical trials have found that a liberal oxygenation strategy in multiple inpatient settings may be harmful. Furthermore, a conservative strategy is what has been recommended in guidelines. Conversely, the relevance of this recent concept has been challenged in a large trial of a critically ill population (ICU-ROX).
Study design: Randomized clinical trial, unblinded.
Setting: Thirteen sites in France.
Synopsis: In a multicenter randomized clinical trial, investigators enrolled patients with ARDS to either a liberal oxygenation group (PaO2 target 90-105 mm Hg or SpO2 of 96% or greater) or a conservative oxygenation group (PaO2 target 55-70 mm Hg or SpO2 88%-92%). The trial was planned for inclusion of 850 patients, but the data and safety monitoring board decided to stop the trial after inclusion of 205 patients. Although the primary outcome (28-day all-cause mortality) was not significantly different between groups (34.3% vs 26.5%; absolute difference, 7.8%; 95% confidence interval, –4.8 to 20.6), the direction was signaling possible harm and there were five episodes of mesenteric ischemia in the conservative oxygenation group (none in the liberal oxygenation group).
Bottom line: A conservative oxygenation strategy cannot be currently recommended to patients with ARDS in the ICU. A minimum SpO2 of 90% was suggested in an accompanying editorial.
Editorial commentary: Interestingly, the supplemental results of the article show that prone positioning was used much less frequently in the conservative oxygenation group (34.3 vs 51.0%). If the impressive results of Guerin (2013) would be repeated in this population, this difference could help explain the higher observed mortality in the conservative oxygenation group. It is possible that, by aiming to be less aggressive in improving the PaO2, clinicians inadvertently withheld effective treatments for ARDS. The results of this trial bring up several interesting questions, but provide the bedside clinician with few answers. The complex interplay of treatment factors needs to be dissected in future trials.
Citation: Barrot L et al. Liberal or conservative oxygen therapy for acute respiratory distress syndrome. N Eng J Med. 2020;382:999-1008.
Dr. Saraiva is a hospitalist and assistant professor of medicine at UK HealthCare, Lexington, Ky.
Background: Both observational studies and clinical trials have found that a liberal oxygenation strategy in multiple inpatient settings may be harmful. Furthermore, a conservative strategy is what has been recommended in guidelines. Conversely, the relevance of this recent concept has been challenged in a large trial of a critically ill population (ICU-ROX).
Study design: Randomized clinical trial, unblinded.
Setting: Thirteen sites in France.
Synopsis: In a multicenter randomized clinical trial, investigators enrolled patients with ARDS to either a liberal oxygenation group (PaO2 target 90-105 mm Hg or SpO2 of 96% or greater) or a conservative oxygenation group (PaO2 target 55-70 mm Hg or SpO2 88%-92%). The trial was planned for inclusion of 850 patients, but the data and safety monitoring board decided to stop the trial after inclusion of 205 patients. Although the primary outcome (28-day all-cause mortality) was not significantly different between groups (34.3% vs 26.5%; absolute difference, 7.8%; 95% confidence interval, –4.8 to 20.6), the direction was signaling possible harm and there were five episodes of mesenteric ischemia in the conservative oxygenation group (none in the liberal oxygenation group).
Bottom line: A conservative oxygenation strategy cannot be currently recommended to patients with ARDS in the ICU. A minimum SpO2 of 90% was suggested in an accompanying editorial.
Editorial commentary: Interestingly, the supplemental results of the article show that prone positioning was used much less frequently in the conservative oxygenation group (34.3 vs 51.0%). If the impressive results of Guerin (2013) would be repeated in this population, this difference could help explain the higher observed mortality in the conservative oxygenation group. It is possible that, by aiming to be less aggressive in improving the PaO2, clinicians inadvertently withheld effective treatments for ARDS. The results of this trial bring up several interesting questions, but provide the bedside clinician with few answers. The complex interplay of treatment factors needs to be dissected in future trials.
Citation: Barrot L et al. Liberal or conservative oxygen therapy for acute respiratory distress syndrome. N Eng J Med. 2020;382:999-1008.
Dr. Saraiva is a hospitalist and assistant professor of medicine at UK HealthCare, Lexington, Ky.
Number of global deaths by suicide increased over 30 years
The overall global number of deaths by suicide increased by almost 20,000 during the past 30 years, new research shows.
The increase occurred despite a significant decrease in age-specific suicide rates from 1990 through 2019, according to data from the Global Burden of Disease Study 2019.
Population growth, population aging, and changes in population age structure may explain the increase in number of suicide deaths, the investigators note.
“As suicide rates are highest among the elderly (70 years or above) for both genders in almost all regions of the world, the rapidly aging population globally will pose huge challenges for the reduction in the number of suicide deaths in the future,” write the researchers, led by Paul Siu Fai Yip, PhD, of the HKJC Center for Suicide Research and Prevention, University of Hong Kong, China.
The findings were published online Aug. 16 in Injury Prevention.
Global public health concern
Around the world, approximately 800,000 individuals die by suicide each year, while many others attempt suicide. Yet suicide has not received the same level of attention as other global public health concerns, such as HIV/AIDS and cancer, the investigators write.
They examined data from the Global Burden of Disease Study 2019 to assess how demographic and epidemiologic factors contributed to the number of suicide deaths during the past 30 years.
The researchers also analyzed relationships between population growth, population age structure, income level, and gender- and age-specific suicide rates.
The Global Burden of Disease Study 2019 includes information from 204 countries about 369 diseases and injuries by age and gender. The dataset also includes population estimates for each year by location, age group, and gender.
In their analysis, the investigators looked at changes in suicide rates and the number of suicide deaths from 1990 to 2019 by gender and age group in the four income level regions defined by the World Bank. These categories include low-income, lower-middle–income, upper-middle–income, and high-income regions.
Number of deaths versus suicide rates
The number of deaths was 738,799 in 1990 and 758,696 in 2019.
The largest increase in deaths occurred in the lower-middle–income region, where the number of suicide deaths increased by 72,550 (from 232,340 to 304,890).
Population growth (300,942; 1,512.5%) was the major contributor to the overall increase in total number of suicide deaths. The second largest contributor was population age structure (189,512; 952.4%).
However, the effects of these factors were offset to a large extent by the effect of reduction in overall suicide rates (−470,556; −2,364.9%).
Interestingly, the overall suicide rate per 100,000 population decreased from 13.8 in 1990 to 9.8 in 2019.
The upper-middle–income region had the largest decline (−6.25 per 100,000), and the high-income region had the smallest decline (−1.77 per 100,000). Suicide rates also decreased in lower-middle–income (−2.51 per 100,000) and low-income regions (−1.96 per 100,000).
Reasons for the declines across all regions “have yet to be determined,” write the investigators. International efforts coordinated by the United Nations and World Health Organization likely contributed to these declines, they add.
‘Imbalance of resources’
The overall reduction in suicide rate of −4.01 per 100,000 “was mainly due” to reduction in age-specific suicide rates (−6.09; 152%), the researchers report.
This effect was partly offset, however, by the effect of the changing population age structure (2.08; −52%). In the high-income–level region, for example, the reduction in age-specific suicide rate (−3.83; 216.3%) was greater than the increase resulting from the change in population age structure (2.06; −116.3%).
“The overall contribution of population age structure mainly came from the 45-64 (565.2%) and 65+ (528.7%) age groups,” the investigators write. “This effect was observed in middle-income– as well as high-income–level regions, reflecting the global effect of population aging.”
They add that world populations will “experience pronounced and historically unprecedented aging in the coming decades” because of increasing life expectancy and declining fertility.
Men, but not women, had a notable increase in total number of suicide deaths. The significant effect of male population growth (177,128; 890.2% vs. 123,814; 622.3% for women) and male population age structure (120,186; 604.0% vs. 69,325; 348.4%) were the main factors that explained this increase, the investigators note.
However, from 1990 to 2019, the overall suicide rate per 100,000 men decreased from 16.6 to 13.5 (–3.09). The decline in overall suicide rate was even greater for women, from 11.0 to 6.1 (–4.91).
This finding was particularly notable in the upper-middle–income region (–8.12 women vs. –4.37 men per 100,000).
“This study highlighted the considerable imbalance of the resources in carrying out suicide prevention work, especially in low-income and middle-income countries,” the investigators write.
“It is time to revisit this situation to ensure that sufficient resources can be redeployed globally to meet the future challenges,” they add.
The study was funded by a Humanities and Social Sciences Prestigious Fellowship, which Dr. Yip received. He declared no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The overall global number of deaths by suicide increased by almost 20,000 during the past 30 years, new research shows.
The increase occurred despite a significant decrease in age-specific suicide rates from 1990 through 2019, according to data from the Global Burden of Disease Study 2019.
Population growth, population aging, and changes in population age structure may explain the increase in number of suicide deaths, the investigators note.
“As suicide rates are highest among the elderly (70 years or above) for both genders in almost all regions of the world, the rapidly aging population globally will pose huge challenges for the reduction in the number of suicide deaths in the future,” write the researchers, led by Paul Siu Fai Yip, PhD, of the HKJC Center for Suicide Research and Prevention, University of Hong Kong, China.
The findings were published online Aug. 16 in Injury Prevention.
Global public health concern
Around the world, approximately 800,000 individuals die by suicide each year, while many others attempt suicide. Yet suicide has not received the same level of attention as other global public health concerns, such as HIV/AIDS and cancer, the investigators write.
They examined data from the Global Burden of Disease Study 2019 to assess how demographic and epidemiologic factors contributed to the number of suicide deaths during the past 30 years.
The researchers also analyzed relationships between population growth, population age structure, income level, and gender- and age-specific suicide rates.
The Global Burden of Disease Study 2019 includes information from 204 countries about 369 diseases and injuries by age and gender. The dataset also includes population estimates for each year by location, age group, and gender.
In their analysis, the investigators looked at changes in suicide rates and the number of suicide deaths from 1990 to 2019 by gender and age group in the four income level regions defined by the World Bank. These categories include low-income, lower-middle–income, upper-middle–income, and high-income regions.
Number of deaths versus suicide rates
The number of deaths was 738,799 in 1990 and 758,696 in 2019.
The largest increase in deaths occurred in the lower-middle–income region, where the number of suicide deaths increased by 72,550 (from 232,340 to 304,890).
Population growth (300,942; 1,512.5%) was the major contributor to the overall increase in total number of suicide deaths. The second largest contributor was population age structure (189,512; 952.4%).
However, the effects of these factors were offset to a large extent by the effect of reduction in overall suicide rates (−470,556; −2,364.9%).
