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Chewed prasugrel for primary PCI? Forget it!
And cangrelor, in turn, is superior to oral prasugrel, according to the randomized FABOLUS FASTER trial, Marco Valgimigli, MD, PhD, reported at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.
Moreover, contrary to conventional wisdom, chewed prasugrel (Effient) proved no better than swallowing the tablets whole for platelet inhibition, said Dr. Valgimigli, an interventional cardiologist at the University of Bern (Switzerland).
He explained that standard administration of the newer oral P2Y12 inhibitors prasugrel and ticagrelor (Brilinta) in patients undergoing percutaneous coronary intervention (PCI) for ST-elevation MI (STEMI) does not provide optimal early inhibition of platelet aggregation. The parenteral antiplatelet drugs tirofiban and cangrelor have been shown to provide faster and more prolonged inhibition of platelet aggregation than the oral P2Y12 inhibitors.
But there has been no head-to-head comparative data for the glycoprotein IIb/IIIA inhibitor tirofiban (Aggrastat) and the P2Y12 inhibitor cangrelor (Kengreal) in the setting of primary PCI for STEMI. This was the impetus for FABOLUS FASTER, the first study to compare the pharmacodynamic effects of the two parenteral antiplatelet agents. The trial also looked at how these potent parenteral drugs, compared with chewed prasugrel, another previously unexamined yet highly practical issue.
The three-center, multinational, open-label FABOLUS FASTER trial randomized 122 patients undergoing primary PCI for STEMI to one of three arms: a standard intravenous bolus and 2-hour infusion of either the P2Y12 inhibitor cangrelor (Kengreal) or the glycoprotein IIb/IIIA inhibitor tirofiban (Aggrastat), followed in either case by 60 mg of oral prasugrel, or a third arm in which patients didn’t receive either drug but were instead randomized to a 60-mg loading dose of chewed or whole prasugrel tablets.
The primary study endpoint was inhibition of platelet aggregation at 30 minutes as measured by light transmittance aggregometry in response to 20 mcmol/L of adenosine diphosphate (ADP).
Tirofiban was the unequivocal winner with 95% inhibition, as compared with 34.1% with cangrelor, 10.5% with chewed prasugrel, and 6.3% with prasugrel swallowed whole, even though the concentration of prasugrel’s active metabolite was far greater at 62.3 ng/mL after prasugrel was chewed, compared with 17.1 ng/mL when swallowed in integral tablet form.
The rate of nonresponsiveness to tirofiban as defined by greater than 59% platelet aggregation was zero for tirofiban during its 2-hour infusion, then a scant 8% thereafter during repeated testing at 3 and 4-6 hours. In contrast, the cangrelor nonresponsiveness rate was 50%-58% during the 2-hour infusion, rising to 82% at 3 hours.
FABOLUS FASTER, while not powered for clinical endpoints, might nevertheless have important clinical implications, according to Dr. Valgimigli. First, the superiority of the intravenous drugs tirofiban and cangrelor over prasugrel for early, strong platelet inhibition underscores the importance of giving parenteral antiplatelet drugs over oral therapy during the acute phase of STEMI therapy. Moreover, tirofiban’s outstanding performance – and the high residual platelet reactivity associated with cangrelor – makes a strong case for large comparative, randomized trials of the two drugs, with hard clinical endpoints.
Discussant Christoph K. Naber, MD, PhD, opined that he personally doesn’t consider the FABOLUS FASTER results practice changing, for a couple of reasons.
“Platelet inhibition measured by ADP in vitro is not necessarily related to true effects in vivo. We know that platelets are activated by multiple mechanisms, and the ADP pathway is just one of them,” said Dr. Naber, an interventional cardiologist at the Wilhemshaven (Germany) Clinic.
Also, there’s a good reason why no glycoprotein IIb/IIIA inhibitors are approved for treatment of STEMI, and why tirofiban, despite its impressive antiplatelet effects, is currently largely reserved for bailout situations, such as complex lesions with large thrombus burden. It’s because tirofiban’s potent antiplatelet activity is accompanied by a high risk of bleeding, he added.
However, Dr. Valgimigli noted that this conviction about excessive bleeding risk is mainly based on older studies in which glycoprotein IIb/IIIA inhibitors were administered for prolonged duration through femoral access sites. He argued that it’s time for large clinical trials examining the risk/benefit ratio of short infusion of these agents in the contemporary practice of primary PCI for STEMI.
Simultaneously with Dr. Valgimigli’s presentation, the FABOLUS FASTER results were published online (Circulation. 2020 Jun 27; doi: 10.1161/CIRCULATIONAHA.120.046928).
Dr. Valgimigli reported that Medicure, the sponsor of the FABOLUS FASTER trial, provided an institutional research grant to conduct the study. He also disclosed receiving research grants and personal fees outside the scope of this study from a dozen pharmaceutical and medical device companies. Dr. Naber reported having no financial conflicts.
And cangrelor, in turn, is superior to oral prasugrel, according to the randomized FABOLUS FASTER trial, Marco Valgimigli, MD, PhD, reported at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.
Moreover, contrary to conventional wisdom, chewed prasugrel (Effient) proved no better than swallowing the tablets whole for platelet inhibition, said Dr. Valgimigli, an interventional cardiologist at the University of Bern (Switzerland).
He explained that standard administration of the newer oral P2Y12 inhibitors prasugrel and ticagrelor (Brilinta) in patients undergoing percutaneous coronary intervention (PCI) for ST-elevation MI (STEMI) does not provide optimal early inhibition of platelet aggregation. The parenteral antiplatelet drugs tirofiban and cangrelor have been shown to provide faster and more prolonged inhibition of platelet aggregation than the oral P2Y12 inhibitors.
But there has been no head-to-head comparative data for the glycoprotein IIb/IIIA inhibitor tirofiban (Aggrastat) and the P2Y12 inhibitor cangrelor (Kengreal) in the setting of primary PCI for STEMI. This was the impetus for FABOLUS FASTER, the first study to compare the pharmacodynamic effects of the two parenteral antiplatelet agents. The trial also looked at how these potent parenteral drugs, compared with chewed prasugrel, another previously unexamined yet highly practical issue.
The three-center, multinational, open-label FABOLUS FASTER trial randomized 122 patients undergoing primary PCI for STEMI to one of three arms: a standard intravenous bolus and 2-hour infusion of either the P2Y12 inhibitor cangrelor (Kengreal) or the glycoprotein IIb/IIIA inhibitor tirofiban (Aggrastat), followed in either case by 60 mg of oral prasugrel, or a third arm in which patients didn’t receive either drug but were instead randomized to a 60-mg loading dose of chewed or whole prasugrel tablets.
The primary study endpoint was inhibition of platelet aggregation at 30 minutes as measured by light transmittance aggregometry in response to 20 mcmol/L of adenosine diphosphate (ADP).
Tirofiban was the unequivocal winner with 95% inhibition, as compared with 34.1% with cangrelor, 10.5% with chewed prasugrel, and 6.3% with prasugrel swallowed whole, even though the concentration of prasugrel’s active metabolite was far greater at 62.3 ng/mL after prasugrel was chewed, compared with 17.1 ng/mL when swallowed in integral tablet form.
The rate of nonresponsiveness to tirofiban as defined by greater than 59% platelet aggregation was zero for tirofiban during its 2-hour infusion, then a scant 8% thereafter during repeated testing at 3 and 4-6 hours. In contrast, the cangrelor nonresponsiveness rate was 50%-58% during the 2-hour infusion, rising to 82% at 3 hours.
FABOLUS FASTER, while not powered for clinical endpoints, might nevertheless have important clinical implications, according to Dr. Valgimigli. First, the superiority of the intravenous drugs tirofiban and cangrelor over prasugrel for early, strong platelet inhibition underscores the importance of giving parenteral antiplatelet drugs over oral therapy during the acute phase of STEMI therapy. Moreover, tirofiban’s outstanding performance – and the high residual platelet reactivity associated with cangrelor – makes a strong case for large comparative, randomized trials of the two drugs, with hard clinical endpoints.
Discussant Christoph K. Naber, MD, PhD, opined that he personally doesn’t consider the FABOLUS FASTER results practice changing, for a couple of reasons.
“Platelet inhibition measured by ADP in vitro is not necessarily related to true effects in vivo. We know that platelets are activated by multiple mechanisms, and the ADP pathway is just one of them,” said Dr. Naber, an interventional cardiologist at the Wilhemshaven (Germany) Clinic.
Also, there’s a good reason why no glycoprotein IIb/IIIA inhibitors are approved for treatment of STEMI, and why tirofiban, despite its impressive antiplatelet effects, is currently largely reserved for bailout situations, such as complex lesions with large thrombus burden. It’s because tirofiban’s potent antiplatelet activity is accompanied by a high risk of bleeding, he added.
However, Dr. Valgimigli noted that this conviction about excessive bleeding risk is mainly based on older studies in which glycoprotein IIb/IIIA inhibitors were administered for prolonged duration through femoral access sites. He argued that it’s time for large clinical trials examining the risk/benefit ratio of short infusion of these agents in the contemporary practice of primary PCI for STEMI.
Simultaneously with Dr. Valgimigli’s presentation, the FABOLUS FASTER results were published online (Circulation. 2020 Jun 27; doi: 10.1161/CIRCULATIONAHA.120.046928).
Dr. Valgimigli reported that Medicure, the sponsor of the FABOLUS FASTER trial, provided an institutional research grant to conduct the study. He also disclosed receiving research grants and personal fees outside the scope of this study from a dozen pharmaceutical and medical device companies. Dr. Naber reported having no financial conflicts.
And cangrelor, in turn, is superior to oral prasugrel, according to the randomized FABOLUS FASTER trial, Marco Valgimigli, MD, PhD, reported at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.
Moreover, contrary to conventional wisdom, chewed prasugrel (Effient) proved no better than swallowing the tablets whole for platelet inhibition, said Dr. Valgimigli, an interventional cardiologist at the University of Bern (Switzerland).
He explained that standard administration of the newer oral P2Y12 inhibitors prasugrel and ticagrelor (Brilinta) in patients undergoing percutaneous coronary intervention (PCI) for ST-elevation MI (STEMI) does not provide optimal early inhibition of platelet aggregation. The parenteral antiplatelet drugs tirofiban and cangrelor have been shown to provide faster and more prolonged inhibition of platelet aggregation than the oral P2Y12 inhibitors.
But there has been no head-to-head comparative data for the glycoprotein IIb/IIIA inhibitor tirofiban (Aggrastat) and the P2Y12 inhibitor cangrelor (Kengreal) in the setting of primary PCI for STEMI. This was the impetus for FABOLUS FASTER, the first study to compare the pharmacodynamic effects of the two parenteral antiplatelet agents. The trial also looked at how these potent parenteral drugs, compared with chewed prasugrel, another previously unexamined yet highly practical issue.
The three-center, multinational, open-label FABOLUS FASTER trial randomized 122 patients undergoing primary PCI for STEMI to one of three arms: a standard intravenous bolus and 2-hour infusion of either the P2Y12 inhibitor cangrelor (Kengreal) or the glycoprotein IIb/IIIA inhibitor tirofiban (Aggrastat), followed in either case by 60 mg of oral prasugrel, or a third arm in which patients didn’t receive either drug but were instead randomized to a 60-mg loading dose of chewed or whole prasugrel tablets.
The primary study endpoint was inhibition of platelet aggregation at 30 minutes as measured by light transmittance aggregometry in response to 20 mcmol/L of adenosine diphosphate (ADP).
Tirofiban was the unequivocal winner with 95% inhibition, as compared with 34.1% with cangrelor, 10.5% with chewed prasugrel, and 6.3% with prasugrel swallowed whole, even though the concentration of prasugrel’s active metabolite was far greater at 62.3 ng/mL after prasugrel was chewed, compared with 17.1 ng/mL when swallowed in integral tablet form.
The rate of nonresponsiveness to tirofiban as defined by greater than 59% platelet aggregation was zero for tirofiban during its 2-hour infusion, then a scant 8% thereafter during repeated testing at 3 and 4-6 hours. In contrast, the cangrelor nonresponsiveness rate was 50%-58% during the 2-hour infusion, rising to 82% at 3 hours.
FABOLUS FASTER, while not powered for clinical endpoints, might nevertheless have important clinical implications, according to Dr. Valgimigli. First, the superiority of the intravenous drugs tirofiban and cangrelor over prasugrel for early, strong platelet inhibition underscores the importance of giving parenteral antiplatelet drugs over oral therapy during the acute phase of STEMI therapy. Moreover, tirofiban’s outstanding performance – and the high residual platelet reactivity associated with cangrelor – makes a strong case for large comparative, randomized trials of the two drugs, with hard clinical endpoints.
Discussant Christoph K. Naber, MD, PhD, opined that he personally doesn’t consider the FABOLUS FASTER results practice changing, for a couple of reasons.
“Platelet inhibition measured by ADP in vitro is not necessarily related to true effects in vivo. We know that platelets are activated by multiple mechanisms, and the ADP pathway is just one of them,” said Dr. Naber, an interventional cardiologist at the Wilhemshaven (Germany) Clinic.
Also, there’s a good reason why no glycoprotein IIb/IIIA inhibitors are approved for treatment of STEMI, and why tirofiban, despite its impressive antiplatelet effects, is currently largely reserved for bailout situations, such as complex lesions with large thrombus burden. It’s because tirofiban’s potent antiplatelet activity is accompanied by a high risk of bleeding, he added.
However, Dr. Valgimigli noted that this conviction about excessive bleeding risk is mainly based on older studies in which glycoprotein IIb/IIIA inhibitors were administered for prolonged duration through femoral access sites. He argued that it’s time for large clinical trials examining the risk/benefit ratio of short infusion of these agents in the contemporary practice of primary PCI for STEMI.
Simultaneously with Dr. Valgimigli’s presentation, the FABOLUS FASTER results were published online (Circulation. 2020 Jun 27; doi: 10.1161/CIRCULATIONAHA.120.046928).
Dr. Valgimigli reported that Medicure, the sponsor of the FABOLUS FASTER trial, provided an institutional research grant to conduct the study. He also disclosed receiving research grants and personal fees outside the scope of this study from a dozen pharmaceutical and medical device companies. Dr. Naber reported having no financial conflicts.
REPORTING FROM EUROPCR 2020
Sotatercept reversed vascular remodeling in patients with PAH
for patients with pulmonary arterial hypertension (PAH) in a phase 2 trial.
The mean decline change in pulmonary vascular resistance (PVR) after 24 weeks of treatment was significantly greater for patients treated with sotatercept at either of two doses, compared with placebo, David B. Badesch, MD, FCCP, of the University of Colorado, Aurora, reported on behalf of coinvestigators in the PULSAR trial.
“Sotatercept has a novel mechanism of action, rebalancing pro- and antiproliferative signaling through a pathway distinct from the previously approved pulmonary arterial hypertension therapies,” he said in the American Thoracic Society’s virtual clinical trial session.
The drug is a ligand trap with high selectivity for proteins within the tumor growth factor-beta superfamily signaling pathway. Investigators propose a mechanism of action whereby sotatercept promotes a rebalancing of bone morphogenetic protein receptor–II (BMPR-II) signaling to restore vascular homeostasis.
In a preclinical study, sotatercept reduced pulmonary artery pressure, pulmonary arteriolar muscularization and occlusion, right ventricular hypertrophy, and cell proliferation in the lungs of rodent models of pulmonary hypertension (Sci Transl Med. 2020 May 13. doi: 10.1126/scitranslmed.aaz5660).
Two dose levels
The PULSAR trial (NCT03496207) was a phase 2 randomized, double-blind study conducted in the United States, Brazil, Western Europe, and Australia comparing the efficacy and safety of sotatercept vs. placebo added to the standard of care in patients with PAH.
A total of 106 patients with World Health Organization (WHO) group 1 PAH or WHO functional class II or III disease were enrolled. All patients had baseline right-heart e4rcatheterization with PVR of 5 Wood units or more, had baseline 6-minute walk distance from 150 to 550 m, and were on stable treatment with standard-of-care mono, double, or triple therapies, including an endothelin-receptor antagonist, phosphodiesterase 5 inhibitor, soluble guanylate cyclase stimulator, and/or a prostacyclin, including intravenous formulations.
The median patient age was 46 years among 32 patients in the placebo group, and 48.5 years in each sotatercept dose group: 0.3 mg/kg (32 patients) and 0.7 mg/kg (42 patients).
The primary endpoint of PVR change from baseline to week 24, the end of the placebo-controlled treatment period, showed a mean decrease of 162 dynes/cm2 in the 0.3-mg/kg sotatercept group (–20.5%), and a mean decrease of 256 dynes/cm2 in the 0.7-mg/kg group (–33.9%), compared with a mean 16 dyne/cm2 decline in the placebo group (–2,1%). Both doses were associated with significantly larger decreases, compared with placebo (P = .0027 for the 0.3-mg/kg dose, and P < .0001 for the 0.7-mg/kg dose).
Six-minute walk distance, a key secondary endpoint, improved over baseline in each active-drug arm, with a least square (LS) mean improvement of 58 m in the 0.7-mg/kg group, and 50 m in the 0.7-mg/kg group. The prespecified analysis of pooled data from the two sotatercept cohorts showed an LS-mean change of 54 m over baseline, compared with 25 m for the placebo group (nominal P = .03).
Exploratory endpoints also favoring sotatercept over placebo included a 51% reduction in amino-terminal brain natriuretic propeptide (NT-proBNP), and a 20% reduction in mean pulmonary arterial pressure.
There was no significant difference between the study arms in change in cardiac output, however.
Improvements in WHO functional class were seen in 12.5% of patients on placebo, compared with 23% of patients on sotatercept, a difference that was not statistically significant.
Two patients (6%) in the 0.3-mg/kg arm and 10 (24%) in the 0.7-mg/kg arm had a serious treatment-emergent adverse event (TEAE), as did three patients (9%) in the placebo arm. Serious TEAEs included leukopenia, neutropenia, pericardial infusion, tachycardia, chorioretinopathy, peripheral edema, pyrexia, bronchitis, influenza, respiratory tract infection, femur fracture, hypotension, device breakage, syncope, and red blood cell increase.
One patient in the 0.7-mg/kg arm died from cardiac arrest deemed unrelated to study treatment.
TEAEs of special interest included thrombocytopenia in two patients in 0.3– and five patients in the 0.7–mg/kg groups, vs. no patients in the placebo groups. Most patients had existing thrombocytopenia at baseline and all were on concomitant prostacyclin infusions. No patients had grade 3 thrombocytopenia or associated bleeding events.
