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Novel insulin shows early promise for once-weekly treatment
Julio Rosenstock, MD, of the University of Texas, Dallas, presented the data from the phase 2 pivotal study of icodec on June 14 during the virtual American Diabetes Association 80th Scientific Sessions.
Insulin icodec binds to albumin to create a circulating depot with a 196-hour half-life. A once-weekly injection is designed to cover an individual’s basal insulin requirements for a full week with steady insulin release. Because of its concentrated formulation, its injection volume is equivalent to that of daily glargine U100.
“Many people with type 2 diabetes are reluctant to start on insulin therapy due to the need for daily injections. ... I’m truly excited about the potential of such innovative treatments which could reduce the number of basal insulin injections for my patients with diabetes,” Dr. Rosenstock commented in a Novo Nordisk statement.
During his presentation, he added that the product “has the potential to be a major player in the management of type 2 diabetes if eventually approved.”
Charles M. Alexander, MD, an endocrinologist and managing director of Alexander Associates, Gwynedd Valley, Pa., said that “it’s a phase 2 study. Obviously we need to see the phase 3 data, but it’s very encouraging.”
Dr. Alexander, who was global medical director for diabetes in medical affairs at Merck from 2008 to 2015, observed that “the theory is that you have better adherence to once-weekly, compared to daily [dosing], but when you actually do the studies it’s very difficult to prove that.
“I think the big advantage is that the company can develop a coformulation of [the glucagonlike peptide–1 receptor agonist] semaglutide and icodec in the same pen or vial. ... There is a convenience factor of once weekly over daily.”
In fact, he noted, Novo Nordisk is already in phase 1 trials with that product, called icosema.
“Potential to be transformational”
The phase 2, randomized, double-blind, double-dummy, parallel-group, treat-to-target trial included 247 insulin-naive patients with type 2 diabetes with hemoglobin A1c levels of 7.0%-9.5% despite taking metformin, with about half also taking a dipeptidyl peptidase–4 inhibitor.
They were randomized to weekly insulin icodec plus daily placebo (n = 125) or daily insulin glargine U100 plus weekly placebo (n = 122). All participants took seven injections per week with a vial and syringe plus one injection per week with a pen injector. Doses were titrated up or down to achieve blood glucose levels 70-108 mg/dL, with glargine dose adjustments of 2 or 4 units and icodec units of 14 or 28 units.
Participants were a mean age of 59.6 years, had a diabetes duration of 9.7 years, and 56.3% were men. Baseline A1c was 8.0% overall and fasting blood glucose was 181 mg/dL, and both were similar between the two groups.
The primary endpoint, change in A1c from baseline to week 26, dropped 1.33 percentage points with icodec and 1.15 percentage points with glargine, which was not significantly different (P = .08). Estimated mean A1c levels were 6.7% for icodec and 6.9% for glargine.
The icodec result, Dr. Rosenstock said, “is a very impressive final A1c.”
The proportions of patients achieving A1c <7% by week 26 for icodec versus glargine were 72% versus 68%, and for A1c ≤6.5% were 49% and 39%, respectively. Those differences weren’t statistically significant because of lack of power, Dr. Rosenstock observed.
Fasting plasma glucose levels were nearly identical at 26 weeks, with drops of 58 mg/dL with icodec and 54 mg/dL with glargine (P = .34).
However, there was a significant difference in favor of icodec in the 9-point self-monitoring of blood glucose profile, with a difference in mean change from baseline to week 26 of –7.9 mg/dL (P = .01).
Lower postbreakfast and postlunch glucose peaks at 90 minutes accounted for most of the difference, Dr. Rosenstock noted.
Total insulin doses during the last 2 weeks of treatment with icodec versus glargine were 229 versus 284 units/week (P = .01); those translate to approximate daily doses of 33 versus 41 units/day, respectively.
Both groups gained a small amount of weight, 1.5 kg with icodec and 1.6 kg with glargine by week 26 (P = .88).
Hypoglycemia was more common with icodec than glargine, including mild (53.6% vs. 37.7%), moderate or clinically significant (16.0% vs. 9.8%), and severe (1 [0.8%] vs. 0 participants). Corresponding event rates were 508.9 versus 210.8 per 100 patient-years (mild hypoglycemia), 52.5 versus 45.6 per 100 patient-years (moderate or clinically significant), and 1.4 versus 0 per 100 patient-years (severe) for icodec versus glargine.
The difference between the two groups in moderate or clinically significant hypoglycemia wasn’t statistically significant (P = .85), and the duration of hypoglycemia wasn’t longer with icodec, compared with glargine, despite its longer duration of action, Dr. Rosenstock emphasized.
Rates of other adverse events were similar between groups.
“Based on the robustness of these data, further evidence on the role of weekly basal insulin icodec will be pursued in a comprehensive phase 3 clinical development program,” Dr. Rosenstock explained. If those data confirm the phase 2 results, “I believe personally that a weekly basal insulin has the potential to be transformational in the management of people with type 2 diabetes needing insulin therapy.”
Dr. Rosenstock has reported receiving research support from, being on advisory boards for, and/or receiving consulting honoraria from Merck, Pfizer, Sanofi, Novo Nordisk, Eli Lilly, GlaxoSmithKline, AstraZeneca, Janssen, Genentech, Oramed, Boehringer Ingelheim, Applied Therapeutics, and Intarcia. Dr. Alexander has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Julio Rosenstock, MD, of the University of Texas, Dallas, presented the data from the phase 2 pivotal study of icodec on June 14 during the virtual American Diabetes Association 80th Scientific Sessions.
Insulin icodec binds to albumin to create a circulating depot with a 196-hour half-life. A once-weekly injection is designed to cover an individual’s basal insulin requirements for a full week with steady insulin release. Because of its concentrated formulation, its injection volume is equivalent to that of daily glargine U100.
“Many people with type 2 diabetes are reluctant to start on insulin therapy due to the need for daily injections. ... I’m truly excited about the potential of such innovative treatments which could reduce the number of basal insulin injections for my patients with diabetes,” Dr. Rosenstock commented in a Novo Nordisk statement.
During his presentation, he added that the product “has the potential to be a major player in the management of type 2 diabetes if eventually approved.”
Charles M. Alexander, MD, an endocrinologist and managing director of Alexander Associates, Gwynedd Valley, Pa., said that “it’s a phase 2 study. Obviously we need to see the phase 3 data, but it’s very encouraging.”
Dr. Alexander, who was global medical director for diabetes in medical affairs at Merck from 2008 to 2015, observed that “the theory is that you have better adherence to once-weekly, compared to daily [dosing], but when you actually do the studies it’s very difficult to prove that.
“I think the big advantage is that the company can develop a coformulation of [the glucagonlike peptide–1 receptor agonist] semaglutide and icodec in the same pen or vial. ... There is a convenience factor of once weekly over daily.”
In fact, he noted, Novo Nordisk is already in phase 1 trials with that product, called icosema.
“Potential to be transformational”
The phase 2, randomized, double-blind, double-dummy, parallel-group, treat-to-target trial included 247 insulin-naive patients with type 2 diabetes with hemoglobin A1c levels of 7.0%-9.5% despite taking metformin, with about half also taking a dipeptidyl peptidase–4 inhibitor.
They were randomized to weekly insulin icodec plus daily placebo (n = 125) or daily insulin glargine U100 plus weekly placebo (n = 122). All participants took seven injections per week with a vial and syringe plus one injection per week with a pen injector. Doses were titrated up or down to achieve blood glucose levels 70-108 mg/dL, with glargine dose adjustments of 2 or 4 units and icodec units of 14 or 28 units.
Participants were a mean age of 59.6 years, had a diabetes duration of 9.7 years, and 56.3% were men. Baseline A1c was 8.0% overall and fasting blood glucose was 181 mg/dL, and both were similar between the two groups.
The primary endpoint, change in A1c from baseline to week 26, dropped 1.33 percentage points with icodec and 1.15 percentage points with glargine, which was not significantly different (P = .08). Estimated mean A1c levels were 6.7% for icodec and 6.9% for glargine.
The icodec result, Dr. Rosenstock said, “is a very impressive final A1c.”
The proportions of patients achieving A1c <7% by week 26 for icodec versus glargine were 72% versus 68%, and for A1c ≤6.5% were 49% and 39%, respectively. Those differences weren’t statistically significant because of lack of power, Dr. Rosenstock observed.
Fasting plasma glucose levels were nearly identical at 26 weeks, with drops of 58 mg/dL with icodec and 54 mg/dL with glargine (P = .34).
However, there was a significant difference in favor of icodec in the 9-point self-monitoring of blood glucose profile, with a difference in mean change from baseline to week 26 of –7.9 mg/dL (P = .01).
Lower postbreakfast and postlunch glucose peaks at 90 minutes accounted for most of the difference, Dr. Rosenstock noted.
Total insulin doses during the last 2 weeks of treatment with icodec versus glargine were 229 versus 284 units/week (P = .01); those translate to approximate daily doses of 33 versus 41 units/day, respectively.
Both groups gained a small amount of weight, 1.5 kg with icodec and 1.6 kg with glargine by week 26 (P = .88).
Hypoglycemia was more common with icodec than glargine, including mild (53.6% vs. 37.7%), moderate or clinically significant (16.0% vs. 9.8%), and severe (1 [0.8%] vs. 0 participants). Corresponding event rates were 508.9 versus 210.8 per 100 patient-years (mild hypoglycemia), 52.5 versus 45.6 per 100 patient-years (moderate or clinically significant), and 1.4 versus 0 per 100 patient-years (severe) for icodec versus glargine.
The difference between the two groups in moderate or clinically significant hypoglycemia wasn’t statistically significant (P = .85), and the duration of hypoglycemia wasn’t longer with icodec, compared with glargine, despite its longer duration of action, Dr. Rosenstock emphasized.
Rates of other adverse events were similar between groups.
“Based on the robustness of these data, further evidence on the role of weekly basal insulin icodec will be pursued in a comprehensive phase 3 clinical development program,” Dr. Rosenstock explained. If those data confirm the phase 2 results, “I believe personally that a weekly basal insulin has the potential to be transformational in the management of people with type 2 diabetes needing insulin therapy.”
Dr. Rosenstock has reported receiving research support from, being on advisory boards for, and/or receiving consulting honoraria from Merck, Pfizer, Sanofi, Novo Nordisk, Eli Lilly, GlaxoSmithKline, AstraZeneca, Janssen, Genentech, Oramed, Boehringer Ingelheim, Applied Therapeutics, and Intarcia. Dr. Alexander has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Julio Rosenstock, MD, of the University of Texas, Dallas, presented the data from the phase 2 pivotal study of icodec on June 14 during the virtual American Diabetes Association 80th Scientific Sessions.
Insulin icodec binds to albumin to create a circulating depot with a 196-hour half-life. A once-weekly injection is designed to cover an individual’s basal insulin requirements for a full week with steady insulin release. Because of its concentrated formulation, its injection volume is equivalent to that of daily glargine U100.
“Many people with type 2 diabetes are reluctant to start on insulin therapy due to the need for daily injections. ... I’m truly excited about the potential of such innovative treatments which could reduce the number of basal insulin injections for my patients with diabetes,” Dr. Rosenstock commented in a Novo Nordisk statement.
During his presentation, he added that the product “has the potential to be a major player in the management of type 2 diabetes if eventually approved.”
Charles M. Alexander, MD, an endocrinologist and managing director of Alexander Associates, Gwynedd Valley, Pa., said that “it’s a phase 2 study. Obviously we need to see the phase 3 data, but it’s very encouraging.”
Dr. Alexander, who was global medical director for diabetes in medical affairs at Merck from 2008 to 2015, observed that “the theory is that you have better adherence to once-weekly, compared to daily [dosing], but when you actually do the studies it’s very difficult to prove that.
“I think the big advantage is that the company can develop a coformulation of [the glucagonlike peptide–1 receptor agonist] semaglutide and icodec in the same pen or vial. ... There is a convenience factor of once weekly over daily.”
In fact, he noted, Novo Nordisk is already in phase 1 trials with that product, called icosema.
“Potential to be transformational”
The phase 2, randomized, double-blind, double-dummy, parallel-group, treat-to-target trial included 247 insulin-naive patients with type 2 diabetes with hemoglobin A1c levels of 7.0%-9.5% despite taking metformin, with about half also taking a dipeptidyl peptidase–4 inhibitor.
They were randomized to weekly insulin icodec plus daily placebo (n = 125) or daily insulin glargine U100 plus weekly placebo (n = 122). All participants took seven injections per week with a vial and syringe plus one injection per week with a pen injector. Doses were titrated up or down to achieve blood glucose levels 70-108 mg/dL, with glargine dose adjustments of 2 or 4 units and icodec units of 14 or 28 units.
Participants were a mean age of 59.6 years, had a diabetes duration of 9.7 years, and 56.3% were men. Baseline A1c was 8.0% overall and fasting blood glucose was 181 mg/dL, and both were similar between the two groups.
The primary endpoint, change in A1c from baseline to week 26, dropped 1.33 percentage points with icodec and 1.15 percentage points with glargine, which was not significantly different (P = .08). Estimated mean A1c levels were 6.7% for icodec and 6.9% for glargine.
The icodec result, Dr. Rosenstock said, “is a very impressive final A1c.”
The proportions of patients achieving A1c <7% by week 26 for icodec versus glargine were 72% versus 68%, and for A1c ≤6.5% were 49% and 39%, respectively. Those differences weren’t statistically significant because of lack of power, Dr. Rosenstock observed.
Fasting plasma glucose levels were nearly identical at 26 weeks, with drops of 58 mg/dL with icodec and 54 mg/dL with glargine (P = .34).
However, there was a significant difference in favor of icodec in the 9-point self-monitoring of blood glucose profile, with a difference in mean change from baseline to week 26 of –7.9 mg/dL (P = .01).
Lower postbreakfast and postlunch glucose peaks at 90 minutes accounted for most of the difference, Dr. Rosenstock noted.
Total insulin doses during the last 2 weeks of treatment with icodec versus glargine were 229 versus 284 units/week (P = .01); those translate to approximate daily doses of 33 versus 41 units/day, respectively.
Both groups gained a small amount of weight, 1.5 kg with icodec and 1.6 kg with glargine by week 26 (P = .88).
Hypoglycemia was more common with icodec than glargine, including mild (53.6% vs. 37.7%), moderate or clinically significant (16.0% vs. 9.8%), and severe (1 [0.8%] vs. 0 participants). Corresponding event rates were 508.9 versus 210.8 per 100 patient-years (mild hypoglycemia), 52.5 versus 45.6 per 100 patient-years (moderate or clinically significant), and 1.4 versus 0 per 100 patient-years (severe) for icodec versus glargine.
The difference between the two groups in moderate or clinically significant hypoglycemia wasn’t statistically significant (P = .85), and the duration of hypoglycemia wasn’t longer with icodec, compared with glargine, despite its longer duration of action, Dr. Rosenstock emphasized.
Rates of other adverse events were similar between groups.
“Based on the robustness of these data, further evidence on the role of weekly basal insulin icodec will be pursued in a comprehensive phase 3 clinical development program,” Dr. Rosenstock explained. If those data confirm the phase 2 results, “I believe personally that a weekly basal insulin has the potential to be transformational in the management of people with type 2 diabetes needing insulin therapy.”
Dr. Rosenstock has reported receiving research support from, being on advisory boards for, and/or receiving consulting honoraria from Merck, Pfizer, Sanofi, Novo Nordisk, Eli Lilly, GlaxoSmithKline, AstraZeneca, Janssen, Genentech, Oramed, Boehringer Ingelheim, Applied Therapeutics, and Intarcia. Dr. Alexander has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Health experts link rise in Arizona COVID cases to end of stay-at-home order
With new daily coronavirus cases rising in at least two dozen states,
Arizona has emerged as one of the country’s newest coronavirus hot spots, with the weekly average of daily cases more than doubling from 2 weeks ago. The total number of people hospitalized is climbing, too.
Over the past week, Arizona has seen an average of more than 1,300 new COVID-19 cases each day.
After the state’s largest hospital system warned about a shortage of ICU beds, Arizona Gov. Doug Ducey, a Republican, pushed back on claims that the health care system could soon be overwhelmed.
“The entire time we’ve been focused on a possible worst-case scenario with surge capacity for hospital beds, ICU beds and ventilators,” Ducey told reporters on Thursday. “Those are not needed or necessary right now.”
While he acknowledged a spike in positive cases, Ducey said a second stay-at-home order was “not under discussion.”
“We put the stay-at-home order there so we could prepare for what we are going through,” he said.
Some states have reopened more slowly with a set of specific benchmarks for different regions, but Arizona took a more aggressive approach.
The state began easing restrictions on businesses in early May and lifted its statewide lockdown order after May 15. Under Arizona’s reopening plan, businesses are advised to follow federal guidance on social distancing.
There is also no requirement for everyone to wear masks in public.
Public health experts agree: The timing of this spike reflects the state’s reopening.