Interestingly, the overall suicide rate per 100,000 population decreased from 13.8 in 1990 to 9.8 in 2019.
The upper-middle–income region had the largest decline (−6.25 per 100,000), and the high-income region had the smallest decline (−1.77 per 100,000). Suicide rates also decreased in lower-middle–income (−2.51 per 100,000) and low-income regions (−1.96 per 100,000).
Reasons for the declines across all regions “have yet to be determined,” write the investigators. International efforts coordinated by the United Nations and World Health Organization likely contributed to these declines, they add.
‘Imbalance of resources’
The overall reduction in suicide rate of −4.01 per 100,000 “was mainly due” to reduction in age-specific suicide rates (−6.09; 152%), the researchers report.
This effect was partly offset, however, by the effect of the changing population age structure (2.08; −52%). In the high-income–level region, for example, the reduction in age-specific suicide rate (−3.83; 216.3%) was greater than the increase resulting from the change in population age structure (2.06; −116.3%).
“The overall contribution of population age structure mainly came from the 45-64 (565.2%) and 65+ (528.7%) age groups,” the investigators write. “This effect was observed in middle-income– as well as high-income–level regions, reflecting the global effect of population aging.”
They add that world populations will “experience pronounced and historically unprecedented aging in the coming decades” because of increasing life expectancy and declining fertility.
Men, but not women, had a notable increase in total number of suicide deaths. The significant effect of male population growth (177,128; 890.2% vs. 123,814; 622.3% for women) and male population age structure (120,186; 604.0% vs. 69,325; 348.4%) were the main factors that explained this increase, the investigators note.
However, from 1990 to 2019, the overall suicide rate per 100,000 men decreased from 16.6 to 13.5 (–3.09). The decline in overall suicide rate was even greater for women, from 11.0 to 6.1 (–4.91).
This finding was particularly notable in the upper-middle–income region (–8.12 women vs. –4.37 men per 100,000).
“This study highlighted the considerable imbalance of the resources in carrying out suicide prevention work, especially in low-income and middle-income countries,” the investigators write.
“It is time to revisit this situation to ensure that sufficient resources can be redeployed globally to meet the future challenges,” they add.
The study was funded by a Humanities and Social Sciences Prestigious Fellowship, which Dr. Yip received. He declared no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The overall global number of deaths by suicide increased by almost 20,000 during the past 30 years, new research shows.
The increase occurred despite a significant decrease in age-specific suicide rates from 1990 through 2019, according to data from the Global Burden of Disease Study 2019.
Population growth, population aging, and changes in population age structure may explain the increase in number of suicide deaths, the investigators note.
“As suicide rates are highest among the elderly (70 years or above) for both genders in almost all regions of the world, the rapidly aging population globally will pose huge challenges for the reduction in the number of suicide deaths in the future,” write the researchers, led by Paul Siu Fai Yip, PhD, of the HKJC Center for Suicide Research and Prevention, University of Hong Kong, China.
The findings were published online Aug. 16 in Injury Prevention.
Global public health concern
Around the world, approximately 800,000 individuals die by suicide each year, while many others attempt suicide. Yet suicide has not received the same level of attention as other global public health concerns, such as HIV/AIDS and cancer, the investigators write.
They examined data from the Global Burden of Disease Study 2019 to assess how demographic and epidemiologic factors contributed to the number of suicide deaths during the past 30 years.
The researchers also analyzed relationships between population growth, population age structure, income level, and gender- and age-specific suicide rates.
The Global Burden of Disease Study 2019 includes information from 204 countries about 369 diseases and injuries by age and gender. The dataset also includes population estimates for each year by location, age group, and gender.
In their analysis, the investigators looked at changes in suicide rates and the number of suicide deaths from 1990 to 2019 by gender and age group in the four income level regions defined by the World Bank. These categories include low-income, lower-middle–income, upper-middle–income, and high-income regions.
Number of deaths versus suicide rates
The number of deaths was 738,799 in 1990 and 758,696 in 2019.
The largest increase in deaths occurred in the lower-middle–income region, where the number of suicide deaths increased by 72,550 (from 232,340 to 304,890).
Population growth (300,942; 1,512.5%) was the major contributor to the overall increase in total number of suicide deaths. The second largest contributor was population age structure (189,512; 952.4%).
However, the effects of these factors were offset to a large extent by the effect of reduction in overall suicide rates (−470,556; −2,364.9%).
Interestingly, the overall suicide rate per 100,000 population decreased from 13.8 in 1990 to 9.8 in 2019.
The upper-middle–income region had the largest decline (−6.25 per 100,000), and the high-income region had the smallest decline (−1.77 per 100,000). Suicide rates also decreased in lower-middle–income (−2.51 per 100,000) and low-income regions (−1.96 per 100,000).
Reasons for the declines across all regions “have yet to be determined,” write the investigators. International efforts coordinated by the United Nations and World Health Organization likely contributed to these declines, they add.
‘Imbalance of resources’
The overall reduction in suicide rate of −4.01 per 100,000 “was mainly due” to reduction in age-specific suicide rates (−6.09; 152%), the researchers report.
This effect was partly offset, however, by the effect of the changing population age structure (2.08; −52%). In the high-income–level region, for example, the reduction in age-specific suicide rate (−3.83; 216.3%) was greater than the increase resulting from the change in population age structure (2.06; −116.3%).
“The overall contribution of population age structure mainly came from the 45-64 (565.2%) and 65+ (528.7%) age groups,” the investigators write. “This effect was observed in middle-income– as well as high-income–level regions, reflecting the global effect of population aging.”
They add that world populations will “experience pronounced and historically unprecedented aging in the coming decades” because of increasing life expectancy and declining fertility.
Men, but not women, had a notable increase in total number of suicide deaths. The significant effect of male population growth (177,128; 890.2% vs. 123,814; 622.3% for women) and male population age structure (120,186; 604.0% vs. 69,325; 348.4%) were the main factors that explained this increase, the investigators note.
However, from 1990 to 2019, the overall suicide rate per 100,000 men decreased from 16.6 to 13.5 (–3.09). The decline in overall suicide rate was even greater for women, from 11.0 to 6.1 (–4.91).
This finding was particularly notable in the upper-middle–income region (–8.12 women vs. –4.37 men per 100,000).
“This study highlighted the considerable imbalance of the resources in carrying out suicide prevention work, especially in low-income and middle-income countries,” the investigators write.
“It is time to revisit this situation to ensure that sufficient resources can be redeployed globally to meet the future challenges,” they add.
The study was funded by a Humanities and Social Sciences Prestigious Fellowship, which Dr. Yip received. He declared no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Clinical Edge Journal Scan Commentary: Psoriasis September 2021
Several recent studies have evaluated that association between psoriasis and known comorbidities including cardiovascular disease, non-alcoholic fatty liver disease (NAFLD), and malignancy. Several recent studies have added to our understanding of the relationship between these conditions.
Using the largest database of hospitalized patients in the United States, Edgen et al found that hospitalization rates for patients with psoriasis are increasing. While the proportion of patients with psoriasis hospitalized with psoriasis as a primary diagnosis decreased about four-fold over a 20-year period (1999-2018), incidence of hospitalizations with any diagnosis of psoriasis has increased. Hospitalized psoriasis patients are increasingly more likely to have other comorbid conditions as during the study period the proportion of hospitalized psoriasis patients with a Charlson Comorbidity Index score of 3 or higher increased from 13.9% to 30.9%. Psoriasis severity, medication use, and reasons for hospitalization were not reported. The authors suggest that screening and management of comorbidities in the outpatient setting may help reduce preventable psoriasis hospitalizations.
Both NAFLD and cardiovascular disease are well-known psoriasis comorbidities, Gonzalez-Cantaro et al studied two cohorts of patients to better define the relationship between these two conditions. In a European cohort of 76 psoriasis patients and 76 control patients, psoriasis patients with NAFLD had a higher prevalence of subclinical atherosclerosis than both psoriasis patients without NAFLD (61% vs 23%) and age, sex, and BMI-matched controls with NAFLD (61% vs 32%). Psoriasis patients were also more likely that control patients to have insulin resistance, higher weight circumference, and dysplipidemia. Among 162 psoriasis patients who underwent PET and coronary CT angiography, higher hepatic FDG uptake (indicating NAFLD) was associated higher atherosclerotic disease burden. Importantly, both the NAFLD and CAD were subclinical in these patients. While the cross-sectional study design precludes any conclusions about causality, physicians should be aware that these two comorbidities are related. Lower waist circumference and greater physical activity were both associated with lower rates of NAFLD among patients with psoriasis, providing some guidance for counseling patients.
Several recent studies have found that cancer rates among patients with psoriasis are higher than what is observed in the general population. The association of psoriasis with lymphohematologic malignancies (LHM) has been controversial. A systematic review and meta-analysis of 25 observational studies including over 2.5 million subjects (Bellinato et al.) found a 1.55-fold increased risk of LHM in patients with moderate to severe psoriasis. Strikingly, the risk of cutaneous T cell lymphoma (CTCL) was increased 6.22-fold, with more severe psoriasis being associated with the highest risk of CTCL. A causal relationship cannot be established from this type of studies, but the authors hypothesize that drugs used to treat psoriasis or the chronic T cell activation caused by active disease may contribute to the risk of LMH. Additionally, psoriasis and CTCL can share clinical features and some cases may be due to misdiagnosis. Interestingly, two psoriasis comorbities, diabetes and obesity, are also associated with an increased risk of LHM.
Early identification and management of comorbidities can help in reducing morbidity and mortality. With so many psoriasis treatments available, understanding how different therapies may impact comorbid conditions is important in helping dermatologists to choose the best therapy for each individual patient.
Several recent studies have evaluated that association between psoriasis and known comorbidities including cardiovascular disease, non-alcoholic fatty liver disease (NAFLD), and malignancy. Several recent studies have added to our understanding of the relationship between these conditions.
Using the largest database of hospitalized patients in the United States, Edgen et al found that hospitalization rates for patients with psoriasis are increasing. While the proportion of patients with psoriasis hospitalized with psoriasis as a primary diagnosis decreased about four-fold over a 20-year period (1999-2018), incidence of hospitalizations with any diagnosis of psoriasis has increased. Hospitalized psoriasis patients are increasingly more likely to have other comorbid conditions as during the study period the proportion of hospitalized psoriasis patients with a Charlson Comorbidity Index score of 3 or higher increased from 13.9% to 30.9%. Psoriasis severity, medication use, and reasons for hospitalization were not reported. The authors suggest that screening and management of comorbidities in the outpatient setting may help reduce preventable psoriasis hospitalizations.