One patient in the 0.3-mg/kg group and six patients in the 0.7-mg/kg group had an increase in hemoglobin.
“This was not a surprise,” Dr. Badesch said. “We were prepared to manage increases in hemoglobin with dose interruption or dose reduction if necessary, and phlebotomy was also an option if needed.”
One patient in the placebo arm, two in the 0.3-mg/kg and three patients in the 0.7-mg/kg arms had TEAEs leading to discontinuation.
TEAEs occurring in 10% or more of all patients in any arm and of any grade were headache, diarrhea, peripheral edema, dizziness, fatigue, hypokalemia, and nausea.
Why no cardiac improvement?
In the question-and-answer session following the online presentation, facilitator Steven M. Kawut MD, MS, of the University of Pennsylvania and Pennsylvania Hospital in Philadelphia, remarked on the surprising lack of an apparent cardiac benefit in the study.
“You showed pretty robust decreases in NT-proBNP, decreases in pulmonary vascular resistance and right atrial pressure, and increases in 6-minute walk distance, so it’s a bit surprising that cardiac output didn’t change,” he said.
“Unlike other medications that have been tried in this field and have had a significant pulmonary vasodilatory effect, this drug is acting largely on the structure of pulmonary blood vessels,” Dr. Badesch replied. “We have thought that its primary effect is likely remodeling of the pulmonary arteries and arterioles, decreasing pulmonary vascular resistance. Unlike other drugs that have been tested in the field, it probably has no direct inotropic effect, and that may explain why cardiac output didn’t improve.”
He said that there is some echocardiographic evidence that suggests a change in right ventricular function over time. Those data are currently being analyzed, and “it’s possible that we’ll see an effect on cardiac output later.”
As of June 22, 2020, 94 of 97 patients who opted to participate in an 18-month extension period of the trial were still enrolled, and 64 patients have now been treated with sotatercept for at least 12 months.
A phase 3 trial is in the works.
The study was supported by Acceleron Pharma. Badesch disclosed research support from and consulting/advising for the company and others. Dr. Kawut has disclosed grants from several companies and travel support from ATS and the Pulmonary Hypertension Association.
for patients with pulmonary arterial hypertension (PAH) in a phase 2 trial.
The mean decline change in pulmonary vascular resistance (PVR) after 24 weeks of treatment was significantly greater for patients treated with sotatercept at either of two doses, compared with placebo, David B. Badesch, MD, FCCP, of the University of Colorado, Aurora, reported on behalf of coinvestigators in the PULSAR trial.
“Sotatercept has a novel mechanism of action, rebalancing pro- and antiproliferative signaling through a pathway distinct from the previously approved pulmonary arterial hypertension therapies,” he said in the American Thoracic Society’s virtual clinical trial session.
The drug is a ligand trap with high selectivity for proteins within the tumor growth factor-beta superfamily signaling pathway. Investigators propose a mechanism of action whereby sotatercept promotes a rebalancing of bone morphogenetic protein receptor–II (BMPR-II) signaling to restore vascular homeostasis.
In a preclinical study, sotatercept reduced pulmonary artery pressure, pulmonary arteriolar muscularization and occlusion, right ventricular hypertrophy, and cell proliferation in the lungs of rodent models of pulmonary hypertension (Sci Transl Med. 2020 May 13. doi: 10.1126/scitranslmed.aaz5660).
Two dose levels
The PULSAR trial (NCT03496207) was a phase 2 randomized, double-blind study conducted in the United States, Brazil, Western Europe, and Australia comparing the efficacy and safety of sotatercept vs. placebo added to the standard of care in patients with PAH.
A total of 106 patients with World Health Organization (WHO) group 1 PAH or WHO functional class II or III disease were enrolled. All patients had baseline right-heart e4rcatheterization with PVR of 5 Wood units or more, had baseline 6-minute walk distance from 150 to 550 m, and were on stable treatment with standard-of-care mono, double, or triple therapies, including an endothelin-receptor antagonist, phosphodiesterase 5 inhibitor, soluble guanylate cyclase stimulator, and/or a prostacyclin, including intravenous formulations.
The median patient age was 46 years among 32 patients in the placebo group, and 48.5 years in each sotatercept dose group: 0.3 mg/kg (32 patients) and 0.7 mg/kg (42 patients).
The primary endpoint of PVR change from baseline to week 24, the end of the placebo-controlled treatment period, showed a mean decrease of 162 dynes/cm2 in the 0.3-mg/kg sotatercept group (–20.5%), and a mean decrease of 256 dynes/cm2 in the 0.7-mg/kg group (–33.9%), compared with a mean 16 dyne/cm2 decline in the placebo group (–2,1%). Both doses were associated with significantly larger decreases, compared with placebo (P = .0027 for the 0.3-mg/kg dose, and P < .0001 for the 0.7-mg/kg dose).
Six-minute walk distance, a key secondary endpoint, improved over baseline in each active-drug arm, with a least square (LS) mean improvement of 58 m in the 0.7-mg/kg group, and 50 m in the 0.7-mg/kg group. The prespecified analysis of pooled data from the two sotatercept cohorts showed an LS-mean change of 54 m over baseline, compared with 25 m for the placebo group (nominal P = .03).
Exploratory endpoints also favoring sotatercept over placebo included a 51% reduction in amino-terminal brain natriuretic propeptide (NT-proBNP), and a 20% reduction in mean pulmonary arterial pressure.
There was no significant difference between the study arms in change in cardiac output, however.
Improvements in WHO functional class were seen in 12.5% of patients on placebo, compared with 23% of patients on sotatercept, a difference that was not statistically significant.
Two patients (6%) in the 0.3-mg/kg arm and 10 (24%) in the 0.7-mg/kg arm had a serious treatment-emergent adverse event (TEAE), as did three patients (9%) in the placebo arm. Serious TEAEs included leukopenia, neutropenia, pericardial infusion, tachycardia, chorioretinopathy, peripheral edema, pyrexia, bronchitis, influenza, respiratory tract infection, femur fracture, hypotension, device breakage, syncope, and red blood cell increase.
One patient in the 0.7-mg/kg arm died from cardiac arrest deemed unrelated to study treatment.
TEAEs of special interest included thrombocytopenia in two patients in 0.3– and five patients in the 0.7–mg/kg groups, vs. no patients in the placebo groups. Most patients had existing thrombocytopenia at baseline and all were on concomitant prostacyclin infusions. No patients had grade 3 thrombocytopenia or associated bleeding events.
One patient in the 0.3-mg/kg group and six patients in the 0.7-mg/kg group had an increase in hemoglobin.
“This was not a surprise,” Dr. Badesch said. “We were prepared to manage increases in hemoglobin with dose interruption or dose reduction if necessary, and phlebotomy was also an option if needed.”
One patient in the placebo arm, two in the 0.3-mg/kg and three patients in the 0.7-mg/kg arms had TEAEs leading to discontinuation.
TEAEs occurring in 10% or more of all patients in any arm and of any grade were headache, diarrhea, peripheral edema, dizziness, fatigue, hypokalemia, and nausea.
Why no cardiac improvement?
In the question-and-answer session following the online presentation, facilitator Steven M. Kawut MD, MS, of the University of Pennsylvania and Pennsylvania Hospital in Philadelphia, remarked on the surprising lack of an apparent cardiac benefit in the study.
“You showed pretty robust decreases in NT-proBNP, decreases in pulmonary vascular resistance and right atrial pressure, and increases in 6-minute walk distance, so it’s a bit surprising that cardiac output didn’t change,” he said.
“Unlike other medications that have been tried in this field and have had a significant pulmonary vasodilatory effect, this drug is acting largely on the structure of pulmonary blood vessels,” Dr. Badesch replied. “We have thought that its primary effect is likely remodeling of the pulmonary arteries and arterioles, decreasing pulmonary vascular resistance. Unlike other drugs that have been tested in the field, it probably has no direct inotropic effect, and that may explain why cardiac output didn’t improve.”
He said that there is some echocardiographic evidence that suggests a change in right ventricular function over time. Those data are currently being analyzed, and “it’s possible that we’ll see an effect on cardiac output later.”
As of June 22, 2020, 94 of 97 patients who opted to participate in an 18-month extension period of the trial were still enrolled, and 64 patients have now been treated with sotatercept for at least 12 months.
A phase 3 trial is in the works.
The study was supported by Acceleron Pharma. Badesch disclosed research support from and consulting/advising for the company and others. Dr. Kawut has disclosed grants from several companies and travel support from ATS and the Pulmonary Hypertension Association.
for patients with pulmonary arterial hypertension (PAH) in a phase 2 trial.
The mean decline change in pulmonary vascular resistance (PVR) after 24 weeks of treatment was significantly greater for patients treated with sotatercept at either of two doses, compared with placebo, David B. Badesch, MD, FCCP, of the University of Colorado, Aurora, reported on behalf of coinvestigators in the PULSAR trial.
“Sotatercept has a novel mechanism of action, rebalancing pro- and antiproliferative signaling through a pathway distinct from the previously approved pulmonary arterial hypertension therapies,” he said in the American Thoracic Society’s virtual clinical trial session.
The drug is a ligand trap with high selectivity for proteins within the tumor growth factor-beta superfamily signaling pathway. Investigators propose a mechanism of action whereby sotatercept promotes a rebalancing of bone morphogenetic protein receptor–II (BMPR-II) signaling to restore vascular homeostasis.
In a preclinical study, sotatercept reduced pulmonary artery pressure, pulmonary arteriolar muscularization and occlusion, right ventricular hypertrophy, and cell proliferation in the lungs of rodent models of pulmonary hypertension (Sci Transl Med. 2020 May 13. doi: 10.1126/scitranslmed.aaz5660).
Two dose levels
The PULSAR trial (NCT03496207) was a phase 2 randomized, double-blind study conducted in the United States, Brazil, Western Europe, and Australia comparing the efficacy and safety of sotatercept vs. placebo added to the standard of care in patients with PAH.
A total of 106 patients with World Health Organization (WHO) group 1 PAH or WHO functional class II or III disease were enrolled. All patients had baseline right-heart e4rcatheterization with PVR of 5 Wood units or more, had baseline 6-minute walk distance from 150 to 550 m, and were on stable treatment with standard-of-care mono, double, or triple therapies, including an endothelin-receptor antagonist, phosphodiesterase 5 inhibitor, soluble guanylate cyclase stimulator, and/or a prostacyclin, including intravenous formulations.
The median patient age was 46 years among 32 patients in the placebo group, and 48.5 years in each sotatercept dose group: 0.3 mg/kg (32 patients) and 0.7 mg/kg (42 patients).
The primary endpoint of PVR change from baseline to week 24, the end of the placebo-controlled treatment period, showed a mean decrease of 162 dynes/cm2 in the 0.3-mg/kg sotatercept group (–20.5%), and a mean decrease of 256 dynes/cm2 in the 0.7-mg/kg group (–33.9%), compared with a mean 16 dyne/cm2 decline in the placebo group (–2,1%). Both doses were associated with significantly larger decreases, compared with placebo (P = .0027 for the 0.3-mg/kg dose, and P < .0001 for the 0.7-mg/kg dose).
Six-minute walk distance, a key secondary endpoint, improved over baseline in each active-drug arm, with a least square (LS) mean improvement of 58 m in the 0.7-mg/kg group, and 50 m in the 0.7-mg/kg group. The prespecified analysis of pooled data from the two sotatercept cohorts showed an LS-mean change of 54 m over baseline, compared with 25 m for the placebo group (nominal P = .03).
Exploratory endpoints also favoring sotatercept over placebo included a 51% reduction in amino-terminal brain natriuretic propeptide (NT-proBNP), and a 20% reduction in mean pulmonary arterial pressure.
There was no significant difference between the study arms in change in cardiac output, however.
Improvements in WHO functional class were seen in 12.5% of patients on placebo, compared with 23% of patients on sotatercept, a difference that was not statistically significant.
Two patients (6%) in the 0.3-mg/kg arm and 10 (24%) in the 0.7-mg/kg arm had a serious treatment-emergent adverse event (TEAE), as did three patients (9%) in the placebo arm. Serious TEAEs included leukopenia, neutropenia, pericardial infusion, tachycardia, chorioretinopathy, peripheral edema, pyrexia, bronchitis, influenza, respiratory tract infection, femur fracture, hypotension, device breakage, syncope, and red blood cell increase.
One patient in the 0.7-mg/kg arm died from cardiac arrest deemed unrelated to study treatment.
TEAEs of special interest included thrombocytopenia in two patients in 0.3– and five patients in the 0.7–mg/kg groups, vs. no patients in the placebo groups. Most patients had existing thrombocytopenia at baseline and all were on concomitant prostacyclin infusions. No patients had grade 3 thrombocytopenia or associated bleeding events.
One patient in the 0.3-mg/kg group and six patients in the 0.7-mg/kg group had an increase in hemoglobin.
“This was not a surprise,” Dr. Badesch said. “We were prepared to manage increases in hemoglobin with dose interruption or dose reduction if necessary, and phlebotomy was also an option if needed.”
One patient in the placebo arm, two in the 0.3-mg/kg and three patients in the 0.7-mg/kg arms had TEAEs leading to discontinuation.
TEAEs occurring in 10% or more of all patients in any arm and of any grade were headache, diarrhea, peripheral edema, dizziness, fatigue, hypokalemia, and nausea.
Why no cardiac improvement?
In the question-and-answer session following the online presentation, facilitator Steven M. Kawut MD, MS, of the University of Pennsylvania and Pennsylvania Hospital in Philadelphia, remarked on the surprising lack of an apparent cardiac benefit in the study.
“You showed pretty robust decreases in NT-proBNP, decreases in pulmonary vascular resistance and right atrial pressure, and increases in 6-minute walk distance, so it’s a bit surprising that cardiac output didn’t change,” he said.
“Unlike other medications that have been tried in this field and have had a significant pulmonary vasodilatory effect, this drug is acting largely on the structure of pulmonary blood vessels,” Dr. Badesch replied. “We have thought that its primary effect is likely remodeling of the pulmonary arteries and arterioles, decreasing pulmonary vascular resistance. Unlike other drugs that have been tested in the field, it probably has no direct inotropic effect, and that may explain why cardiac output didn’t improve.”
He said that there is some echocardiographic evidence that suggests a change in right ventricular function over time. Those data are currently being analyzed, and “it’s possible that we’ll see an effect on cardiac output later.”
As of June 22, 2020, 94 of 97 patients who opted to participate in an 18-month extension period of the trial were still enrolled, and 64 patients have now been treated with sotatercept for at least 12 months.
A phase 3 trial is in the works.
The study was supported by Acceleron Pharma. Badesch disclosed research support from and consulting/advising for the company and others. Dr. Kawut has disclosed grants from several companies and travel support from ATS and the Pulmonary Hypertension Association.
FROM ATS 2020
Pride profile: Sarah Jones, PA-C
Sarah Jones, PA-C, is a physician assistant on the overnight hospitalist team at Indiana University Health Methodist Hospital in Indianapolis, where she has worked for about 8 years. She studied chemistry and biology as an undergraduate at the University of Indianapolis, and then attended PA school at Butler University in Indianapolis. She came out as lesbian/queer just before PA school. She joined the Society of Hospital Medicine in 2020 and serves on SHM’s Diversity and Inclusion Special Interest Group.
How important is it to you to openly identify as a physician assistant who is a member of the LGBTQ community?
I think it’s important to show other people that I am part of the LGBTQ community and that I’ve been able to overcome obstacles and pursue this career and be successful. I can help other people and be in that role [of mentor], and show people that they can do it, too.
What challenges have you faced because of your sexual orientation in the different stages of your career, from training to practicing as a physician assistant?
When my training started, I was much closer to the time when I came out, so my confidence level was a little bit low. I was much more fearful at that point about how people would view me – if I would be thought of as inferior, or not taken as seriously, or that I wasn’t intelligent. I think over the years I’ve grown into this role and it’s helped me become more confident, because I know who I am now. And it’s not something that definitely defines me but I’m confident that I know medicine, and I know how to treat patients and that confidence has gotten much better.
So far at work, everyone’s been great, all my coworkers have been great. I’ve never once felt that my sexuality was holding anyone back from getting to know me better.
Have you heard about the experiences of other LGBTQ clinicians who may not have been as fortunate as you, especially transgender people?
There is just a lot of ignorance around LGBTQ persons and especially transgender persons, because people don’t understand it, they don’t get it. So their first inclination is to not approve of it, or be scared of it, or just automatically think that it’s wrong.
If someone’s sexuality comes across much more “obviously” than that of other people, for example, if there’s a gay man who’s a little more flamboyant, [it could be an issue for some patients]. I know there are some gay male nurses who have had patients who don’t want them serving as their nurse, because they’re “obviously” gay. Or a queer woman clinician who has more of an edgier haircut or looks a little bit more masculine; I know that there have been some patients who have said certain things to them that have been discriminating.
Have you been especially conscious of how you ‘wear’ your sexual orientation? Have you ever had to change how you’ve presented yourself, lest you have some unpleasant reaction?
I think initially, yes. I would say I’m a little more on the androgynous side with my style. When I was coming out I was trying to figure out where I was and who I was and how I wanted to be, and for the longest time I was dressing more femininely and I wasn’t as comfortable. Since then, I’ve had times where I’ve had short hair or a little bit more of a masculine haircut and wear more masculine clothes and things like that, and I feel much more comfortable doing that.
It’s kind of hard to play the part of a more masculine LGBTQ person at work when you just wear scrubs. I probably don’t portray it as much – I don’t make it as obvious as some other people, but I’ve definitely never shied away from having a conversation with anyone about it.
Health care is an intimate profession because of your close interaction with patients and others. Did being a member of the LGBTQ community factor into your decision to enter the health care field, either for or against?
There were times when I didn’t feel well or my mental health was not great because I didn’t know where I was, or hadn’t accepted myself, and I really needed someone who could help me talk through things and try to figure out what my life path was going to be. When I figured those things out with the help of other people, it was life-changing. I respected those people, and that’s what I wanted to do and how I wanted to help. I think that was part of why I got into medicine.
What progress have you seen with regard to LGBTQ health care professionals and patients over the past 5 to 10 years, including subtle changes in culture, attitude, or workplace policies?
Just being interviewed for a profile like this is a step in the right direction. Never once did I think that I would be highlighted for being an LGBTQ person, especially in the workplace.