“Perhaps, Arizona will be a warning sign to other areas,” said Katherine Ellingson, an epidemiologist at the University of Arizona. “We never had that consistent downward trend that would signal it’s time to reopen and we have everything in place to do it safely.”
Before Arizona lifted its stay-at-home order, only about 5% of COVID-19 tests registered as positive. On Monday, that number was around 16%.
A slower reopening gives public health agencies time to identify whether cases are rising and then respond with contact tracing and isolating those who are infected.
“With a fast, rapid reopening, we don’t have the time to mobilize those resources,” said Ellingson.
Maricopa County, home to about 60% of the state’s population, has ramped up contact tracing in recent weeks, but it may not have enough capacity if the surge in cases continues.
Dr. Peter Hotez said the spike in Arizona, as well as in parts of Texas such as Houston, Dallas and Austin, is the consequence of removing restrictions too quickly and without a public health system that can keep pace.
“It was just ‘open it up’ and then more or less business as usual, with a little bit of window dressing,” said Hotez, the dean for the National School of Tropical Medicine at Baylor College of Medicine in Houston. “This is not an abstract number of cases. We’re seeing people pile into intensive care units.”
Arizona’s governor has also faced criticism from the mayors of Arizona’s two biggest cities for not putting in place more stringent requirements.
“There is a pandemic and it’s spreading uncontrollably,” said Tucson Mayor Regina Romero, a Democrat. Ducey, she said, “is just putting up his hands and saying ‘the spread is happening and we just have to go about our business.’”
And the governor’s executive order forbids local governments from implementing their own extra measures, which adds to Romero’s frustration. Texas has a similar measure.
“What he did was pretty much tie the hands of mayors and public health officials,” Romero said.
Arizona’s hospital industry has tried to tamp down fears that it’s on the verge of a crisis. Hospitals are still performing elective surgeries.
“It’s very unfortunate because hospitals right now in Arizona are quite busy with elective procedures,” said Saskia Popescu, a Phoenix-based epidemiologist with George Mason University. “You throw in increasing cases of COVID, and that’s going to very much stress your hospital systems.”
Phoenix’s triple-digit summer temperatures actually may fuel the spread of the virus. People forgo outdoor activities and retreat to air-conditioned indoor spaces, where the risk of transmitting the virus goes up significantly.
“My concern is we’re going to see a lot more people in close quarters for prolonged periods of time,” Popescu said.
Since the stay-at-home order was lifted, Popescu and others say they’ve seen people returning to a pre-pandemic mindset, neglecting to wear masks or maintain social distance. Videos of crowded bars have only propelled these fears.
On Thursday, however, Arizona’s top doctor stressed there were also dangers to keeping the state on lockdown, including the mental health effects of loneliness and isolation.
“We know that it’s in the community. We are not going to be able to stop the spread. And so we can’t stop living as well,” said Dr. Cara Christ, health director for the Arizona Department of Health Services.
But Dr. Quinn Snyder, an emergency medicine physician in Mesa, Arizona, said there needs to be more consistent messaging on public health measures like wearing masks.
“Frankly, I just think a wholesale reevaluation of where we’re at is critical right now, but I can tell you that we’re not doing nearly enough,” said Snyder, who has seen the uptick in seriously ill COVID-19 patients firsthand.
“If we continue to head down this path, the virus will press our health care facilities beyond capacity, where we’re going to have to be making tough decisions like who gets a ventilator and who doesn’t.”
A version of this article originally appeared on Kaiser Health News, which is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
With new daily coronavirus cases rising in at least two dozen states,
Arizona has emerged as one of the country’s newest coronavirus hot spots, with the weekly average of daily cases more than doubling from 2 weeks ago. The total number of people hospitalized is climbing, too.
Over the past week, Arizona has seen an average of more than 1,300 new COVID-19 cases each day.
After the state’s largest hospital system warned about a shortage of ICU beds, Arizona Gov. Doug Ducey, a Republican, pushed back on claims that the health care system could soon be overwhelmed.
“The entire time we’ve been focused on a possible worst-case scenario with surge capacity for hospital beds, ICU beds and ventilators,” Ducey told reporters on Thursday. “Those are not needed or necessary right now.”
While he acknowledged a spike in positive cases, Ducey said a second stay-at-home order was “not under discussion.”
“We put the stay-at-home order there so we could prepare for what we are going through,” he said.
Some states have reopened more slowly with a set of specific benchmarks for different regions, but Arizona took a more aggressive approach.
The state began easing restrictions on businesses in early May and lifted its statewide lockdown order after May 15. Under Arizona’s reopening plan, businesses are advised to follow federal guidance on social distancing.
There is also no requirement for everyone to wear masks in public.
Public health experts agree: The timing of this spike reflects the state’s reopening.
“Perhaps, Arizona will be a warning sign to other areas,” said Katherine Ellingson, an epidemiologist at the University of Arizona. “We never had that consistent downward trend that would signal it’s time to reopen and we have everything in place to do it safely.”
Before Arizona lifted its stay-at-home order, only about 5% of COVID-19 tests registered as positive. On Monday, that number was around 16%.
A slower reopening gives public health agencies time to identify whether cases are rising and then respond with contact tracing and isolating those who are infected.
“With a fast, rapid reopening, we don’t have the time to mobilize those resources,” said Ellingson.
Maricopa County, home to about 60% of the state’s population, has ramped up contact tracing in recent weeks, but it may not have enough capacity if the surge in cases continues.
Dr. Peter Hotez said the spike in Arizona, as well as in parts of Texas such as Houston, Dallas and Austin, is the consequence of removing restrictions too quickly and without a public health system that can keep pace.
“It was just ‘open it up’ and then more or less business as usual, with a little bit of window dressing,” said Hotez, the dean for the National School of Tropical Medicine at Baylor College of Medicine in Houston. “This is not an abstract number of cases. We’re seeing people pile into intensive care units.”
Arizona’s governor has also faced criticism from the mayors of Arizona’s two biggest cities for not putting in place more stringent requirements.
“There is a pandemic and it’s spreading uncontrollably,” said Tucson Mayor Regina Romero, a Democrat. Ducey, she said, “is just putting up his hands and saying ‘the spread is happening and we just have to go about our business.’”
And the governor’s executive order forbids local governments from implementing their own extra measures, which adds to Romero’s frustration. Texas has a similar measure.
“What he did was pretty much tie the hands of mayors and public health officials,” Romero said.
Arizona’s hospital industry has tried to tamp down fears that it’s on the verge of a crisis. Hospitals are still performing elective surgeries.
“It’s very unfortunate because hospitals right now in Arizona are quite busy with elective procedures,” said Saskia Popescu, a Phoenix-based epidemiologist with George Mason University. “You throw in increasing cases of COVID, and that’s going to very much stress your hospital systems.”
Phoenix’s triple-digit summer temperatures actually may fuel the spread of the virus. People forgo outdoor activities and retreat to air-conditioned indoor spaces, where the risk of transmitting the virus goes up significantly.
“My concern is we’re going to see a lot more people in close quarters for prolonged periods of time,” Popescu said.
Since the stay-at-home order was lifted, Popescu and others say they’ve seen people returning to a pre-pandemic mindset, neglecting to wear masks or maintain social distance. Videos of crowded bars have only propelled these fears.
On Thursday, however, Arizona’s top doctor stressed there were also dangers to keeping the state on lockdown, including the mental health effects of loneliness and isolation.
“We know that it’s in the community. We are not going to be able to stop the spread. And so we can’t stop living as well,” said Dr. Cara Christ, health director for the Arizona Department of Health Services.
But Dr. Quinn Snyder, an emergency medicine physician in Mesa, Arizona, said there needs to be more consistent messaging on public health measures like wearing masks.
“Frankly, I just think a wholesale reevaluation of where we’re at is critical right now, but I can tell you that we’re not doing nearly enough,” said Snyder, who has seen the uptick in seriously ill COVID-19 patients firsthand.
“If we continue to head down this path, the virus will press our health care facilities beyond capacity, where we’re going to have to be making tough decisions like who gets a ventilator and who doesn’t.”
A version of this article originally appeared on Kaiser Health News, which is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
With new daily coronavirus cases rising in at least two dozen states,
Arizona has emerged as one of the country’s newest coronavirus hot spots, with the weekly average of daily cases more than doubling from 2 weeks ago. The total number of people hospitalized is climbing, too.
Over the past week, Arizona has seen an average of more than 1,300 new COVID-19 cases each day.
After the state’s largest hospital system warned about a shortage of ICU beds, Arizona Gov. Doug Ducey, a Republican, pushed back on claims that the health care system could soon be overwhelmed.
“The entire time we’ve been focused on a possible worst-case scenario with surge capacity for hospital beds, ICU beds and ventilators,” Ducey told reporters on Thursday. “Those are not needed or necessary right now.”
While he acknowledged a spike in positive cases, Ducey said a second stay-at-home order was “not under discussion.”
“We put the stay-at-home order there so we could prepare for what we are going through,” he said.
Some states have reopened more slowly with a set of specific benchmarks for different regions, but Arizona took a more aggressive approach.
The state began easing restrictions on businesses in early May and lifted its statewide lockdown order after May 15. Under Arizona’s reopening plan, businesses are advised to follow federal guidance on social distancing.
There is also no requirement for everyone to wear masks in public.
Public health experts agree: The timing of this spike reflects the state’s reopening.
“Perhaps, Arizona will be a warning sign to other areas,” said Katherine Ellingson, an epidemiologist at the University of Arizona. “We never had that consistent downward trend that would signal it’s time to reopen and we have everything in place to do it safely.”
Before Arizona lifted its stay-at-home order, only about 5% of COVID-19 tests registered as positive. On Monday, that number was around 16%.
A slower reopening gives public health agencies time to identify whether cases are rising and then respond with contact tracing and isolating those who are infected.
“With a fast, rapid reopening, we don’t have the time to mobilize those resources,” said Ellingson.
Maricopa County, home to about 60% of the state’s population, has ramped up contact tracing in recent weeks, but it may not have enough capacity if the surge in cases continues.
Dr. Peter Hotez said the spike in Arizona, as well as in parts of Texas such as Houston, Dallas and Austin, is the consequence of removing restrictions too quickly and without a public health system that can keep pace.
“It was just ‘open it up’ and then more or less business as usual, with a little bit of window dressing,” said Hotez, the dean for the National School of Tropical Medicine at Baylor College of Medicine in Houston. “This is not an abstract number of cases. We’re seeing people pile into intensive care units.”
Arizona’s governor has also faced criticism from the mayors of Arizona’s two biggest cities for not putting in place more stringent requirements.
“There is a pandemic and it’s spreading uncontrollably,” said Tucson Mayor Regina Romero, a Democrat. Ducey, she said, “is just putting up his hands and saying ‘the spread is happening and we just have to go about our business.’”
And the governor’s executive order forbids local governments from implementing their own extra measures, which adds to Romero’s frustration. Texas has a similar measure.
“What he did was pretty much tie the hands of mayors and public health officials,” Romero said.
Arizona’s hospital industry has tried to tamp down fears that it’s on the verge of a crisis. Hospitals are still performing elective surgeries.
“It’s very unfortunate because hospitals right now in Arizona are quite busy with elective procedures,” said Saskia Popescu, a Phoenix-based epidemiologist with George Mason University. “You throw in increasing cases of COVID, and that’s going to very much stress your hospital systems.”
Phoenix’s triple-digit summer temperatures actually may fuel the spread of the virus. People forgo outdoor activities and retreat to air-conditioned indoor spaces, where the risk of transmitting the virus goes up significantly.
“My concern is we’re going to see a lot more people in close quarters for prolonged periods of time,” Popescu said.
Since the stay-at-home order was lifted, Popescu and others say they’ve seen people returning to a pre-pandemic mindset, neglecting to wear masks or maintain social distance. Videos of crowded bars have only propelled these fears.
On Thursday, however, Arizona’s top doctor stressed there were also dangers to keeping the state on lockdown, including the mental health effects of loneliness and isolation.
“We know that it’s in the community. We are not going to be able to stop the spread. And so we can’t stop living as well,” said Dr. Cara Christ, health director for the Arizona Department of Health Services.
But Dr. Quinn Snyder, an emergency medicine physician in Mesa, Arizona, said there needs to be more consistent messaging on public health measures like wearing masks.
“Frankly, I just think a wholesale reevaluation of where we’re at is critical right now, but I can tell you that we’re not doing nearly enough,” said Snyder, who has seen the uptick in seriously ill COVID-19 patients firsthand.
“If we continue to head down this path, the virus will press our health care facilities beyond capacity, where we’re going to have to be making tough decisions like who gets a ventilator and who doesn’t.”
A version of this article originally appeared on Kaiser Health News, which is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
CAC scoring pinpoints stenoses in asymptomatic diabetes patients
For diabetes patients with no cardiovascular symptoms despite certain risk factors, incorporating coronary calcium scoring into a silent myocardial ischemia screening algorithm may be an effective and cost-conscious strategy that avoids missed coronary stenoses suitable for revascularization, results of a recent study suggest.
Zero patients in need of revascularization were missed in a risk stratification model in which screening for silent myocardial ischemia (SMI) was done only for patients with peripheral artery disease, severe nephropathy, or a high coronary artery calcium (CAC) score, according to investigator Paul Valensi, MD.
In practical terms, that means stress myocardial scintigraphy to detect SMI could be reserved for patients with evidence of target organ damage or a CAC score of 100 or higher, according to Dr. Valensi, head of the department of endocrinology, diabetology, and nutrition at Jean Verdier Hospital in Bondy, France.
“The strategy appears to be a good compromise, and the most cost effective strategy,” Dr. Valensi said in a presentation of the results at the virtual annual scientific sessions of the American Diabetes Association.
Utility of CAC scoring in diabetes
This algorithm proposed by Dr. Valenti and colleagues is a “reasonable” approach to guide risk stratification in asymptomatic diabetes patients, said Matthew J. Budoff, MD, professor of medicine and director of cardiac CT at Harbor-UCLA Medical Center in Torrance, Calif.
“Calcium scoring could certainly help you identify those patients (at increased risk) as a first-line test, because if their calcium score is zero, their chance of having obstructive disease is probably either zero or very close to zero,” Dr. Budoff said in an interview.
Using CAC scores to assess cardiovascular risk in asymptomatic adults with diabetes was supported by 2010 guidelines from the American College of Cardiology and the American Heart Association, Dr. Budoff said, while 2019 guidelines from the European Society of Cardiology (ESC) describe CAC score combined with CT as a potential risk modifier in the evaluation of certain asymptomatic patients with diabetes.
“We are starting to see that we might be able to understand diabetes better and the cardiovascular implications by understanding how much plaque (patients) have at the time that we see them,” Dr. Budoff said in a presentation on use of CAC scans he gave earlier at the virtual ADA meeting.
In the interview, Dr. Budoff also noted that CAC scores may be particularly useful for guiding use of statins, PCSK9 (proprotein convertase subtilisin kexin 9) inhibitors, or other treatments in patients with diabetes: “There are a lot of therapies that we can apply, if we knew somebody was at higher risk, that would potentially help them avoid a heart attack, stroke, or cardiovascular death,” he said.
CAC scoring and coronary artery stenoses
Although about 20% of patients with type 2 diabetes have SMI, screening for it is “debated,” according to Dr. Valensi.
The recent ESC guidelines state that while routine screening for coronary artery disease in asymptomatic diabetics is not recommended, stress testing or coronary angiography “may be indicated” in asymptomatic diabetics in the very-high cardiovascular risk category.
That position is based on a lack of benefit seen with a broad screening strategy, the guidelines say, possibly due in part to low event rates in randomized controlled trials that have studied the approach.
Using CAC scoring could change the equation by helping to identify a greater proportion of type 2 diabetics with SMI, according to Dr. Valensi.
“The role of the CAC score in the strategy of detection of SMI needs to be defined, and this role may depend on the a priori cardiovascular risk,” he said.
Dr. Valensi and colleagues accordingly tested several different approaches to selecting asymptomatic diabetic patients for SMI screening to see how they would perform in finding patients with coronary stenoses eligible for revascularization.
Their study included 416 diabetes patients with diabetes at very high cardiovascular risk but with no cardiac history or symptoms. A total of 40 patients (9.6%) had SMI, including 15 patients in which coronary stenoses were found; of those, 11 (73.5%) underwent a revascularization procedure.
They found that, by performing myocardial scintigraphy only in those patients with peripheral artery disease or severe nephropathy, they would have missed 6 patients with coronary stenosis suitable for revascularization among the 275 patients who did not meet those target organ damage criteria.
By contrast, zero patients would have been missed by performing myocardial scintigraphy in patients who either met those target organ damage criteria, or who had an elevated CAC score.
“We suggest screening for SMI, using stress myocardial CT scanning and coronary stenosis screening, only the patients with peripheral artery disease or severe nephropathy or with a high CAC score over 100 Agatston units,” said Dr. Valensi.
Dr. Valensi reported disclosures related to Merck Sharp Dohme, Novo Nordisk, Pierre Fabre, Eli Lilly, Bristol-Myers Squibb, AstraZeneca, Daiichi-Sankyo, and others. Coauthors provided no disclosures related to the research. Dr. Budoff reported that he has served as a paid consultant to GE.