Both NAFLD and cardiovascular disease are well-known psoriasis comorbidities, Gonzalez-Cantaro et al studied two cohorts of patients to better define the relationship between these two conditions. In a European cohort of 76 psoriasis patients and 76 control patients, psoriasis patients with NAFLD had a higher prevalence of subclinical atherosclerosis than both psoriasis patients without NAFLD (61% vs 23%) and age, sex, and BMI-matched controls with NAFLD (61% vs 32%). Psoriasis patients were also more likely that control patients to have insulin resistance, higher weight circumference, and dysplipidemia. Among 162 psoriasis patients who underwent PET and coronary CT angiography, higher hepatic FDG uptake (indicating NAFLD) was associated higher atherosclerotic disease burden. Importantly, both the NAFLD and CAD were subclinical in these patients. While the cross-sectional study design precludes any conclusions about causality, physicians should be aware that these two comorbidities are related. Lower waist circumference and greater physical activity were both associated with lower rates of NAFLD among patients with psoriasis, providing some guidance for counseling patients.
Several recent studies have found that cancer rates among patients with psoriasis are higher than what is observed in the general population. The association of psoriasis with lymphohematologic malignancies (LHM) has been controversial. A systematic review and meta-analysis of 25 observational studies including over 2.5 million subjects (Bellinato et al.) found a 1.55-fold increased risk of LHM in patients with moderate to severe psoriasis. Strikingly, the risk of cutaneous T cell lymphoma (CTCL) was increased 6.22-fold, with more severe psoriasis being associated with the highest risk of CTCL. A causal relationship cannot be established from this type of studies, but the authors hypothesize that drugs used to treat psoriasis or the chronic T cell activation caused by active disease may contribute to the risk of LMH. Additionally, psoriasis and CTCL can share clinical features and some cases may be due to misdiagnosis. Interestingly, two psoriasis comorbities, diabetes and obesity, are also associated with an increased risk of LHM.
Early identification and management of comorbidities can help in reducing morbidity and mortality. With so many psoriasis treatments available, understanding how different therapies may impact comorbid conditions is important in helping dermatologists to choose the best therapy for each individual patient.
Several recent studies have evaluated that association between psoriasis and known comorbidities including cardiovascular disease, non-alcoholic fatty liver disease (NAFLD), and malignancy. Several recent studies have added to our understanding of the relationship between these conditions.
Using the largest database of hospitalized patients in the United States, Edgen et al found that hospitalization rates for patients with psoriasis are increasing. While the proportion of patients with psoriasis hospitalized with psoriasis as a primary diagnosis decreased about four-fold over a 20-year period (1999-2018), incidence of hospitalizations with any diagnosis of psoriasis has increased. Hospitalized psoriasis patients are increasingly more likely to have other comorbid conditions as during the study period the proportion of hospitalized psoriasis patients with a Charlson Comorbidity Index score of 3 or higher increased from 13.9% to 30.9%. Psoriasis severity, medication use, and reasons for hospitalization were not reported. The authors suggest that screening and management of comorbidities in the outpatient setting may help reduce preventable psoriasis hospitalizations.
Both NAFLD and cardiovascular disease are well-known psoriasis comorbidities, Gonzalez-Cantaro et al studied two cohorts of patients to better define the relationship between these two conditions. In a European cohort of 76 psoriasis patients and 76 control patients, psoriasis patients with NAFLD had a higher prevalence of subclinical atherosclerosis than both psoriasis patients without NAFLD (61% vs 23%) and age, sex, and BMI-matched controls with NAFLD (61% vs 32%). Psoriasis patients were also more likely that control patients to have insulin resistance, higher weight circumference, and dysplipidemia. Among 162 psoriasis patients who underwent PET and coronary CT angiography, higher hepatic FDG uptake (indicating NAFLD) was associated higher atherosclerotic disease burden. Importantly, both the NAFLD and CAD were subclinical in these patients. While the cross-sectional study design precludes any conclusions about causality, physicians should be aware that these two comorbidities are related. Lower waist circumference and greater physical activity were both associated with lower rates of NAFLD among patients with psoriasis, providing some guidance for counseling patients.
Several recent studies have found that cancer rates among patients with psoriasis are higher than what is observed in the general population. The association of psoriasis with lymphohematologic malignancies (LHM) has been controversial. A systematic review and meta-analysis of 25 observational studies including over 2.5 million subjects (Bellinato et al.) found a 1.55-fold increased risk of LHM in patients with moderate to severe psoriasis. Strikingly, the risk of cutaneous T cell lymphoma (CTCL) was increased 6.22-fold, with more severe psoriasis being associated with the highest risk of CTCL. A causal relationship cannot be established from this type of studies, but the authors hypothesize that drugs used to treat psoriasis or the chronic T cell activation caused by active disease may contribute to the risk of LMH. Additionally, psoriasis and CTCL can share clinical features and some cases may be due to misdiagnosis. Interestingly, two psoriasis comorbities, diabetes and obesity, are also associated with an increased risk of LHM.
Early identification and management of comorbidities can help in reducing morbidity and mortality. With so many psoriasis treatments available, understanding how different therapies may impact comorbid conditions is important in helping dermatologists to choose the best therapy for each individual patient.
Report urges complete residency overhaul
from the Graduate Medical Education Review Committee (UGRC) of the Coalition for Physician Accountability.
The 275-page report presents preliminary findings that were released in April 2021 and a long list of stakeholder comments. According to the report, the coalition will meet soon to discuss the final recommendations and consider next steps toward implementation.
The UGRC includes representatives of national medical organizations, medical schools, and residency programs. Among the organizations that participated in the report’s creation are the American Medical Association, the National Board of Medical Examiners, the American Osteopathic Association, the National Board of Osteopathic Medical Examiners, the Educational Commission for Foreign Medical Graduates, and the Association of American Medical Colleges.
The report identifies a list of challenges that affect the transition of medical students into residency programs and beyond. They include:
- Too much focus on finding and filling residency positions instead of “assuring learner competence and readiness for residency training”
- Inattention to assuring congruence between applicant goals and program missions
- Overreliance on licensure exam scores rather than “valid, trustworthy measures of students’ competence and clinical abilities”
- Increasing financial costs to students
- Individual and systemic biases in the UME-GME transition, as well as inequities related to international medical graduates
Seeking a common framework for competence
Overall, the report calls for increased standardization of how students are evaluated in medical school and how residency programs evaluate students. Less reliance should be placed on the numerical scores of the U.S. Medical Licensing Examination (USMLE), the report says, and more attention should be paid to the direct observation of student performance in clinical situations. In addition, the various organizations involved in the UME-GME transition process are asked to work better together.
To develop better methods of evaluating medical students and residents, UME and GME educators should jointly define and implement a common framework and set of competencies to apply to learners across the UME-GME transition, the report suggests.
While emphasizing the need for a broader student assessment framework, the report says, USMLE scores should also continue to be used in judging residency applicants. “Assessment information should be shared in residency applications and a postmatch learner handover. Licensing examinations should be used for their intended purpose to ensure requisite competence.”
Among the committee’s three dozen recommendations are the following:
- The Centers for Medicare & Medicaid Services should change the GME funding structure so that the initial residency period is calculated starting with the second year of postgraduate training. This change would allow residents to reconsider their career choices. Currently, if a resident decides to switch to another program or specialty after beginning training, the hospital may not receive full GME funding, so may be less likely to approve the change.
- Residency programs should improve recruitment practices to increase specialty-specific diversity of residents. Medical educators should also receive additional training regarding antiracism, avoiding bias, and ensuring equity.
- The self-reported demographic information of applicants to residency programs should be measured and shared with stakeholders, including the programs and medical schools, to promote equity. “A residency program that finds bias in its selection process could go back in real time to find qualified applicants who may have been missed, potentially improving outcomes,” the report notes.
- An interactive database of GME program and specialty track information should be created and made available to all applicants, medical schools, and residency programs at no cost to applicants. “Applicants and their advisors should be able to sort the information according to demographic and educational features that may significantly impact the likelihood of matching at a program.”
Less than half of applicants get in-depth reviews
The 2020 National Resident Matching Program Program Director Survey found that only 49% of applications received in-depth review. In light of this, the report suggests that the application system be updated to use modern information technology, including discrete fields for key data to expedite application reviews.
Many applications have been discarded because of various filters used to block consideration of certain applications. The report suggests that new filters be designed to ensure that each detects meaningful differences among applicants and promotes review based on mission alignment and likelihood of success in a program. Filters should be improved to decrease the likelihood of random exclusions of qualified applicants.
Specialty-specific, just-in-time training for all incoming first-year residents is also suggested to support the transition from the role of student to a physician ready to assume increased responsibility for patient care. In addition, the report urges adequate time be allowed between medical school graduation and residency to enable new residents to relocate and find homes.
The report also calls for a standardized process in the United States for initial licensing of doctors at entrance to residency in order to streamline the process of credentialing for both residency training and continuing practice.
Osteopathic students’ dilemma
To promote equitable treatment of applicants regardless of licensure examination requirements, comparable exams with different scales (COMLEX-USA and USMLE) should be reported within the electronic application system in a single field, the report said.
Osteopathic students, who make up 25% of U.S. medical students, must take the COMLEX-USA exam, but residency programs may filter them out if they don’t also take the USMLE exam. Thus, many osteopathic students take both exams, incurring extra time, cost, and stress.
The UGRC recommends creating a combined field in the electronic residency application service that normalizes the scores between the two exams. Residency programs could then filter applications based only on the single normalized score.
This approach makes sense from the viewpoint that it would reduce the pressure on osteopathic students to take the USMLE, Bryan Carmody, MD, an outspoken critic of various current training policies, said in an interview. But it could also have serious disadvantages.
For one thing, only osteopathic students can take the COMLEX-USA exam, he noted. If they don’t like their score, they can then take the USMLE test to get a higher score – an option that allopathic students don’t have. It’s not clear that they’d be prevented from doing this under the UGRC recommendation.
Second, he said, osteopathic students, on average, don’t do as well as allopathic students on the UMSLE exam. If they only take the COMLEX-USA test, they’re competing against other students who don’t do as well on tests as allopathic students do. If their scores were normalized with those of the USMLE test takers, they’d gain an unfair advantage against students who can only take the USMLE, including international medical graduates.
Although Dr. Carmody admitted that osteopathic students face a harder challenge than allopathic students in matching to residency programs, he said that the UGRC approach to the licensing exams might actually penalize them further. As a result of the scores of the two exams being averaged, residency program directors might discount the scores of all osteopathic students.