I think that there are more companies, particularly in health care, and more hospitals that are coming out in support of their LGBTQ employees, especially during Pride month. IU Health walks every year in the Pride parade, which last year was about 3 hours long. Five years previously it was only 30 minutes long. So there are more employers getting involved and recognizing their employees as well. Companies and health care facilities are trying to be more cognizant of their LGBTQ employees and patients and trying to make them more comfortable.
What main steps toward more progress would you like to see?
There needs to be greater understanding that people who undergo discrimination actually have more negative health outcomes like heart disease, high blood pressure, and stroke. There needs to be better medical coverage in the LGBTQ community, especially for transgender persons and LGBTQ people who are trying to start families. We need better mental health access, more affordable mental health access, particularly for LGBTQ youth, and we definitely need to continue to raise awareness with hopes that we can eradicate the violence against, and killing of, black transgender persons.
How do you see the Society of Hospital Medicine’s role in this regard?
SHM has a big platform and can certainly reach a lot of people, especially hospitalists who see LGBTQ patients every day. With SHM’s help and the continued training of hospitalists who are members of the society, we can reach out to other clinicians, and to their organizations, and help teach them. SHM really has a good platform to be able to do that, and do it well.
Can you recall a specific interaction with an LGBTQ patient that left you with a potent feeling that “this is what it’s all about”?
I do remember a transgender patient who was homeless. They didn’t have insurance, they couldn’t afford their hormone treatment, and I remember they were struggling with some mental health issues and were “acting out” overnight. Some of the nurses were not using the correct pronouns. I’m more cognizant of their struggles because I’m a member of the LGBTQ community and I was able to recognize this.
I sat down and I talked with the patient for quite a while, we were able to form a bond, and I was able to get a little bit more information from them, and by the end of the night, they felt much better. And just being able to be their voice, when they weren’t able to express exactly how they were feeling, was something that made me thankful that I went into medicine, to help other LGBTQ patients.
I’ve had many LGBTQ patients in the hospital whom I’ve been able to form a bit of a bond with, just knowing that the patient could be me.
Sarah Jones, PA-C, is a physician assistant on the overnight hospitalist team at Indiana University Health Methodist Hospital in Indianapolis, where she has worked for about 8 years. She studied chemistry and biology as an undergraduate at the University of Indianapolis, and then attended PA school at Butler University in Indianapolis. She came out as lesbian/queer just before PA school. She joined the Society of Hospital Medicine in 2020 and serves on SHM’s Diversity and Inclusion Special Interest Group.
How important is it to you to openly identify as a physician assistant who is a member of the LGBTQ community?
I think it’s important to show other people that I am part of the LGBTQ community and that I’ve been able to overcome obstacles and pursue this career and be successful. I can help other people and be in that role [of mentor], and show people that they can do it, too.
What challenges have you faced because of your sexual orientation in the different stages of your career, from training to practicing as a physician assistant?
When my training started, I was much closer to the time when I came out, so my confidence level was a little bit low. I was much more fearful at that point about how people would view me – if I would be thought of as inferior, or not taken as seriously, or that I wasn’t intelligent. I think over the years I’ve grown into this role and it’s helped me become more confident, because I know who I am now. And it’s not something that definitely defines me but I’m confident that I know medicine, and I know how to treat patients and that confidence has gotten much better.
So far at work, everyone’s been great, all my coworkers have been great. I’ve never once felt that my sexuality was holding anyone back from getting to know me better.
Have you heard about the experiences of other LGBTQ clinicians who may not have been as fortunate as you, especially transgender people?
There is just a lot of ignorance around LGBTQ persons and especially transgender persons, because people don’t understand it, they don’t get it. So their first inclination is to not approve of it, or be scared of it, or just automatically think that it’s wrong.
If someone’s sexuality comes across much more “obviously” than that of other people, for example, if there’s a gay man who’s a little more flamboyant, [it could be an issue for some patients]. I know there are some gay male nurses who have had patients who don’t want them serving as their nurse, because they’re “obviously” gay. Or a queer woman clinician who has more of an edgier haircut or looks a little bit more masculine; I know that there have been some patients who have said certain things to them that have been discriminating.
Have you been especially conscious of how you ‘wear’ your sexual orientation? Have you ever had to change how you’ve presented yourself, lest you have some unpleasant reaction?
I think initially, yes. I would say I’m a little more on the androgynous side with my style. When I was coming out I was trying to figure out where I was and who I was and how I wanted to be, and for the longest time I was dressing more femininely and I wasn’t as comfortable. Since then, I’ve had times where I’ve had short hair or a little bit more of a masculine haircut and wear more masculine clothes and things like that, and I feel much more comfortable doing that.
It’s kind of hard to play the part of a more masculine LGBTQ person at work when you just wear scrubs. I probably don’t portray it as much – I don’t make it as obvious as some other people, but I’ve definitely never shied away from having a conversation with anyone about it.
Health care is an intimate profession because of your close interaction with patients and others. Did being a member of the LGBTQ community factor into your decision to enter the health care field, either for or against?
There were times when I didn’t feel well or my mental health was not great because I didn’t know where I was, or hadn’t accepted myself, and I really needed someone who could help me talk through things and try to figure out what my life path was going to be. When I figured those things out with the help of other people, it was life-changing. I respected those people, and that’s what I wanted to do and how I wanted to help. I think that was part of why I got into medicine.
What progress have you seen with regard to LGBTQ health care professionals and patients over the past 5 to 10 years, including subtle changes in culture, attitude, or workplace policies?
Just being interviewed for a profile like this is a step in the right direction. Never once did I think that I would be highlighted for being an LGBTQ person, especially in the workplace.
I think that there are more companies, particularly in health care, and more hospitals that are coming out in support of their LGBTQ employees, especially during Pride month. IU Health walks every year in the Pride parade, which last year was about 3 hours long. Five years previously it was only 30 minutes long. So there are more employers getting involved and recognizing their employees as well. Companies and health care facilities are trying to be more cognizant of their LGBTQ employees and patients and trying to make them more comfortable.
What main steps toward more progress would you like to see?
There needs to be greater understanding that people who undergo discrimination actually have more negative health outcomes like heart disease, high blood pressure, and stroke. There needs to be better medical coverage in the LGBTQ community, especially for transgender persons and LGBTQ people who are trying to start families. We need better mental health access, more affordable mental health access, particularly for LGBTQ youth, and we definitely need to continue to raise awareness with hopes that we can eradicate the violence against, and killing of, black transgender persons.
How do you see the Society of Hospital Medicine’s role in this regard?
SHM has a big platform and can certainly reach a lot of people, especially hospitalists who see LGBTQ patients every day. With SHM’s help and the continued training of hospitalists who are members of the society, we can reach out to other clinicians, and to their organizations, and help teach them. SHM really has a good platform to be able to do that, and do it well.
Can you recall a specific interaction with an LGBTQ patient that left you with a potent feeling that “this is what it’s all about”?
I do remember a transgender patient who was homeless. They didn’t have insurance, they couldn’t afford their hormone treatment, and I remember they were struggling with some mental health issues and were “acting out” overnight. Some of the nurses were not using the correct pronouns. I’m more cognizant of their struggles because I’m a member of the LGBTQ community and I was able to recognize this.
I sat down and I talked with the patient for quite a while, we were able to form a bond, and I was able to get a little bit more information from them, and by the end of the night, they felt much better. And just being able to be their voice, when they weren’t able to express exactly how they were feeling, was something that made me thankful that I went into medicine, to help other LGBTQ patients.
I’ve had many LGBTQ patients in the hospital whom I’ve been able to form a bit of a bond with, just knowing that the patient could be me.
Sarah Jones, PA-C, is a physician assistant on the overnight hospitalist team at Indiana University Health Methodist Hospital in Indianapolis, where she has worked for about 8 years. She studied chemistry and biology as an undergraduate at the University of Indianapolis, and then attended PA school at Butler University in Indianapolis. She came out as lesbian/queer just before PA school. She joined the Society of Hospital Medicine in 2020 and serves on SHM’s Diversity and Inclusion Special Interest Group.
How important is it to you to openly identify as a physician assistant who is a member of the LGBTQ community?
I think it’s important to show other people that I am part of the LGBTQ community and that I’ve been able to overcome obstacles and pursue this career and be successful. I can help other people and be in that role [of mentor], and show people that they can do it, too.
What challenges have you faced because of your sexual orientation in the different stages of your career, from training to practicing as a physician assistant?
When my training started, I was much closer to the time when I came out, so my confidence level was a little bit low. I was much more fearful at that point about how people would view me – if I would be thought of as inferior, or not taken as seriously, or that I wasn’t intelligent. I think over the years I’ve grown into this role and it’s helped me become more confident, because I know who I am now. And it’s not something that definitely defines me but I’m confident that I know medicine, and I know how to treat patients and that confidence has gotten much better.
So far at work, everyone’s been great, all my coworkers have been great. I’ve never once felt that my sexuality was holding anyone back from getting to know me better.
Have you heard about the experiences of other LGBTQ clinicians who may not have been as fortunate as you, especially transgender people?
There is just a lot of ignorance around LGBTQ persons and especially transgender persons, because people don’t understand it, they don’t get it. So their first inclination is to not approve of it, or be scared of it, or just automatically think that it’s wrong.
If someone’s sexuality comes across much more “obviously” than that of other people, for example, if there’s a gay man who’s a little more flamboyant, [it could be an issue for some patients]. I know there are some gay male nurses who have had patients who don’t want them serving as their nurse, because they’re “obviously” gay. Or a queer woman clinician who has more of an edgier haircut or looks a little bit more masculine; I know that there have been some patients who have said certain things to them that have been discriminating.
Have you been especially conscious of how you ‘wear’ your sexual orientation? Have you ever had to change how you’ve presented yourself, lest you have some unpleasant reaction?
I think initially, yes. I would say I’m a little more on the androgynous side with my style. When I was coming out I was trying to figure out where I was and who I was and how I wanted to be, and for the longest time I was dressing more femininely and I wasn’t as comfortable. Since then, I’ve had times where I’ve had short hair or a little bit more of a masculine haircut and wear more masculine clothes and things like that, and I feel much more comfortable doing that.
It’s kind of hard to play the part of a more masculine LGBTQ person at work when you just wear scrubs. I probably don’t portray it as much – I don’t make it as obvious as some other people, but I’ve definitely never shied away from having a conversation with anyone about it.
Health care is an intimate profession because of your close interaction with patients and others. Did being a member of the LGBTQ community factor into your decision to enter the health care field, either for or against?
There were times when I didn’t feel well or my mental health was not great because I didn’t know where I was, or hadn’t accepted myself, and I really needed someone who could help me talk through things and try to figure out what my life path was going to be. When I figured those things out with the help of other people, it was life-changing. I respected those people, and that’s what I wanted to do and how I wanted to help. I think that was part of why I got into medicine.
What progress have you seen with regard to LGBTQ health care professionals and patients over the past 5 to 10 years, including subtle changes in culture, attitude, or workplace policies?
Just being interviewed for a profile like this is a step in the right direction. Never once did I think that I would be highlighted for being an LGBTQ person, especially in the workplace.
I think that there are more companies, particularly in health care, and more hospitals that are coming out in support of their LGBTQ employees, especially during Pride month. IU Health walks every year in the Pride parade, which last year was about 3 hours long. Five years previously it was only 30 minutes long. So there are more employers getting involved and recognizing their employees as well. Companies and health care facilities are trying to be more cognizant of their LGBTQ employees and patients and trying to make them more comfortable.
What main steps toward more progress would you like to see?
There needs to be greater understanding that people who undergo discrimination actually have more negative health outcomes like heart disease, high blood pressure, and stroke. There needs to be better medical coverage in the LGBTQ community, especially for transgender persons and LGBTQ people who are trying to start families. We need better mental health access, more affordable mental health access, particularly for LGBTQ youth, and we definitely need to continue to raise awareness with hopes that we can eradicate the violence against, and killing of, black transgender persons.
How do you see the Society of Hospital Medicine’s role in this regard?
SHM has a big platform and can certainly reach a lot of people, especially hospitalists who see LGBTQ patients every day. With SHM’s help and the continued training of hospitalists who are members of the society, we can reach out to other clinicians, and to their organizations, and help teach them. SHM really has a good platform to be able to do that, and do it well.
Can you recall a specific interaction with an LGBTQ patient that left you with a potent feeling that “this is what it’s all about”?
I do remember a transgender patient who was homeless. They didn’t have insurance, they couldn’t afford their hormone treatment, and I remember they were struggling with some mental health issues and were “acting out” overnight. Some of the nurses were not using the correct pronouns. I’m more cognizant of their struggles because I’m a member of the LGBTQ community and I was able to recognize this.
I sat down and I talked with the patient for quite a while, we were able to form a bond, and I was able to get a little bit more information from them, and by the end of the night, they felt much better. And just being able to be their voice, when they weren’t able to express exactly how they were feeling, was something that made me thankful that I went into medicine, to help other LGBTQ patients.
I’ve had many LGBTQ patients in the hospital whom I’ve been able to form a bit of a bond with, just knowing that the patient could be me.
New data back use of medical cannabis for epilepsy, pain, anxiety
Two new studies offer positive news about medical cannabis, suggesting that marijuana products improve physical and cognitive symptoms, boost quality of life, and rarely produce signs of problematic use.
In one study, patients with epilepsy who used medical cannabis were nearly half as likely to have needed an emergency department visit within the last 30 days as was a control group. In the other study, 3 of 54 subjects who used medical cannabis showed signs of possible cannabis use disorder (CUD) over 12 months.
The findings show that “there is improvement in a range of outcome variables, and the adverse effects seem to be minimal, compared to what we might have hypothesized based on the bulk of the literature on the negative effects of cannabis on health outcomes,” cannabis researcher Ziva Cooper, PhD, of the University of California at Los Angeles, said in an interview. Dr. Cooper moderated a session about the studies at the virtual annual meeting of the College on Problems of Drug Dependence.
In one study, cannabis researcher Ryan Vandrey, PhD, of Johns Hopkins University, Baltimore, and colleagues compared medical cannabis users (number, 808; mean age, 38; percentage female, 63%) to a control group of people who were interested in medical cannabis (n, 468; mean age, 35; percentage female, 62%).
In both groups, 79% were White. The groups had similar levels of primary medical conditions, such as neurologic (38% and 36%, respectively, for the medical cannabis group and control group) and chronic pain (25% and 23%, respectively.)
The wide majority of those in the medical cannabis group – 58% – were cannabidiol (CBD) users, relying on a component of cannabis (marijuana) that does not make people high. Fewer than 20% used tetrahydrocannabinol (THC), which does make people high, or a combination of both CBD and THC.
Most of those in the medical cannabis group used the drug as an adjunct (39%) to other treatments or last-resort (29%) treatment instead of first line (11%) or second line (18%).
In patients with epilepsy, about 45% of controls reported a past-month ED visit, compared with about 25% of medical cannabis users. The gap in past-month hospital admissions was even wider, at about 35% for the controls and about 15% for the medical cannabis.
After an initial survey, the researchers followed subjects prospectively; some either started or stopped using medical cannabis. From baseline to follow-up, those in the medical cannabis group improved more, compared with those in the control group on a variety of measures of quality of life, anxiety, and depression.
“Folks who were in the control condition at baseline and then initiated cannabis use started to look more like the baseline cannabis users,” Dr. Vandrey said. “The folks who were cannabis users at baseline and then stopped for whatever reason started to look like the controls. And the controls [who never started using medical cannabis] stayed the same.”
As for adverse effects, two-thirds of medical cannabis users reported no problems; the highest number, 14%, reported high cost.
As for limitations, Dr. Vandrey reported missing data, a reliance on self-reports, and poor follow-up with about a third of participants agreeing to complete follow-up assessments. “We are continuing to collect data on this,” he said, “and we’re hoping we’ll be able to drill down more as we get bigger.”
The study was funded by the Realm of Caring Foundation.
In the other study, led by cannabis researcher Staci Gruber, PhD, of McLean Hospital in Belmont, Mass., and Harvard Medical School in Boston, researchers tracked 54 subjects (mean age, 49; 20 male and 34 female; 48 white) for up to 2 years after they began medical cannabis use. Most had pain (36) or anxiety/PTSD (31), and all had to have abstained from recreational cannabis use for at least 1 year.
At follow-ups, the users reported improved mood and anxiety via various measures, and they saw some improvement in quality of life. “We did not see worsening cognitive performance,” Dr. Gruber said. “In fact,
Research has suggested that as many as 30% of recreational cannabis users develop cannabis use disorder (CUD), Dr. Gruber said. But only 3 of the 54 patients showed signs of possible CUD at 12 months, she said, even though frequency of use jumped substantially vs. baseline.
Information about study funding was not available.
Dr. Cooper disclosed relationships with FSD Pharma, Beckley Canopy Therapeutics, and Insys Therapeutics. Dr. Vandrey disclosed work with Zynerba Pharmaceuticals, Canopy Health Innovations, and FSD Pharma. Dr. Gruber reported no disclosures.
Two new studies offer positive news about medical cannabis, suggesting that marijuana products improve physical and cognitive symptoms, boost quality of life, and rarely produce signs of problematic use.
In one study, patients with epilepsy who used medical cannabis were nearly half as likely to have needed an emergency department visit within the last 30 days as was a control group. In the other study, 3 of 54 subjects who used medical cannabis showed signs of possible cannabis use disorder (CUD) over 12 months.
The findings show that “there is improvement in a range of outcome variables, and the adverse effects seem to be minimal, compared to what we might have hypothesized based on the bulk of the literature on the negative effects of cannabis on health outcomes,” cannabis researcher Ziva Cooper, PhD, of the University of California at Los Angeles, said in an interview. Dr. Cooper moderated a session about the studies at the virtual annual meeting of the College on Problems of Drug Dependence.
In one study, cannabis researcher Ryan Vandrey, PhD, of Johns Hopkins University, Baltimore, and colleagues compared medical cannabis users (number, 808; mean age, 38; percentage female, 63%) to a control group of people who were interested in medical cannabis (n, 468; mean age, 35; percentage female, 62%).
In both groups, 79% were White. The groups had similar levels of primary medical conditions, such as neurologic (38% and 36%, respectively, for the medical cannabis group and control group) and chronic pain (25% and 23%, respectively.)
The wide majority of those in the medical cannabis group – 58% – were cannabidiol (CBD) users, relying on a component of cannabis (marijuana) that does not make people high. Fewer than 20% used tetrahydrocannabinol (THC), which does make people high, or a combination of both CBD and THC.