SOURCE: Berkane N et al. ADA 2020. Abstract 8-OR.
For diabetes patients with no cardiovascular symptoms despite certain risk factors, incorporating coronary calcium scoring into a silent myocardial ischemia screening algorithm may be an effective and cost-conscious strategy that avoids missed coronary stenoses suitable for revascularization, results of a recent study suggest.
Zero patients in need of revascularization were missed in a risk stratification model in which screening for silent myocardial ischemia (SMI) was done only for patients with peripheral artery disease, severe nephropathy, or a high coronary artery calcium (CAC) score, according to investigator Paul Valensi, MD.
In practical terms, that means stress myocardial scintigraphy to detect SMI could be reserved for patients with evidence of target organ damage or a CAC score of 100 or higher, according to Dr. Valensi, head of the department of endocrinology, diabetology, and nutrition at Jean Verdier Hospital in Bondy, France.
“The strategy appears to be a good compromise, and the most cost effective strategy,” Dr. Valensi said in a presentation of the results at the virtual annual scientific sessions of the American Diabetes Association.
Utility of CAC scoring in diabetes
This algorithm proposed by Dr. Valenti and colleagues is a “reasonable” approach to guide risk stratification in asymptomatic diabetes patients, said Matthew J. Budoff, MD, professor of medicine and director of cardiac CT at Harbor-UCLA Medical Center in Torrance, Calif.
“Calcium scoring could certainly help you identify those patients (at increased risk) as a first-line test, because if their calcium score is zero, their chance of having obstructive disease is probably either zero or very close to zero,” Dr. Budoff said in an interview.
Using CAC scores to assess cardiovascular risk in asymptomatic adults with diabetes was supported by 2010 guidelines from the American College of Cardiology and the American Heart Association, Dr. Budoff said, while 2019 guidelines from the European Society of Cardiology (ESC) describe CAC score combined with CT as a potential risk modifier in the evaluation of certain asymptomatic patients with diabetes.
“We are starting to see that we might be able to understand diabetes better and the cardiovascular implications by understanding how much plaque (patients) have at the time that we see them,” Dr. Budoff said in a presentation on use of CAC scans he gave earlier at the virtual ADA meeting.
In the interview, Dr. Budoff also noted that CAC scores may be particularly useful for guiding use of statins, PCSK9 (proprotein convertase subtilisin kexin 9) inhibitors, or other treatments in patients with diabetes: “There are a lot of therapies that we can apply, if we knew somebody was at higher risk, that would potentially help them avoid a heart attack, stroke, or cardiovascular death,” he said.
CAC scoring and coronary artery stenoses
Although about 20% of patients with type 2 diabetes have SMI, screening for it is “debated,” according to Dr. Valensi.
The recent ESC guidelines state that while routine screening for coronary artery disease in asymptomatic diabetics is not recommended, stress testing or coronary angiography “may be indicated” in asymptomatic diabetics in the very-high cardiovascular risk category.
That position is based on a lack of benefit seen with a broad screening strategy, the guidelines say, possibly due in part to low event rates in randomized controlled trials that have studied the approach.
Using CAC scoring could change the equation by helping to identify a greater proportion of type 2 diabetics with SMI, according to Dr. Valensi.
“The role of the CAC score in the strategy of detection of SMI needs to be defined, and this role may depend on the a priori cardiovascular risk,” he said.
Dr. Valensi and colleagues accordingly tested several different approaches to selecting asymptomatic diabetic patients for SMI screening to see how they would perform in finding patients with coronary stenoses eligible for revascularization.
Their study included 416 diabetes patients with diabetes at very high cardiovascular risk but with no cardiac history or symptoms. A total of 40 patients (9.6%) had SMI, including 15 patients in which coronary stenoses were found; of those, 11 (73.5%) underwent a revascularization procedure.
They found that, by performing myocardial scintigraphy only in those patients with peripheral artery disease or severe nephropathy, they would have missed 6 patients with coronary stenosis suitable for revascularization among the 275 patients who did not meet those target organ damage criteria.
By contrast, zero patients would have been missed by performing myocardial scintigraphy in patients who either met those target organ damage criteria, or who had an elevated CAC score.
“We suggest screening for SMI, using stress myocardial CT scanning and coronary stenosis screening, only the patients with peripheral artery disease or severe nephropathy or with a high CAC score over 100 Agatston units,” said Dr. Valensi.
Dr. Valensi reported disclosures related to Merck Sharp Dohme, Novo Nordisk, Pierre Fabre, Eli Lilly, Bristol-Myers Squibb, AstraZeneca, Daiichi-Sankyo, and others. Coauthors provided no disclosures related to the research. Dr. Budoff reported that he has served as a paid consultant to GE.
SOURCE: Berkane N et al. ADA 2020. Abstract 8-OR.
For diabetes patients with no cardiovascular symptoms despite certain risk factors, incorporating coronary calcium scoring into a silent myocardial ischemia screening algorithm may be an effective and cost-conscious strategy that avoids missed coronary stenoses suitable for revascularization, results of a recent study suggest.
Zero patients in need of revascularization were missed in a risk stratification model in which screening for silent myocardial ischemia (SMI) was done only for patients with peripheral artery disease, severe nephropathy, or a high coronary artery calcium (CAC) score, according to investigator Paul Valensi, MD.
In practical terms, that means stress myocardial scintigraphy to detect SMI could be reserved for patients with evidence of target organ damage or a CAC score of 100 or higher, according to Dr. Valensi, head of the department of endocrinology, diabetology, and nutrition at Jean Verdier Hospital in Bondy, France.
“The strategy appears to be a good compromise, and the most cost effective strategy,” Dr. Valensi said in a presentation of the results at the virtual annual scientific sessions of the American Diabetes Association.
Utility of CAC scoring in diabetes
This algorithm proposed by Dr. Valenti and colleagues is a “reasonable” approach to guide risk stratification in asymptomatic diabetes patients, said Matthew J. Budoff, MD, professor of medicine and director of cardiac CT at Harbor-UCLA Medical Center in Torrance, Calif.
“Calcium scoring could certainly help you identify those patients (at increased risk) as a first-line test, because if their calcium score is zero, their chance of having obstructive disease is probably either zero or very close to zero,” Dr. Budoff said in an interview.
Using CAC scores to assess cardiovascular risk in asymptomatic adults with diabetes was supported by 2010 guidelines from the American College of Cardiology and the American Heart Association, Dr. Budoff said, while 2019 guidelines from the European Society of Cardiology (ESC) describe CAC score combined with CT as a potential risk modifier in the evaluation of certain asymptomatic patients with diabetes.
“We are starting to see that we might be able to understand diabetes better and the cardiovascular implications by understanding how much plaque (patients) have at the time that we see them,” Dr. Budoff said in a presentation on use of CAC scans he gave earlier at the virtual ADA meeting.
In the interview, Dr. Budoff also noted that CAC scores may be particularly useful for guiding use of statins, PCSK9 (proprotein convertase subtilisin kexin 9) inhibitors, or other treatments in patients with diabetes: “There are a lot of therapies that we can apply, if we knew somebody was at higher risk, that would potentially help them avoid a heart attack, stroke, or cardiovascular death,” he said.
CAC scoring and coronary artery stenoses
Although about 20% of patients with type 2 diabetes have SMI, screening for it is “debated,” according to Dr. Valensi.
The recent ESC guidelines state that while routine screening for coronary artery disease in asymptomatic diabetics is not recommended, stress testing or coronary angiography “may be indicated” in asymptomatic diabetics in the very-high cardiovascular risk category.
That position is based on a lack of benefit seen with a broad screening strategy, the guidelines say, possibly due in part to low event rates in randomized controlled trials that have studied the approach.
Using CAC scoring could change the equation by helping to identify a greater proportion of type 2 diabetics with SMI, according to Dr. Valensi.
“The role of the CAC score in the strategy of detection of SMI needs to be defined, and this role may depend on the a priori cardiovascular risk,” he said.
Dr. Valensi and colleagues accordingly tested several different approaches to selecting asymptomatic diabetic patients for SMI screening to see how they would perform in finding patients with coronary stenoses eligible for revascularization.
Their study included 416 diabetes patients with diabetes at very high cardiovascular risk but with no cardiac history or symptoms. A total of 40 patients (9.6%) had SMI, including 15 patients in which coronary stenoses were found; of those, 11 (73.5%) underwent a revascularization procedure.
They found that, by performing myocardial scintigraphy only in those patients with peripheral artery disease or severe nephropathy, they would have missed 6 patients with coronary stenosis suitable for revascularization among the 275 patients who did not meet those target organ damage criteria.
By contrast, zero patients would have been missed by performing myocardial scintigraphy in patients who either met those target organ damage criteria, or who had an elevated CAC score.
“We suggest screening for SMI, using stress myocardial CT scanning and coronary stenosis screening, only the patients with peripheral artery disease or severe nephropathy or with a high CAC score over 100 Agatston units,” said Dr. Valensi.
Dr. Valensi reported disclosures related to Merck Sharp Dohme, Novo Nordisk, Pierre Fabre, Eli Lilly, Bristol-Myers Squibb, AstraZeneca, Daiichi-Sankyo, and others. Coauthors provided no disclosures related to the research. Dr. Budoff reported that he has served as a paid consultant to GE.
SOURCE: Berkane N et al. ADA 2020. Abstract 8-OR.
FROM ADA 2020
DAPA-HF: Dapagliflozin slows T2D onset in heart failure patients
Dapagliflozin treatment of patients with heart failure but without diabetes in the DAPA-HF trial led to a one-third cut in the relative incidence of new-onset diabetes over a median follow-up of 18 months in a prespecified analysis from the multicenter trial that included 2,605 heart failure patients without diabetes at baseline.
The findings represented the first evidence that a drug from dapagliflozin’s class, the sodium-glucose cotransporter 2 (SGLT2) inhibitors, could prevent or slow the onset of type 2 diabetes. It represents “an additional benefit” that dapagliflozin (Farxiga) offers to patients with heart failure with reduced ejection fraction (HFrEF) like those enrolled in the DAPA-HF trial, Silvio E. Inzucchi, MD, said at the virtual annual scientific sessions of the American Diabetes Association. DAPA-HF had previously proved that treatment with this drug significantly reduced the study’s primary endpoint of cardiovascular death or heart failure worsening.
During 18 months of follow-up, 7.1% of patients in the placebo arm developed type 2 diabetes, compared with 4.9% in those who received dapagliflozin, a 2.2% absolute difference and a 32% relative risk reduction that was statistically significant for this prespecified but “exploratory” endpoint, reported Dr. Inzucchi, an endocrinologist and professor of medicine at Yale University, New Haven, Conn.
For this analysis, a hemoglobin A1c level of at least 6.5% measured in two consecutive assessments was the criterion for diagnosing incident diabetes. The 2,605 enrolled patients without diabetes in the DAPA-HF trial represented 55% of the entire trial cohort of 4,744 patients with HFrEF.
The 32% relative risk reduction for incident diabetes was primarily relevant to enrolled patients with prediabetes at entry, who constituted 67% of the enrolled cohort based on the usual definition of prediabetes, an A1c of 5.7%-6.4%.
Among all 157 (6%) of the DAPA-HF patients who developed diabetes during the trial, 150 (96%) occurred in patients with prediabetes by the usual definition; 136 of the incident cases (87%) had prediabetes by a more stringent criterion of an A1c of 6.0%-6.4%.
To put the preventive efficacy of dapagliflozin into more context, Dr. Inzucchi cited the 31% relative protection rate exerted by metformin in the Diabetes Prevention Program study (N Engl J Med. 2002 Feb 7;346[6]:393-403).
The findings showed that “dapagliflozin is the first medication demonstrated to reduce both incident type 2 diabetes and mortality in a single trial,” as well as the first agent from the SGLT2 inhibitor class to show a diabetes prevention effect, Dr. Inzucchi noted. Patients with both heart failure and diabetes are known to have a substantially increased mortality risk, compared with patients with just one of these diseases, and the potent risk posed by the confluence of both was confirmed in the results Dr. Inzucchi reported.
The 157 HFrEF patients in the trial who developed diabetes had a statistically significant 70% increased incidence of all-cause mortality during the trial’s follow-up, compared with similar HFrEF patients who remained free from a diabetes diagnosis, and they also had a significant 77% relative increase in their incidence of cardiovascular death. This analysis failed to show that incident diabetes had a significant impact on hospitalizations for heart failure coupled with cardiovascular death, another endpoint of the trial.
“This is a tremendously important analysis. We recognize that diabetes is an important factor that can forecast heart failure risk, even over relatively short follow-up. A drug that targets both diseases can be quite beneficial,” commented Muthiah Vaduganathan, MD, a cardiologist at Brigham and Women’s Hospital in Boston.
The impact of dapagliflozin on average A1c levels during the DAPA-HF trial was minimal, reducing levels by an average of 0.04% among those who entered with prediabetes and by 0.05% among the other patients. This suggests that the mechanisms by which dapagliflozin reduced incident diabetes was by routes that did not involve simply reducing hyperglycemia, and the observed decrease in incident diabetes was not apparently caused by “masking” of hyperglycemia by dapagliflozin, said Dr. Inzucchi.
One possibility is that dapagliflozin, which also improved quality of life and reduced hospitalizations in the DAPA-HF trial, led to improved function and mobility among patients that had beneficial effects on their insulin sensitivity, Dr. Vaduganathan speculated in an interview.
The new finding of dapagliflozin’s benefit “is great news,” commented Yehuda Handelsman, MD, an endocrinologist and diabetes specialist who is medical director of the Metabolic Institute of America in Tarzana, Calif. “It’s an impressive and important result, and another reason to use dapagliflozin in patients with HFrEF, a group of patients whom you want to prevent from having worse outcomes” by developing diabetes.
The DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial enrolled HFrEF patients at 410 centers in 20 countries during February 2017–August 2018. The study’s primary endpoint was the composite incidence of cardiovascular death or worsening heart failure, which occurred in 16.3% of patients randomized to receive dapagliflozin and in 21.2% of control patients on standard care but on placebo instead of the study drug, a statistically significant relative risk reduction of 26% (N Engl J Med. 2019 Nov 21;381[21]:1995-2008). In the 2,605-patient subgroup without type 2 diabetes at baseline the primary endpoint fell by a statistically significant 27% with dapagliflozin treatment, the first time an SGLT2 inhibitor drug was shown effective for reducing this endpoint in patients with HFrEF but without diabetes. DAPA-HF did not enroll any patients with type 1 diabetes.
DAPA-HF was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Inzucchi has been a consultant to AstraZeneca and to Abbott, Boehringer Ingelheim, Merck, Novo Nordisk, Sanofi/Lexicon, and vTv Therapeutics. Dr. Vaduganathan has been an adviser to AstraZeneca and to Amgen, Baxter, Bayer, Boehringer Ingelheim, Cytokinetics, and Relypsa. Dr. Handelsman has been a consultant to several drug companies including AstraZeneca.
SOURCE: Inzucchi SE et al. ADA 2020, abstract 271-OR.
Dapagliflozin treatment of patients with heart failure but without diabetes in the DAPA-HF trial led to a one-third cut in the relative incidence of new-onset diabetes over a median follow-up of 18 months in a prespecified analysis from the multicenter trial that included 2,605 heart failure patients without diabetes at baseline.
The findings represented the first evidence that a drug from dapagliflozin’s class, the sodium-glucose cotransporter 2 (SGLT2) inhibitors, could prevent or slow the onset of type 2 diabetes. It represents “an additional benefit” that dapagliflozin (Farxiga) offers to patients with heart failure with reduced ejection fraction (HFrEF) like those enrolled in the DAPA-HF trial, Silvio E. Inzucchi, MD, said at the virtual annual scientific sessions of the American Diabetes Association. DAPA-HF had previously proved that treatment with this drug significantly reduced the study’s primary endpoint of cardiovascular death or heart failure worsening.
During 18 months of follow-up, 7.1% of patients in the placebo arm developed type 2 diabetes, compared with 4.9% in those who received dapagliflozin, a 2.2% absolute difference and a 32% relative risk reduction that was statistically significant for this prespecified but “exploratory” endpoint, reported Dr. Inzucchi, an endocrinologist and professor of medicine at Yale University, New Haven, Conn.
For this analysis, a hemoglobin A1c level of at least 6.5% measured in two consecutive assessments was the criterion for diagnosing incident diabetes. The 2,605 enrolled patients without diabetes in the DAPA-HF trial represented 55% of the entire trial cohort of 4,744 patients with HFrEF.
The 32% relative risk reduction for incident diabetes was primarily relevant to enrolled patients with prediabetes at entry, who constituted 67% of the enrolled cohort based on the usual definition of prediabetes, an A1c of 5.7%-6.4%.
Among all 157 (6%) of the DAPA-HF patients who developed diabetes during the trial, 150 (96%) occurred in patients with prediabetes by the usual definition; 136 of the incident cases (87%) had prediabetes by a more stringent criterion of an A1c of 6.0%-6.4%.