A version of this article first appeared on Medscape.com.
from the Graduate Medical Education Review Committee (UGRC) of the Coalition for Physician Accountability.
The 275-page report presents preliminary findings that were released in April 2021 and a long list of stakeholder comments. According to the report, the coalition will meet soon to discuss the final recommendations and consider next steps toward implementation.
The UGRC includes representatives of national medical organizations, medical schools, and residency programs. Among the organizations that participated in the report’s creation are the American Medical Association, the National Board of Medical Examiners, the American Osteopathic Association, the National Board of Osteopathic Medical Examiners, the Educational Commission for Foreign Medical Graduates, and the Association of American Medical Colleges.
The report identifies a list of challenges that affect the transition of medical students into residency programs and beyond. They include:
- Too much focus on finding and filling residency positions instead of “assuring learner competence and readiness for residency training”
- Inattention to assuring congruence between applicant goals and program missions
- Overreliance on licensure exam scores rather than “valid, trustworthy measures of students’ competence and clinical abilities”
- Increasing financial costs to students
- Individual and systemic biases in the UME-GME transition, as well as inequities related to international medical graduates
Seeking a common framework for competence
Overall, the report calls for increased standardization of how students are evaluated in medical school and how residency programs evaluate students. Less reliance should be placed on the numerical scores of the U.S. Medical Licensing Examination (USMLE), the report says, and more attention should be paid to the direct observation of student performance in clinical situations. In addition, the various organizations involved in the UME-GME transition process are asked to work better together.
To develop better methods of evaluating medical students and residents, UME and GME educators should jointly define and implement a common framework and set of competencies to apply to learners across the UME-GME transition, the report suggests.
While emphasizing the need for a broader student assessment framework, the report says, USMLE scores should also continue to be used in judging residency applicants. “Assessment information should be shared in residency applications and a postmatch learner handover. Licensing examinations should be used for their intended purpose to ensure requisite competence.”
Among the committee’s three dozen recommendations are the following:
- The Centers for Medicare & Medicaid Services should change the GME funding structure so that the initial residency period is calculated starting with the second year of postgraduate training. This change would allow residents to reconsider their career choices. Currently, if a resident decides to switch to another program or specialty after beginning training, the hospital may not receive full GME funding, so may be less likely to approve the change.
- Residency programs should improve recruitment practices to increase specialty-specific diversity of residents. Medical educators should also receive additional training regarding antiracism, avoiding bias, and ensuring equity.
- The self-reported demographic information of applicants to residency programs should be measured and shared with stakeholders, including the programs and medical schools, to promote equity. “A residency program that finds bias in its selection process could go back in real time to find qualified applicants who may have been missed, potentially improving outcomes,” the report notes.
- An interactive database of GME program and specialty track information should be created and made available to all applicants, medical schools, and residency programs at no cost to applicants. “Applicants and their advisors should be able to sort the information according to demographic and educational features that may significantly impact the likelihood of matching at a program.”
Less than half of applicants get in-depth reviews
The 2020 National Resident Matching Program Program Director Survey found that only 49% of applications received in-depth review. In light of this, the report suggests that the application system be updated to use modern information technology, including discrete fields for key data to expedite application reviews.
Many applications have been discarded because of various filters used to block consideration of certain applications. The report suggests that new filters be designed to ensure that each detects meaningful differences among applicants and promotes review based on mission alignment and likelihood of success in a program. Filters should be improved to decrease the likelihood of random exclusions of qualified applicants.
Specialty-specific, just-in-time training for all incoming first-year residents is also suggested to support the transition from the role of student to a physician ready to assume increased responsibility for patient care. In addition, the report urges adequate time be allowed between medical school graduation and residency to enable new residents to relocate and find homes.
The report also calls for a standardized process in the United States for initial licensing of doctors at entrance to residency in order to streamline the process of credentialing for both residency training and continuing practice.
Osteopathic students’ dilemma
To promote equitable treatment of applicants regardless of licensure examination requirements, comparable exams with different scales (COMLEX-USA and USMLE) should be reported within the electronic application system in a single field, the report said.
Osteopathic students, who make up 25% of U.S. medical students, must take the COMLEX-USA exam, but residency programs may filter them out if they don’t also take the USMLE exam. Thus, many osteopathic students take both exams, incurring extra time, cost, and stress.
The UGRC recommends creating a combined field in the electronic residency application service that normalizes the scores between the two exams. Residency programs could then filter applications based only on the single normalized score.
This approach makes sense from the viewpoint that it would reduce the pressure on osteopathic students to take the USMLE, Bryan Carmody, MD, an outspoken critic of various current training policies, said in an interview. But it could also have serious disadvantages.
For one thing, only osteopathic students can take the COMLEX-USA exam, he noted. If they don’t like their score, they can then take the USMLE test to get a higher score – an option that allopathic students don’t have. It’s not clear that they’d be prevented from doing this under the UGRC recommendation.
Second, he said, osteopathic students, on average, don’t do as well as allopathic students on the UMSLE exam. If they only take the COMLEX-USA test, they’re competing against other students who don’t do as well on tests as allopathic students do. If their scores were normalized with those of the USMLE test takers, they’d gain an unfair advantage against students who can only take the USMLE, including international medical graduates.
Although Dr. Carmody admitted that osteopathic students face a harder challenge than allopathic students in matching to residency programs, he said that the UGRC approach to the licensing exams might actually penalize them further. As a result of the scores of the two exams being averaged, residency program directors might discount the scores of all osteopathic students.
A version of this article first appeared on Medscape.com.
from the Graduate Medical Education Review Committee (UGRC) of the Coalition for Physician Accountability.
The 275-page report presents preliminary findings that were released in April 2021 and a long list of stakeholder comments. According to the report, the coalition will meet soon to discuss the final recommendations and consider next steps toward implementation.
The UGRC includes representatives of national medical organizations, medical schools, and residency programs. Among the organizations that participated in the report’s creation are the American Medical Association, the National Board of Medical Examiners, the American Osteopathic Association, the National Board of Osteopathic Medical Examiners, the Educational Commission for Foreign Medical Graduates, and the Association of American Medical Colleges.
The report identifies a list of challenges that affect the transition of medical students into residency programs and beyond. They include:
- Too much focus on finding and filling residency positions instead of “assuring learner competence and readiness for residency training”
- Inattention to assuring congruence between applicant goals and program missions
- Overreliance on licensure exam scores rather than “valid, trustworthy measures of students’ competence and clinical abilities”
- Increasing financial costs to students
- Individual and systemic biases in the UME-GME transition, as well as inequities related to international medical graduates
Seeking a common framework for competence
Overall, the report calls for increased standardization of how students are evaluated in medical school and how residency programs evaluate students. Less reliance should be placed on the numerical scores of the U.S. Medical Licensing Examination (USMLE), the report says, and more attention should be paid to the direct observation of student performance in clinical situations. In addition, the various organizations involved in the UME-GME transition process are asked to work better together.
To develop better methods of evaluating medical students and residents, UME and GME educators should jointly define and implement a common framework and set of competencies to apply to learners across the UME-GME transition, the report suggests.
While emphasizing the need for a broader student assessment framework, the report says, USMLE scores should also continue to be used in judging residency applicants. “Assessment information should be shared in residency applications and a postmatch learner handover. Licensing examinations should be used for their intended purpose to ensure requisite competence.”
Among the committee’s three dozen recommendations are the following:
- The Centers for Medicare & Medicaid Services should change the GME funding structure so that the initial residency period is calculated starting with the second year of postgraduate training. This change would allow residents to reconsider their career choices. Currently, if a resident decides to switch to another program or specialty after beginning training, the hospital may not receive full GME funding, so may be less likely to approve the change.
- Residency programs should improve recruitment practices to increase specialty-specific diversity of residents. Medical educators should also receive additional training regarding antiracism, avoiding bias, and ensuring equity.
- The self-reported demographic information of applicants to residency programs should be measured and shared with stakeholders, including the programs and medical schools, to promote equity. “A residency program that finds bias in its selection process could go back in real time to find qualified applicants who may have been missed, potentially improving outcomes,” the report notes.
- An interactive database of GME program and specialty track information should be created and made available to all applicants, medical schools, and residency programs at no cost to applicants. “Applicants and their advisors should be able to sort the information according to demographic and educational features that may significantly impact the likelihood of matching at a program.”
Less than half of applicants get in-depth reviews
The 2020 National Resident Matching Program Program Director Survey found that only 49% of applications received in-depth review. In light of this, the report suggests that the application system be updated to use modern information technology, including discrete fields for key data to expedite application reviews.
Many applications have been discarded because of various filters used to block consideration of certain applications. The report suggests that new filters be designed to ensure that each detects meaningful differences among applicants and promotes review based on mission alignment and likelihood of success in a program. Filters should be improved to decrease the likelihood of random exclusions of qualified applicants.
Specialty-specific, just-in-time training for all incoming first-year residents is also suggested to support the transition from the role of student to a physician ready to assume increased responsibility for patient care. In addition, the report urges adequate time be allowed between medical school graduation and residency to enable new residents to relocate and find homes.
The report also calls for a standardized process in the United States for initial licensing of doctors at entrance to residency in order to streamline the process of credentialing for both residency training and continuing practice.
Osteopathic students’ dilemma
To promote equitable treatment of applicants regardless of licensure examination requirements, comparable exams with different scales (COMLEX-USA and USMLE) should be reported within the electronic application system in a single field, the report said.
Osteopathic students, who make up 25% of U.S. medical students, must take the COMLEX-USA exam, but residency programs may filter them out if they don’t also take the USMLE exam. Thus, many osteopathic students take both exams, incurring extra time, cost, and stress.
The UGRC recommends creating a combined field in the electronic residency application service that normalizes the scores between the two exams. Residency programs could then filter applications based only on the single normalized score.
This approach makes sense from the viewpoint that it would reduce the pressure on osteopathic students to take the USMLE, Bryan Carmody, MD, an outspoken critic of various current training policies, said in an interview. But it could also have serious disadvantages.
For one thing, only osteopathic students can take the COMLEX-USA exam, he noted. If they don’t like their score, they can then take the USMLE test to get a higher score – an option that allopathic students don’t have. It’s not clear that they’d be prevented from doing this under the UGRC recommendation.
Second, he said, osteopathic students, on average, don’t do as well as allopathic students on the UMSLE exam. If they only take the COMLEX-USA test, they’re competing against other students who don’t do as well on tests as allopathic students do. If their scores were normalized with those of the USMLE test takers, they’d gain an unfair advantage against students who can only take the USMLE, including international medical graduates.