Most of those in the medical cannabis group used the drug as an adjunct (39%) to other treatments or last-resort (29%) treatment instead of first line (11%) or second line (18%).
In patients with epilepsy, about 45% of controls reported a past-month ED visit, compared with about 25% of medical cannabis users. The gap in past-month hospital admissions was even wider, at about 35% for the controls and about 15% for the medical cannabis.
After an initial survey, the researchers followed subjects prospectively; some either started or stopped using medical cannabis. From baseline to follow-up, those in the medical cannabis group improved more, compared with those in the control group on a variety of measures of quality of life, anxiety, and depression.
“Folks who were in the control condition at baseline and then initiated cannabis use started to look more like the baseline cannabis users,” Dr. Vandrey said. “The folks who were cannabis users at baseline and then stopped for whatever reason started to look like the controls. And the controls [who never started using medical cannabis] stayed the same.”
As for adverse effects, two-thirds of medical cannabis users reported no problems; the highest number, 14%, reported high cost.
As for limitations, Dr. Vandrey reported missing data, a reliance on self-reports, and poor follow-up with about a third of participants agreeing to complete follow-up assessments. “We are continuing to collect data on this,” he said, “and we’re hoping we’ll be able to drill down more as we get bigger.”
The study was funded by the Realm of Caring Foundation.
In the other study, led by cannabis researcher Staci Gruber, PhD, of McLean Hospital in Belmont, Mass., and Harvard Medical School in Boston, researchers tracked 54 subjects (mean age, 49; 20 male and 34 female; 48 white) for up to 2 years after they began medical cannabis use. Most had pain (36) or anxiety/PTSD (31), and all had to have abstained from recreational cannabis use for at least 1 year.
At follow-ups, the users reported improved mood and anxiety via various measures, and they saw some improvement in quality of life. “We did not see worsening cognitive performance,” Dr. Gruber said. “In fact,
Research has suggested that as many as 30% of recreational cannabis users develop cannabis use disorder (CUD), Dr. Gruber said. But only 3 of the 54 patients showed signs of possible CUD at 12 months, she said, even though frequency of use jumped substantially vs. baseline.
Information about study funding was not available.
Dr. Cooper disclosed relationships with FSD Pharma, Beckley Canopy Therapeutics, and Insys Therapeutics. Dr. Vandrey disclosed work with Zynerba Pharmaceuticals, Canopy Health Innovations, and FSD Pharma. Dr. Gruber reported no disclosures.
Two new studies offer positive news about medical cannabis, suggesting that marijuana products improve physical and cognitive symptoms, boost quality of life, and rarely produce signs of problematic use.
In one study, patients with epilepsy who used medical cannabis were nearly half as likely to have needed an emergency department visit within the last 30 days as was a control group. In the other study, 3 of 54 subjects who used medical cannabis showed signs of possible cannabis use disorder (CUD) over 12 months.
The findings show that “there is improvement in a range of outcome variables, and the adverse effects seem to be minimal, compared to what we might have hypothesized based on the bulk of the literature on the negative effects of cannabis on health outcomes,” cannabis researcher Ziva Cooper, PhD, of the University of California at Los Angeles, said in an interview. Dr. Cooper moderated a session about the studies at the virtual annual meeting of the College on Problems of Drug Dependence.
In one study, cannabis researcher Ryan Vandrey, PhD, of Johns Hopkins University, Baltimore, and colleagues compared medical cannabis users (number, 808; mean age, 38; percentage female, 63%) to a control group of people who were interested in medical cannabis (n, 468; mean age, 35; percentage female, 62%).
In both groups, 79% were White. The groups had similar levels of primary medical conditions, such as neurologic (38% and 36%, respectively, for the medical cannabis group and control group) and chronic pain (25% and 23%, respectively.)
The wide majority of those in the medical cannabis group – 58% – were cannabidiol (CBD) users, relying on a component of cannabis (marijuana) that does not make people high. Fewer than 20% used tetrahydrocannabinol (THC), which does make people high, or a combination of both CBD and THC.
Most of those in the medical cannabis group used the drug as an adjunct (39%) to other treatments or last-resort (29%) treatment instead of first line (11%) or second line (18%).
In patients with epilepsy, about 45% of controls reported a past-month ED visit, compared with about 25% of medical cannabis users. The gap in past-month hospital admissions was even wider, at about 35% for the controls and about 15% for the medical cannabis.
After an initial survey, the researchers followed subjects prospectively; some either started or stopped using medical cannabis. From baseline to follow-up, those in the medical cannabis group improved more, compared with those in the control group on a variety of measures of quality of life, anxiety, and depression.
“Folks who were in the control condition at baseline and then initiated cannabis use started to look more like the baseline cannabis users,” Dr. Vandrey said. “The folks who were cannabis users at baseline and then stopped for whatever reason started to look like the controls. And the controls [who never started using medical cannabis] stayed the same.”
As for adverse effects, two-thirds of medical cannabis users reported no problems; the highest number, 14%, reported high cost.
As for limitations, Dr. Vandrey reported missing data, a reliance on self-reports, and poor follow-up with about a third of participants agreeing to complete follow-up assessments. “We are continuing to collect data on this,” he said, “and we’re hoping we’ll be able to drill down more as we get bigger.”
The study was funded by the Realm of Caring Foundation.
In the other study, led by cannabis researcher Staci Gruber, PhD, of McLean Hospital in Belmont, Mass., and Harvard Medical School in Boston, researchers tracked 54 subjects (mean age, 49; 20 male and 34 female; 48 white) for up to 2 years after they began medical cannabis use. Most had pain (36) or anxiety/PTSD (31), and all had to have abstained from recreational cannabis use for at least 1 year.
At follow-ups, the users reported improved mood and anxiety via various measures, and they saw some improvement in quality of life. “We did not see worsening cognitive performance,” Dr. Gruber said. “In fact,
Research has suggested that as many as 30% of recreational cannabis users develop cannabis use disorder (CUD), Dr. Gruber said. But only 3 of the 54 patients showed signs of possible CUD at 12 months, she said, even though frequency of use jumped substantially vs. baseline.
Information about study funding was not available.
Dr. Cooper disclosed relationships with FSD Pharma, Beckley Canopy Therapeutics, and Insys Therapeutics. Dr. Vandrey disclosed work with Zynerba Pharmaceuticals, Canopy Health Innovations, and FSD Pharma. Dr. Gruber reported no disclosures.
FROM CPDD 2020
App links overdosing people to nearby volunteers with naloxone
Naloxone can reverse opioid overdoses, but time is crucial and its effectiveness wanes if medics can’t arrive right away. Now, a new app links overdose victims or their companions to trained volunteers nearby who may be able to administer the drug much faster.
Over a 1-year period, about half of 112 participants in a Philadelphia trial said they’d responded to overdoses via the app, and about half used it to report overdoses, according to a study released at the virtual annual meeting of the College on Problems of Drug Dependence.
“Thanks to the app, there may have been a life saved about twice a month that otherwise wouldn’t have been,” said public health researcher and study coauthor Stephen Lankenau, PhD, of Drexel University, Philadelphia, in an interview.
Philadelphia has the largest opioid overdose rate of any large city, Dr. Lankenau said, and people who overdose are often reluctant to call 911. “Police are often alerted when it’s determined that it’s a drug-related call. They’re concerned that police could show up and someone will get arrested.”
However, the app, called UnityPhilly, doesn’t remove professional medics from the picture. It’s designed to be a supplement to the existing first-response system – “it’s not meant to replace 911” – and allow a faster response to overdoses when minutes matter, Dr. Lankenau said.
“If someone is adamantly opposed to calling 911,” he said, “this may not be the best intervention for them.”
Here’s how the app works: Participants who overdose themselves or witness an overdose can send out an alert to nearby app users. When an alert goes out, the app also attempts to dial 911, although the participant can bypass this.
Nearby responders can reply by pressing “En route” and then go to the address of the overdose with a provided supply of naloxone (Narcan). The amateur responders, many of whom are or were opioid users themselves, are trained in how to administer the drug.
The study authors recruited 112 participants from the Philadelphia neighborhood of Kensington and tracked them from 2019 to 2020. About half (n = 57) reported using opioids within the past 30 days, and those participants had an average age of 42 years, were 54% men, and were 74% non-Hispanic white. Only 19% were employed, and 42% had been recently homeless. Nearly 80% had overdosed before, and all had witnessed overdoses.
The other participants (n = 55), defined as “community members,” had less experience with opioids (44% had misused them before), although 91% had witnessed overdoses. Their average age was 42 years, 56% were women, 53% were employed, and 16% had been recently homeless.
The percentages who reported being en route to an overdose was 47% (opioid users) and 46% (community members).
“The idea of people being trained as community responders has been around for quite a while, and there are hundreds of programs across the country. People are willing to carry naloxone and respond if they see an overdose in front of them,” Dr. Lankenau said. “Here, you have people becoming civilian responders to events they wouldn’t otherwise know about. This creates a community of individuals who can help out immediately and augment the work that emergency responders do.”
Opioid users who download the app may be drawn to the idea of responders who are nonjudgmental and supportive, compared with professional medics. “The system has not done well by people with substance abuse disorders,” said addiction medicine specialist Sukhpreet Klaire, MD, of the British Columbia Center on Substance Use in Vancouver. “In terms of overdose reversal, you may prefer that someone else [other than a medic] give you Narcan and support you through this experience. When it’s over after you’re reversed, you have a sudden onset of withdrawal symptoms. You feel terrible, and you don’t want to be sitting in an ambulance. You want to be in a supportive environment.”
As for adverse effects, there was concern that opioid users might take more risks with an app safety net in place. However, no one reported more risky behavior in interviews, Dr. Lankenau said.
The 3-year program costs $215,000, he said, and the next step is to get funding for a Philadelphia citywide trial.
The study was funded by the National Institute of Drug Abuse. Dr. Lankenau reported no relevant disclosures. Dr. Klaire disclosed participating in a research fellowship and a research in addiction medical scholars program, both funded by NIDA.
Naloxone can reverse opioid overdoses, but time is crucial and its effectiveness wanes if medics can’t arrive right away. Now, a new app links overdose victims or their companions to trained volunteers nearby who may be able to administer the drug much faster.
Over a 1-year period, about half of 112 participants in a Philadelphia trial said they’d responded to overdoses via the app, and about half used it to report overdoses, according to a study released at the virtual annual meeting of the College on Problems of Drug Dependence.
“Thanks to the app, there may have been a life saved about twice a month that otherwise wouldn’t have been,” said public health researcher and study coauthor Stephen Lankenau, PhD, of Drexel University, Philadelphia, in an interview.
Philadelphia has the largest opioid overdose rate of any large city, Dr. Lankenau said, and people who overdose are often reluctant to call 911. “Police are often alerted when it’s determined that it’s a drug-related call. They’re concerned that police could show up and someone will get arrested.”
However, the app, called UnityPhilly, doesn’t remove professional medics from the picture. It’s designed to be a supplement to the existing first-response system – “it’s not meant to replace 911” – and allow a faster response to overdoses when minutes matter, Dr. Lankenau said.
“If someone is adamantly opposed to calling 911,” he said, “this may not be the best intervention for them.”
Here’s how the app works: Participants who overdose themselves or witness an overdose can send out an alert to nearby app users. When an alert goes out, the app also attempts to dial 911, although the participant can bypass this.
Nearby responders can reply by pressing “En route” and then go to the address of the overdose with a provided supply of naloxone (Narcan). The amateur responders, many of whom are or were opioid users themselves, are trained in how to administer the drug.
The study authors recruited 112 participants from the Philadelphia neighborhood of Kensington and tracked them from 2019 to 2020. About half (n = 57) reported using opioids within the past 30 days, and those participants had an average age of 42 years, were 54% men, and were 74% non-Hispanic white. Only 19% were employed, and 42% had been recently homeless. Nearly 80% had overdosed before, and all had witnessed overdoses.
The other participants (n = 55), defined as “community members,” had less experience with opioids (44% had misused them before), although 91% had witnessed overdoses. Their average age was 42 years, 56% were women, 53% were employed, and 16% had been recently homeless.
The percentages who reported being en route to an overdose was 47% (opioid users) and 46% (community members).
“The idea of people being trained as community responders has been around for quite a while, and there are hundreds of programs across the country. People are willing to carry naloxone and respond if they see an overdose in front of them,” Dr. Lankenau said. “Here, you have people becoming civilian responders to events they wouldn’t otherwise know about. This creates a community of individuals who can help out immediately and augment the work that emergency responders do.”
Opioid users who download the app may be drawn to the idea of responders who are nonjudgmental and supportive, compared with professional medics. “The system has not done well by people with substance abuse disorders,” said addiction medicine specialist Sukhpreet Klaire, MD, of the British Columbia Center on Substance Use in Vancouver. “In terms of overdose reversal, you may prefer that someone else [other than a medic] give you Narcan and support you through this experience. When it’s over after you’re reversed, you have a sudden onset of withdrawal symptoms. You feel terrible, and you don’t want to be sitting in an ambulance. You want to be in a supportive environment.”
As for adverse effects, there was concern that opioid users might take more risks with an app safety net in place. However, no one reported more risky behavior in interviews, Dr. Lankenau said.
The 3-year program costs $215,000, he said, and the next step is to get funding for a Philadelphia citywide trial.
The study was funded by the National Institute of Drug Abuse. Dr. Lankenau reported no relevant disclosures. Dr. Klaire disclosed participating in a research fellowship and a research in addiction medical scholars program, both funded by NIDA.
Naloxone can reverse opioid overdoses, but time is crucial and its effectiveness wanes if medics can’t arrive right away. Now, a new app links overdose victims or their companions to trained volunteers nearby who may be able to administer the drug much faster.
Over a 1-year period, about half of 112 participants in a Philadelphia trial said they’d responded to overdoses via the app, and about half used it to report overdoses, according to a study released at the virtual annual meeting of the College on Problems of Drug Dependence.
“Thanks to the app, there may have been a life saved about twice a month that otherwise wouldn’t have been,” said public health researcher and study coauthor Stephen Lankenau, PhD, of Drexel University, Philadelphia, in an interview.
Philadelphia has the largest opioid overdose rate of any large city, Dr. Lankenau said, and people who overdose are often reluctant to call 911. “Police are often alerted when it’s determined that it’s a drug-related call. They’re concerned that police could show up and someone will get arrested.”
However, the app, called UnityPhilly, doesn’t remove professional medics from the picture. It’s designed to be a supplement to the existing first-response system – “it’s not meant to replace 911” – and allow a faster response to overdoses when minutes matter, Dr. Lankenau said.
“If someone is adamantly opposed to calling 911,” he said, “this may not be the best intervention for them.”
Here’s how the app works: Participants who overdose themselves or witness an overdose can send out an alert to nearby app users. When an alert goes out, the app also attempts to dial 911, although the participant can bypass this.
Nearby responders can reply by pressing “En route” and then go to the address of the overdose with a provided supply of naloxone (Narcan). The amateur responders, many of whom are or were opioid users themselves, are trained in how to administer the drug.
The study authors recruited 112 participants from the Philadelphia neighborhood of Kensington and tracked them from 2019 to 2020. About half (n = 57) reported using opioids within the past 30 days, and those participants had an average age of 42 years, were 54% men, and were 74% non-Hispanic white. Only 19% were employed, and 42% had been recently homeless. Nearly 80% had overdosed before, and all had witnessed overdoses.
The other participants (n = 55), defined as “community members,” had less experience with opioids (44% had misused them before), although 91% had witnessed overdoses. Their average age was 42 years, 56% were women, 53% were employed, and 16% had been recently homeless.
The percentages who reported being en route to an overdose was 47% (opioid users) and 46% (community members).
“The idea of people being trained as community responders has been around for quite a while, and there are hundreds of programs across the country. People are willing to carry naloxone and respond if they see an overdose in front of them,” Dr. Lankenau said. “Here, you have people becoming civilian responders to events they wouldn’t otherwise know about. This creates a community of individuals who can help out immediately and augment the work that emergency responders do.”
Opioid users who download the app may be drawn to the idea of responders who are nonjudgmental and supportive, compared with professional medics. “The system has not done well by people with substance abuse disorders,” said addiction medicine specialist Sukhpreet Klaire, MD, of the British Columbia Center on Substance Use in Vancouver. “In terms of overdose reversal, you may prefer that someone else [other than a medic] give you Narcan and support you through this experience. When it’s over after you’re reversed, you have a sudden onset of withdrawal symptoms. You feel terrible, and you don’t want to be sitting in an ambulance. You want to be in a supportive environment.”
As for adverse effects, there was concern that opioid users might take more risks with an app safety net in place. However, no one reported more risky behavior in interviews, Dr. Lankenau said.
The 3-year program costs $215,000, he said, and the next step is to get funding for a Philadelphia citywide trial.
The study was funded by the National Institute of Drug Abuse. Dr. Lankenau reported no relevant disclosures. Dr. Klaire disclosed participating in a research fellowship and a research in addiction medical scholars program, both funded by NIDA.
FROM CPDD 2020
Declines in infant mortality tempered by disparities
Age-adjusted infant mortality dropped 11% from 2000 to 2017 in the United States, but the even larger decline for infants born to black women still left a death rate more than twice as high as those of white or Hispanic infants, according to a new analysis from the National Center for Health Statistics.
while the crude mortality rate fell 16% from 6.89 to 5.79, reported Anne K. Driscoll, PhD, and Danielle M. Ely, PhD, of the NCHS.
Over that same time period, age-adjusted infant mortality for births to black women went from 13.59 per 1,000 to 11.19, a drop of 18%. By comparison, age-adjusted mortality declined 7% from 5.59 per 1,000 for infants born to Hispanic women to 5.21 in 2017, they said in a National Vital Statistics Report.
Changes in maternal age distribution had an important effect on infant mortality. Women aged under 25 years, who have higher mortality rates, were less likely to give birth in 2017 than in 2000, and women aged 30-39 years, who have the lowest rates, made up a larger share of births in 2017, they pointed out.
It was, however, changes in age-specific mortality rates (ASMRs) that had the largest influence on the overall drop in the crude mortality rate, accounting for about two-thirds of the overall decline, the NCHS researchers said, noting that the effect varied by race and Hispanic origin.
Births to non-Hispanic white women mirrored the national situation: Approximately two-thirds (68.7%) of the decrease in infant mortality came from changes in ASMRs and one-third (31.3%) from changes in maternal age distribution. Among non-Hispanic black women, the distribution was 95.2% ASMRs and 4.8% age distribution, Dr. Driscoll and Dr. Ely reported based on data from the National Vital Statistics System.