To put the preventive efficacy of dapagliflozin into more context, Dr. Inzucchi cited the 31% relative protection rate exerted by metformin in the Diabetes Prevention Program study (N Engl J Med. 2002 Feb 7;346[6]:393-403).
The findings showed that “dapagliflozin is the first medication demonstrated to reduce both incident type 2 diabetes and mortality in a single trial,” as well as the first agent from the SGLT2 inhibitor class to show a diabetes prevention effect, Dr. Inzucchi noted. Patients with both heart failure and diabetes are known to have a substantially increased mortality risk, compared with patients with just one of these diseases, and the potent risk posed by the confluence of both was confirmed in the results Dr. Inzucchi reported.
The 157 HFrEF patients in the trial who developed diabetes had a statistically significant 70% increased incidence of all-cause mortality during the trial’s follow-up, compared with similar HFrEF patients who remained free from a diabetes diagnosis, and they also had a significant 77% relative increase in their incidence of cardiovascular death. This analysis failed to show that incident diabetes had a significant impact on hospitalizations for heart failure coupled with cardiovascular death, another endpoint of the trial.
“This is a tremendously important analysis. We recognize that diabetes is an important factor that can forecast heart failure risk, even over relatively short follow-up. A drug that targets both diseases can be quite beneficial,” commented Muthiah Vaduganathan, MD, a cardiologist at Brigham and Women’s Hospital in Boston.
The impact of dapagliflozin on average A1c levels during the DAPA-HF trial was minimal, reducing levels by an average of 0.04% among those who entered with prediabetes and by 0.05% among the other patients. This suggests that the mechanisms by which dapagliflozin reduced incident diabetes was by routes that did not involve simply reducing hyperglycemia, and the observed decrease in incident diabetes was not apparently caused by “masking” of hyperglycemia by dapagliflozin, said Dr. Inzucchi.
One possibility is that dapagliflozin, which also improved quality of life and reduced hospitalizations in the DAPA-HF trial, led to improved function and mobility among patients that had beneficial effects on their insulin sensitivity, Dr. Vaduganathan speculated in an interview.
The new finding of dapagliflozin’s benefit “is great news,” commented Yehuda Handelsman, MD, an endocrinologist and diabetes specialist who is medical director of the Metabolic Institute of America in Tarzana, Calif. “It’s an impressive and important result, and another reason to use dapagliflozin in patients with HFrEF, a group of patients whom you want to prevent from having worse outcomes” by developing diabetes.
The DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial enrolled HFrEF patients at 410 centers in 20 countries during February 2017–August 2018. The study’s primary endpoint was the composite incidence of cardiovascular death or worsening heart failure, which occurred in 16.3% of patients randomized to receive dapagliflozin and in 21.2% of control patients on standard care but on placebo instead of the study drug, a statistically significant relative risk reduction of 26% (N Engl J Med. 2019 Nov 21;381[21]:1995-2008). In the 2,605-patient subgroup without type 2 diabetes at baseline the primary endpoint fell by a statistically significant 27% with dapagliflozin treatment, the first time an SGLT2 inhibitor drug was shown effective for reducing this endpoint in patients with HFrEF but without diabetes. DAPA-HF did not enroll any patients with type 1 diabetes.
DAPA-HF was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Inzucchi has been a consultant to AstraZeneca and to Abbott, Boehringer Ingelheim, Merck, Novo Nordisk, Sanofi/Lexicon, and vTv Therapeutics. Dr. Vaduganathan has been an adviser to AstraZeneca and to Amgen, Baxter, Bayer, Boehringer Ingelheim, Cytokinetics, and Relypsa. Dr. Handelsman has been a consultant to several drug companies including AstraZeneca.
SOURCE: Inzucchi SE et al. ADA 2020, abstract 271-OR.
Dapagliflozin treatment of patients with heart failure but without diabetes in the DAPA-HF trial led to a one-third cut in the relative incidence of new-onset diabetes over a median follow-up of 18 months in a prespecified analysis from the multicenter trial that included 2,605 heart failure patients without diabetes at baseline.
The findings represented the first evidence that a drug from dapagliflozin’s class, the sodium-glucose cotransporter 2 (SGLT2) inhibitors, could prevent or slow the onset of type 2 diabetes. It represents “an additional benefit” that dapagliflozin (Farxiga) offers to patients with heart failure with reduced ejection fraction (HFrEF) like those enrolled in the DAPA-HF trial, Silvio E. Inzucchi, MD, said at the virtual annual scientific sessions of the American Diabetes Association. DAPA-HF had previously proved that treatment with this drug significantly reduced the study’s primary endpoint of cardiovascular death or heart failure worsening.
During 18 months of follow-up, 7.1% of patients in the placebo arm developed type 2 diabetes, compared with 4.9% in those who received dapagliflozin, a 2.2% absolute difference and a 32% relative risk reduction that was statistically significant for this prespecified but “exploratory” endpoint, reported Dr. Inzucchi, an endocrinologist and professor of medicine at Yale University, New Haven, Conn.
For this analysis, a hemoglobin A1c level of at least 6.5% measured in two consecutive assessments was the criterion for diagnosing incident diabetes. The 2,605 enrolled patients without diabetes in the DAPA-HF trial represented 55% of the entire trial cohort of 4,744 patients with HFrEF.
The 32% relative risk reduction for incident diabetes was primarily relevant to enrolled patients with prediabetes at entry, who constituted 67% of the enrolled cohort based on the usual definition of prediabetes, an A1c of 5.7%-6.4%.
Among all 157 (6%) of the DAPA-HF patients who developed diabetes during the trial, 150 (96%) occurred in patients with prediabetes by the usual definition; 136 of the incident cases (87%) had prediabetes by a more stringent criterion of an A1c of 6.0%-6.4%.
To put the preventive efficacy of dapagliflozin into more context, Dr. Inzucchi cited the 31% relative protection rate exerted by metformin in the Diabetes Prevention Program study (N Engl J Med. 2002 Feb 7;346[6]:393-403).
The findings showed that “dapagliflozin is the first medication demonstrated to reduce both incident type 2 diabetes and mortality in a single trial,” as well as the first agent from the SGLT2 inhibitor class to show a diabetes prevention effect, Dr. Inzucchi noted. Patients with both heart failure and diabetes are known to have a substantially increased mortality risk, compared with patients with just one of these diseases, and the potent risk posed by the confluence of both was confirmed in the results Dr. Inzucchi reported.
The 157 HFrEF patients in the trial who developed diabetes had a statistically significant 70% increased incidence of all-cause mortality during the trial’s follow-up, compared with similar HFrEF patients who remained free from a diabetes diagnosis, and they also had a significant 77% relative increase in their incidence of cardiovascular death. This analysis failed to show that incident diabetes had a significant impact on hospitalizations for heart failure coupled with cardiovascular death, another endpoint of the trial.
“This is a tremendously important analysis. We recognize that diabetes is an important factor that can forecast heart failure risk, even over relatively short follow-up. A drug that targets both diseases can be quite beneficial,” commented Muthiah Vaduganathan, MD, a cardiologist at Brigham and Women’s Hospital in Boston.
The impact of dapagliflozin on average A1c levels during the DAPA-HF trial was minimal, reducing levels by an average of 0.04% among those who entered with prediabetes and by 0.05% among the other patients. This suggests that the mechanisms by which dapagliflozin reduced incident diabetes was by routes that did not involve simply reducing hyperglycemia, and the observed decrease in incident diabetes was not apparently caused by “masking” of hyperglycemia by dapagliflozin, said Dr. Inzucchi.
One possibility is that dapagliflozin, which also improved quality of life and reduced hospitalizations in the DAPA-HF trial, led to improved function and mobility among patients that had beneficial effects on their insulin sensitivity, Dr. Vaduganathan speculated in an interview.
The new finding of dapagliflozin’s benefit “is great news,” commented Yehuda Handelsman, MD, an endocrinologist and diabetes specialist who is medical director of the Metabolic Institute of America in Tarzana, Calif. “It’s an impressive and important result, and another reason to use dapagliflozin in patients with HFrEF, a group of patients whom you want to prevent from having worse outcomes” by developing diabetes.
The DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial enrolled HFrEF patients at 410 centers in 20 countries during February 2017–August 2018. The study’s primary endpoint was the composite incidence of cardiovascular death or worsening heart failure, which occurred in 16.3% of patients randomized to receive dapagliflozin and in 21.2% of control patients on standard care but on placebo instead of the study drug, a statistically significant relative risk reduction of 26% (N Engl J Med. 2019 Nov 21;381[21]:1995-2008). In the 2,605-patient subgroup without type 2 diabetes at baseline the primary endpoint fell by a statistically significant 27% with dapagliflozin treatment, the first time an SGLT2 inhibitor drug was shown effective for reducing this endpoint in patients with HFrEF but without diabetes. DAPA-HF did not enroll any patients with type 1 diabetes.
DAPA-HF was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Inzucchi has been a consultant to AstraZeneca and to Abbott, Boehringer Ingelheim, Merck, Novo Nordisk, Sanofi/Lexicon, and vTv Therapeutics. Dr. Vaduganathan has been an adviser to AstraZeneca and to Amgen, Baxter, Bayer, Boehringer Ingelheim, Cytokinetics, and Relypsa. Dr. Handelsman has been a consultant to several drug companies including AstraZeneca.
SOURCE: Inzucchi SE et al. ADA 2020, abstract 271-OR.
FROM ADA 2020
Dairy doesn’t do a body good in midlife women
Dairy consumption does not improve bone mineral density (BMD) or reduce the risk of osteoporotic fracture in women starting menopause, a new analysis of the Study of Women’s Health Across the Nation (SWAN) indicates.
And this was regardless of baseline menopausal status, say Taylor Wallace, PhD, of George Mason University, Fairfax, Va., and colleagues in their article published online in Menopause.
“Our previous work indicated a potential premenopausal critical window in regard to the effectiveness of calcium supplements,” they noted.
Clifford Rosen, MD, professor of medicine, Tufts University, Boston, said in an interview that he believes the study reinforces earlier work that dairy intake in women aged 45-55 years does not affect the rate of bone loss or fractures.
“The SWAN study is longitudinal and with sufficient numbers to support their conclusion,” Dr. Rosen said.
SWAN study: White women consume the most dairy
As dairy is known to be one of the foremost sources of calcium, along with other bone beneficial nutrients, Dr. Wallace and colleagues decided to examine intake of this food type with long-term bone health using the SWAN data.
The SWAN bone substudy started in 1996 and involved 3,302 pre- or early perimenopausal women aged 42-53 years. The sample size for the annualized rate of BMD loss and fracture analysis involved 1955 women.
A modified food frequency questionnaire was used at baseline, at visit 5, and again at visit 9 to record daily dairy consumption, among many other food items.
“Women were classified into four dairy groups based on this cumulative average dairy intake,” Wallace and colleagues note. Intake was grouped into < 0.5 servings/day; 0.5 to < 1.5 servings/day; 1.5 to < 2.5 servings/day, and ≥ 2.5 servings/day.
“Non-Hispanic white individuals were more likely to consume higher amounts of dairy compared to African American, Chinese, and Japanese individuals,” the authors noted.
They found no significant differences for baseline age, body mass index, femoral neck and lumbar spine BMD, calcium supplement use, or fracture history by dairy intake group.
There were also no differences in the hazard ratios or relative risk of nontraumatic fractures by frequency of daily dairy intake.
Findings on dairy and bone are inconsistent
The authors caution that several factors should be taken into account when considering these new findings.
“First, dairy intake was low [overall] among SWAN participants, with 65% reporting consumption of < 1.5 servings/day,” they point out.
Dairy intake was also “particularly low” among racial groups other than whites, which may be due to higher rates of lactose intolerance among ethnic minorities, they speculate.
They previously reported that the use of calcium dietary supplements in SWAN was associated with a lower annualized rate of femoral neck BMD loss as well as BMD loss at the lumbar spine over 10 years of follow-up, mainly in women who were premenopausal at baseline.
But no associations were observed in the risk of bone fracture in any women in that analysis, regardless of menopausal status.
In this new analysis, there were no significant differences in calcium supplement use across the dairy intake groups.
Dr. Wallace and colleagues also noted that the relevance of dairy product intake for bone health has been in question as some observational studies have even “suggested consumption to be associated with an increased risk of fractures.”
The lead author of one of these studies, Karl Michaelsson, MD, PhD, of Uppsala (Sweden) University, said in an interview that his study had looked only at milk intake, and the lack of benefit on bone health from high milk consumption may not apply to all dairy products.
We “may need to look at different types of dairy products,” he said.
Summing up, Stephanie Faubion, MD, MBA, medical director of the North American Menopause Society, said the new SWAN findings do add to the evidence base, “albeit inconsistent ... suggesting a lack of benefit from dairy intake on BMD and fracture risk.”
Vitamin D data were not available; dairy may help in this respect
Dr. Rosen also noted that no information was available on vitamin D levels in patients involved in SWAN, which he believes is a limitation of the study.
Nevertheless, “it is important to recognize that elderly individuals who increase their dairy intake may have health benefits as recognized in the Nurses’ Health Study, possibly due to increased protein intake, higher vitamin D levels, or greater calcium intake,” he observed.
A randomized trial of enhanced dairy intake in long-term care residents is currently underway, which should provide answers for a much more vulnerable population than those in the SWAN cohort, Dr. Rosen concluded.
Dr. Wallace has reported serving on the scientific advisory board of the Vitamin Shoppe and has received research support from the National Dairy Council and scientific consulting fees from several food companies. Dr. Rosen has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Dairy consumption does not improve bone mineral density (BMD) or reduce the risk of osteoporotic fracture in women starting menopause, a new analysis of the Study of Women’s Health Across the Nation (SWAN) indicates.
And this was regardless of baseline menopausal status, say Taylor Wallace, PhD, of George Mason University, Fairfax, Va., and colleagues in their article published online in Menopause.
“Our previous work indicated a potential premenopausal critical window in regard to the effectiveness of calcium supplements,” they noted.
Clifford Rosen, MD, professor of medicine, Tufts University, Boston, said in an interview that he believes the study reinforces earlier work that dairy intake in women aged 45-55 years does not affect the rate of bone loss or fractures.
“The SWAN study is longitudinal and with sufficient numbers to support their conclusion,” Dr. Rosen said.
SWAN study: White women consume the most dairy
As dairy is known to be one of the foremost sources of calcium, along with other bone beneficial nutrients, Dr. Wallace and colleagues decided to examine intake of this food type with long-term bone health using the SWAN data.
The SWAN bone substudy started in 1996 and involved 3,302 pre- or early perimenopausal women aged 42-53 years. The sample size for the annualized rate of BMD loss and fracture analysis involved 1955 women.
A modified food frequency questionnaire was used at baseline, at visit 5, and again at visit 9 to record daily dairy consumption, among many other food items.
“Women were classified into four dairy groups based on this cumulative average dairy intake,” Wallace and colleagues note. Intake was grouped into < 0.5 servings/day; 0.5 to < 1.5 servings/day; 1.5 to < 2.5 servings/day, and ≥ 2.5 servings/day.
“Non-Hispanic white individuals were more likely to consume higher amounts of dairy compared to African American, Chinese, and Japanese individuals,” the authors noted.
They found no significant differences for baseline age, body mass index, femoral neck and lumbar spine BMD, calcium supplement use, or fracture history by dairy intake group.
There were also no differences in the hazard ratios or relative risk of nontraumatic fractures by frequency of daily dairy intake.
Findings on dairy and bone are inconsistent
The authors caution that several factors should be taken into account when considering these new findings.
“First, dairy intake was low [overall] among SWAN participants, with 65% reporting consumption of < 1.5 servings/day,” they point out.
Dairy intake was also “particularly low” among racial groups other than whites, which may be due to higher rates of lactose intolerance among ethnic minorities, they speculate.
They previously reported that the use of calcium dietary supplements in SWAN was associated with a lower annualized rate of femoral neck BMD loss as well as BMD loss at the lumbar spine over 10 years of follow-up, mainly in women who were premenopausal at baseline.
But no associations were observed in the risk of bone fracture in any women in that analysis, regardless of menopausal status.
In this new analysis, there were no significant differences in calcium supplement use across the dairy intake groups.
Dr. Wallace and colleagues also noted that the relevance of dairy product intake for bone health has been in question as some observational studies have even “suggested consumption to be associated with an increased risk of fractures.”
The lead author of one of these studies, Karl Michaelsson, MD, PhD, of Uppsala (Sweden) University, said in an interview that his study had looked only at milk intake, and the lack of benefit on bone health from high milk consumption may not apply to all dairy products.
We “may need to look at different types of dairy products,” he said.
Summing up, Stephanie Faubion, MD, MBA, medical director of the North American Menopause Society, said the new SWAN findings do add to the evidence base, “albeit inconsistent ... suggesting a lack of benefit from dairy intake on BMD and fracture risk.”
Vitamin D data were not available; dairy may help in this respect
Dr. Rosen also noted that no information was available on vitamin D levels in patients involved in SWAN, which he believes is a limitation of the study.