Although Dr. Carmody admitted that osteopathic students face a harder challenge than allopathic students in matching to residency programs, he said that the UGRC approach to the licensing exams might actually penalize them further. As a result of the scores of the two exams being averaged, residency program directors might discount the scores of all osteopathic students.
A version of this article first appeared on Medscape.com.
FDA OKs IV Briviact for seizures in kids as young as 1 month
All three brivaracetam formulations (tablets, oral solution, and IV) may now be used. The approval marks the first time that the IV formulation will be available for children, the company said in a news release.
The medication is already approved in the United States as monotherapy and adjunctive therapy in adults with epilepsy.
In an open-label follow-up pediatric study, an estimated 71.4% of patients aged 1 month to 17 years with partial-onset seizures remained on brivaracetam therapy at 1 year, and 64.3% did so at 2 years, the company reported.
“We often see children with seizures hospitalized, so it’s important to have a therapy like Briviact IV that can offer rapid administration in an effective dose when needed and does not require titration,” Raman Sankar, MD, PhD, distinguished professor and chief of pediatric neurology, University of California, Los Angeles, said in the release.
“The availability of the oral dose forms also allows continuity of treatment when these young patients are transitioning from hospital to home,” he added.
Safety profile
Dr. Sankar noted that with approval now of both the IV and oral formulations for partial-onset seizures in such young children, “we have a new option that helps meet a critical need in pediatric epilepsy.”
The most common adverse reactions with brivaracetam include somnolence and sedation, dizziness, fatigue, nausea, and vomiting. In the pediatric clinical trials, the safety profile for pediatric patients was similar to adults.
In the adult trials, psychiatric adverse reactions, including nonpsychotic and psychotic symptoms, were reported in approximately 13% of adults taking at least 50 mg/day of brivaracetam compared with 8% taking placebo.
Psychiatric adverse reactions were also observed in open-label pediatric trials and were generally similar to those observed in adults.
Patients should be advised to report these symptoms immediately to a health care professional, the company noted.
A version of this article first appeared on Medscape.com.
All three brivaracetam formulations (tablets, oral solution, and IV) may now be used. The approval marks the first time that the IV formulation will be available for children, the company said in a news release.
The medication is already approved in the United States as monotherapy and adjunctive therapy in adults with epilepsy.
In an open-label follow-up pediatric study, an estimated 71.4% of patients aged 1 month to 17 years with partial-onset seizures remained on brivaracetam therapy at 1 year, and 64.3% did so at 2 years, the company reported.
“We often see children with seizures hospitalized, so it’s important to have a therapy like Briviact IV that can offer rapid administration in an effective dose when needed and does not require titration,” Raman Sankar, MD, PhD, distinguished professor and chief of pediatric neurology, University of California, Los Angeles, said in the release.
“The availability of the oral dose forms also allows continuity of treatment when these young patients are transitioning from hospital to home,” he added.
Safety profile
Dr. Sankar noted that with approval now of both the IV and oral formulations for partial-onset seizures in such young children, “we have a new option that helps meet a critical need in pediatric epilepsy.”
The most common adverse reactions with brivaracetam include somnolence and sedation, dizziness, fatigue, nausea, and vomiting. In the pediatric clinical trials, the safety profile for pediatric patients was similar to adults.
In the adult trials, psychiatric adverse reactions, including nonpsychotic and psychotic symptoms, were reported in approximately 13% of adults taking at least 50 mg/day of brivaracetam compared with 8% taking placebo.
Psychiatric adverse reactions were also observed in open-label pediatric trials and were generally similar to those observed in adults.
Patients should be advised to report these symptoms immediately to a health care professional, the company noted.
A version of this article first appeared on Medscape.com.
All three brivaracetam formulations (tablets, oral solution, and IV) may now be used. The approval marks the first time that the IV formulation will be available for children, the company said in a news release.
The medication is already approved in the United States as monotherapy and adjunctive therapy in adults with epilepsy.
In an open-label follow-up pediatric study, an estimated 71.4% of patients aged 1 month to 17 years with partial-onset seizures remained on brivaracetam therapy at 1 year, and 64.3% did so at 2 years, the company reported.
“We often see children with seizures hospitalized, so it’s important to have a therapy like Briviact IV that can offer rapid administration in an effective dose when needed and does not require titration,” Raman Sankar, MD, PhD, distinguished professor and chief of pediatric neurology, University of California, Los Angeles, said in the release.
“The availability of the oral dose forms also allows continuity of treatment when these young patients are transitioning from hospital to home,” he added.
Safety profile
Dr. Sankar noted that with approval now of both the IV and oral formulations for partial-onset seizures in such young children, “we have a new option that helps meet a critical need in pediatric epilepsy.”
The most common adverse reactions with brivaracetam include somnolence and sedation, dizziness, fatigue, nausea, and vomiting. In the pediatric clinical trials, the safety profile for pediatric patients was similar to adults.
In the adult trials, psychiatric adverse reactions, including nonpsychotic and psychotic symptoms, were reported in approximately 13% of adults taking at least 50 mg/day of brivaracetam compared with 8% taking placebo.
Psychiatric adverse reactions were also observed in open-label pediatric trials and were generally similar to those observed in adults.
Patients should be advised to report these symptoms immediately to a health care professional, the company noted.
A version of this article first appeared on Medscape.com.
Alcohol ups risk for atrial fibrillation episode hours later
Consuming alcohol increases the risk for an atrial fibrillation (AF) episode hours later, according to a study published online Aug. 30 in Annals of Internal Medicine.
Past research has associated long-term alcohol consumption with the development of AF, and abstinence from alcohol has been associated with a lower overall AF burden. However, lead study author Greg Marcus, MD, a cardioelectrophysiolgist at the University of California, San Francisco, noted that many patients say that alcohol is a trigger for discrete AF episodes.
To test whether that was possible, the researchers enrolled 100 patients who had a history of AF events and who consumed at least one drink per month. Participants wore a transdermal alcohol sensor and an ambulatory, single-lead electrocardiogram device for 4 weeks. They were instructed to press a button on the electrocardiogram device each time they consumed a standard alcoholic beverage. In addition, blood samples were tested for phosphatidylethanol (PEth) at the participants’ 2-week and 4-week visits. PEth is a phospholipid formed in the blood after alcohol intake. It remains in the blood for up to 4 weeks after alcohol consumption.
The study findings confirmed what the patients had reported. The odds of an AF episode were 38% greater with every 0.1% increase in peak blood alcohol concentration over the previous 12 hours (odds ratio [OR], 1.38; 95% confidence interval, 1.04-1.83; P = .024). Moreover, an episode of AF was associated with twofold greater odds (OR, 2.02; 95% CI, 1.38-3.17) of having consumed one alcoholic drink in the past 4 hours. It was associated with more than threefold greater odds of having consumed two or more drinks (OR, 3.58; 95% CI, 1.63-7.89).
“The major takeaway is, among atrial fibrillation patients, consuming alcohol substantially heightened their risk for any given atrial fibrillation event in the subsequent few hours,” Dr. Marcus said. “The more alcohol consumed, the higher that risk.”
The acute effect of alcohol on these arrhythmias also means that modifying alcohol consumption could immediately benefit some patients. “These data combined with other evidence suggest that recommending minimizing or completely eliminating alcohol will likely be helpful to them,” Dr. Marcus said.
The study’s reliance on wearables and sensors was impressive, said Mariann R. Piano, PhD, director of the Center for Research Development and Scholarship, Vanderbilt University, Nashville, Tenn. Often, these types of studies are “self-reported and confounded by recall bias,” she said. But this study passively documented arrhythmia events and blood alcohol level without any patient input. The additional measures of alcohol consumption were used to validate the blood alcohol sensor.
The study’s focus on patients with a history of AF highlighted a high-risk patient group, according to Dr. Piano, who coauthored an editorial about the study. However, the findings may not be applicable to the general population.
Dr. Marcus said alcohol’s role in causing these types of arrhythmias is probably a matter of degree. AF patients are more prone to events than is the general population and are therefore more sensitive to alcohol, he said. But excessive alcohol consumption could increase the chance of AF in the general population.
The study is not without its limitations, however. For instance, “it would have been really ideal if we knew what that blood alcohol was” before an episode, Dr. Piano said. The number of drinks is a good start, but two drinks can affect persons differently, depending on their weight and height. Also, baseline PEth values suggest that patients had been drinking before the study, she said. Ideally, patients could have been asked to abstain from alcohol for a period before the study to determine a negative baseline PEth value and minimize the effects of previous drinking on AF episodes.
Moving forward, this research should inform how clinicians care for their AF patients, both experts agree. “We need to talk to patients about how much they drink,” Dr. Piano said. In addition, patients should be advised to closely monitor what they’re drinking.
“This definitely sharpens the focus of the importance of a thorough alcohol history when we see an atrial fibrillation patient and to counsel them to reduce or eliminate alcohol, even among those that don’t have alcohol use disorders,” Dr. Marcus said.
Preliminary results of the study were presented as a late-breaking clinical trials presentation at the American College of Cardiology meeting in May.
Dr. Marcus has received grants from Baylis, Jawbone, and Eight Sleep and has received personal fees from InCarda and Johnson & Johnson. Coauthors have received personal fees from VivaLNK, Huba Pharmaceuticals, Johnson & Johnson, and Merck and grants from Samsung and Amgen Inc. The editorialists have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Consuming alcohol increases the risk for an atrial fibrillation (AF) episode hours later, according to a study published online Aug. 30 in Annals of Internal Medicine.
Past research has associated long-term alcohol consumption with the development of AF, and abstinence from alcohol has been associated with a lower overall AF burden. However, lead study author Greg Marcus, MD, a cardioelectrophysiolgist at the University of California, San Francisco, noted that many patients say that alcohol is a trigger for discrete AF episodes.
To test whether that was possible, the researchers enrolled 100 patients who had a history of AF events and who consumed at least one drink per month. Participants wore a transdermal alcohol sensor and an ambulatory, single-lead electrocardiogram device for 4 weeks. They were instructed to press a button on the electrocardiogram device each time they consumed a standard alcoholic beverage. In addition, blood samples were tested for phosphatidylethanol (PEth) at the participants’ 2-week and 4-week visits. PEth is a phospholipid formed in the blood after alcohol intake. It remains in the blood for up to 4 weeks after alcohol consumption.
The study findings confirmed what the patients had reported. The odds of an AF episode were 38% greater with every 0.1% increase in peak blood alcohol concentration over the previous 12 hours (odds ratio [OR], 1.38; 95% confidence interval, 1.04-1.83; P = .024). Moreover, an episode of AF was associated with twofold greater odds (OR, 2.02; 95% CI, 1.38-3.17) of having consumed one alcoholic drink in the past 4 hours. It was associated with more than threefold greater odds of having consumed two or more drinks (OR, 3.58; 95% CI, 1.63-7.89).