The disparity between the two trends went even further for infants born to Hispanic women. Changes in ASMRs were responsible for 133.7% of the overall change in crude mortality versus –33.7% for changes in maternal age distribution. “If no changes occurred in the ASMRs, the changes in the maternal age distribution would have resulted in a higher mortality rate in 2017,” they explained.
The declines in the ASMRs may be related to incremental improved survival of preterm and low-birthweight infants in certain groups. “While little or no progress has been made to lower [these] two key risk factors for poor birth outcomes, progress has been made in lowering the mortality rates of at-risk infants across maternal age and race and Hispanic origin, resulting in lower ASMRs for all age groups,” the investigators suggested.
It also is possible that “changes in other factors, such as maternal education and cigarette smoking during pregnancy, may have indirectly resulted in declining ASMRs for all age groups over time,” they added.
SOURCE: Driscoll AK, Ely DM. National Vital Statistics Reports. 2020;69(5):1-18.
Age-adjusted infant mortality dropped 11% from 2000 to 2017 in the United States, but the even larger decline for infants born to black women still left a death rate more than twice as high as those of white or Hispanic infants, according to a new analysis from the National Center for Health Statistics.
while the crude mortality rate fell 16% from 6.89 to 5.79, reported Anne K. Driscoll, PhD, and Danielle M. Ely, PhD, of the NCHS.
Over that same time period, age-adjusted infant mortality for births to black women went from 13.59 per 1,000 to 11.19, a drop of 18%. By comparison, age-adjusted mortality declined 7% from 5.59 per 1,000 for infants born to Hispanic women to 5.21 in 2017, they said in a National Vital Statistics Report.
Changes in maternal age distribution had an important effect on infant mortality. Women aged under 25 years, who have higher mortality rates, were less likely to give birth in 2017 than in 2000, and women aged 30-39 years, who have the lowest rates, made up a larger share of births in 2017, they pointed out.
It was, however, changes in age-specific mortality rates (ASMRs) that had the largest influence on the overall drop in the crude mortality rate, accounting for about two-thirds of the overall decline, the NCHS researchers said, noting that the effect varied by race and Hispanic origin.
Births to non-Hispanic white women mirrored the national situation: Approximately two-thirds (68.7%) of the decrease in infant mortality came from changes in ASMRs and one-third (31.3%) from changes in maternal age distribution. Among non-Hispanic black women, the distribution was 95.2% ASMRs and 4.8% age distribution, Dr. Driscoll and Dr. Ely reported based on data from the National Vital Statistics System.
The disparity between the two trends went even further for infants born to Hispanic women. Changes in ASMRs were responsible for 133.7% of the overall change in crude mortality versus –33.7% for changes in maternal age distribution. “If no changes occurred in the ASMRs, the changes in the maternal age distribution would have resulted in a higher mortality rate in 2017,” they explained.
The declines in the ASMRs may be related to incremental improved survival of preterm and low-birthweight infants in certain groups. “While little or no progress has been made to lower [these] two key risk factors for poor birth outcomes, progress has been made in lowering the mortality rates of at-risk infants across maternal age and race and Hispanic origin, resulting in lower ASMRs for all age groups,” the investigators suggested.
It also is possible that “changes in other factors, such as maternal education and cigarette smoking during pregnancy, may have indirectly resulted in declining ASMRs for all age groups over time,” they added.
SOURCE: Driscoll AK, Ely DM. National Vital Statistics Reports. 2020;69(5):1-18.
Age-adjusted infant mortality dropped 11% from 2000 to 2017 in the United States, but the even larger decline for infants born to black women still left a death rate more than twice as high as those of white or Hispanic infants, according to a new analysis from the National Center for Health Statistics.
while the crude mortality rate fell 16% from 6.89 to 5.79, reported Anne K. Driscoll, PhD, and Danielle M. Ely, PhD, of the NCHS.
Over that same time period, age-adjusted infant mortality for births to black women went from 13.59 per 1,000 to 11.19, a drop of 18%. By comparison, age-adjusted mortality declined 7% from 5.59 per 1,000 for infants born to Hispanic women to 5.21 in 2017, they said in a National Vital Statistics Report.
Changes in maternal age distribution had an important effect on infant mortality. Women aged under 25 years, who have higher mortality rates, were less likely to give birth in 2017 than in 2000, and women aged 30-39 years, who have the lowest rates, made up a larger share of births in 2017, they pointed out.
It was, however, changes in age-specific mortality rates (ASMRs) that had the largest influence on the overall drop in the crude mortality rate, accounting for about two-thirds of the overall decline, the NCHS researchers said, noting that the effect varied by race and Hispanic origin.
Births to non-Hispanic white women mirrored the national situation: Approximately two-thirds (68.7%) of the decrease in infant mortality came from changes in ASMRs and one-third (31.3%) from changes in maternal age distribution. Among non-Hispanic black women, the distribution was 95.2% ASMRs and 4.8% age distribution, Dr. Driscoll and Dr. Ely reported based on data from the National Vital Statistics System.
The disparity between the two trends went even further for infants born to Hispanic women. Changes in ASMRs were responsible for 133.7% of the overall change in crude mortality versus –33.7% for changes in maternal age distribution. “If no changes occurred in the ASMRs, the changes in the maternal age distribution would have resulted in a higher mortality rate in 2017,” they explained.
The declines in the ASMRs may be related to incremental improved survival of preterm and low-birthweight infants in certain groups. “While little or no progress has been made to lower [these] two key risk factors for poor birth outcomes, progress has been made in lowering the mortality rates of at-risk infants across maternal age and race and Hispanic origin, resulting in lower ASMRs for all age groups,” the investigators suggested.
It also is possible that “changes in other factors, such as maternal education and cigarette smoking during pregnancy, may have indirectly resulted in declining ASMRs for all age groups over time,” they added.
SOURCE: Driscoll AK, Ely DM. National Vital Statistics Reports. 2020;69(5):1-18.
Take-home test strips allow drug users to detect fentanyl
Illicit drug users seem to overwhelmingly appreciate being able to use take-home test strips to detect the extremely common presence of dangerous fentanyl in opioids and other drugs, a new study finds. More than 95% said they’d use the inexpensive strips again.
said study lead author addiction medicine specialist Sukhpreet Klaire, MD, of the British Columbia Center on Substance Use in Vancouver, in an interview.
Dr. Klaire presented the study findings at the virtual annual meeting of the College on Problems of Drug Dependence.
Researchers in Vancouver distributed take-home fentanyl test strip kits at 10 sites that allow users to test their illicit drugs. The 218 participants performed 1,680 tests, mainly (73%) for opioids, over 3 months in 2019. Of the participants, 61% were male, and the average age was 36 (interquartile range, 29-47). About 30% described themselves as indigenous Canadians (First Nations).
About 90% of the opioid samples tested at home were positive for fentanyl, about the same level as samples tested at clinics. Fentanyl is very potent and linked to the huge rise in overdose deaths in the United States.
Fentanyl test strips aren’t new. According to the Harm Reduction Coalition, they originally were developed to detect fentanyl in urine samples but were jury-rigged in Vancouver to work on samples of illicit drugs. “We literally just repurposed it,” Dr. Klaire said. “It’s the same strip.”
Users test their drugs by dissolving a small sample in water. Then then dip the test strip, which provides readings similar to those in a pregnancy test. If a sample turns up positive for fentanyl, Dr. Klaire said, users may discard the drug or “be more careful with it.”
When asked what they would do if a sample turned up positive, 27% said they’d make a “positive change,” such as using less or using more slowly (n = 45) or making sure that someone else is present in case of an overdose (n = 26). But most, 71%, reported no change in behavior.
Previously, researchers in Rhode Island and North Carolina also found that some users adopted safer behaviors – such as throwing out their drugs or using less often – after testing their drugs with the strips.
The strips cost about 75 cents, Dr. Klaire said.
Harm-reduction strategies are controversial, and fentanyl test strips aren’t any exemption. “The entire approach is based on the premise that a drug user poised to use a drug is making rational choices, is weighing pros and cons, and is thinking completely logically about his or her drug use. Based on my clinical experience, I know this could not be further from the truth,” wrote Elinore F. McCance-Katz, MD, PhD, assistant secretary for Mental Health and Substance Use with the Department of Health & Human Services, in a 2018 blog post.
But Dr. Klaire said the patients in the new study are highly dependent on opioids. “The drug supply is heavily contaminated [with fentanyl],” he said, “but even when people know it’s contaminated, they still need to go ahead and use it.”
In an interview, epidemiologist Brandon Marshall, PhD, of Brown University, Providence, R.I., who has conducted fentanyl test strip research, called the study results “compelling.”
“The researchers found that the fentanyl test strips had a very high level of acceptability – over 95% said they would use the strips again – which is remarkably similar to what we found in our work here in Rhode Island,” he said. “Taken together, these studies show that take-home test strips are a feasible, acceptable, and effective strategy for people who use drugs to reduce their risk of fentanyl overdose.”
He added that “fentanyl test strips help people make more informed decisions about their drug use and reducing their risk of overdose.”
However, he said, “one of important limitations of the strips is that they do not detect all contaminants that put persons at risk of overdose. Just because a test result is negative does not mean that the drug is 100% safe.”
Kimberly Sue, MD, PhD, medical director of the National Harm Reduction Coalition, said in an interview that the research is “important,” but noted that many drug users already have been using fentanyl test strips on their own. “We should be focusing on investing in variety of other interventions that could keep more people safe against nonfatal and fatal opioid overdoses, including structural interventions such as safe supply, housing and community with appropriate supports, low barrier access to medication for opioid use disorder, and safe consumption spaces,” she said.
No study funding was reported. Dr. Klaire disclosed participating in a research fellowship and a research in addiction medical scholars program, both funded by the National Institute of Drug Abuse. Dr. Sue reported no relevant disclosures. Dr. Marshall reported that he has collaborated frequently with one of the coauthors of the Vancouver study.
Illicit drug users seem to overwhelmingly appreciate being able to use take-home test strips to detect the extremely common presence of dangerous fentanyl in opioids and other drugs, a new study finds. More than 95% said they’d use the inexpensive strips again.
said study lead author addiction medicine specialist Sukhpreet Klaire, MD, of the British Columbia Center on Substance Use in Vancouver, in an interview.
Dr. Klaire presented the study findings at the virtual annual meeting of the College on Problems of Drug Dependence.
Researchers in Vancouver distributed take-home fentanyl test strip kits at 10 sites that allow users to test their illicit drugs. The 218 participants performed 1,680 tests, mainly (73%) for opioids, over 3 months in 2019. Of the participants, 61% were male, and the average age was 36 (interquartile range, 29-47). About 30% described themselves as indigenous Canadians (First Nations).
About 90% of the opioid samples tested at home were positive for fentanyl, about the same level as samples tested at clinics. Fentanyl is very potent and linked to the huge rise in overdose deaths in the United States.
Fentanyl test strips aren’t new. According to the Harm Reduction Coalition, they originally were developed to detect fentanyl in urine samples but were jury-rigged in Vancouver to work on samples of illicit drugs. “We literally just repurposed it,” Dr. Klaire said. “It’s the same strip.”
Users test their drugs by dissolving a small sample in water. Then then dip the test strip, which provides readings similar to those in a pregnancy test. If a sample turns up positive for fentanyl, Dr. Klaire said, users may discard the drug or “be more careful with it.”
When asked what they would do if a sample turned up positive, 27% said they’d make a “positive change,” such as using less or using more slowly (n = 45) or making sure that someone else is present in case of an overdose (n = 26). But most, 71%, reported no change in behavior.
Previously, researchers in Rhode Island and North Carolina also found that some users adopted safer behaviors – such as throwing out their drugs or using less often – after testing their drugs with the strips.
The strips cost about 75 cents, Dr. Klaire said.
Harm-reduction strategies are controversial, and fentanyl test strips aren’t any exemption. “The entire approach is based on the premise that a drug user poised to use a drug is making rational choices, is weighing pros and cons, and is thinking completely logically about his or her drug use. Based on my clinical experience, I know this could not be further from the truth,” wrote Elinore F. McCance-Katz, MD, PhD, assistant secretary for Mental Health and Substance Use with the Department of Health & Human Services, in a 2018 blog post.
But Dr. Klaire said the patients in the new study are highly dependent on opioids. “The drug supply is heavily contaminated [with fentanyl],” he said, “but even when people know it’s contaminated, they still need to go ahead and use it.”
In an interview, epidemiologist Brandon Marshall, PhD, of Brown University, Providence, R.I., who has conducted fentanyl test strip research, called the study results “compelling.”
“The researchers found that the fentanyl test strips had a very high level of acceptability – over 95% said they would use the strips again – which is remarkably similar to what we found in our work here in Rhode Island,” he said. “Taken together, these studies show that take-home test strips are a feasible, acceptable, and effective strategy for people who use drugs to reduce their risk of fentanyl overdose.”
He added that “fentanyl test strips help people make more informed decisions about their drug use and reducing their risk of overdose.”
However, he said, “one of important limitations of the strips is that they do not detect all contaminants that put persons at risk of overdose. Just because a test result is negative does not mean that the drug is 100% safe.”
Kimberly Sue, MD, PhD, medical director of the National Harm Reduction Coalition, said in an interview that the research is “important,” but noted that many drug users already have been using fentanyl test strips on their own. “We should be focusing on investing in variety of other interventions that could keep more people safe against nonfatal and fatal opioid overdoses, including structural interventions such as safe supply, housing and community with appropriate supports, low barrier access to medication for opioid use disorder, and safe consumption spaces,” she said.
No study funding was reported. Dr. Klaire disclosed participating in a research fellowship and a research in addiction medical scholars program, both funded by the National Institute of Drug Abuse. Dr. Sue reported no relevant disclosures. Dr. Marshall reported that he has collaborated frequently with one of the coauthors of the Vancouver study.
Illicit drug users seem to overwhelmingly appreciate being able to use take-home test strips to detect the extremely common presence of dangerous fentanyl in opioids and other drugs, a new study finds. More than 95% said they’d use the inexpensive strips again.
said study lead author addiction medicine specialist Sukhpreet Klaire, MD, of the British Columbia Center on Substance Use in Vancouver, in an interview.
Dr. Klaire presented the study findings at the virtual annual meeting of the College on Problems of Drug Dependence.
Researchers in Vancouver distributed take-home fentanyl test strip kits at 10 sites that allow users to test their illicit drugs. The 218 participants performed 1,680 tests, mainly (73%) for opioids, over 3 months in 2019. Of the participants, 61% were male, and the average age was 36 (interquartile range, 29-47). About 30% described themselves as indigenous Canadians (First Nations).
About 90% of the opioid samples tested at home were positive for fentanyl, about the same level as samples tested at clinics. Fentanyl is very potent and linked to the huge rise in overdose deaths in the United States.
Fentanyl test strips aren’t new. According to the Harm Reduction Coalition, they originally were developed to detect fentanyl in urine samples but were jury-rigged in Vancouver to work on samples of illicit drugs. “We literally just repurposed it,” Dr. Klaire said. “It’s the same strip.”
Users test their drugs by dissolving a small sample in water. Then then dip the test strip, which provides readings similar to those in a pregnancy test. If a sample turns up positive for fentanyl, Dr. Klaire said, users may discard the drug or “be more careful with it.”
When asked what they would do if a sample turned up positive, 27% said they’d make a “positive change,” such as using less or using more slowly (n = 45) or making sure that someone else is present in case of an overdose (n = 26). But most, 71%, reported no change in behavior.
Previously, researchers in Rhode Island and North Carolina also found that some users adopted safer behaviors – such as throwing out their drugs or using less often – after testing their drugs with the strips.
The strips cost about 75 cents, Dr. Klaire said.
Harm-reduction strategies are controversial, and fentanyl test strips aren’t any exemption. “The entire approach is based on the premise that a drug user poised to use a drug is making rational choices, is weighing pros and cons, and is thinking completely logically about his or her drug use. Based on my clinical experience, I know this could not be further from the truth,” wrote Elinore F. McCance-Katz, MD, PhD, assistant secretary for Mental Health and Substance Use with the Department of Health & Human Services, in a 2018 blog post.
But Dr. Klaire said the patients in the new study are highly dependent on opioids. “The drug supply is heavily contaminated [with fentanyl],” he said, “but even when people know it’s contaminated, they still need to go ahead and use it.”
In an interview, epidemiologist Brandon Marshall, PhD, of Brown University, Providence, R.I., who has conducted fentanyl test strip research, called the study results “compelling.”
“The researchers found that the fentanyl test strips had a very high level of acceptability – over 95% said they would use the strips again – which is remarkably similar to what we found in our work here in Rhode Island,” he said. “Taken together, these studies show that take-home test strips are a feasible, acceptable, and effective strategy for people who use drugs to reduce their risk of fentanyl overdose.”
He added that “fentanyl test strips help people make more informed decisions about their drug use and reducing their risk of overdose.”
However, he said, “one of important limitations of the strips is that they do not detect all contaminants that put persons at risk of overdose. Just because a test result is negative does not mean that the drug is 100% safe.”
Kimberly Sue, MD, PhD, medical director of the National Harm Reduction Coalition, said in an interview that the research is “important,” but noted that many drug users already have been using fentanyl test strips on their own. “We should be focusing on investing in variety of other interventions that could keep more people safe against nonfatal and fatal opioid overdoses, including structural interventions such as safe supply, housing and community with appropriate supports, low barrier access to medication for opioid use disorder, and safe consumption spaces,” she said.
No study funding was reported. Dr. Klaire disclosed participating in a research fellowship and a research in addiction medical scholars program, both funded by the National Institute of Drug Abuse. Dr. Sue reported no relevant disclosures. Dr. Marshall reported that he has collaborated frequently with one of the coauthors of the Vancouver study.
FROM CPDD 2020
Cushing’s and COVID-19: Nontraditional symptoms keys to assessment, treatments
Do not rely on more traditional signs and symptoms of COVID-19 like fever and dyspnea when assessing patients with Cushing’s syndrome for the novel coronavirus, Rosario Pivonello, MD, PhD, and colleagues urged.
Physicians evaluating patients with Cushing’s syndrome for COVID-19 “should be suspicious of any change in health status of their patients with Cushing’s syndrome, rather than relying on fever and [dyspnea] as typical features,” Dr. Pivonello, an endocrinologist with the University of Naples (Italy) Federico II, and colleagues wrote in a commentary published in The Lancet Diabetes & Endocrinology.