Nevertheless, “it is important to recognize that elderly individuals who increase their dairy intake may have health benefits as recognized in the Nurses’ Health Study, possibly due to increased protein intake, higher vitamin D levels, or greater calcium intake,” he observed.
A randomized trial of enhanced dairy intake in long-term care residents is currently underway, which should provide answers for a much more vulnerable population than those in the SWAN cohort, Dr. Rosen concluded.
Dr. Wallace has reported serving on the scientific advisory board of the Vitamin Shoppe and has received research support from the National Dairy Council and scientific consulting fees from several food companies. Dr. Rosen has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Dairy consumption does not improve bone mineral density (BMD) or reduce the risk of osteoporotic fracture in women starting menopause, a new analysis of the Study of Women’s Health Across the Nation (SWAN) indicates.
And this was regardless of baseline menopausal status, say Taylor Wallace, PhD, of George Mason University, Fairfax, Va., and colleagues in their article published online in Menopause.
“Our previous work indicated a potential premenopausal critical window in regard to the effectiveness of calcium supplements,” they noted.
Clifford Rosen, MD, professor of medicine, Tufts University, Boston, said in an interview that he believes the study reinforces earlier work that dairy intake in women aged 45-55 years does not affect the rate of bone loss or fractures.
“The SWAN study is longitudinal and with sufficient numbers to support their conclusion,” Dr. Rosen said.
SWAN study: White women consume the most dairy
As dairy is known to be one of the foremost sources of calcium, along with other bone beneficial nutrients, Dr. Wallace and colleagues decided to examine intake of this food type with long-term bone health using the SWAN data.
The SWAN bone substudy started in 1996 and involved 3,302 pre- or early perimenopausal women aged 42-53 years. The sample size for the annualized rate of BMD loss and fracture analysis involved 1955 women.
A modified food frequency questionnaire was used at baseline, at visit 5, and again at visit 9 to record daily dairy consumption, among many other food items.
“Women were classified into four dairy groups based on this cumulative average dairy intake,” Wallace and colleagues note. Intake was grouped into < 0.5 servings/day; 0.5 to < 1.5 servings/day; 1.5 to < 2.5 servings/day, and ≥ 2.5 servings/day.
“Non-Hispanic white individuals were more likely to consume higher amounts of dairy compared to African American, Chinese, and Japanese individuals,” the authors noted.
They found no significant differences for baseline age, body mass index, femoral neck and lumbar spine BMD, calcium supplement use, or fracture history by dairy intake group.
There were also no differences in the hazard ratios or relative risk of nontraumatic fractures by frequency of daily dairy intake.
Findings on dairy and bone are inconsistent
The authors caution that several factors should be taken into account when considering these new findings.
“First, dairy intake was low [overall] among SWAN participants, with 65% reporting consumption of < 1.5 servings/day,” they point out.
Dairy intake was also “particularly low” among racial groups other than whites, which may be due to higher rates of lactose intolerance among ethnic minorities, they speculate.
They previously reported that the use of calcium dietary supplements in SWAN was associated with a lower annualized rate of femoral neck BMD loss as well as BMD loss at the lumbar spine over 10 years of follow-up, mainly in women who were premenopausal at baseline.
But no associations were observed in the risk of bone fracture in any women in that analysis, regardless of menopausal status.
In this new analysis, there were no significant differences in calcium supplement use across the dairy intake groups.
Dr. Wallace and colleagues also noted that the relevance of dairy product intake for bone health has been in question as some observational studies have even “suggested consumption to be associated with an increased risk of fractures.”
The lead author of one of these studies, Karl Michaelsson, MD, PhD, of Uppsala (Sweden) University, said in an interview that his study had looked only at milk intake, and the lack of benefit on bone health from high milk consumption may not apply to all dairy products.
We “may need to look at different types of dairy products,” he said.
Summing up, Stephanie Faubion, MD, MBA, medical director of the North American Menopause Society, said the new SWAN findings do add to the evidence base, “albeit inconsistent ... suggesting a lack of benefit from dairy intake on BMD and fracture risk.”
Vitamin D data were not available; dairy may help in this respect
Dr. Rosen also noted that no information was available on vitamin D levels in patients involved in SWAN, which he believes is a limitation of the study.
Nevertheless, “it is important to recognize that elderly individuals who increase their dairy intake may have health benefits as recognized in the Nurses’ Health Study, possibly due to increased protein intake, higher vitamin D levels, or greater calcium intake,” he observed.
A randomized trial of enhanced dairy intake in long-term care residents is currently underway, which should provide answers for a much more vulnerable population than those in the SWAN cohort, Dr. Rosen concluded.
Dr. Wallace has reported serving on the scientific advisory board of the Vitamin Shoppe and has received research support from the National Dairy Council and scientific consulting fees from several food companies. Dr. Rosen has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FDA revokes emergency use of hydroxychloroquine
The U.S. Food and Drug Administration revoked its decision from March 28 allowing use of hydroxychloroquine and chloroquine to treat people hospitalized with COVID-19 under an emergency use authorization (EUA).
“Based on its ongoing analysis of the EUA and emerging scientific data, the FDA determined that chloroquine and hydroxychloroquine are unlikely to be effective in treating COVID-19 for the authorized uses in the EUA,” the agency announced in a June 15 statement.
The FDA also warned today that the use of hydroxychloroquine or chloroquine may have a potential drug interaction with the investigational antiviral drug remdesivir that limits its effectiveness against COVID-19.
Remdesivir was granted emergency use authorization by the FDA on May 1.
“Based on a recently completed nonclinical laboratory study, the FDA is revising the fact sheet for healthcare providers that accompanies the drug to state that coadministration of remdesivir and chloroquine phosphate or hydroxychloroquine sulfate is not recommended as it may result in reduced antiviral activity of remdesivir. The agency is not aware of instances of this reduced activity occurring in the clinical setting but is continuing to evaluate all data related to remdesivir,” the FDA said in a news release.
Controversy over hydroxychloroquine
Even with such federal permission, since late March the use of these two agents has been mired in controversy.
President Donald J. Trump promoted the use of hydroxychloroquine and chloroquine to treat Americans with COVID-19, while scientific studies raised questions about their safety and effectiveness. Recent research, for example, pointed to elevated cardiovascular risks, as reported by Medscape Medical News.
The FDA acknowledged this recent evidence. “Additionally, in light of ongoing serious cardiac adverse events and other potential serious side effects, the known and potential benefits of chloroquine and hydroxychloroquine no longer outweigh the known and potential risks for the authorized use.”
The full suspension of the EUA follows a warning the agency issued on April 24. The FDA’s Safety Communication cautioned against use of the two agents outside of a hospital setting, citing an increase in outpatient prescriptions and “reports of serious heart rhythm problems.”
“While additional clinical trials continue to evaluate the potential benefit of these drugs in treating or preventing COVID-19, we determined the emergency use authorization was no longer appropriate,” based on a rigorous assessment by scientists in our Center for Drug Evaluation and Research,” Patrizia Cavazzoni, MD, acting director of CDER, noted in the FDA statement.
This article first appeared on Medscape.com.
The U.S. Food and Drug Administration revoked its decision from March 28 allowing use of hydroxychloroquine and chloroquine to treat people hospitalized with COVID-19 under an emergency use authorization (EUA).
“Based on its ongoing analysis of the EUA and emerging scientific data, the FDA determined that chloroquine and hydroxychloroquine are unlikely to be effective in treating COVID-19 for the authorized uses in the EUA,” the agency announced in a June 15 statement.
The FDA also warned today that the use of hydroxychloroquine or chloroquine may have a potential drug interaction with the investigational antiviral drug remdesivir that limits its effectiveness against COVID-19.
Remdesivir was granted emergency use authorization by the FDA on May 1.
“Based on a recently completed nonclinical laboratory study, the FDA is revising the fact sheet for healthcare providers that accompanies the drug to state that coadministration of remdesivir and chloroquine phosphate or hydroxychloroquine sulfate is not recommended as it may result in reduced antiviral activity of remdesivir. The agency is not aware of instances of this reduced activity occurring in the clinical setting but is continuing to evaluate all data related to remdesivir,” the FDA said in a news release.
Controversy over hydroxychloroquine
Even with such federal permission, since late March the use of these two agents has been mired in controversy.
President Donald J. Trump promoted the use of hydroxychloroquine and chloroquine to treat Americans with COVID-19, while scientific studies raised questions about their safety and effectiveness. Recent research, for example, pointed to elevated cardiovascular risks, as reported by Medscape Medical News.
The FDA acknowledged this recent evidence. “Additionally, in light of ongoing serious cardiac adverse events and other potential serious side effects, the known and potential benefits of chloroquine and hydroxychloroquine no longer outweigh the known and potential risks for the authorized use.”
The full suspension of the EUA follows a warning the agency issued on April 24. The FDA’s Safety Communication cautioned against use of the two agents outside of a hospital setting, citing an increase in outpatient prescriptions and “reports of serious heart rhythm problems.”
“While additional clinical trials continue to evaluate the potential benefit of these drugs in treating or preventing COVID-19, we determined the emergency use authorization was no longer appropriate,” based on a rigorous assessment by scientists in our Center for Drug Evaluation and Research,” Patrizia Cavazzoni, MD, acting director of CDER, noted in the FDA statement.
This article first appeared on Medscape.com.
The U.S. Food and Drug Administration revoked its decision from March 28 allowing use of hydroxychloroquine and chloroquine to treat people hospitalized with COVID-19 under an emergency use authorization (EUA).
“Based on its ongoing analysis of the EUA and emerging scientific data, the FDA determined that chloroquine and hydroxychloroquine are unlikely to be effective in treating COVID-19 for the authorized uses in the EUA,” the agency announced in a June 15 statement.
The FDA also warned today that the use of hydroxychloroquine or chloroquine may have a potential drug interaction with the investigational antiviral drug remdesivir that limits its effectiveness against COVID-19.
Remdesivir was granted emergency use authorization by the FDA on May 1.
“Based on a recently completed nonclinical laboratory study, the FDA is revising the fact sheet for healthcare providers that accompanies the drug to state that coadministration of remdesivir and chloroquine phosphate or hydroxychloroquine sulfate is not recommended as it may result in reduced antiviral activity of remdesivir. The agency is not aware of instances of this reduced activity occurring in the clinical setting but is continuing to evaluate all data related to remdesivir,” the FDA said in a news release.
Controversy over hydroxychloroquine
Even with such federal permission, since late March the use of these two agents has been mired in controversy.
President Donald J. Trump promoted the use of hydroxychloroquine and chloroquine to treat Americans with COVID-19, while scientific studies raised questions about their safety and effectiveness. Recent research, for example, pointed to elevated cardiovascular risks, as reported by Medscape Medical News.
The FDA acknowledged this recent evidence. “Additionally, in light of ongoing serious cardiac adverse events and other potential serious side effects, the known and potential benefits of chloroquine and hydroxychloroquine no longer outweigh the known and potential risks for the authorized use.”
The full suspension of the EUA follows a warning the agency issued on April 24. The FDA’s Safety Communication cautioned against use of the two agents outside of a hospital setting, citing an increase in outpatient prescriptions and “reports of serious heart rhythm problems.”
“While additional clinical trials continue to evaluate the potential benefit of these drugs in treating or preventing COVID-19, we determined the emergency use authorization was no longer appropriate,” based on a rigorous assessment by scientists in our Center for Drug Evaluation and Research,” Patrizia Cavazzoni, MD, acting director of CDER, noted in the FDA statement.
This article first appeared on Medscape.com.
Perfect storm of SARS-CoV-2 during flu season
COVID-19 now. The urban phase of the U.S. pandemic is leveling somewhat, while the rural phase is accelerating – in part because of food processing and handling industries. The pediatric burden has been surprisingly small, with the multisystem inflammatory disease (MIS-c) in children noted in several hundred cases now being seen across the country.
Next wave? Given ongoing COVID-19 disease, controversy rages about when and how to re-open the country. Regardless how more reopening occurs over the next months, we should expect a next or ongoing COVID-19 wave, particularly given loss of social distancing during social justice protests. A sawtooth disease prevalence pattern is predicted by many experts: a drop in prevalence leading to reopening, leading to scattered prevalence increases and regional if not local restriction tightening, followed by another drop in prevalence. Then “rinse and repeat” until 70% of the population is immune either by disease experience or vaccine-induced immunity, likely sometime in 2021.
Influenza too. A COVID-19 up-cycle is likely during influenza season, although influenza season’s onset could be altered because of whatever social distancing rules are in place in November and December. That said, we need to consider the worst. We have seen what happens if we fail to prepare and then react only after a prevalent respiratory infection has surged into the overall population. Best estimates are that at most 20% of the U.S. population is currently immune to SARS-CoV-2. Given that at least some of that 20% of individuals currently immune to SARS-CoV-2 will lose their neutralizing antibody over the next 4-6 months, we can still expect 70%-80% of the U.S. population to be susceptible to SARS-CoV-2 infection in the fall of 2020.
Pediatric preparedness. As pediatric providers, we have struggled with lower patient loads and dramatic income losses/declines. Many clinics/offices’ attendance remain less than 50% of pre–COVID-19 levels, with necessary furloughs of personnel and spotty office hours. But influenza is coming, and SARS-CoV-2 will not be gone yet. How do we prepare for concurrent influenza and COVID-19?
The annual purchase/administration of influenza vaccine in summer/fall is expensive, time consuming, and logistically difficult even in the best times. Given the loss of income, likely reluctance of patients to come to clinics/offices if COVID-19 is still circulating, and likely need for some form of social distancing during late summer and early fall, how will providers, health departments, and hospitals implement influenza vaccine administration this year?
Minimize double whammy infections. It is easy to understand why we should maximize influenza protection in SARS-CoV-2 vulnerables (elderly or persons with existing comorbidities). But is it as critical for otherwise healthy children? My answer is yes.
Children are not currently known as SARS-CoV-2 vectors, but children are excellent influenza vectors, shedding higher titers for longer than other age groups. As with SARS-CoV-2, influenza exposure is cumulative, i.e., the more intense and more frequently a person is exposed, the more likely that infection/disease will result. So, the fewer who get and can transmit influenza during the COVID-19 pandemic, the fewer people are likely to get a double whammy of SARS-CoV-2 concurrent or in tandem with influenza. Double whammy infections likely would further increase the medical care burden and return us to March-April crisis mode.
One alarming new question is whether recent influenza could make children vulnerable to SARS-CoV-2 and trigger hospitalizations. A surge in pediatric plus adult COVID-19 disease plus a surge in all-ages influenza disease would likely break the medical care system, at least in some areas.
Staggering COVID-19 burden. As of June 8, we have had approximately 2 million SARS-CoV-2 cases with 500,000 hospitalizations and 120,000 deaths. Over the past 10 years, total annual U.S. influenza hospitalizations ranged from 180,000 (2011-2012) to 825,000 (2017-2018). The interquartile range for hospitalization length of stay for influenza is 4-6 days1 vs. 15-23 days2 for SARS-CoV-2. One COVID-19 hospitalization uses hospital resources roughly equal to four influenza hospitalizations. To date COVID-19 hospitalizations have used resources equal to an estimated 1.9 million influenza hospitalizations – over twice the worst influenza season in this century – and we are still on the rise. We are likely not even halfway to truly controlling the U.S. pandemic, so expect another 500,000 hospitalizations – equal to another 1.9 million influenza hospitalizations. Further, pneumonia deaths have skyrocketed this year when COVID-19 was superimposed on the last third of influenza season. One hope is that widespread use of antivirals (for example, new antivirals, convalescent plasma, or other interventions) can reduce length of stay by 30% for COVID-19 hospitalizations, yet even with that the numbers remain grim.
Less influenza disease can free up medical resources. Planning ahead could prevent a bad influenza season (for example, up to 850,000 hospitalizations just for influenza). Can we preemptively use vaccine to reduce influenza hospitalizations below 2011-2012 levels – less than 150,000 hospitalizations? Perhaps, if we start by reducing pediatric influenza.
1. Aim to exceed 75% influenza vaccine uptake in your patients.
a. It is ambitious, but if there was ever a year that needed influenza herd immunity, it is 2020-2021.
2. Review practice/group/institution plans for vaccine purchase and ensure adequate personnel to administer vaccine.
3. Plan safe and efficient processes to vaccinate large numbers in August through November.
a. Consider that routine and influenza vaccines can be given concurrently with the annual uptick in school and sports physical examinations.
b. What social distancing and masking rules will be needed?
i. Will patients need to bring their own masks, or will you supply them?
c. What extra supplies and efforts are needed, e.g. hand sanitizer, new signage, 6-foot interval markings on floors or sidewalks, families calling from parking lot to announce their arrivals, etc.?
d. Remember younger patients need two doses before Dec 1, 2020.
e. Be creative, for example, are parking-lot tents for influenza vaccination feasible?
f. Can we partner with other providers to implement influenza vaccine–specific mass clinics?