“The major takeaway is, among atrial fibrillation patients, consuming alcohol substantially heightened their risk for any given atrial fibrillation event in the subsequent few hours,” Dr. Marcus said. “The more alcohol consumed, the higher that risk.”
The acute effect of alcohol on these arrhythmias also means that modifying alcohol consumption could immediately benefit some patients. “These data combined with other evidence suggest that recommending minimizing or completely eliminating alcohol will likely be helpful to them,” Dr. Marcus said.
The study’s reliance on wearables and sensors was impressive, said Mariann R. Piano, PhD, director of the Center for Research Development and Scholarship, Vanderbilt University, Nashville, Tenn. Often, these types of studies are “self-reported and confounded by recall bias,” she said. But this study passively documented arrhythmia events and blood alcohol level without any patient input. The additional measures of alcohol consumption were used to validate the blood alcohol sensor.
The study’s focus on patients with a history of AF highlighted a high-risk patient group, according to Dr. Piano, who coauthored an editorial about the study. However, the findings may not be applicable to the general population.
Dr. Marcus said alcohol’s role in causing these types of arrhythmias is probably a matter of degree. AF patients are more prone to events than is the general population and are therefore more sensitive to alcohol, he said. But excessive alcohol consumption could increase the chance of AF in the general population.
The study is not without its limitations, however. For instance, “it would have been really ideal if we knew what that blood alcohol was” before an episode, Dr. Piano said. The number of drinks is a good start, but two drinks can affect persons differently, depending on their weight and height. Also, baseline PEth values suggest that patients had been drinking before the study, she said. Ideally, patients could have been asked to abstain from alcohol for a period before the study to determine a negative baseline PEth value and minimize the effects of previous drinking on AF episodes.
Moving forward, this research should inform how clinicians care for their AF patients, both experts agree. “We need to talk to patients about how much they drink,” Dr. Piano said. In addition, patients should be advised to closely monitor what they’re drinking.
“This definitely sharpens the focus of the importance of a thorough alcohol history when we see an atrial fibrillation patient and to counsel them to reduce or eliminate alcohol, even among those that don’t have alcohol use disorders,” Dr. Marcus said.
Preliminary results of the study were presented as a late-breaking clinical trials presentation at the American College of Cardiology meeting in May.
Dr. Marcus has received grants from Baylis, Jawbone, and Eight Sleep and has received personal fees from InCarda and Johnson & Johnson. Coauthors have received personal fees from VivaLNK, Huba Pharmaceuticals, Johnson & Johnson, and Merck and grants from Samsung and Amgen Inc. The editorialists have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Consuming alcohol increases the risk for an atrial fibrillation (AF) episode hours later, according to a study published online Aug. 30 in Annals of Internal Medicine.
Past research has associated long-term alcohol consumption with the development of AF, and abstinence from alcohol has been associated with a lower overall AF burden. However, lead study author Greg Marcus, MD, a cardioelectrophysiolgist at the University of California, San Francisco, noted that many patients say that alcohol is a trigger for discrete AF episodes.
To test whether that was possible, the researchers enrolled 100 patients who had a history of AF events and who consumed at least one drink per month. Participants wore a transdermal alcohol sensor and an ambulatory, single-lead electrocardiogram device for 4 weeks. They were instructed to press a button on the electrocardiogram device each time they consumed a standard alcoholic beverage. In addition, blood samples were tested for phosphatidylethanol (PEth) at the participants’ 2-week and 4-week visits. PEth is a phospholipid formed in the blood after alcohol intake. It remains in the blood for up to 4 weeks after alcohol consumption.
The study findings confirmed what the patients had reported. The odds of an AF episode were 38% greater with every 0.1% increase in peak blood alcohol concentration over the previous 12 hours (odds ratio [OR], 1.38; 95% confidence interval, 1.04-1.83; P = .024). Moreover, an episode of AF was associated with twofold greater odds (OR, 2.02; 95% CI, 1.38-3.17) of having consumed one alcoholic drink in the past 4 hours. It was associated with more than threefold greater odds of having consumed two or more drinks (OR, 3.58; 95% CI, 1.63-7.89).
“The major takeaway is, among atrial fibrillation patients, consuming alcohol substantially heightened their risk for any given atrial fibrillation event in the subsequent few hours,” Dr. Marcus said. “The more alcohol consumed, the higher that risk.”
The acute effect of alcohol on these arrhythmias also means that modifying alcohol consumption could immediately benefit some patients. “These data combined with other evidence suggest that recommending minimizing or completely eliminating alcohol will likely be helpful to them,” Dr. Marcus said.
The study’s reliance on wearables and sensors was impressive, said Mariann R. Piano, PhD, director of the Center for Research Development and Scholarship, Vanderbilt University, Nashville, Tenn. Often, these types of studies are “self-reported and confounded by recall bias,” she said. But this study passively documented arrhythmia events and blood alcohol level without any patient input. The additional measures of alcohol consumption were used to validate the blood alcohol sensor.
The study’s focus on patients with a history of AF highlighted a high-risk patient group, according to Dr. Piano, who coauthored an editorial about the study. However, the findings may not be applicable to the general population.
Dr. Marcus said alcohol’s role in causing these types of arrhythmias is probably a matter of degree. AF patients are more prone to events than is the general population and are therefore more sensitive to alcohol, he said. But excessive alcohol consumption could increase the chance of AF in the general population.
The study is not without its limitations, however. For instance, “it would have been really ideal if we knew what that blood alcohol was” before an episode, Dr. Piano said. The number of drinks is a good start, but two drinks can affect persons differently, depending on their weight and height. Also, baseline PEth values suggest that patients had been drinking before the study, she said. Ideally, patients could have been asked to abstain from alcohol for a period before the study to determine a negative baseline PEth value and minimize the effects of previous drinking on AF episodes.
Moving forward, this research should inform how clinicians care for their AF patients, both experts agree. “We need to talk to patients about how much they drink,” Dr. Piano said. In addition, patients should be advised to closely monitor what they’re drinking.
“This definitely sharpens the focus of the importance of a thorough alcohol history when we see an atrial fibrillation patient and to counsel them to reduce or eliminate alcohol, even among those that don’t have alcohol use disorders,” Dr. Marcus said.
Preliminary results of the study were presented as a late-breaking clinical trials presentation at the American College of Cardiology meeting in May.
Dr. Marcus has received grants from Baylis, Jawbone, and Eight Sleep and has received personal fees from InCarda and Johnson & Johnson. Coauthors have received personal fees from VivaLNK, Huba Pharmaceuticals, Johnson & Johnson, and Merck and grants from Samsung and Amgen Inc. The editorialists have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Clinical Edge Journal Scan Commentary: RA September 2021
Herpes zoster infection is another well-known complication of RA and its treatment, including glucocorticoid therapy. An increased incidence has recently been noted in people who use JAK inhibitors, though other bDMARDs including TNF inhibitors are also known to increase risk. Redeker et al. compare the incidence of herpes zoster in people with RA using csDMARDs, bDMARDs, and tsDMARDs using a German prospective RA registry. In nearly 14,000 patients, 559 cases of herpes zoster were documented; after adjusting for age, sex, and glucocorticoid use, an increased risk was noted for treatment with monoclonal anti-TNF therapy, B-cell directed therapy, and JAK inhibitors compared to csDMARDs, whereas soluble TNF receptor fusion protein, T cell costimulation modulators and IL-6 inhibitors were not associated with a higher risk of herpes zoster compared with csDMARDs. Unfortunately, zoster vaccination status was not extracted for all patients. The study confirms what we already know with direct risk comparison between different agents and underscores the importance of vaccination in RA patients, especially those being treated with glucocorticoids and tsDMARDs.
Finally, another important consideration in the use of bDMARDs is the increase in cancer risk due to a potential reduction in immunosurveillance. Initial meta-analyses of clinical trials of anti-TNF agents highlighted an early increase in cancer risk, though later studies including meta-analyses and registry studies with longer follow-up durations have been equivocal. Huss et al. examine a Swedish registry of people with RA and no prior history of cancer and found a small increase in cancer-risk in patients with RA compared to the general population (HR 1.2). However, there was no increase in overall cancer incidence in patients treated with TNF inhibitors, rituximab, abatacept, or JAK inhibitors compared to RA patients naïve to bDMARDs and tsDMARDs. Interestingly, urinary tract cancer risk was slightly increased in several treatment groups, though the effect size was small. Considering the generally long duration of follow-up (with the exception of JAK inhibitors), this study is very reassuring regarding long-term risk of cancer of bDMARD use and useful in counseling people with RA on therapeutic risks.
Herpes zoster infection is another well-known complication of RA and its treatment, including glucocorticoid therapy. An increased incidence has recently been noted in people who use JAK inhibitors, though other bDMARDs including TNF inhibitors are also known to increase risk. Redeker et al. compare the incidence of herpes zoster in people with RA using csDMARDs, bDMARDs, and tsDMARDs using a German prospective RA registry. In nearly 14,000 patients, 559 cases of herpes zoster were documented; after adjusting for age, sex, and glucocorticoid use, an increased risk was noted for treatment with monoclonal anti-TNF therapy, B-cell directed therapy, and JAK inhibitors compared to csDMARDs, whereas soluble TNF receptor fusion protein, T cell costimulation modulators and IL-6 inhibitors were not associated with a higher risk of herpes zoster compared with csDMARDs. Unfortunately, zoster vaccination status was not extracted for all patients. The study confirms what we already know with direct risk comparison between different agents and underscores the importance of vaccination in RA patients, especially those being treated with glucocorticoids and tsDMARDs.
Finally, another important consideration in the use of bDMARDs is the increase in cancer risk due to a potential reduction in immunosurveillance. Initial meta-analyses of clinical trials of anti-TNF agents highlighted an early increase in cancer risk, though later studies including meta-analyses and registry studies with longer follow-up durations have been equivocal. Huss et al. examine a Swedish registry of people with RA and no prior history of cancer and found a small increase in cancer-risk in patients with RA compared to the general population (HR 1.2). However, there was no increase in overall cancer incidence in patients treated with TNF inhibitors, rituximab, abatacept, or JAK inhibitors compared to RA patients naïve to bDMARDs and tsDMARDs. Interestingly, urinary tract cancer risk was slightly increased in several treatment groups, though the effect size was small. Considering the generally long duration of follow-up (with the exception of JAK inhibitors), this study is very reassuring regarding long-term risk of cancer of bDMARD use and useful in counseling people with RA on therapeutic risks.