COVID-19 symptoms are a unique concern among patients with Cushing’s syndrome because many of the cardiometabolic and immune impairments that place someone at higher risk of more severe disease or mortality for the novel coronavirus – such as obesity, hypertension, diabetes, and immunodeficiency syndromes – are also shared with Cushing’s syndrome.
Increased cardiovascular risk factors and susceptibility to severe infection are “two leading causes of death” for patients with Cushing’s syndrome, Dr. Pivonello and colleagues noted.
The immunocompromised state of patients with Cushing’s syndrome may make detection of COVID-19 infection difficult, the authors say. For example, fever is a common symptom of patients with COVID-19, but in patients with active Cushing’s syndrome, “low-grade chronic inflammation and the poor immune response might limit febrile response in the early phase of infection,” Dr. Pivonello and colleagues wrote.
In other cases, because Cushing’s syndrome and COVID-19 have overlapping symptoms, it may be difficult to attribute a particular symptom to either disease. Dyspnea is a common symptom of COVID-19, but may present in Cushing’s syndrome because of “cardiac insufficiency or weakness of respiratory muscles,” the authors wrote. Instead, physicians should look to other COVID-19 symptoms, such as cough, dysgeusia, anosmia, and diarrhea, for signs of the disease.
Patients with Cushing’s syndrome may also be predisposed to a more severe course of COVID-19 because of the prevalence of obesity, hypertension, or diabetes in these patients, which have been identified as comorbidities that increase the likelihood of severe COVID-19 and progression to acute respiratory distress syndrome (ARDS). “However, a key element in the development of ARDS during COVID-19 is the exaggerated cellular response induced by the cytokine increase, leading to massive alveolar–capillary wall damage and a decline in gas exchange,” Dr. Pivonello and colleagues wrote. “Because patients with Cushing’s syndrome might not mount a normal cytokine response, these patients might [paradoxically] be less prone to develop severe ARDS with COVID-19.”
As both Cushing’s syndrome and COVID-19 are associated with hypercoagulability, the authors “strongly advise” using low-molecular-weight heparin in hospitalized patients with active Cushing’s syndrome who develop COVID-19. In both diseases, there is also a risk of longer duration of viral infections and opportunistic infections such as atypical bacterial and invasive fungal infections. For this reason, the authors also recommended patients with Cushing’s syndrome who have COVID-19 be placed on prolonged antiviral and broad-spectrum antibiotic treatment as a prophylactic measure.
During the pandemic, avoiding surgery for Cushing’s syndrome should be considered to reduce the likelihood of acquiring COVID-19 in a hospital setting, the authors wrote. Medical therapy can be temporarily used where appropriate, such as using ketoconazole, metyrapone, osilodrostat, and etomidate to lower cortisol levels. They acknowledge that some cases of malignant Cushing’s syndrome may require “expeditious definitive diagnosis and proper surgical resolution.”
After remission, while infection risk should be significantly lowered, other comorbidities like obesity, hypertension, diabetes, and thromboembolic diathesis may remain. “Because these are features associated with an increased death risk in patients with COVID-19, patients with Cushing’s syndrome in remission should be considered a high-risk population and consequently adopt adequate self-protection strategies to [minimize] contagion risk,” the authors wrote.
Dr. Pivonello reported relationships with Novartis, Strongbridge Biopharma, HRA Pharma, Ipsen, Shire, and Pfizer, Corcept Therapeutics, IBSA Farmaceutici, Ferring, and Italfarmaco in the form of receiving grants and/or personal fees. One coauthor reported receiving grants and/or nonfinancial support from Takeda, Ipsen, Shire, Pfizer, and Corcept Therapeutics. One coauthor reported receiving grants and personal fees from Novartis and Strongbridge, and grants from Millendo Therapeutics. Another coauthor reported receiving grants and/or personal fees from Novartis, Ipsen, Shire, Pfizer, Italfarmaco, Lilly, Merck, and Novo Nordisk. The other authors reported no relevant conflicts of interest.
SOURCE: Pivonello R et al. Lancet Diabetes Endocrinol. 2020 Jun 9. doi: 10.1016/S2213-8587(20)30215-1.
Do not rely on more traditional signs and symptoms of COVID-19 like fever and dyspnea when assessing patients with Cushing’s syndrome for the novel coronavirus, Rosario Pivonello, MD, PhD, and colleagues urged.
Physicians evaluating patients with Cushing’s syndrome for COVID-19 “should be suspicious of any change in health status of their patients with Cushing’s syndrome, rather than relying on fever and [dyspnea] as typical features,” Dr. Pivonello, an endocrinologist with the University of Naples (Italy) Federico II, and colleagues wrote in a commentary published in The Lancet Diabetes & Endocrinology.
COVID-19 symptoms are a unique concern among patients with Cushing’s syndrome because many of the cardiometabolic and immune impairments that place someone at higher risk of more severe disease or mortality for the novel coronavirus – such as obesity, hypertension, diabetes, and immunodeficiency syndromes – are also shared with Cushing’s syndrome.
Increased cardiovascular risk factors and susceptibility to severe infection are “two leading causes of death” for patients with Cushing’s syndrome, Dr. Pivonello and colleagues noted.
The immunocompromised state of patients with Cushing’s syndrome may make detection of COVID-19 infection difficult, the authors say. For example, fever is a common symptom of patients with COVID-19, but in patients with active Cushing’s syndrome, “low-grade chronic inflammation and the poor immune response might limit febrile response in the early phase of infection,” Dr. Pivonello and colleagues wrote.
In other cases, because Cushing’s syndrome and COVID-19 have overlapping symptoms, it may be difficult to attribute a particular symptom to either disease. Dyspnea is a common symptom of COVID-19, but may present in Cushing’s syndrome because of “cardiac insufficiency or weakness of respiratory muscles,” the authors wrote. Instead, physicians should look to other COVID-19 symptoms, such as cough, dysgeusia, anosmia, and diarrhea, for signs of the disease.
Patients with Cushing’s syndrome may also be predisposed to a more severe course of COVID-19 because of the prevalence of obesity, hypertension, or diabetes in these patients, which have been identified as comorbidities that increase the likelihood of severe COVID-19 and progression to acute respiratory distress syndrome (ARDS). “However, a key element in the development of ARDS during COVID-19 is the exaggerated cellular response induced by the cytokine increase, leading to massive alveolar–capillary wall damage and a decline in gas exchange,” Dr. Pivonello and colleagues wrote. “Because patients with Cushing’s syndrome might not mount a normal cytokine response, these patients might [paradoxically] be less prone to develop severe ARDS with COVID-19.”
As both Cushing’s syndrome and COVID-19 are associated with hypercoagulability, the authors “strongly advise” using low-molecular-weight heparin in hospitalized patients with active Cushing’s syndrome who develop COVID-19. In both diseases, there is also a risk of longer duration of viral infections and opportunistic infections such as atypical bacterial and invasive fungal infections. For this reason, the authors also recommended patients with Cushing’s syndrome who have COVID-19 be placed on prolonged antiviral and broad-spectrum antibiotic treatment as a prophylactic measure.
During the pandemic, avoiding surgery for Cushing’s syndrome should be considered to reduce the likelihood of acquiring COVID-19 in a hospital setting, the authors wrote. Medical therapy can be temporarily used where appropriate, such as using ketoconazole, metyrapone, osilodrostat, and etomidate to lower cortisol levels. They acknowledge that some cases of malignant Cushing’s syndrome may require “expeditious definitive diagnosis and proper surgical resolution.”
After remission, while infection risk should be significantly lowered, other comorbidities like obesity, hypertension, diabetes, and thromboembolic diathesis may remain. “Because these are features associated with an increased death risk in patients with COVID-19, patients with Cushing’s syndrome in remission should be considered a high-risk population and consequently adopt adequate self-protection strategies to [minimize] contagion risk,” the authors wrote.
Dr. Pivonello reported relationships with Novartis, Strongbridge Biopharma, HRA Pharma, Ipsen, Shire, and Pfizer, Corcept Therapeutics, IBSA Farmaceutici, Ferring, and Italfarmaco in the form of receiving grants and/or personal fees. One coauthor reported receiving grants and/or nonfinancial support from Takeda, Ipsen, Shire, Pfizer, and Corcept Therapeutics. One coauthor reported receiving grants and personal fees from Novartis and Strongbridge, and grants from Millendo Therapeutics. Another coauthor reported receiving grants and/or personal fees from Novartis, Ipsen, Shire, Pfizer, Italfarmaco, Lilly, Merck, and Novo Nordisk. The other authors reported no relevant conflicts of interest.
SOURCE: Pivonello R et al. Lancet Diabetes Endocrinol. 2020 Jun 9. doi: 10.1016/S2213-8587(20)30215-1.
Do not rely on more traditional signs and symptoms of COVID-19 like fever and dyspnea when assessing patients with Cushing’s syndrome for the novel coronavirus, Rosario Pivonello, MD, PhD, and colleagues urged.
Physicians evaluating patients with Cushing’s syndrome for COVID-19 “should be suspicious of any change in health status of their patients with Cushing’s syndrome, rather than relying on fever and [dyspnea] as typical features,” Dr. Pivonello, an endocrinologist with the University of Naples (Italy) Federico II, and colleagues wrote in a commentary published in The Lancet Diabetes & Endocrinology.
COVID-19 symptoms are a unique concern among patients with Cushing’s syndrome because many of the cardiometabolic and immune impairments that place someone at higher risk of more severe disease or mortality for the novel coronavirus – such as obesity, hypertension, diabetes, and immunodeficiency syndromes – are also shared with Cushing’s syndrome.
Increased cardiovascular risk factors and susceptibility to severe infection are “two leading causes of death” for patients with Cushing’s syndrome, Dr. Pivonello and colleagues noted.
The immunocompromised state of patients with Cushing’s syndrome may make detection of COVID-19 infection difficult, the authors say. For example, fever is a common symptom of patients with COVID-19, but in patients with active Cushing’s syndrome, “low-grade chronic inflammation and the poor immune response might limit febrile response in the early phase of infection,” Dr. Pivonello and colleagues wrote.
In other cases, because Cushing’s syndrome and COVID-19 have overlapping symptoms, it may be difficult to attribute a particular symptom to either disease. Dyspnea is a common symptom of COVID-19, but may present in Cushing’s syndrome because of “cardiac insufficiency or weakness of respiratory muscles,” the authors wrote. Instead, physicians should look to other COVID-19 symptoms, such as cough, dysgeusia, anosmia, and diarrhea, for signs of the disease.
Patients with Cushing’s syndrome may also be predisposed to a more severe course of COVID-19 because of the prevalence of obesity, hypertension, or diabetes in these patients, which have been identified as comorbidities that increase the likelihood of severe COVID-19 and progression to acute respiratory distress syndrome (ARDS). “However, a key element in the development of ARDS during COVID-19 is the exaggerated cellular response induced by the cytokine increase, leading to massive alveolar–capillary wall damage and a decline in gas exchange,” Dr. Pivonello and colleagues wrote. “Because patients with Cushing’s syndrome might not mount a normal cytokine response, these patients might [paradoxically] be less prone to develop severe ARDS with COVID-19.”
As both Cushing’s syndrome and COVID-19 are associated with hypercoagulability, the authors “strongly advise” using low-molecular-weight heparin in hospitalized patients with active Cushing’s syndrome who develop COVID-19. In both diseases, there is also a risk of longer duration of viral infections and opportunistic infections such as atypical bacterial and invasive fungal infections. For this reason, the authors also recommended patients with Cushing’s syndrome who have COVID-19 be placed on prolonged antiviral and broad-spectrum antibiotic treatment as a prophylactic measure.
During the pandemic, avoiding surgery for Cushing’s syndrome should be considered to reduce the likelihood of acquiring COVID-19 in a hospital setting, the authors wrote. Medical therapy can be temporarily used where appropriate, such as using ketoconazole, metyrapone, osilodrostat, and etomidate to lower cortisol levels. They acknowledge that some cases of malignant Cushing’s syndrome may require “expeditious definitive diagnosis and proper surgical resolution.”
After remission, while infection risk should be significantly lowered, other comorbidities like obesity, hypertension, diabetes, and thromboembolic diathesis may remain. “Because these are features associated with an increased death risk in patients with COVID-19, patients with Cushing’s syndrome in remission should be considered a high-risk population and consequently adopt adequate self-protection strategies to [minimize] contagion risk,” the authors wrote.
Dr. Pivonello reported relationships with Novartis, Strongbridge Biopharma, HRA Pharma, Ipsen, Shire, and Pfizer, Corcept Therapeutics, IBSA Farmaceutici, Ferring, and Italfarmaco in the form of receiving grants and/or personal fees. One coauthor reported receiving grants and/or nonfinancial support from Takeda, Ipsen, Shire, Pfizer, and Corcept Therapeutics. One coauthor reported receiving grants and personal fees from Novartis and Strongbridge, and grants from Millendo Therapeutics. Another coauthor reported receiving grants and/or personal fees from Novartis, Ipsen, Shire, Pfizer, Italfarmaco, Lilly, Merck, and Novo Nordisk. The other authors reported no relevant conflicts of interest.
SOURCE: Pivonello R et al. Lancet Diabetes Endocrinol. 2020 Jun 9. doi: 10.1016/S2213-8587(20)30215-1.
FROM THE LANCET DIABETES & ENDOCRINOLOGY
Community programs improve psychosis outcomes
Community-based services that tap into local environments not only reduce the duration of untreated psychosis (DUP) but also provide improved long-term outcomes for patients with first-episode psychosis (FEP), results of two new studies show.
In the first study, investigators led by Vinod Srihari, MD, director of specialized treatment early in psychosis at Yale University, New Haven, Conn., developed a program to reduce DUP to complement their first-episode service (FES).
Through a combination of mass media and social media campaigns, outreach events with local professionals, and rapid triage, the team was able to nearly halve the time from diagnosis to initiation of antipsychotic treatment.
In the second study, a team led by Delbert G. Robinson, MD, of Hofstra University, Hempstead, N.Y., conducted a 5-year follow-up of RAISE-ETP, the first U.S. randomized trial to compare a 2-year comprehensive early intervention service (EIS) with usual care.
These trial results showed that, among more than 400 FEP patients, the EIS significantly improved both symptoms and quality of life and reduced inpatient days in comparison with standard care.
The research was scheduled to be presented at the Congress of the Schizophrenia International Research Society (SIRS) 2020, but the meeting was canceled because of the coronavirus pandemic.
Norwegian model
Dr. Srihari and colleagues note that a specialized treatment early in psychosis (STEP), which delivers a specialty team–based FES, was established at their institution in 2006.
However, in a bid to reduce DUP, in 2015 they launched MindMap, a 4-year early-detection campaign based on the Scandinavian TIPS Early Detection in Psychosis Study.
Dr. Srihari said in an interview that they visited the team that developed the TIPS program in Norway “to try to understand what elements of their approach had resulted in a successful reduction of DUP.”
He pointed out that the health care system in Norway has “more reliable pathways to care, with an ability to route people in more predictable ways from primary care to secondary care, and so on.”
In the United States, “there’s no expectation that people will go through a primary care provider,” he said. He noted that patients “make their way to specialty care in many different ways.”
Dr. Srihari said, “The other change we realized we’d have to make was that, since TIPS had been completed many years back, the media environment had changed substantially.
“At the time that TIPS was done, there was no such thing as social media, whereas when we began to think about designing our campaign, we thought social media would be a very efficient and also cost-effective way to target young people.”
MindMap, which covered a 10-town catchment area that has a population of 400,000, targeted both demand- and supply-side aspects of DUP. The former focused on delays in identifying illness and help-seeking, and the latter concentrated on referral and treatment access delays.
The researchers used a combination of mass media and social media messaging, professional detailing, and the rapid triage of referrals.
The media campaign included Facebook, Twitter, and other social media platforms that allowed the team to “target individuals in a somewhat more fine-grained way than mass media allows,” Dr. Srihari said. They focused on individuals in a particular age range and geographic location.
The professional detailing encompassed mental health agencies, emergency departments, and inpatient units, as well as colleges, college counseling centers, high schools, and police departments. The team hosted meetings, “often at local restaurants, where we provided a meal and provided some general education about what our mission was,” said Dr. Srihari. The researchers followed up these meetings with more in-person visits.
“The third arm was finding ways to basically eliminate any kind of a waiting time at our front door, such as ensuring that transportation issues were circumvented, in addition to cutting through any ambivalence they might have about finally making the leap to come to the center.”
More rapid treatment
Over the course of the baseline year and the 4 years of the MindMap program, almost 1,500 individuals were assessed. Of these, approximately 200 were eligible, and almost all were enrolled.
The researchers measured DUP at two time points from the onset of psychosis – the initiation of antipsychotic treatment (DUP1) and the initiation of FES care. Across the study period, they found that DUP1 fell significantly between the pre- and postprogram assessments, from 329 days to 185 days (P = .03). By contrast, there was no change over the same period for the Prevention and Recovery in Early Psychosis FES program in Boston, which served as a comparator.
There was also a cumulative effect on DUP, with each year of the 4-year program associated with a 46-day reduction in DUP1. However, the significant reduction was restricted to the third quintile of DUP1 and was not found in the other quintiles of DUP1 or for DUP2, despite all measures showing a consistent trend for reduction over time.
Dr. Srihari acknowledges that the team was “disappointed” that DUP2 did not fall significantly in their study. He suggested, “It might take longer for agencies to change their workloads and refer patients to STEP, which is what ended up resulting in the DUP2 not dropping as quickly.”
To see whether there was indeed a time lag in changes to practice, the team conducted an analysis in which they cut out the first year from the results and analyzed only the last 3 years. Then “we do see a decline in DUP2,” he said.
The study’s full results are currently being prepared for publication, and the investigators are considering relaunching the initiative.
“The question we are having now is how to resource the campaign without the research funds and which parts of it we think we can launch sustainably so we can continue the reduction of DUP,” Dr. Srihari said.
Plans may include developing partnerships with local businesses to help fund the media costs and working with the state government to build a learning health care network, which would make it easier for mental health agencies to consult with the team on problematic cases.
“We’re trying to reduce DUP referrals on the supply side by providing this kind of learning health collaborative ... that we also think might be fiscally a more sustainable way to do this vs. what we did in MindMap,” which would be “very expensive” to implement on a statewide basis, Dr. Srihari added.