Ramping up to give seasonal influenza vaccine in 2020 is daunting. But if we do not prepare, it will be even more difficult. Let’s make this the mildest influenza season in memory by vaccinating more than any time in memory – and by doing so, we can hope to blunt medical care burdens despite ongoing COVID-19 disease.
Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Kansas City (Mo.). Children’s Mercy receives funding from GlaxoSmithKline, Merck, and Pfizer for vaccine research studies on which Dr. Harrison is an investigator. Email him at pdnews@mdedge.com.
References
1.. HCUP Statistical Brief #253. 2019 Oct.
2. medrxiv. 2020 Apr 10. doi: 10.1101/2020.04.07.20057299.
COVID-19 now. The urban phase of the U.S. pandemic is leveling somewhat, while the rural phase is accelerating – in part because of food processing and handling industries. The pediatric burden has been surprisingly small, with the multisystem inflammatory disease (MIS-c) in children noted in several hundred cases now being seen across the country.
Next wave? Given ongoing COVID-19 disease, controversy rages about when and how to re-open the country. Regardless how more reopening occurs over the next months, we should expect a next or ongoing COVID-19 wave, particularly given loss of social distancing during social justice protests. A sawtooth disease prevalence pattern is predicted by many experts: a drop in prevalence leading to reopening, leading to scattered prevalence increases and regional if not local restriction tightening, followed by another drop in prevalence. Then “rinse and repeat” until 70% of the population is immune either by disease experience or vaccine-induced immunity, likely sometime in 2021.
Influenza too. A COVID-19 up-cycle is likely during influenza season, although influenza season’s onset could be altered because of whatever social distancing rules are in place in November and December. That said, we need to consider the worst. We have seen what happens if we fail to prepare and then react only after a prevalent respiratory infection has surged into the overall population. Best estimates are that at most 20% of the U.S. population is currently immune to SARS-CoV-2. Given that at least some of that 20% of individuals currently immune to SARS-CoV-2 will lose their neutralizing antibody over the next 4-6 months, we can still expect 70%-80% of the U.S. population to be susceptible to SARS-CoV-2 infection in the fall of 2020.
Pediatric preparedness. As pediatric providers, we have struggled with lower patient loads and dramatic income losses/declines. Many clinics/offices’ attendance remain less than 50% of pre–COVID-19 levels, with necessary furloughs of personnel and spotty office hours. But influenza is coming, and SARS-CoV-2 will not be gone yet. How do we prepare for concurrent influenza and COVID-19?
The annual purchase/administration of influenza vaccine in summer/fall is expensive, time consuming, and logistically difficult even in the best times. Given the loss of income, likely reluctance of patients to come to clinics/offices if COVID-19 is still circulating, and likely need for some form of social distancing during late summer and early fall, how will providers, health departments, and hospitals implement influenza vaccine administration this year?
Minimize double whammy infections. It is easy to understand why we should maximize influenza protection in SARS-CoV-2 vulnerables (elderly or persons with existing comorbidities). But is it as critical for otherwise healthy children? My answer is yes.
Children are not currently known as SARS-CoV-2 vectors, but children are excellent influenza vectors, shedding higher titers for longer than other age groups. As with SARS-CoV-2, influenza exposure is cumulative, i.e., the more intense and more frequently a person is exposed, the more likely that infection/disease will result. So, the fewer who get and can transmit influenza during the COVID-19 pandemic, the fewer people are likely to get a double whammy of SARS-CoV-2 concurrent or in tandem with influenza. Double whammy infections likely would further increase the medical care burden and return us to March-April crisis mode.
One alarming new question is whether recent influenza could make children vulnerable to SARS-CoV-2 and trigger hospitalizations. A surge in pediatric plus adult COVID-19 disease plus a surge in all-ages influenza disease would likely break the medical care system, at least in some areas.
Staggering COVID-19 burden. As of June 8, we have had approximately 2 million SARS-CoV-2 cases with 500,000 hospitalizations and 120,000 deaths. Over the past 10 years, total annual U.S. influenza hospitalizations ranged from 180,000 (2011-2012) to 825,000 (2017-2018). The interquartile range for hospitalization length of stay for influenza is 4-6 days1 vs. 15-23 days2 for SARS-CoV-2. One COVID-19 hospitalization uses hospital resources roughly equal to four influenza hospitalizations. To date COVID-19 hospitalizations have used resources equal to an estimated 1.9 million influenza hospitalizations – over twice the worst influenza season in this century – and we are still on the rise. We are likely not even halfway to truly controlling the U.S. pandemic, so expect another 500,000 hospitalizations – equal to another 1.9 million influenza hospitalizations. Further, pneumonia deaths have skyrocketed this year when COVID-19 was superimposed on the last third of influenza season. One hope is that widespread use of antivirals (for example, new antivirals, convalescent plasma, or other interventions) can reduce length of stay by 30% for COVID-19 hospitalizations, yet even with that the numbers remain grim.
Less influenza disease can free up medical resources. Planning ahead could prevent a bad influenza season (for example, up to 850,000 hospitalizations just for influenza). Can we preemptively use vaccine to reduce influenza hospitalizations below 2011-2012 levels – less than 150,000 hospitalizations? Perhaps, if we start by reducing pediatric influenza.
1. Aim to exceed 75% influenza vaccine uptake in your patients.
a. It is ambitious, but if there was ever a year that needed influenza herd immunity, it is 2020-2021.
2. Review practice/group/institution plans for vaccine purchase and ensure adequate personnel to administer vaccine.
3. Plan safe and efficient processes to vaccinate large numbers in August through November.
a. Consider that routine and influenza vaccines can be given concurrently with the annual uptick in school and sports physical examinations.
b. What social distancing and masking rules will be needed?
i. Will patients need to bring their own masks, or will you supply them?
c. What extra supplies and efforts are needed, e.g. hand sanitizer, new signage, 6-foot interval markings on floors or sidewalks, families calling from parking lot to announce their arrivals, etc.?
d. Remember younger patients need two doses before Dec 1, 2020.
e. Be creative, for example, are parking-lot tents for influenza vaccination feasible?
f. Can we partner with other providers to implement influenza vaccine–specific mass clinics?
Ramping up to give seasonal influenza vaccine in 2020 is daunting. But if we do not prepare, it will be even more difficult. Let’s make this the mildest influenza season in memory by vaccinating more than any time in memory – and by doing so, we can hope to blunt medical care burdens despite ongoing COVID-19 disease.
Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Kansas City (Mo.). Children’s Mercy receives funding from GlaxoSmithKline, Merck, and Pfizer for vaccine research studies on which Dr. Harrison is an investigator. Email him at pdnews@mdedge.com.
References
1.. HCUP Statistical Brief #253. 2019 Oct.
2. medrxiv. 2020 Apr 10. doi: 10.1101/2020.04.07.20057299.
COVID-19 now. The urban phase of the U.S. pandemic is leveling somewhat, while the rural phase is accelerating – in part because of food processing and handling industries. The pediatric burden has been surprisingly small, with the multisystem inflammatory disease (MIS-c) in children noted in several hundred cases now being seen across the country.
Next wave? Given ongoing COVID-19 disease, controversy rages about when and how to re-open the country. Regardless how more reopening occurs over the next months, we should expect a next or ongoing COVID-19 wave, particularly given loss of social distancing during social justice protests. A sawtooth disease prevalence pattern is predicted by many experts: a drop in prevalence leading to reopening, leading to scattered prevalence increases and regional if not local restriction tightening, followed by another drop in prevalence. Then “rinse and repeat” until 70% of the population is immune either by disease experience or vaccine-induced immunity, likely sometime in 2021.
Influenza too. A COVID-19 up-cycle is likely during influenza season, although influenza season’s onset could be altered because of whatever social distancing rules are in place in November and December. That said, we need to consider the worst. We have seen what happens if we fail to prepare and then react only after a prevalent respiratory infection has surged into the overall population. Best estimates are that at most 20% of the U.S. population is currently immune to SARS-CoV-2. Given that at least some of that 20% of individuals currently immune to SARS-CoV-2 will lose their neutralizing antibody over the next 4-6 months, we can still expect 70%-80% of the U.S. population to be susceptible to SARS-CoV-2 infection in the fall of 2020.
Pediatric preparedness. As pediatric providers, we have struggled with lower patient loads and dramatic income losses/declines. Many clinics/offices’ attendance remain less than 50% of pre–COVID-19 levels, with necessary furloughs of personnel and spotty office hours. But influenza is coming, and SARS-CoV-2 will not be gone yet. How do we prepare for concurrent influenza and COVID-19?
The annual purchase/administration of influenza vaccine in summer/fall is expensive, time consuming, and logistically difficult even in the best times. Given the loss of income, likely reluctance of patients to come to clinics/offices if COVID-19 is still circulating, and likely need for some form of social distancing during late summer and early fall, how will providers, health departments, and hospitals implement influenza vaccine administration this year?
Minimize double whammy infections. It is easy to understand why we should maximize influenza protection in SARS-CoV-2 vulnerables (elderly or persons with existing comorbidities). But is it as critical for otherwise healthy children? My answer is yes.
Children are not currently known as SARS-CoV-2 vectors, but children are excellent influenza vectors, shedding higher titers for longer than other age groups. As with SARS-CoV-2, influenza exposure is cumulative, i.e., the more intense and more frequently a person is exposed, the more likely that infection/disease will result. So, the fewer who get and can transmit influenza during the COVID-19 pandemic, the fewer people are likely to get a double whammy of SARS-CoV-2 concurrent or in tandem with influenza. Double whammy infections likely would further increase the medical care burden and return us to March-April crisis mode.
One alarming new question is whether recent influenza could make children vulnerable to SARS-CoV-2 and trigger hospitalizations. A surge in pediatric plus adult COVID-19 disease plus a surge in all-ages influenza disease would likely break the medical care system, at least in some areas.
Staggering COVID-19 burden. As of June 8, we have had approximately 2 million SARS-CoV-2 cases with 500,000 hospitalizations and 120,000 deaths. Over the past 10 years, total annual U.S. influenza hospitalizations ranged from 180,000 (2011-2012) to 825,000 (2017-2018). The interquartile range for hospitalization length of stay for influenza is 4-6 days1 vs. 15-23 days2 for SARS-CoV-2. One COVID-19 hospitalization uses hospital resources roughly equal to four influenza hospitalizations. To date COVID-19 hospitalizations have used resources equal to an estimated 1.9 million influenza hospitalizations – over twice the worst influenza season in this century – and we are still on the rise. We are likely not even halfway to truly controlling the U.S. pandemic, so expect another 500,000 hospitalizations – equal to another 1.9 million influenza hospitalizations. Further, pneumonia deaths have skyrocketed this year when COVID-19 was superimposed on the last third of influenza season. One hope is that widespread use of antivirals (for example, new antivirals, convalescent plasma, or other interventions) can reduce length of stay by 30% for COVID-19 hospitalizations, yet even with that the numbers remain grim.
Less influenza disease can free up medical resources. Planning ahead could prevent a bad influenza season (for example, up to 850,000 hospitalizations just for influenza). Can we preemptively use vaccine to reduce influenza hospitalizations below 2011-2012 levels – less than 150,000 hospitalizations? Perhaps, if we start by reducing pediatric influenza.
1. Aim to exceed 75% influenza vaccine uptake in your patients.
a. It is ambitious, but if there was ever a year that needed influenza herd immunity, it is 2020-2021.
2. Review practice/group/institution plans for vaccine purchase and ensure adequate personnel to administer vaccine.
3. Plan safe and efficient processes to vaccinate large numbers in August through November.
a. Consider that routine and influenza vaccines can be given concurrently with the annual uptick in school and sports physical examinations.
b. What social distancing and masking rules will be needed?
i. Will patients need to bring their own masks, or will you supply them?
c. What extra supplies and efforts are needed, e.g. hand sanitizer, new signage, 6-foot interval markings on floors or sidewalks, families calling from parking lot to announce their arrivals, etc.?
d. Remember younger patients need two doses before Dec 1, 2020.
e. Be creative, for example, are parking-lot tents for influenza vaccination feasible?
f. Can we partner with other providers to implement influenza vaccine–specific mass clinics?
Ramping up to give seasonal influenza vaccine in 2020 is daunting. But if we do not prepare, it will be even more difficult. Let’s make this the mildest influenza season in memory by vaccinating more than any time in memory – and by doing so, we can hope to blunt medical care burdens despite ongoing COVID-19 disease.
Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Kansas City (Mo.). Children’s Mercy receives funding from GlaxoSmithKline, Merck, and Pfizer for vaccine research studies on which Dr. Harrison is an investigator. Email him at pdnews@mdedge.com.
References
1.. HCUP Statistical Brief #253. 2019 Oct.
2. medrxiv. 2020 Apr 10. doi: 10.1101/2020.04.07.20057299.
Learning the ICU
Although deployment of hospitalists into ICUs during the COVID-19 crisis varies widely, in that sense it reflects the pre-COVID hospital landscape of variable involvement, in which many hospitalists pressed into this role expressed discomfort practicing critical care beyond their scope of training, according to a survey published in the Journal of Hospital Medicine in 2018.1 “Hospitalists frequently deliver critical care services without adequate training or support, most prevalently in rural hospitals,” the authors concluded.
A Critical Care for the Hospitalist Series of resources and lectures developed by Eric Siegal, MD, a pulmonologist in Milwaukee, Wisc., and David Aymond, MD, a hospitalist in Alexandria, La., is available on the SHM website. They recommend that hospitalists trying to get oriented to working in the ICU start with the online courses on fluid resuscitation, mechanical ventilation, and noninvasive ventilation.
“Ninety-five percent of management of COVID-19 patients is nothing other than practicing sound critical care medicine,” Dr. Siegal said. “If you want to take effective care of sick COVID patients, you need to develop good foundational critical care skills and knowledge. Without them, you’re doing stuff without understand it.”
Dr. Aymond also encourages hospitalists to develop a stronger understanding of key physiological concepts by reviewing the critical care clinical topics compiled at SHM’s website.
References
1. Sweigart JR et al. Characterizing hospitalist practice and perceptions of critical care delivery. J Hosp Med. 2018 Jan;13(1):6-12.
Although deployment of hospitalists into ICUs during the COVID-19 crisis varies widely, in that sense it reflects the pre-COVID hospital landscape of variable involvement, in which many hospitalists pressed into this role expressed discomfort practicing critical care beyond their scope of training, according to a survey published in the Journal of Hospital Medicine in 2018.1 “Hospitalists frequently deliver critical care services without adequate training or support, most prevalently in rural hospitals,” the authors concluded.
A Critical Care for the Hospitalist Series of resources and lectures developed by Eric Siegal, MD, a pulmonologist in Milwaukee, Wisc., and David Aymond, MD, a hospitalist in Alexandria, La., is available on the SHM website. They recommend that hospitalists trying to get oriented to working in the ICU start with the online courses on fluid resuscitation, mechanical ventilation, and noninvasive ventilation.
“Ninety-five percent of management of COVID-19 patients is nothing other than practicing sound critical care medicine,” Dr. Siegal said. “If you want to take effective care of sick COVID patients, you need to develop good foundational critical care skills and knowledge. Without them, you’re doing stuff without understand it.”
Dr. Aymond also encourages hospitalists to develop a stronger understanding of key physiological concepts by reviewing the critical care clinical topics compiled at SHM’s website.
References
1. Sweigart JR et al. Characterizing hospitalist practice and perceptions of critical care delivery. J Hosp Med. 2018 Jan;13(1):6-12.
Although deployment of hospitalists into ICUs during the COVID-19 crisis varies widely, in that sense it reflects the pre-COVID hospital landscape of variable involvement, in which many hospitalists pressed into this role expressed discomfort practicing critical care beyond their scope of training, according to a survey published in the Journal of Hospital Medicine in 2018.1 “Hospitalists frequently deliver critical care services without adequate training or support, most prevalently in rural hospitals,” the authors concluded.
A Critical Care for the Hospitalist Series of resources and lectures developed by Eric Siegal, MD, a pulmonologist in Milwaukee, Wisc., and David Aymond, MD, a hospitalist in Alexandria, La., is available on the SHM website. They recommend that hospitalists trying to get oriented to working in the ICU start with the online courses on fluid resuscitation, mechanical ventilation, and noninvasive ventilation.
“Ninety-five percent of management of COVID-19 patients is nothing other than practicing sound critical care medicine,” Dr. Siegal said. “If you want to take effective care of sick COVID patients, you need to develop good foundational critical care skills and knowledge. Without them, you’re doing stuff without understand it.”
Dr. Aymond also encourages hospitalists to develop a stronger understanding of key physiological concepts by reviewing the critical care clinical topics compiled at SHM’s website.
References
1. Sweigart JR et al. Characterizing hospitalist practice and perceptions of critical care delivery. J Hosp Med. 2018 Jan;13(1):6-12.
Renal denervation response similar regardless of CV risks, comorbidities
In a new analysis of international registry data, renal denervation resulted in similar reduced blood pressure levels in patients with varying high-risk comorbidities and across a range of cardiovascular risk scores.