Herpes zoster infection is another well-known complication of RA and its treatment, including glucocorticoid therapy. An increased incidence has recently been noted in people who use JAK inhibitors, though other bDMARDs including TNF inhibitors are also known to increase risk. Redeker et al. compare the incidence of herpes zoster in people with RA using csDMARDs, bDMARDs, and tsDMARDs using a German prospective RA registry. In nearly 14,000 patients, 559 cases of herpes zoster were documented; after adjusting for age, sex, and glucocorticoid use, an increased risk was noted for treatment with monoclonal anti-TNF therapy, B-cell directed therapy, and JAK inhibitors compared to csDMARDs, whereas soluble TNF receptor fusion protein, T cell costimulation modulators and IL-6 inhibitors were not associated with a higher risk of herpes zoster compared with csDMARDs. Unfortunately, zoster vaccination status was not extracted for all patients. The study confirms what we already know with direct risk comparison between different agents and underscores the importance of vaccination in RA patients, especially those being treated with glucocorticoids and tsDMARDs.
Finally, another important consideration in the use of bDMARDs is the increase in cancer risk due to a potential reduction in immunosurveillance. Initial meta-analyses of clinical trials of anti-TNF agents highlighted an early increase in cancer risk, though later studies including meta-analyses and registry studies with longer follow-up durations have been equivocal. Huss et al. examine a Swedish registry of people with RA and no prior history of cancer and found a small increase in cancer-risk in patients with RA compared to the general population (HR 1.2). However, there was no increase in overall cancer incidence in patients treated with TNF inhibitors, rituximab, abatacept, or JAK inhibitors compared to RA patients naïve to bDMARDs and tsDMARDs. Interestingly, urinary tract cancer risk was slightly increased in several treatment groups, though the effect size was small. Considering the generally long duration of follow-up (with the exception of JAK inhibitors), this study is very reassuring regarding long-term risk of cancer of bDMARD use and useful in counseling people with RA on therapeutic risks.
Self-described ‘assassin,’ now doctor, indicted for 1M illegal opioid doses
A according to the U.S. Department of Justice. The substances include oxycodone and morphine.
Adrian Dexter Talbot, MD, 55, of Slidell, La., is also charged with maintaining a medical clinic for the purpose of illegally distributing controlled substances, per the indictment.
Because the opioid prescriptions were filled using beneficiaries’ health insurance, Dr. Talbot is also charged with defrauding Medicare, Medicaid, and Blue Cross and Blue Shield of Louisiana of more than $5.1 million.
When contacted by this news organization for comment on the case via Twitter, Dr. Talbot or a representative responded with a link to his self-published book on Amazon. In his author bio, Dr. Talbot refers to himself as “a former assassin,” “retired military commander,” and “leader of the Medellin Cartel’s New York operations at the age of 16.” The Medellin Cartel is a notorious drug distribution empire.
Dr. Talbot is listed as the author of another book on Google Books detailing his time as a “former teenage assassin” and leader of the cartel, told as he struggles with early onset Alzheimer’s.
Dr. Talbot could spend decades in prison
According to the National Institute on Drug Abuse, 444 residents of the Bayou State lost their lives because of an opioid-related drug overdose in 2018. During that year, the state’s health care providers wrote more than 79.4 opioid prescriptions for every 100 persons, which puts the state in the top five in the United States in 2018, when the average U.S. rate was 51.4 prescriptions per 100 persons.
Charged with one count each of conspiracy to unlawfully distribute and dispense controlled substances and maintaining drug-involved premises and conspiracy to commit health care fraud, Dr. Talbot is also charged with four counts of unlawfully distributing and dispensing controlled substances. He is scheduled for a federal court appearance on September 10.
In addition to presigning prescriptions for individuals he didn’t meet or examine, federal officials allege Dr. Talbot hired another health care provider to similarly presign prescriptions for people who weren’t examined at a medical practice in Slidell, where Dr. Talbot was employed. The DOJ says Dr. Talbot took a full-time job in Pineville, La., and presigned prescriptions while no longer physically present at the Slidell clinic.
A speaker’s bio for Dr. Talbot indicates he worked as chief of medical services for the Alexandria Veterans Affairs Health Care System in Pineville.
According to the DOJ’s indictment, Dr. Talbot was aware that patients were filling the prescriptions that were provided outside the scope of professional practice and not for a legitimate medical purpose. This is what triggered the DOJ’s fraudulent billing claim.
Dr. Talbot faces a maximum penalty of 10 years for conspiracy to commit health care fraud and 20 years each for the other counts, if convicted.
Dr. Talbot was candidate for local coroner
In February 2015, Dr. Talbot announced his candidacy for coroner for St. Tammany Parish, about an hour’s drive south of New Orleans, reported the Times Picayune. The seat was open because the previous coroner had resigned and ultimately pleaded guilty to a federal corruption charge.
The Times Picayune reported at the time that Dr. Talbot was a U.S. Navy veteran, in addition to serving as medical director and a primary care physician at the Medical Care Center in Slidell. Among the services provided to his patients were evaluations and treatment for substance use and mental health disorders, according to a press release issued by Dr. Talbot’s campaign.
Dr. Talbot’s medical license was issued in 1999 and inactive as of 2017, per the Louisiana State Board of Medical Examiners.
Louisiana expects $325M in multistate settlement with opioid companies
Louisiana is a party to a multistate and multijurisdictional lawsuit where the state is expected to receive more than $325 million in a settlement reached with drug distributors Cardinal, McKesson, and AmerisourceBergen, and drug manufacturer Johnson & Johnson, reported the Louisiana Illuminator in July. The total settlement may reach $26 billion dollars.
The Associated Press reported in July that there have been at least $40 billion in completed or proposed settlements, penalties, and fines between governments as a result of the opioid epidemic since 2007.
That total doesn’t include a proposed settlement involving members of the Sackler family, who own Purdue Pharmaceuticals, which manufactured and marketed the opioid painkiller OxyContin. The Sackler family have agreed to pay approximately $4.3 billion and surrender ownership of their bankrupt company, reported NPR. The family’s proposed settlement is part of a deal involving Purdue Pharmaceuticals worth more than $10 billion, reported Reuters.
In 2020, there were more than 81,000 drug overdose deaths, the highest number recorded in a 12-month period, per the U.S. Centers for Disease Control and Prevention. Fentanyl, an illicitly manufactured synthetic opioid, was the lead driver of those deaths.
A version of this article first appeared on Medscape.com.
A according to the U.S. Department of Justice. The substances include oxycodone and morphine.
Adrian Dexter Talbot, MD, 55, of Slidell, La., is also charged with maintaining a medical clinic for the purpose of illegally distributing controlled substances, per the indictment.
Because the opioid prescriptions were filled using beneficiaries’ health insurance, Dr. Talbot is also charged with defrauding Medicare, Medicaid, and Blue Cross and Blue Shield of Louisiana of more than $5.1 million.
When contacted by this news organization for comment on the case via Twitter, Dr. Talbot or a representative responded with a link to his self-published book on Amazon. In his author bio, Dr. Talbot refers to himself as “a former assassin,” “retired military commander,” and “leader of the Medellin Cartel’s New York operations at the age of 16.” The Medellin Cartel is a notorious drug distribution empire.
Dr. Talbot is listed as the author of another book on Google Books detailing his time as a “former teenage assassin” and leader of the cartel, told as he struggles with early onset Alzheimer’s.
Dr. Talbot could spend decades in prison
According to the National Institute on Drug Abuse, 444 residents of the Bayou State lost their lives because of an opioid-related drug overdose in 2018. During that year, the state’s health care providers wrote more than 79.4 opioid prescriptions for every 100 persons, which puts the state in the top five in the United States in 2018, when the average U.S. rate was 51.4 prescriptions per 100 persons.
Charged with one count each of conspiracy to unlawfully distribute and dispense controlled substances and maintaining drug-involved premises and conspiracy to commit health care fraud, Dr. Talbot is also charged with four counts of unlawfully distributing and dispensing controlled substances. He is scheduled for a federal court appearance on September 10.
In addition to presigning prescriptions for individuals he didn’t meet or examine, federal officials allege Dr. Talbot hired another health care provider to similarly presign prescriptions for people who weren’t examined at a medical practice in Slidell, where Dr. Talbot was employed. The DOJ says Dr. Talbot took a full-time job in Pineville, La., and presigned prescriptions while no longer physically present at the Slidell clinic.
A speaker’s bio for Dr. Talbot indicates he worked as chief of medical services for the Alexandria Veterans Affairs Health Care System in Pineville.
According to the DOJ’s indictment, Dr. Talbot was aware that patients were filling the prescriptions that were provided outside the scope of professional practice and not for a legitimate medical purpose. This is what triggered the DOJ’s fraudulent billing claim.
Dr. Talbot faces a maximum penalty of 10 years for conspiracy to commit health care fraud and 20 years each for the other counts, if convicted.
Dr. Talbot was candidate for local coroner
In February 2015, Dr. Talbot announced his candidacy for coroner for St. Tammany Parish, about an hour’s drive south of New Orleans, reported the Times Picayune. The seat was open because the previous coroner had resigned and ultimately pleaded guilty to a federal corruption charge.
The Times Picayune reported at the time that Dr. Talbot was a U.S. Navy veteran, in addition to serving as medical director and a primary care physician at the Medical Care Center in Slidell. Among the services provided to his patients were evaluations and treatment for substance use and mental health disorders, according to a press release issued by Dr. Talbot’s campaign.
Dr. Talbot’s medical license was issued in 1999 and inactive as of 2017, per the Louisiana State Board of Medical Examiners.
Louisiana expects $325M in multistate settlement with opioid companies
Louisiana is a party to a multistate and multijurisdictional lawsuit where the state is expected to receive more than $325 million in a settlement reached with drug distributors Cardinal, McKesson, and AmerisourceBergen, and drug manufacturer Johnson & Johnson, reported the Louisiana Illuminator in July. The total settlement may reach $26 billion dollars.
The Associated Press reported in July that there have been at least $40 billion in completed or proposed settlements, penalties, and fines between governments as a result of the opioid epidemic since 2007.
That total doesn’t include a proposed settlement involving members of the Sackler family, who own Purdue Pharmaceuticals, which manufactured and marketed the opioid painkiller OxyContin. The Sackler family have agreed to pay approximately $4.3 billion and surrender ownership of their bankrupt company, reported NPR. The family’s proposed settlement is part of a deal involving Purdue Pharmaceuticals worth more than $10 billion, reported Reuters.