Long-term benefit
In the second study, Dr. Robinson and colleagues highlight that EISs have been implemented worldwide for FEP patients and have been associated with improved outcomes.
However, these services typically provide care for a limited period, and cross-sectional follow-up studies have identified few advantages in comparison with standard care.
To provide a more robust longitudinal assessment of the ongoing effects of an EIS, the team conducted a 5-year follow-up of the first U.S.-based, multicenter, randomized clinical trial comparing an EIS, NAVIGATE, with usual clinical care in FEP.
RAISE-ETP was conducted at 34 sites across the United States. Seventeen sites provided NAVIGATE to 223 individuals with FEP, and the remaining 17 sites provided usual care to 181 patients.
NAVIGATE, which continued for 2 years, consisted of treatments and services delivered by a coordinated team of providers. Those services included the following:
- Education on schizophrenia and its treatment for patients and their families.
- Symptom and relapse prevention medication, using a computerized decision support system.
- Strategies for illness management building personal resilience.
- A supported employment/education model.
Patients were assessed every 6 months for up to 60 months via a video link using the Heinrichs-Carpenter Quality of Life Scale (QLS) and the Positive and Negative Syndrome Scale (PANSS).
The average age of the participants was 23 years; 78% of those who received NAVIGATE and 66% of those who received usual care were male. The opportunity for each participant to engage in NAVIGATE treatment lasted an average of 33.8 months. The longest was 44.4 months.
Over 5 years, NAVIGATE was associated with a significant improvement over usual care in QLS scores by an average of 13.14 units (P < .001). PANSS scores improved by an average of 7.73 units (P < .002). QLS scores were not affected either by the length of opportunity to participate in NAVIGATE or by DUP, the team reports. Patients who received NAVIGATE also had an average of 2.5 fewer inpatient days, compared with those on usual care (P = .02).
The investigators note that the study “provides compelling evidence of a substantial long-term benefit for FEP treatment with the NAVIGATE EIS, compared with standard care.”
A ‘great message’
Commenting on the findings in an interview, Ragy R. Girgis, MD, associate professor of clinical psychiatry at Columbia University, New York, and the New York State Psychiatric Institute, said
Dr. Girgis, who was not involved in either study, said that the research is “a great message.” He noted that it is “really important for people to know and it’s really important that we’re still doing research in those areas.”
However, he noted that psychosocial interventions such as these “sometimes take a lot of work.” Dr. Girgis said that it is “so easy to just give people a medication” but that approach has its own disadvantages, including adverse effects and sometimes a lack of efficacy.
“Psychosocial interventions, on the other hand, are very well tolerated by people. They are very effective, but they may require a lot more manpower, and in some ways they can also be more expensive.
“So this is a dialectic that we oftentimes have to deal with when we figure out the right balance between psychosocial vs. medication types of treatments,” he said.
STEP has received research funding from the National Institutes of Health and the Patrick and Catherine Weldon Donaghue Medical Research Foundation. RAISE-ETP was funded by the National Institute of Mental Health as part of the Recovery After an Initial Schizophrenia Episode (RAISE) Project. Dr. Gopal is an employee of Janssen Research & Development, and owns stock/equity in Johnson & Johnson. Dr. Girgis has received research support from Genentech, BioAdvantex, Allegran/Forest, and Otsuka, and royalties from Wipf and Stock and Routledge/Taylor and Francis.
A version of this article originally appeared on Medscape.com.
Community-based services that tap into local environments not only reduce the duration of untreated psychosis (DUP) but also provide improved long-term outcomes for patients with first-episode psychosis (FEP), results of two new studies show.
In the first study, investigators led by Vinod Srihari, MD, director of specialized treatment early in psychosis at Yale University, New Haven, Conn., developed a program to reduce DUP to complement their first-episode service (FES).
Through a combination of mass media and social media campaigns, outreach events with local professionals, and rapid triage, the team was able to nearly halve the time from diagnosis to initiation of antipsychotic treatment.
In the second study, a team led by Delbert G. Robinson, MD, of Hofstra University, Hempstead, N.Y., conducted a 5-year follow-up of RAISE-ETP, the first U.S. randomized trial to compare a 2-year comprehensive early intervention service (EIS) with usual care.
These trial results showed that, among more than 400 FEP patients, the EIS significantly improved both symptoms and quality of life and reduced inpatient days in comparison with standard care.
The research was scheduled to be presented at the Congress of the Schizophrenia International Research Society (SIRS) 2020, but the meeting was canceled because of the coronavirus pandemic.
Norwegian model
Dr. Srihari and colleagues note that a specialized treatment early in psychosis (STEP), which delivers a specialty team–based FES, was established at their institution in 2006.
However, in a bid to reduce DUP, in 2015 they launched MindMap, a 4-year early-detection campaign based on the Scandinavian TIPS Early Detection in Psychosis Study.
Dr. Srihari said in an interview that they visited the team that developed the TIPS program in Norway “to try to understand what elements of their approach had resulted in a successful reduction of DUP.”
He pointed out that the health care system in Norway has “more reliable pathways to care, with an ability to route people in more predictable ways from primary care to secondary care, and so on.”
In the United States, “there’s no expectation that people will go through a primary care provider,” he said. He noted that patients “make their way to specialty care in many different ways.”
Dr. Srihari said, “The other change we realized we’d have to make was that, since TIPS had been completed many years back, the media environment had changed substantially.
“At the time that TIPS was done, there was no such thing as social media, whereas when we began to think about designing our campaign, we thought social media would be a very efficient and also cost-effective way to target young people.”
MindMap, which covered a 10-town catchment area that has a population of 400,000, targeted both demand- and supply-side aspects of DUP. The former focused on delays in identifying illness and help-seeking, and the latter concentrated on referral and treatment access delays.
The researchers used a combination of mass media and social media messaging, professional detailing, and the rapid triage of referrals.
The media campaign included Facebook, Twitter, and other social media platforms that allowed the team to “target individuals in a somewhat more fine-grained way than mass media allows,” Dr. Srihari said. They focused on individuals in a particular age range and geographic location.
The professional detailing encompassed mental health agencies, emergency departments, and inpatient units, as well as colleges, college counseling centers, high schools, and police departments. The team hosted meetings, “often at local restaurants, where we provided a meal and provided some general education about what our mission was,” said Dr. Srihari. The researchers followed up these meetings with more in-person visits.
“The third arm was finding ways to basically eliminate any kind of a waiting time at our front door, such as ensuring that transportation issues were circumvented, in addition to cutting through any ambivalence they might have about finally making the leap to come to the center.”
More rapid treatment
Over the course of the baseline year and the 4 years of the MindMap program, almost 1,500 individuals were assessed. Of these, approximately 200 were eligible, and almost all were enrolled.
The researchers measured DUP at two time points from the onset of psychosis – the initiation of antipsychotic treatment (DUP1) and the initiation of FES care. Across the study period, they found that DUP1 fell significantly between the pre- and postprogram assessments, from 329 days to 185 days (P = .03). By contrast, there was no change over the same period for the Prevention and Recovery in Early Psychosis FES program in Boston, which served as a comparator.
There was also a cumulative effect on DUP, with each year of the 4-year program associated with a 46-day reduction in DUP1. However, the significant reduction was restricted to the third quintile of DUP1 and was not found in the other quintiles of DUP1 or for DUP2, despite all measures showing a consistent trend for reduction over time.
Dr. Srihari acknowledges that the team was “disappointed” that DUP2 did not fall significantly in their study. He suggested, “It might take longer for agencies to change their workloads and refer patients to STEP, which is what ended up resulting in the DUP2 not dropping as quickly.”
To see whether there was indeed a time lag in changes to practice, the team conducted an analysis in which they cut out the first year from the results and analyzed only the last 3 years. Then “we do see a decline in DUP2,” he said.
The study’s full results are currently being prepared for publication, and the investigators are considering relaunching the initiative.
“The question we are having now is how to resource the campaign without the research funds and which parts of it we think we can launch sustainably so we can continue the reduction of DUP,” Dr. Srihari said.
Plans may include developing partnerships with local businesses to help fund the media costs and working with the state government to build a learning health care network, which would make it easier for mental health agencies to consult with the team on problematic cases.
“We’re trying to reduce DUP referrals on the supply side by providing this kind of learning health collaborative ... that we also think might be fiscally a more sustainable way to do this vs. what we did in MindMap,” which would be “very expensive” to implement on a statewide basis, Dr. Srihari added.
Long-term benefit
In the second study, Dr. Robinson and colleagues highlight that EISs have been implemented worldwide for FEP patients and have been associated with improved outcomes.
However, these services typically provide care for a limited period, and cross-sectional follow-up studies have identified few advantages in comparison with standard care.
To provide a more robust longitudinal assessment of the ongoing effects of an EIS, the team conducted a 5-year follow-up of the first U.S.-based, multicenter, randomized clinical trial comparing an EIS, NAVIGATE, with usual clinical care in FEP.
RAISE-ETP was conducted at 34 sites across the United States. Seventeen sites provided NAVIGATE to 223 individuals with FEP, and the remaining 17 sites provided usual care to 181 patients.
NAVIGATE, which continued for 2 years, consisted of treatments and services delivered by a coordinated team of providers. Those services included the following:
- Education on schizophrenia and its treatment for patients and their families.
- Symptom and relapse prevention medication, using a computerized decision support system.
- Strategies for illness management building personal resilience.
- A supported employment/education model.
Patients were assessed every 6 months for up to 60 months via a video link using the Heinrichs-Carpenter Quality of Life Scale (QLS) and the Positive and Negative Syndrome Scale (PANSS).
The average age of the participants was 23 years; 78% of those who received NAVIGATE and 66% of those who received usual care were male. The opportunity for each participant to engage in NAVIGATE treatment lasted an average of 33.8 months. The longest was 44.4 months.
Over 5 years, NAVIGATE was associated with a significant improvement over usual care in QLS scores by an average of 13.14 units (P < .001). PANSS scores improved by an average of 7.73 units (P < .002). QLS scores were not affected either by the length of opportunity to participate in NAVIGATE or by DUP, the team reports. Patients who received NAVIGATE also had an average of 2.5 fewer inpatient days, compared with those on usual care (P = .02).
The investigators note that the study “provides compelling evidence of a substantial long-term benefit for FEP treatment with the NAVIGATE EIS, compared with standard care.”
A ‘great message’
Commenting on the findings in an interview, Ragy R. Girgis, MD, associate professor of clinical psychiatry at Columbia University, New York, and the New York State Psychiatric Institute, said
Dr. Girgis, who was not involved in either study, said that the research is “a great message.” He noted that it is “really important for people to know and it’s really important that we’re still doing research in those areas.”
However, he noted that psychosocial interventions such as these “sometimes take a lot of work.” Dr. Girgis said that it is “so easy to just give people a medication” but that approach has its own disadvantages, including adverse effects and sometimes a lack of efficacy.
“Psychosocial interventions, on the other hand, are very well tolerated by people. They are very effective, but they may require a lot more manpower, and in some ways they can also be more expensive.
“So this is a dialectic that we oftentimes have to deal with when we figure out the right balance between psychosocial vs. medication types of treatments,” he said.
STEP has received research funding from the National Institutes of Health and the Patrick and Catherine Weldon Donaghue Medical Research Foundation. RAISE-ETP was funded by the National Institute of Mental Health as part of the Recovery After an Initial Schizophrenia Episode (RAISE) Project. Dr. Gopal is an employee of Janssen Research & Development, and owns stock/equity in Johnson & Johnson. Dr. Girgis has received research support from Genentech, BioAdvantex, Allegran/Forest, and Otsuka, and royalties from Wipf and Stock and Routledge/Taylor and Francis.
A version of this article originally appeared on Medscape.com.
Community-based services that tap into local environments not only reduce the duration of untreated psychosis (DUP) but also provide improved long-term outcomes for patients with first-episode psychosis (FEP), results of two new studies show.
In the first study, investigators led by Vinod Srihari, MD, director of specialized treatment early in psychosis at Yale University, New Haven, Conn., developed a program to reduce DUP to complement their first-episode service (FES).
Through a combination of mass media and social media campaigns, outreach events with local professionals, and rapid triage, the team was able to nearly halve the time from diagnosis to initiation of antipsychotic treatment.
In the second study, a team led by Delbert G. Robinson, MD, of Hofstra University, Hempstead, N.Y., conducted a 5-year follow-up of RAISE-ETP, the first U.S. randomized trial to compare a 2-year comprehensive early intervention service (EIS) with usual care.
These trial results showed that, among more than 400 FEP patients, the EIS significantly improved both symptoms and quality of life and reduced inpatient days in comparison with standard care.
The research was scheduled to be presented at the Congress of the Schizophrenia International Research Society (SIRS) 2020, but the meeting was canceled because of the coronavirus pandemic.
Norwegian model
Dr. Srihari and colleagues note that a specialized treatment early in psychosis (STEP), which delivers a specialty team–based FES, was established at their institution in 2006.
However, in a bid to reduce DUP, in 2015 they launched MindMap, a 4-year early-detection campaign based on the Scandinavian TIPS Early Detection in Psychosis Study.
Dr. Srihari said in an interview that they visited the team that developed the TIPS program in Norway “to try to understand what elements of their approach had resulted in a successful reduction of DUP.”
He pointed out that the health care system in Norway has “more reliable pathways to care, with an ability to route people in more predictable ways from primary care to secondary care, and so on.”
In the United States, “there’s no expectation that people will go through a primary care provider,” he said. He noted that patients “make their way to specialty care in many different ways.”
Dr. Srihari said, “The other change we realized we’d have to make was that, since TIPS had been completed many years back, the media environment had changed substantially.
“At the time that TIPS was done, there was no such thing as social media, whereas when we began to think about designing our campaign, we thought social media would be a very efficient and also cost-effective way to target young people.”
MindMap, which covered a 10-town catchment area that has a population of 400,000, targeted both demand- and supply-side aspects of DUP. The former focused on delays in identifying illness and help-seeking, and the latter concentrated on referral and treatment access delays.
The researchers used a combination of mass media and social media messaging, professional detailing, and the rapid triage of referrals.
The media campaign included Facebook, Twitter, and other social media platforms that allowed the team to “target individuals in a somewhat more fine-grained way than mass media allows,” Dr. Srihari said. They focused on individuals in a particular age range and geographic location.
The professional detailing encompassed mental health agencies, emergency departments, and inpatient units, as well as colleges, college counseling centers, high schools, and police departments. The team hosted meetings, “often at local restaurants, where we provided a meal and provided some general education about what our mission was,” said Dr. Srihari. The researchers followed up these meetings with more in-person visits.
“The third arm was finding ways to basically eliminate any kind of a waiting time at our front door, such as ensuring that transportation issues were circumvented, in addition to cutting through any ambivalence they might have about finally making the leap to come to the center.”
More rapid treatment
Over the course of the baseline year and the 4 years of the MindMap program, almost 1,500 individuals were assessed. Of these, approximately 200 were eligible, and almost all were enrolled.
The researchers measured DUP at two time points from the onset of psychosis – the initiation of antipsychotic treatment (DUP1) and the initiation of FES care. Across the study period, they found that DUP1 fell significantly between the pre- and postprogram assessments, from 329 days to 185 days (P = .03). By contrast, there was no change over the same period for the Prevention and Recovery in Early Psychosis FES program in Boston, which served as a comparator.
There was also a cumulative effect on DUP, with each year of the 4-year program associated with a 46-day reduction in DUP1. However, the significant reduction was restricted to the third quintile of DUP1 and was not found in the other quintiles of DUP1 or for DUP2, despite all measures showing a consistent trend for reduction over time.
Dr. Srihari acknowledges that the team was “disappointed” that DUP2 did not fall significantly in their study. He suggested, “It might take longer for agencies to change their workloads and refer patients to STEP, which is what ended up resulting in the DUP2 not dropping as quickly.”
To see whether there was indeed a time lag in changes to practice, the team conducted an analysis in which they cut out the first year from the results and analyzed only the last 3 years. Then “we do see a decline in DUP2,” he said.
The study’s full results are currently being prepared for publication, and the investigators are considering relaunching the initiative.
“The question we are having now is how to resource the campaign without the research funds and which parts of it we think we can launch sustainably so we can continue the reduction of DUP,” Dr. Srihari said.
Plans may include developing partnerships with local businesses to help fund the media costs and working with the state government to build a learning health care network, which would make it easier for mental health agencies to consult with the team on problematic cases.
“We’re trying to reduce DUP referrals on the supply side by providing this kind of learning health collaborative ... that we also think might be fiscally a more sustainable way to do this vs. what we did in MindMap,” which would be “very expensive” to implement on a statewide basis, Dr. Srihari added.
Long-term benefit
In the second study, Dr. Robinson and colleagues highlight that EISs have been implemented worldwide for FEP patients and have been associated with improved outcomes.
However, these services typically provide care for a limited period, and cross-sectional follow-up studies have identified few advantages in comparison with standard care.
To provide a more robust longitudinal assessment of the ongoing effects of an EIS, the team conducted a 5-year follow-up of the first U.S.-based, multicenter, randomized clinical trial comparing an EIS, NAVIGATE, with usual clinical care in FEP.
RAISE-ETP was conducted at 34 sites across the United States. Seventeen sites provided NAVIGATE to 223 individuals with FEP, and the remaining 17 sites provided usual care to 181 patients.
NAVIGATE, which continued for 2 years, consisted of treatments and services delivered by a coordinated team of providers. Those services included the following:
- Education on schizophrenia and its treatment for patients and their families.
- Symptom and relapse prevention medication, using a computerized decision support system.
- Strategies for illness management building personal resilience.
- A supported employment/education model.
Patients were assessed every 6 months for up to 60 months via a video link using the Heinrichs-Carpenter Quality of Life Scale (QLS) and the Positive and Negative Syndrome Scale (PANSS).
The average age of the participants was 23 years; 78% of those who received NAVIGATE and 66% of those who received usual care were male. The opportunity for each participant to engage in NAVIGATE treatment lasted an average of 33.8 months. The longest was 44.4 months.
Over 5 years, NAVIGATE was associated with a significant improvement over usual care in QLS scores by an average of 13.14 units (P < .001). PANSS scores improved by an average of 7.73 units (P < .002). QLS scores were not affected either by the length of opportunity to participate in NAVIGATE or by DUP, the team reports. Patients who received NAVIGATE also had an average of 2.5 fewer inpatient days, compared with those on usual care (P = .02).
The investigators note that the study “provides compelling evidence of a substantial long-term benefit for FEP treatment with the NAVIGATE EIS, compared with standard care.”