At 3 years, 24-hour systolic BP was reduced by an average of –8.9 mm Hg overall, with slightly higher or lower readings seen in those with higher cardiovascular risk scores (–10.4 mm Hg) and 65 years or older (–10.2 mm Hg). Similar reductions were seen in those with resistant hypertension (–8.7 mm Hg), diabetes (–8.6 mm Hg), isolated systolic hypertension (–10.1 mm Hg), chronic kidney disease (–10.1 mm Hg), or atrial fibrillation (–10.0 mm Hg).
“In the largest international registry of its kind, the efficacy of renal denervation was similar in patients with and without baseline conditions associated with increased sympathetic activity and irrespective of ASCVD [atherosclerotic cardiovascular disease] risk,” first author Felix Mahfoud, MD, said in an interview.
Dr. Mahfoud, from University Hospital of Saarland, Homburg, Germany, and colleagues published their analysis in the Journal of the American College of Cardiology.
The article reported a post hoc analysis of data from the Global SYMPLICITY Registry (GSR), an international, Medtronic-funded effort that includes 2,652 patients with uncontrolled hypertension treated with a Symplicity denervation system. Data were obtained from 196 centers in 45 countries.
“Blood pressure reductions were durable and sustained to 3 years and the rates of new-onset, end-stage renal disease and elevation in serum creatinine levels were very low in patients at high and low [cardiovascular] risk,” reported Dr. Mahfoud.
As expected, adverse event rates were higher for patients with higher baseline cardiovascular risk. “Elevated rates were also seen in patients with [atrial fibrillation] and diabetes, identifying these subgroups who might derive even greater clinical benefit from improved BP control using renal denervation,” said Dr. Mahfoud.
Asked which patients might be optimal candidates for renal denervation, Dr. Mahfoud recommended the technology for “patients with uncontrolled hypertension on medication, patients with nonadherence, unwillingness, or intolerability to medication, and patients with combined systolic and diastolic hypertension.”
Analyses limited by incomplete data
Stephen C. Textor, MD, has concerns over the amount of missing data in the GSR database and its continued use as a repository of information on renal denervation.
“I am a bit lukewarm on this paper in part because of the nature of the registry data they’re using,” he added in an interview. “The problem I see is that the registry is not terribly uniform as to what information they collect on each patient, not terribly uniform in terms of how the procedure is performed, and not terribly uniform on how they follow up patients.”
Indeed, the post hoc subgroup analyses represent only a limited subset because of incomplete data, added Dr. Textor, a nephrologist at the Cleveland Clinic in Rochester, Minn.
“Remarkably, only 504 [patients] had “matched” data for office [systolic BP] levels at the time points defined in the report,” he wrote in an editorial comment accompanying the registry report (J Am Coll Cardiol. 2020 Jun 16;75[23]:2889-91).
Similarly, the researchers were able to calculate baseline atherosclerotic cardiovascular risk scores in only 1,485 patients (56% of total), primarily because of missing cholesterol measurements.
“They simply did these paired comparison that may have included a couple hundred cases, and on average, there were no differences in response, but what I would have liked to see is a multivariate analysis, where you have all the data on everybody and look at what are the factors that impact response?” Dr. Textor said in the interview.
“They really couldn’t do that because they just, they’re just too many holes in the data,” he added.
On the bright side, Dr. Textor noted that, while the impact overall on systolic BP was “modest,” the standard deviations in some cases were large, indicating that some people had large reductions of systolic BP of more than 30-40 mm Hg.
“There is a belief out there that there are some people that really benefit from this, but how to identify them has been the question,” Dr. Textor said.
Enthusiasm for renal denervation plummeted after results from the SYMPLICITY HTN-3 showed the procedure failing to meet its efficacy endpoint in resistant hypertension. The procedure was associated with a 14–mm Hg fall in systolic BP, compared with an 11–mm Hg drop in the “sham” control group (N Engl J Med. 2014 Apr 10;370:1393-401). However, post hoc analysis of the trial revealed significant shortcomings in design and execution.
No renal denervation device is approved in the United States. The Symplicity device used in this registry is approved in the European Union.
In early 2020, the Food and Drug Administration promised a rigorous review of new renal denervation trials. Subsequently, primary results from the SPYRAL HTN-OFF MED pivotal trial were presented at the annual meeting of the American College of Cardiology in March and showed promising efficacy.
SPYRAL HTN OFF-MED was designed in collaboration with the FDA to obtain meaningful evidence of whether renal denervation performed with the Symplicity Spyral multielectrode catheter (Medtronic Vascular) could reduce BP in patients not taking antihypertensive medication.
Dr. Mahfoud reported he has received speaking honoraria from Medtronic and ReCor. Two other authors are employees of Medtronic. Dr. Textor reported no relationships relevant to the contents of this paper. The Global SYMPLICITY Registry is funded by Medtronic Vascular.
SOURCE: Mahfoud F et al. J Am Coll Cardiol. 2020 June 16;75:2879-88.
This article was updated 6/16/20.
In a new analysis of international registry data, renal denervation resulted in similar reduced blood pressure levels in patients with varying high-risk comorbidities and across a range of cardiovascular risk scores.
At 3 years, 24-hour systolic BP was reduced by an average of –8.9 mm Hg overall, with slightly higher or lower readings seen in those with higher cardiovascular risk scores (–10.4 mm Hg) and 65 years or older (–10.2 mm Hg). Similar reductions were seen in those with resistant hypertension (–8.7 mm Hg), diabetes (–8.6 mm Hg), isolated systolic hypertension (–10.1 mm Hg), chronic kidney disease (–10.1 mm Hg), or atrial fibrillation (–10.0 mm Hg).
“In the largest international registry of its kind, the efficacy of renal denervation was similar in patients with and without baseline conditions associated with increased sympathetic activity and irrespective of ASCVD [atherosclerotic cardiovascular disease] risk,” first author Felix Mahfoud, MD, said in an interview.
Dr. Mahfoud, from University Hospital of Saarland, Homburg, Germany, and colleagues published their analysis in the Journal of the American College of Cardiology.
The article reported a post hoc analysis of data from the Global SYMPLICITY Registry (GSR), an international, Medtronic-funded effort that includes 2,652 patients with uncontrolled hypertension treated with a Symplicity denervation system. Data were obtained from 196 centers in 45 countries.
“Blood pressure reductions were durable and sustained to 3 years and the rates of new-onset, end-stage renal disease and elevation in serum creatinine levels were very low in patients at high and low [cardiovascular] risk,” reported Dr. Mahfoud.
As expected, adverse event rates were higher for patients with higher baseline cardiovascular risk. “Elevated rates were also seen in patients with [atrial fibrillation] and diabetes, identifying these subgroups who might derive even greater clinical benefit from improved BP control using renal denervation,” said Dr. Mahfoud.
Asked which patients might be optimal candidates for renal denervation, Dr. Mahfoud recommended the technology for “patients with uncontrolled hypertension on medication, patients with nonadherence, unwillingness, or intolerability to medication, and patients with combined systolic and diastolic hypertension.”
Analyses limited by incomplete data
Stephen C. Textor, MD, has concerns over the amount of missing data in the GSR database and its continued use as a repository of information on renal denervation.
“I am a bit lukewarm on this paper in part because of the nature of the registry data they’re using,” he added in an interview. “The problem I see is that the registry is not terribly uniform as to what information they collect on each patient, not terribly uniform in terms of how the procedure is performed, and not terribly uniform on how they follow up patients.”
Indeed, the post hoc subgroup analyses represent only a limited subset because of incomplete data, added Dr. Textor, a nephrologist at the Cleveland Clinic in Rochester, Minn.
“Remarkably, only 504 [patients] had “matched” data for office [systolic BP] levels at the time points defined in the report,” he wrote in an editorial comment accompanying the registry report (J Am Coll Cardiol. 2020 Jun 16;75[23]:2889-91).
Similarly, the researchers were able to calculate baseline atherosclerotic cardiovascular risk scores in only 1,485 patients (56% of total), primarily because of missing cholesterol measurements.
“They simply did these paired comparison that may have included a couple hundred cases, and on average, there were no differences in response, but what I would have liked to see is a multivariate analysis, where you have all the data on everybody and look at what are the factors that impact response?” Dr. Textor said in the interview.
“They really couldn’t do that because they just, they’re just too many holes in the data,” he added.
On the bright side, Dr. Textor noted that, while the impact overall on systolic BP was “modest,” the standard deviations in some cases were large, indicating that some people had large reductions of systolic BP of more than 30-40 mm Hg.
“There is a belief out there that there are some people that really benefit from this, but how to identify them has been the question,” Dr. Textor said.
Enthusiasm for renal denervation plummeted after results from the SYMPLICITY HTN-3 showed the procedure failing to meet its efficacy endpoint in resistant hypertension. The procedure was associated with a 14–mm Hg fall in systolic BP, compared with an 11–mm Hg drop in the “sham” control group (N Engl J Med. 2014 Apr 10;370:1393-401). However, post hoc analysis of the trial revealed significant shortcomings in design and execution.
No renal denervation device is approved in the United States. The Symplicity device used in this registry is approved in the European Union.
In early 2020, the Food and Drug Administration promised a rigorous review of new renal denervation trials. Subsequently, primary results from the SPYRAL HTN-OFF MED pivotal trial were presented at the annual meeting of the American College of Cardiology in March and showed promising efficacy.
SPYRAL HTN OFF-MED was designed in collaboration with the FDA to obtain meaningful evidence of whether renal denervation performed with the Symplicity Spyral multielectrode catheter (Medtronic Vascular) could reduce BP in patients not taking antihypertensive medication.
Dr. Mahfoud reported he has received speaking honoraria from Medtronic and ReCor. Two other authors are employees of Medtronic. Dr. Textor reported no relationships relevant to the contents of this paper. The Global SYMPLICITY Registry is funded by Medtronic Vascular.
SOURCE: Mahfoud F et al. J Am Coll Cardiol. 2020 June 16;75:2879-88.
This article was updated 6/16/20.
In a new analysis of international registry data, renal denervation resulted in similar reduced blood pressure levels in patients with varying high-risk comorbidities and across a range of cardiovascular risk scores.
At 3 years, 24-hour systolic BP was reduced by an average of –8.9 mm Hg overall, with slightly higher or lower readings seen in those with higher cardiovascular risk scores (–10.4 mm Hg) and 65 years or older (–10.2 mm Hg). Similar reductions were seen in those with resistant hypertension (–8.7 mm Hg), diabetes (–8.6 mm Hg), isolated systolic hypertension (–10.1 mm Hg), chronic kidney disease (–10.1 mm Hg), or atrial fibrillation (–10.0 mm Hg).
“In the largest international registry of its kind, the efficacy of renal denervation was similar in patients with and without baseline conditions associated with increased sympathetic activity and irrespective of ASCVD [atherosclerotic cardiovascular disease] risk,” first author Felix Mahfoud, MD, said in an interview.
Dr. Mahfoud, from University Hospital of Saarland, Homburg, Germany, and colleagues published their analysis in the Journal of the American College of Cardiology.
The article reported a post hoc analysis of data from the Global SYMPLICITY Registry (GSR), an international, Medtronic-funded effort that includes 2,652 patients with uncontrolled hypertension treated with a Symplicity denervation system. Data were obtained from 196 centers in 45 countries.
“Blood pressure reductions were durable and sustained to 3 years and the rates of new-onset, end-stage renal disease and elevation in serum creatinine levels were very low in patients at high and low [cardiovascular] risk,” reported Dr. Mahfoud.
As expected, adverse event rates were higher for patients with higher baseline cardiovascular risk. “Elevated rates were also seen in patients with [atrial fibrillation] and diabetes, identifying these subgroups who might derive even greater clinical benefit from improved BP control using renal denervation,” said Dr. Mahfoud.
Asked which patients might be optimal candidates for renal denervation, Dr. Mahfoud recommended the technology for “patients with uncontrolled hypertension on medication, patients with nonadherence, unwillingness, or intolerability to medication, and patients with combined systolic and diastolic hypertension.”
Analyses limited by incomplete data
Stephen C. Textor, MD, has concerns over the amount of missing data in the GSR database and its continued use as a repository of information on renal denervation.
“I am a bit lukewarm on this paper in part because of the nature of the registry data they’re using,” he added in an interview. “The problem I see is that the registry is not terribly uniform as to what information they collect on each patient, not terribly uniform in terms of how the procedure is performed, and not terribly uniform on how they follow up patients.”
Indeed, the post hoc subgroup analyses represent only a limited subset because of incomplete data, added Dr. Textor, a nephrologist at the Cleveland Clinic in Rochester, Minn.
“Remarkably, only 504 [patients] had “matched” data for office [systolic BP] levels at the time points defined in the report,” he wrote in an editorial comment accompanying the registry report (J Am Coll Cardiol. 2020 Jun 16;75[23]:2889-91).
Similarly, the researchers were able to calculate baseline atherosclerotic cardiovascular risk scores in only 1,485 patients (56% of total), primarily because of missing cholesterol measurements.
“They simply did these paired comparison that may have included a couple hundred cases, and on average, there were no differences in response, but what I would have liked to see is a multivariate analysis, where you have all the data on everybody and look at what are the factors that impact response?” Dr. Textor said in the interview.
“They really couldn’t do that because they just, they’re just too many holes in the data,” he added.
On the bright side, Dr. Textor noted that, while the impact overall on systolic BP was “modest,” the standard deviations in some cases were large, indicating that some people had large reductions of systolic BP of more than 30-40 mm Hg.
“There is a belief out there that there are some people that really benefit from this, but how to identify them has been the question,” Dr. Textor said.
Enthusiasm for renal denervation plummeted after results from the SYMPLICITY HTN-3 showed the procedure failing to meet its efficacy endpoint in resistant hypertension. The procedure was associated with a 14–mm Hg fall in systolic BP, compared with an 11–mm Hg drop in the “sham” control group (N Engl J Med. 2014 Apr 10;370:1393-401). However, post hoc analysis of the trial revealed significant shortcomings in design and execution.
No renal denervation device is approved in the United States. The Symplicity device used in this registry is approved in the European Union.
In early 2020, the Food and Drug Administration promised a rigorous review of new renal denervation trials. Subsequently, primary results from the SPYRAL HTN-OFF MED pivotal trial were presented at the annual meeting of the American College of Cardiology in March and showed promising efficacy.
SPYRAL HTN OFF-MED was designed in collaboration with the FDA to obtain meaningful evidence of whether renal denervation performed with the Symplicity Spyral multielectrode catheter (Medtronic Vascular) could reduce BP in patients not taking antihypertensive medication.
Dr. Mahfoud reported he has received speaking honoraria from Medtronic and ReCor. Two other authors are employees of Medtronic. Dr. Textor reported no relationships relevant to the contents of this paper. The Global SYMPLICITY Registry is funded by Medtronic Vascular.
SOURCE: Mahfoud F et al. J Am Coll Cardiol. 2020 June 16;75:2879-88.
This article was updated 6/16/20.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Cognitive-behavioral therapy a standout for better immune function
Psychosocial interventions, particularly cognitive-behavioral therapy (CBT), are associated with enhanced immune system function, new research suggests.
Results of a systematic review and meta-analysis that included 56 randomized controlled trials and more than 4,000 participants showed that over time, psychosocial interventions appeared to augment beneficial immune system function while concurrently decreasing harmful immune system function in comparison with control conditions.
“These associations were most reliable for cognitive-behavioral therapy and multiple or combined interventions and for studies that assessed proinflammatory cytokines or markers, which are key indicators of inflammation in the body,” study investigator George M. Slavich, PhD, said in an interview.
“The analysis helps address the question of which types of psychosocial interventions are most consistently associated with changes in immune system function, under what conditions, and for whom. This knowledge could, in turn, be used to inform research efforts and public policy aimed at using psychosocial interventions to improve immune-related health outcomes,” added Dr. Slavich, director of the Laboratory for Stress Assessment and Research, University of California, Los Angeles.
The study was published online June 3 in JAMA Psychiatry.
Link to serious physical, mental illnesses
There is substantial evidence that the immune system plays a role in a variety of mental and physical health problems. Such problems include anxiety disorders, depression, suicide, schizophrenia, cardiovascular disease, autoimmune disorders, and neurodegenerative diseases. It has been recently suggested that more than half of all deaths worldwide are attributable to inflammation-related conditions.
Although pharmacologic interventions can play a role in addressing inflammation, they are not without drawbacks, most notably, cost and adverse side effects.
The World Health Organization, the National Academy of Medicine, the National Institutes of Health, and other groups have emphasized the importance of addressing global disease burden through psychosocial interventions when possible.
Such recommendations are supported by scientific evidence. Previous research has shown that immune system processes are influenced by a variety of social, neurocognitive, and behavioral factors.
Given such findings, researchers have examined the effects of interventions that reduce stress or bolster psychological resources on immune system function.
However, such research has yielded conflicting findings. Some studies show that psychosocial interventions clearly enhance immunity, whereas others do not.
In addition, questions remain regarding which types of interventions reliably improve immune system function, under what conditions, and for whom.