In 2020, there were more than 81,000 drug overdose deaths, the highest number recorded in a 12-month period, per the U.S. Centers for Disease Control and Prevention. Fentanyl, an illicitly manufactured synthetic opioid, was the lead driver of those deaths.
A version of this article first appeared on Medscape.com.
A according to the U.S. Department of Justice. The substances include oxycodone and morphine.
Adrian Dexter Talbot, MD, 55, of Slidell, La., is also charged with maintaining a medical clinic for the purpose of illegally distributing controlled substances, per the indictment.
Because the opioid prescriptions were filled using beneficiaries’ health insurance, Dr. Talbot is also charged with defrauding Medicare, Medicaid, and Blue Cross and Blue Shield of Louisiana of more than $5.1 million.
When contacted by this news organization for comment on the case via Twitter, Dr. Talbot or a representative responded with a link to his self-published book on Amazon. In his author bio, Dr. Talbot refers to himself as “a former assassin,” “retired military commander,” and “leader of the Medellin Cartel’s New York operations at the age of 16.” The Medellin Cartel is a notorious drug distribution empire.
Dr. Talbot is listed as the author of another book on Google Books detailing his time as a “former teenage assassin” and leader of the cartel, told as he struggles with early onset Alzheimer’s.
Dr. Talbot could spend decades in prison
According to the National Institute on Drug Abuse, 444 residents of the Bayou State lost their lives because of an opioid-related drug overdose in 2018. During that year, the state’s health care providers wrote more than 79.4 opioid prescriptions for every 100 persons, which puts the state in the top five in the United States in 2018, when the average U.S. rate was 51.4 prescriptions per 100 persons.
Charged with one count each of conspiracy to unlawfully distribute and dispense controlled substances and maintaining drug-involved premises and conspiracy to commit health care fraud, Dr. Talbot is also charged with four counts of unlawfully distributing and dispensing controlled substances. He is scheduled for a federal court appearance on September 10.
In addition to presigning prescriptions for individuals he didn’t meet or examine, federal officials allege Dr. Talbot hired another health care provider to similarly presign prescriptions for people who weren’t examined at a medical practice in Slidell, where Dr. Talbot was employed. The DOJ says Dr. Talbot took a full-time job in Pineville, La., and presigned prescriptions while no longer physically present at the Slidell clinic.
A speaker’s bio for Dr. Talbot indicates he worked as chief of medical services for the Alexandria Veterans Affairs Health Care System in Pineville.
According to the DOJ’s indictment, Dr. Talbot was aware that patients were filling the prescriptions that were provided outside the scope of professional practice and not for a legitimate medical purpose. This is what triggered the DOJ’s fraudulent billing claim.
Dr. Talbot faces a maximum penalty of 10 years for conspiracy to commit health care fraud and 20 years each for the other counts, if convicted.
Dr. Talbot was candidate for local coroner
In February 2015, Dr. Talbot announced his candidacy for coroner for St. Tammany Parish, about an hour’s drive south of New Orleans, reported the Times Picayune. The seat was open because the previous coroner had resigned and ultimately pleaded guilty to a federal corruption charge.
The Times Picayune reported at the time that Dr. Talbot was a U.S. Navy veteran, in addition to serving as medical director and a primary care physician at the Medical Care Center in Slidell. Among the services provided to his patients were evaluations and treatment for substance use and mental health disorders, according to a press release issued by Dr. Talbot’s campaign.
Dr. Talbot’s medical license was issued in 1999 and inactive as of 2017, per the Louisiana State Board of Medical Examiners.
Louisiana expects $325M in multistate settlement with opioid companies
Louisiana is a party to a multistate and multijurisdictional lawsuit where the state is expected to receive more than $325 million in a settlement reached with drug distributors Cardinal, McKesson, and AmerisourceBergen, and drug manufacturer Johnson & Johnson, reported the Louisiana Illuminator in July. The total settlement may reach $26 billion dollars.
The Associated Press reported in July that there have been at least $40 billion in completed or proposed settlements, penalties, and fines between governments as a result of the opioid epidemic since 2007.
That total doesn’t include a proposed settlement involving members of the Sackler family, who own Purdue Pharmaceuticals, which manufactured and marketed the opioid painkiller OxyContin. The Sackler family have agreed to pay approximately $4.3 billion and surrender ownership of their bankrupt company, reported NPR. The family’s proposed settlement is part of a deal involving Purdue Pharmaceuticals worth more than $10 billion, reported Reuters.
In 2020, there were more than 81,000 drug overdose deaths, the highest number recorded in a 12-month period, per the U.S. Centers for Disease Control and Prevention. Fentanyl, an illicitly manufactured synthetic opioid, was the lead driver of those deaths.
A version of this article first appeared on Medscape.com.
Clinical Edge Journal Scan Commentary: Prostate Cancer September 2021
In the study by Sternberg et al, radiographic progression-free survival (rPFS) and safety were compared between patients aged > 70 and younger than age 70 who were enrolled in the CARD study. In the CARD study, patients with metastatic castrate-resistant prostate cancer (mCRPC) were randomized to cabazitaxel versus abiraterone or enzlutamide after having failed previous treatment. Patients aged > 70 who received cabazitaxel had a higher rPFS than those who received abiraterone or enzalutamide. Grade > 3 adverse effects were identified in 58% of patients receiving cabazitaxel versus 49% in those receiving abiraterone or enzalutamide.
In the study by Smith et al., quality of life (QoL) as measured via time to deterioration of patient report outcomes (PRO) was evaluated in patients enrolled on the ARAMIS trial (darolutamide versus placebo in patients with non-metastatic castrate-resistant prostate cancer (nmCRPC). PRO was assessed via surveys as an exploratory endpoint in this study via FACT-P PCS (prostate cancer subscale) and EORTC QLQ-PR25. Overall, the findings were consistent with either an overall improvement in QoL or improvement in urinary and bowel symptoms over time. In a separate study, Fallah et al conducted a pooled analysis of survival and safety outcomes of 3 second generation androgen receptor blockers (apalutamide, darolutamide, and enzalutamide) in men with nmCRPC. They compared results for men age under 80 versus those 80 and above. Metastasis-free survival and overall survival were higher for the treatment groups compared with placebo groups for both age categories. Side effects were slightly higher in the group aged 80 and above.
In summary, quality of life is an endpoint of critical importance to patients. Inclusion of patient reported outcomes as measured via surveys that provide quantitative assessments aid providers in discussing treatment options with patients. In addition, such QoL instruments aid in assessments based on age. Age bias is common in oncology, and the included studies provide further evidence that age alone should not be a reason to adjust treatment recommendations. Inclusion of geriatric assessments into such studies may further aid in determining risks and benefits of particular prostate cancer treatments in future studies
In the study by Sternberg et al, radiographic progression-free survival (rPFS) and safety were compared between patients aged > 70 and younger than age 70 who were enrolled in the CARD study. In the CARD study, patients with metastatic castrate-resistant prostate cancer (mCRPC) were randomized to cabazitaxel versus abiraterone or enzlutamide after having failed previous treatment. Patients aged > 70 who received cabazitaxel had a higher rPFS than those who received abiraterone or enzalutamide. Grade > 3 adverse effects were identified in 58% of patients receiving cabazitaxel versus 49% in those receiving abiraterone or enzalutamide.
In the study by Smith et al., quality of life (QoL) as measured via time to deterioration of patient report outcomes (PRO) was evaluated in patients enrolled on the ARAMIS trial (darolutamide versus placebo in patients with non-metastatic castrate-resistant prostate cancer (nmCRPC). PRO was assessed via surveys as an exploratory endpoint in this study via FACT-P PCS (prostate cancer subscale) and EORTC QLQ-PR25. Overall, the findings were consistent with either an overall improvement in QoL or improvement in urinary and bowel symptoms over time. In a separate study, Fallah et al conducted a pooled analysis of survival and safety outcomes of 3 second generation androgen receptor blockers (apalutamide, darolutamide, and enzalutamide) in men with nmCRPC. They compared results for men age under 80 versus those 80 and above. Metastasis-free survival and overall survival were higher for the treatment groups compared with placebo groups for both age categories. Side effects were slightly higher in the group aged 80 and above.
In summary, quality of life is an endpoint of critical importance to patients. Inclusion of patient reported outcomes as measured via surveys that provide quantitative assessments aid providers in discussing treatment options with patients. In addition, such QoL instruments aid in assessments based on age. Age bias is common in oncology, and the included studies provide further evidence that age alone should not be a reason to adjust treatment recommendations. Inclusion of geriatric assessments into such studies may further aid in determining risks and benefits of particular prostate cancer treatments in future studies
In the study by Sternberg et al, radiographic progression-free survival (rPFS) and safety were compared between patients aged > 70 and younger than age 70 who were enrolled in the CARD study. In the CARD study, patients with metastatic castrate-resistant prostate cancer (mCRPC) were randomized to cabazitaxel versus abiraterone or enzlutamide after having failed previous treatment. Patients aged > 70 who received cabazitaxel had a higher rPFS than those who received abiraterone or enzalutamide. Grade > 3 adverse effects were identified in 58% of patients receiving cabazitaxel versus 49% in those receiving abiraterone or enzalutamide.
In the study by Smith et al., quality of life (QoL) as measured via time to deterioration of patient report outcomes (PRO) was evaluated in patients enrolled on the ARAMIS trial (darolutamide versus placebo in patients with non-metastatic castrate-resistant prostate cancer (nmCRPC). PRO was assessed via surveys as an exploratory endpoint in this study via FACT-P PCS (prostate cancer subscale) and EORTC QLQ-PR25. Overall, the findings were consistent with either an overall improvement in QoL or improvement in urinary and bowel symptoms over time. In a separate study, Fallah et al conducted a pooled analysis of survival and safety outcomes of 3 second generation androgen receptor blockers (apalutamide, darolutamide, and enzalutamide) in men with nmCRPC. They compared results for men age under 80 versus those 80 and above. Metastasis-free survival and overall survival were higher for the treatment groups compared with placebo groups for both age categories. Side effects were slightly higher in the group aged 80 and above.
In summary, quality of life is an endpoint of critical importance to patients. Inclusion of patient reported outcomes as measured via surveys that provide quantitative assessments aid providers in discussing treatment options with patients. In addition, such QoL instruments aid in assessments based on age. Age bias is common in oncology, and the included studies provide further evidence that age alone should not be a reason to adjust treatment recommendations. Inclusion of geriatric assessments into such studies may further aid in determining risks and benefits of particular prostate cancer treatments in future studies