A ‘great message’
Commenting on the findings in an interview, Ragy R. Girgis, MD, associate professor of clinical psychiatry at Columbia University, New York, and the New York State Psychiatric Institute, said
Dr. Girgis, who was not involved in either study, said that the research is “a great message.” He noted that it is “really important for people to know and it’s really important that we’re still doing research in those areas.”
However, he noted that psychosocial interventions such as these “sometimes take a lot of work.” Dr. Girgis said that it is “so easy to just give people a medication” but that approach has its own disadvantages, including adverse effects and sometimes a lack of efficacy.
“Psychosocial interventions, on the other hand, are very well tolerated by people. They are very effective, but they may require a lot more manpower, and in some ways they can also be more expensive.
“So this is a dialectic that we oftentimes have to deal with when we figure out the right balance between psychosocial vs. medication types of treatments,” he said.
STEP has received research funding from the National Institutes of Health and the Patrick and Catherine Weldon Donaghue Medical Research Foundation. RAISE-ETP was funded by the National Institute of Mental Health as part of the Recovery After an Initial Schizophrenia Episode (RAISE) Project. Dr. Gopal is an employee of Janssen Research & Development, and owns stock/equity in Johnson & Johnson. Dr. Girgis has received research support from Genentech, BioAdvantex, Allegran/Forest, and Otsuka, and royalties from Wipf and Stock and Routledge/Taylor and Francis.
A version of this article originally appeared on Medscape.com.
Lifestyle changes may explain skin lesions in pandemic-era patients
such as lockdown conditions, which may be clarified with additional research.
Lindy P. Fox, MD, professor of dermatology at the University of California, San Francisco, who was not an author of either study, urged caution in interpreting these results. Data from the American Academy of Dermatology and a recent paper from the British Journal of Dermatology suggest a real association exists, at in least some patients. “It’s going to be true that most patients with toe lesions are PCR [polymerase chain reaction]-negative because it tends to be a late phenomenon when patients are no longer shedding virus,” Dr. Fox said in an interview.
Reports about chickenpox-like vesicles, urticaria, and other skin lesions in SARS-CoV-2 patients have circulated in the clinical literature and the media. Acute acro-ischemia has been cited as a potential sign of infection in adolescents and children.
One of the European studies, which was published in JAMA Dermatology, explored this association in 20 patients aged 1-18 years (mean age, 12.3 years), who presented with new-onset acral inflammatory lesions in their hands and feet at La Fe University Hospital, in Valencia, during the country’s peak quarantine period in April. Investigators conducted blood tests and reverse transcriptase–PCR (RT-PCR) for SARS-CoV-2, and six patients had skin biopsies.
Juncal Roca-Ginés, MD, of the department of dermatology, at the Hospital Universitario y Politécnico in La Fe, and coauthors, identified acral erythema in 6 (30%) of the cases, dactylitis in 4 (20%), purpuric maculopapules in 7 (35%), and a mixed pattern in 3 (15%). Serologic and viral testing yielded no positive results for SARS-CoV-2 or other viruses, and none of the patients exhibited COVID-19 symptoms such as fever, dry cough, sore throat, myalgia, or taste or smell disorders. In other findings, 45% of the patients had a history of vascular reactive disease of the hands, and 75% reported walking barefoot in their homes while staying at home. Only two patients reported taking medications.
In the six patients who had a biopsy, the findings were characteristic of chillblains, “confirming the clinical impression,” the authors wrote. Concluding that they could not show a relationship between acute acral skin changes and COVID-19, they noted that “other studies with improved microbiologic tests or molecular techniques aimed at demonstrating the presence of SARS-CoV-2 in the skin may help to clarify this problem.”
The other case series, which was also published in JAMA Dermatology and included 31 adults at a hospital in Brussels, who had recently developed chillblains, also looked for a connection between SARS-CoV-2 and chilblains, in April. Most of the participants were in their teens or 20s. Lesions had appeared on hands, feet, or on both extremities within 1-30 days of consultation, presenting as erythematous or purplish erythematous macules, occasionally with central vesicular or bullous lesions or necrotic areas. Patients reported pain, burning, and itching.
Skin biopsies were obtained in 22 patients and confirmed the diagnosis of chilblains; of the 15 with immunofluorescence analyses, 7 patients were found to have vasculitis of small-diameter vessels.
Of the 31 patients, 20 (64%) reported mild symptoms consistent with SARS-CoV-2, yet none of the RT-PCR or serologic test results showed signs of the virus in all 31 patients. “Because some patients had experienced chilblains for more than 15 days [under 30 days or less] at the time of inclusion, we can reasonably exclude the possibility that serologic testing was done too soon,” observed the authors. They also didn’t find eosinopenia, lymphopenia, and hyperferritinemia, which have been associated with COVID-19, they added.
Changes in lifestyle conditions during the pandemic may explain the appearance of these lesions, according to the authors of both studies, who mentioned that walking around in socks or bare feet and reduced physical activity could have indirectly led to the development of skin lesions.
It’s also possible that young people have less severe disease and a delayed reaction to the virus, Ignacio Torres-Navarro, MD, a dermatologist with La Fe University and the Spanish study’s corresponding author, said in an interview. Their feet may lack maturity in neurovascular regulation and/or the eccrine glands, which can happen in other diseases such as neutrophilic idiopathic eccrine hidradenitis. “In this context, perhaps there was an observational bias of the parents to the children when this manifestation was reported in the media. However, nothing has been demonstrated,” he said.
In an accompanying editor’s note, Claudia Hernandez, MD, of the departments of dermatology and pediatrics, Rush University Medical Center, Chicago, and Anna L. Bruckner, MD, of the departments of dermatology and pediatrics at the University of Colorado, Aurora, wrote that “it is still unclear whether a viral cytopathic process vs a viral reaction pattern or other mechanism is responsible for ‘COVID toes.’ ” Lack of confirmatory testing and reliance on indirect evidence of infection complicates this further, they noted, adding that “dermatologists must be aware of the protean cutaneous findings that are possibly associated with COVID-19, even if our understanding of their origins remains incomplete.”
In an interview, Dr. Fox, a member of the AAD’s’s COVID-19 Registry task force, offered other possible reasons for the negative antibody tests in the studies. The assay might not have been testing the correct antigen, or the timing of the test might not have been optimal. “More studies will help this become less controversial,” she said.
The authors of the two case series acknowledged potential limitations of their studies. Neither was large in scope: Both took place over a week’s time and included small cohorts. The Belgian study had no control group or long-term follow-up. Little is still known about the clinical manifestations and detection methods for SARS-CoV-2, noted the authors of the Spanish study.
The Spanish study received funding La Fe University Hospital’s department of dermatology, and the authors had no disclosures. The Belgian study received support from the Fondation Saint-Luc, which provided academic funding for its lead author, Marie Baeck, MD, PhD. Another author of this study received personal fees from the Fondation Saint-Luc and personal fees and nonfinancial support from Bioderma. The authors of the editor’s note had no disclosures.
SOURCES: Roca-Ginés J et al. JAMA Dermatol. 2020 Jun 25. doi: 10.1001/jamadermatol.2020.2340; Herman A et al. JAMA Dermatol. 2020 Jun 25. doi: 10.1001/jamadermatol.2020.2368.
such as lockdown conditions, which may be clarified with additional research.
Lindy P. Fox, MD, professor of dermatology at the University of California, San Francisco, who was not an author of either study, urged caution in interpreting these results. Data from the American Academy of Dermatology and a recent paper from the British Journal of Dermatology suggest a real association exists, at in least some patients. “It’s going to be true that most patients with toe lesions are PCR [polymerase chain reaction]-negative because it tends to be a late phenomenon when patients are no longer shedding virus,” Dr. Fox said in an interview.
Reports about chickenpox-like vesicles, urticaria, and other skin lesions in SARS-CoV-2 patients have circulated in the clinical literature and the media. Acute acro-ischemia has been cited as a potential sign of infection in adolescents and children.
One of the European studies, which was published in JAMA Dermatology, explored this association in 20 patients aged 1-18 years (mean age, 12.3 years), who presented with new-onset acral inflammatory lesions in their hands and feet at La Fe University Hospital, in Valencia, during the country’s peak quarantine period in April. Investigators conducted blood tests and reverse transcriptase–PCR (RT-PCR) for SARS-CoV-2, and six patients had skin biopsies.
Juncal Roca-Ginés, MD, of the department of dermatology, at the Hospital Universitario y Politécnico in La Fe, and coauthors, identified acral erythema in 6 (30%) of the cases, dactylitis in 4 (20%), purpuric maculopapules in 7 (35%), and a mixed pattern in 3 (15%). Serologic and viral testing yielded no positive results for SARS-CoV-2 or other viruses, and none of the patients exhibited COVID-19 symptoms such as fever, dry cough, sore throat, myalgia, or taste or smell disorders. In other findings, 45% of the patients had a history of vascular reactive disease of the hands, and 75% reported walking barefoot in their homes while staying at home. Only two patients reported taking medications.
In the six patients who had a biopsy, the findings were characteristic of chillblains, “confirming the clinical impression,” the authors wrote. Concluding that they could not show a relationship between acute acral skin changes and COVID-19, they noted that “other studies with improved microbiologic tests or molecular techniques aimed at demonstrating the presence of SARS-CoV-2 in the skin may help to clarify this problem.”
The other case series, which was also published in JAMA Dermatology and included 31 adults at a hospital in Brussels, who had recently developed chillblains, also looked for a connection between SARS-CoV-2 and chilblains, in April. Most of the participants were in their teens or 20s. Lesions had appeared on hands, feet, or on both extremities within 1-30 days of consultation, presenting as erythematous or purplish erythematous macules, occasionally with central vesicular or bullous lesions or necrotic areas. Patients reported pain, burning, and itching.
Skin biopsies were obtained in 22 patients and confirmed the diagnosis of chilblains; of the 15 with immunofluorescence analyses, 7 patients were found to have vasculitis of small-diameter vessels.
Of the 31 patients, 20 (64%) reported mild symptoms consistent with SARS-CoV-2, yet none of the RT-PCR or serologic test results showed signs of the virus in all 31 patients. “Because some patients had experienced chilblains for more than 15 days [under 30 days or less] at the time of inclusion, we can reasonably exclude the possibility that serologic testing was done too soon,” observed the authors. They also didn’t find eosinopenia, lymphopenia, and hyperferritinemia, which have been associated with COVID-19, they added.
Changes in lifestyle conditions during the pandemic may explain the appearance of these lesions, according to the authors of both studies, who mentioned that walking around in socks or bare feet and reduced physical activity could have indirectly led to the development of skin lesions.
It’s also possible that young people have less severe disease and a delayed reaction to the virus, Ignacio Torres-Navarro, MD, a dermatologist with La Fe University and the Spanish study’s corresponding author, said in an interview. Their feet may lack maturity in neurovascular regulation and/or the eccrine glands, which can happen in other diseases such as neutrophilic idiopathic eccrine hidradenitis. “In this context, perhaps there was an observational bias of the parents to the children when this manifestation was reported in the media. However, nothing has been demonstrated,” he said.
In an accompanying editor’s note, Claudia Hernandez, MD, of the departments of dermatology and pediatrics, Rush University Medical Center, Chicago, and Anna L. Bruckner, MD, of the departments of dermatology and pediatrics at the University of Colorado, Aurora, wrote that “it is still unclear whether a viral cytopathic process vs a viral reaction pattern or other mechanism is responsible for ‘COVID toes.’ ” Lack of confirmatory testing and reliance on indirect evidence of infection complicates this further, they noted, adding that “dermatologists must be aware of the protean cutaneous findings that are possibly associated with COVID-19, even if our understanding of their origins remains incomplete.”
In an interview, Dr. Fox, a member of the AAD’s’s COVID-19 Registry task force, offered other possible reasons for the negative antibody tests in the studies. The assay might not have been testing the correct antigen, or the timing of the test might not have been optimal. “More studies will help this become less controversial,” she said.
The authors of the two case series acknowledged potential limitations of their studies. Neither was large in scope: Both took place over a week’s time and included small cohorts. The Belgian study had no control group or long-term follow-up. Little is still known about the clinical manifestations and detection methods for SARS-CoV-2, noted the authors of the Spanish study.
The Spanish study received funding La Fe University Hospital’s department of dermatology, and the authors had no disclosures. The Belgian study received support from the Fondation Saint-Luc, which provided academic funding for its lead author, Marie Baeck, MD, PhD. Another author of this study received personal fees from the Fondation Saint-Luc and personal fees and nonfinancial support from Bioderma. The authors of the editor’s note had no disclosures.
SOURCES: Roca-Ginés J et al. JAMA Dermatol. 2020 Jun 25. doi: 10.1001/jamadermatol.2020.2340; Herman A et al. JAMA Dermatol. 2020 Jun 25. doi: 10.1001/jamadermatol.2020.2368.
such as lockdown conditions, which may be clarified with additional research.
Lindy P. Fox, MD, professor of dermatology at the University of California, San Francisco, who was not an author of either study, urged caution in interpreting these results. Data from the American Academy of Dermatology and a recent paper from the British Journal of Dermatology suggest a real association exists, at in least some patients. “It’s going to be true that most patients with toe lesions are PCR [polymerase chain reaction]-negative because it tends to be a late phenomenon when patients are no longer shedding virus,” Dr. Fox said in an interview.
Reports about chickenpox-like vesicles, urticaria, and other skin lesions in SARS-CoV-2 patients have circulated in the clinical literature and the media. Acute acro-ischemia has been cited as a potential sign of infection in adolescents and children.
One of the European studies, which was published in JAMA Dermatology, explored this association in 20 patients aged 1-18 years (mean age, 12.3 years), who presented with new-onset acral inflammatory lesions in their hands and feet at La Fe University Hospital, in Valencia, during the country’s peak quarantine period in April. Investigators conducted blood tests and reverse transcriptase–PCR (RT-PCR) for SARS-CoV-2, and six patients had skin biopsies.
Juncal Roca-Ginés, MD, of the department of dermatology, at the Hospital Universitario y Politécnico in La Fe, and coauthors, identified acral erythema in 6 (30%) of the cases, dactylitis in 4 (20%), purpuric maculopapules in 7 (35%), and a mixed pattern in 3 (15%). Serologic and viral testing yielded no positive results for SARS-CoV-2 or other viruses, and none of the patients exhibited COVID-19 symptoms such as fever, dry cough, sore throat, myalgia, or taste or smell disorders. In other findings, 45% of the patients had a history of vascular reactive disease of the hands, and 75% reported walking barefoot in their homes while staying at home. Only two patients reported taking medications.
In the six patients who had a biopsy, the findings were characteristic of chillblains, “confirming the clinical impression,” the authors wrote. Concluding that they could not show a relationship between acute acral skin changes and COVID-19, they noted that “other studies with improved microbiologic tests or molecular techniques aimed at demonstrating the presence of SARS-CoV-2 in the skin may help to clarify this problem.”
The other case series, which was also published in JAMA Dermatology and included 31 adults at a hospital in Brussels, who had recently developed chillblains, also looked for a connection between SARS-CoV-2 and chilblains, in April. Most of the participants were in their teens or 20s. Lesions had appeared on hands, feet, or on both extremities within 1-30 days of consultation, presenting as erythematous or purplish erythematous macules, occasionally with central vesicular or bullous lesions or necrotic areas. Patients reported pain, burning, and itching.
Skin biopsies were obtained in 22 patients and confirmed the diagnosis of chilblains; of the 15 with immunofluorescence analyses, 7 patients were found to have vasculitis of small-diameter vessels.
Of the 31 patients, 20 (64%) reported mild symptoms consistent with SARS-CoV-2, yet none of the RT-PCR or serologic test results showed signs of the virus in all 31 patients. “Because some patients had experienced chilblains for more than 15 days [under 30 days or less] at the time of inclusion, we can reasonably exclude the possibility that serologic testing was done too soon,” observed the authors. They also didn’t find eosinopenia, lymphopenia, and hyperferritinemia, which have been associated with COVID-19, they added.
Changes in lifestyle conditions during the pandemic may explain the appearance of these lesions, according to the authors of both studies, who mentioned that walking around in socks or bare feet and reduced physical activity could have indirectly led to the development of skin lesions.
It’s also possible that young people have less severe disease and a delayed reaction to the virus, Ignacio Torres-Navarro, MD, a dermatologist with La Fe University and the Spanish study’s corresponding author, said in an interview. Their feet may lack maturity in neurovascular regulation and/or the eccrine glands, which can happen in other diseases such as neutrophilic idiopathic eccrine hidradenitis. “In this context, perhaps there was an observational bias of the parents to the children when this manifestation was reported in the media. However, nothing has been demonstrated,” he said.
In an accompanying editor’s note, Claudia Hernandez, MD, of the departments of dermatology and pediatrics, Rush University Medical Center, Chicago, and Anna L. Bruckner, MD, of the departments of dermatology and pediatrics at the University of Colorado, Aurora, wrote that “it is still unclear whether a viral cytopathic process vs a viral reaction pattern or other mechanism is responsible for ‘COVID toes.’ ” Lack of confirmatory testing and reliance on indirect evidence of infection complicates this further, they noted, adding that “dermatologists must be aware of the protean cutaneous findings that are possibly associated with COVID-19, even if our understanding of their origins remains incomplete.”
In an interview, Dr. Fox, a member of the AAD’s’s COVID-19 Registry task force, offered other possible reasons for the negative antibody tests in the studies. The assay might not have been testing the correct antigen, or the timing of the test might not have been optimal. “More studies will help this become less controversial,” she said.
The authors of the two case series acknowledged potential limitations of their studies. Neither was large in scope: Both took place over a week’s time and included small cohorts. The Belgian study had no control group or long-term follow-up. Little is still known about the clinical manifestations and detection methods for SARS-CoV-2, noted the authors of the Spanish study.
The Spanish study received funding La Fe University Hospital’s department of dermatology, and the authors had no disclosures. The Belgian study received support from the Fondation Saint-Luc, which provided academic funding for its lead author, Marie Baeck, MD, PhD. Another author of this study received personal fees from the Fondation Saint-Luc and personal fees and nonfinancial support from Bioderma. The authors of the editor’s note had no disclosures.
SOURCES: Roca-Ginés J et al. JAMA Dermatol. 2020 Jun 25. doi: 10.1001/jamadermatol.2020.2340; Herman A et al. JAMA Dermatol. 2020 Jun 25. doi: 10.1001/jamadermatol.2020.2368.