“Research has shown that psychological factors – such as life stress, negative emotions, and social support – are associated with changes in immune system function,” Dr. Slavich noted.
“In addition, there is growing appreciation that immune system processes involved in inflammation may contribute to peoples’ risk for several major mental and physical health problems, including anxiety disorders, depression, heart disease, and autoimmune and neurodegenerative disorders.”
First study of its kind
To shed light on these potential links, the researchers conducted what they believe is the first systematic review and meta-analysis of randomized clinical trials of the effects of psychosocial interventions on immune system outcomes.
As part of the review, Dr. Slavich and colleagues estimated the associations between eight psychosocial interventions and seven markers of immune system function.
The eight psychosocial interventions were behavior therapy, cognitive therapy, CBT, CBT plus additive treatment or mode of delivery, bereavement or supportive therapy, multiple or combined interventions, other psychotherapy, and psychoeducation.
The seven immune outcomes that might be influenced by these interventions are proinflammatory cytokines and markers, anti-inflammatory cytokines, antibodies, immune cell counts, natural killer cell activity, viral load, and other immune outcomes.
The researchers also examined nine potential factors that might moderate the associations between psychosocial interventions and immune system function.
They searched a variety of databases for all relevant randomized controlled trials published through Dec. 31, 2018. Studies were eligible for inclusion if they included a psychosocial intervention and immune outcome, as well as preintervention and postintervention immunologic assessments.
The researchers identified 4,621 studies. Of these studies, 62 were eligible for inclusion; 56, which included 4,060 patients, were included in the final meta-analysis.
Results showed that psychosocial interventions were associated with enhanced immune system function (P < .001). There was relatively low heterogeneity between studies in these effect sizes, which, the investigators said, indicates that the association was relatively consistent across studies and conditions.
The meta-analysis showed that individuals who were assigned to a psychosocial intervention condition demonstrated a 14.7% improvement (95% confidence interval [CI], 5.7%–23.8%) in beneficial immune system function compared with their counterparts who were assigned to a control condition.
Similarly, participants who received psychosocial interventions demonstrated an 18.0% decrease (95% CI, 7.2%–28.8%) in harmful immune system function over time.
A standout
Regarding the effect of the type of intervention on the association, only CBT (31 studies; P < .001) and multiple or combined interventions (seven studies; P = .01) were significantly associated with changes in immune system outcomes.
The analysis also found that interventions that included a group component were more consistently associated with enhanced immune function than were those that did not include a group component. Nevertheless, this difference did not reach statistical significance (P = .06).
Contrary to the researchers’ expectations, the analysis also revealed that intervention length did not moderate the association between psychosocial interventions and immune system function (P = .93).
With respect to the type of immune marker studied, the meta-analysis found that psychosocial interventions had significantly different associations with the various immune markers studied. Of the seven immune outcomes investigated, only proinflammatory cytokine or marker levels (33 studies; P < .001) and immune cell counts (27 studies; P < .001) were significantly associated with the psychosocial interventions examined.
and were robust across age, sex, and intervention duration.
These results suggest that psychosocial interventions – particularly CBT and multiple or combined psychotherapeutic modalities – may play an important role in improving immune-related health outcomes.
Such interventions may not only be effective, they may also prove to be affordable alternatives to current therapeutic options. The mean length of a CBT intervention in the meta-analysis was 10.4 weeks, which the investigators equated with a total cost of $1,560 per patient.
“By comparison, the cost of using infliximab to reduce inflammation in persons with an autoimmune disorder is approximately $25,000 per patient per year,” they wrote.
“The results suggest the possibility that psychotherapy may be helpful for reducing inflammation and improving immune-related health in certain circumstances,” Dr. Slavich concluded. “However, the studies that we examined differed in terms of their quality, and we did not examine health outcomes in the present investigation.
“Therefore, more research needs to be done to determine how the present findings might be translated into treatment options or public policy.”
A path to better health
In an accompanying editorial, Veronika Engert, PhD, Joshua A. Grant, PhD, and Bernhard Strauss, PhD, noted that although infectious disease was once the primary cause of death in society, it has been supplanted by other complex and chronic illnesses, which often do not follow simple cause-and-effect associations.
“Rather,” they wrote, “these illnesses develop from a complex milieu of biological, psychological, and social factors that may also influence the disease progress and its prognosis. Against this backdrop, the meta-analysis by Shields and colleagues is an important confirmation of the biopsychosocial model.”
The editorialists explained that recent psychophysiological, neurobiological, and epigenetic research offers a glimpse into the relationship between psychological and social factors in pathogenesis. Nevertheless, the authors noted that a comprehensive examination of the potential effects of psychosocial interventions on immune parameters in various physical health conditions has been lacking.
“The evidence provided by Shields et al. is exactly what is needed to more fully shift treatment from an illness-centered to a patient-centered approach,” they wrote. “To that end, this meta-analysis may serve as a guide for policy makers aiming to improve immune-associated health.”
The research was supported by a Society in Science–Branco Weiss Fellowship, Brain and Behavior Research, and the National Institutes of Health. Dr. Slavich, Dr. Engert, Dr. Grant, and Dr. Strauss have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Psychosocial interventions, particularly cognitive-behavioral therapy (CBT), are associated with enhanced immune system function, new research suggests.
Results of a systematic review and meta-analysis that included 56 randomized controlled trials and more than 4,000 participants showed that over time, psychosocial interventions appeared to augment beneficial immune system function while concurrently decreasing harmful immune system function in comparison with control conditions.
“These associations were most reliable for cognitive-behavioral therapy and multiple or combined interventions and for studies that assessed proinflammatory cytokines or markers, which are key indicators of inflammation in the body,” study investigator George M. Slavich, PhD, said in an interview.
“The analysis helps address the question of which types of psychosocial interventions are most consistently associated with changes in immune system function, under what conditions, and for whom. This knowledge could, in turn, be used to inform research efforts and public policy aimed at using psychosocial interventions to improve immune-related health outcomes,” added Dr. Slavich, director of the Laboratory for Stress Assessment and Research, University of California, Los Angeles.
The study was published online June 3 in JAMA Psychiatry.
Link to serious physical, mental illnesses
There is substantial evidence that the immune system plays a role in a variety of mental and physical health problems. Such problems include anxiety disorders, depression, suicide, schizophrenia, cardiovascular disease, autoimmune disorders, and neurodegenerative diseases. It has been recently suggested that more than half of all deaths worldwide are attributable to inflammation-related conditions.
Although pharmacologic interventions can play a role in addressing inflammation, they are not without drawbacks, most notably, cost and adverse side effects.
The World Health Organization, the National Academy of Medicine, the National Institutes of Health, and other groups have emphasized the importance of addressing global disease burden through psychosocial interventions when possible.
Such recommendations are supported by scientific evidence. Previous research has shown that immune system processes are influenced by a variety of social, neurocognitive, and behavioral factors.
Given such findings, researchers have examined the effects of interventions that reduce stress or bolster psychological resources on immune system function.
However, such research has yielded conflicting findings. Some studies show that psychosocial interventions clearly enhance immunity, whereas others do not.
In addition, questions remain regarding which types of interventions reliably improve immune system function, under what conditions, and for whom.
“Research has shown that psychological factors – such as life stress, negative emotions, and social support – are associated with changes in immune system function,” Dr. Slavich noted.
“In addition, there is growing appreciation that immune system processes involved in inflammation may contribute to peoples’ risk for several major mental and physical health problems, including anxiety disorders, depression, heart disease, and autoimmune and neurodegenerative disorders.”
First study of its kind
To shed light on these potential links, the researchers conducted what they believe is the first systematic review and meta-analysis of randomized clinical trials of the effects of psychosocial interventions on immune system outcomes.
As part of the review, Dr. Slavich and colleagues estimated the associations between eight psychosocial interventions and seven markers of immune system function.
The eight psychosocial interventions were behavior therapy, cognitive therapy, CBT, CBT plus additive treatment or mode of delivery, bereavement or supportive therapy, multiple or combined interventions, other psychotherapy, and psychoeducation.
The seven immune outcomes that might be influenced by these interventions are proinflammatory cytokines and markers, anti-inflammatory cytokines, antibodies, immune cell counts, natural killer cell activity, viral load, and other immune outcomes.
The researchers also examined nine potential factors that might moderate the associations between psychosocial interventions and immune system function.
They searched a variety of databases for all relevant randomized controlled trials published through Dec. 31, 2018. Studies were eligible for inclusion if they included a psychosocial intervention and immune outcome, as well as preintervention and postintervention immunologic assessments.
The researchers identified 4,621 studies. Of these studies, 62 were eligible for inclusion; 56, which included 4,060 patients, were included in the final meta-analysis.
Results showed that psychosocial interventions were associated with enhanced immune system function (P < .001). There was relatively low heterogeneity between studies in these effect sizes, which, the investigators said, indicates that the association was relatively consistent across studies and conditions.
The meta-analysis showed that individuals who were assigned to a psychosocial intervention condition demonstrated a 14.7% improvement (95% confidence interval [CI], 5.7%–23.8%) in beneficial immune system function compared with their counterparts who were assigned to a control condition.
Similarly, participants who received psychosocial interventions demonstrated an 18.0% decrease (95% CI, 7.2%–28.8%) in harmful immune system function over time.
A standout
Regarding the effect of the type of intervention on the association, only CBT (31 studies; P < .001) and multiple or combined interventions (seven studies; P = .01) were significantly associated with changes in immune system outcomes.
The analysis also found that interventions that included a group component were more consistently associated with enhanced immune function than were those that did not include a group component. Nevertheless, this difference did not reach statistical significance (P = .06).
Contrary to the researchers’ expectations, the analysis also revealed that intervention length did not moderate the association between psychosocial interventions and immune system function (P = .93).
With respect to the type of immune marker studied, the meta-analysis found that psychosocial interventions had significantly different associations with the various immune markers studied. Of the seven immune outcomes investigated, only proinflammatory cytokine or marker levels (33 studies; P < .001) and immune cell counts (27 studies; P < .001) were significantly associated with the psychosocial interventions examined.
and were robust across age, sex, and intervention duration.
These results suggest that psychosocial interventions – particularly CBT and multiple or combined psychotherapeutic modalities – may play an important role in improving immune-related health outcomes.
Such interventions may not only be effective, they may also prove to be affordable alternatives to current therapeutic options. The mean length of a CBT intervention in the meta-analysis was 10.4 weeks, which the investigators equated with a total cost of $1,560 per patient.
“By comparison, the cost of using infliximab to reduce inflammation in persons with an autoimmune disorder is approximately $25,000 per patient per year,” they wrote.
“The results suggest the possibility that psychotherapy may be helpful for reducing inflammation and improving immune-related health in certain circumstances,” Dr. Slavich concluded. “However, the studies that we examined differed in terms of their quality, and we did not examine health outcomes in the present investigation.
“Therefore, more research needs to be done to determine how the present findings might be translated into treatment options or public policy.”
A path to better health
In an accompanying editorial, Veronika Engert, PhD, Joshua A. Grant, PhD, and Bernhard Strauss, PhD, noted that although infectious disease was once the primary cause of death in society, it has been supplanted by other complex and chronic illnesses, which often do not follow simple cause-and-effect associations.
“Rather,” they wrote, “these illnesses develop from a complex milieu of biological, psychological, and social factors that may also influence the disease progress and its prognosis. Against this backdrop, the meta-analysis by Shields and colleagues is an important confirmation of the biopsychosocial model.”
The editorialists explained that recent psychophysiological, neurobiological, and epigenetic research offers a glimpse into the relationship between psychological and social factors in pathogenesis. Nevertheless, the authors noted that a comprehensive examination of the potential effects of psychosocial interventions on immune parameters in various physical health conditions has been lacking.
“The evidence provided by Shields et al. is exactly what is needed to more fully shift treatment from an illness-centered to a patient-centered approach,” they wrote. “To that end, this meta-analysis may serve as a guide for policy makers aiming to improve immune-associated health.”
The research was supported by a Society in Science–Branco Weiss Fellowship, Brain and Behavior Research, and the National Institutes of Health. Dr. Slavich, Dr. Engert, Dr. Grant, and Dr. Strauss have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Psychosocial interventions, particularly cognitive-behavioral therapy (CBT), are associated with enhanced immune system function, new research suggests.
Results of a systematic review and meta-analysis that included 56 randomized controlled trials and more than 4,000 participants showed that over time, psychosocial interventions appeared to augment beneficial immune system function while concurrently decreasing harmful immune system function in comparison with control conditions.
“These associations were most reliable for cognitive-behavioral therapy and multiple or combined interventions and for studies that assessed proinflammatory cytokines or markers, which are key indicators of inflammation in the body,” study investigator George M. Slavich, PhD, said in an interview.
“The analysis helps address the question of which types of psychosocial interventions are most consistently associated with changes in immune system function, under what conditions, and for whom. This knowledge could, in turn, be used to inform research efforts and public policy aimed at using psychosocial interventions to improve immune-related health outcomes,” added Dr. Slavich, director of the Laboratory for Stress Assessment and Research, University of California, Los Angeles.
The study was published online June 3 in JAMA Psychiatry.
Link to serious physical, mental illnesses
There is substantial evidence that the immune system plays a role in a variety of mental and physical health problems. Such problems include anxiety disorders, depression, suicide, schizophrenia, cardiovascular disease, autoimmune disorders, and neurodegenerative diseases. It has been recently suggested that more than half of all deaths worldwide are attributable to inflammation-related conditions.
Although pharmacologic interventions can play a role in addressing inflammation, they are not without drawbacks, most notably, cost and adverse side effects.
The World Health Organization, the National Academy of Medicine, the National Institutes of Health, and other groups have emphasized the importance of addressing global disease burden through psychosocial interventions when possible.
Such recommendations are supported by scientific evidence. Previous research has shown that immune system processes are influenced by a variety of social, neurocognitive, and behavioral factors.
Given such findings, researchers have examined the effects of interventions that reduce stress or bolster psychological resources on immune system function.
However, such research has yielded conflicting findings. Some studies show that psychosocial interventions clearly enhance immunity, whereas others do not.
In addition, questions remain regarding which types of interventions reliably improve immune system function, under what conditions, and for whom.
“Research has shown that psychological factors – such as life stress, negative emotions, and social support – are associated with changes in immune system function,” Dr. Slavich noted.
“In addition, there is growing appreciation that immune system processes involved in inflammation may contribute to peoples’ risk for several major mental and physical health problems, including anxiety disorders, depression, heart disease, and autoimmune and neurodegenerative disorders.”
First study of its kind
To shed light on these potential links, the researchers conducted what they believe is the first systematic review and meta-analysis of randomized clinical trials of the effects of psychosocial interventions on immune system outcomes.
As part of the review, Dr. Slavich and colleagues estimated the associations between eight psychosocial interventions and seven markers of immune system function.
The eight psychosocial interventions were behavior therapy, cognitive therapy, CBT, CBT plus additive treatment or mode of delivery, bereavement or supportive therapy, multiple or combined interventions, other psychotherapy, and psychoeducation.
The seven immune outcomes that might be influenced by these interventions are proinflammatory cytokines and markers, anti-inflammatory cytokines, antibodies, immune cell counts, natural killer cell activity, viral load, and other immune outcomes.
The researchers also examined nine potential factors that might moderate the associations between psychosocial interventions and immune system function.
They searched a variety of databases for all relevant randomized controlled trials published through Dec. 31, 2018. Studies were eligible for inclusion if they included a psychosocial intervention and immune outcome, as well as preintervention and postintervention immunologic assessments.
The researchers identified 4,621 studies. Of these studies, 62 were eligible for inclusion; 56, which included 4,060 patients, were included in the final meta-analysis.
Results showed that psychosocial interventions were associated with enhanced immune system function (P < .001). There was relatively low heterogeneity between studies in these effect sizes, which, the investigators said, indicates that the association was relatively consistent across studies and conditions.
The meta-analysis showed that individuals who were assigned to a psychosocial intervention condition demonstrated a 14.7% improvement (95% confidence interval [CI], 5.7%–23.8%) in beneficial immune system function compared with their counterparts who were assigned to a control condition.
Similarly, participants who received psychosocial interventions demonstrated an 18.0% decrease (95% CI, 7.2%–28.8%) in harmful immune system function over time.
A standout
Regarding the effect of the type of intervention on the association, only CBT (31 studies; P < .001) and multiple or combined interventions (seven studies; P = .01) were significantly associated with changes in immune system outcomes.
The analysis also found that interventions that included a group component were more consistently associated with enhanced immune function than were those that did not include a group component. Nevertheless, this difference did not reach statistical significance (P = .06).
Contrary to the researchers’ expectations, the analysis also revealed that intervention length did not moderate the association between psychosocial interventions and immune system function (P = .93).
With respect to the type of immune marker studied, the meta-analysis found that psychosocial interventions had significantly different associations with the various immune markers studied. Of the seven immune outcomes investigated, only proinflammatory cytokine or marker levels (33 studies; P < .001) and immune cell counts (27 studies; P < .001) were significantly associated with the psychosocial interventions examined.
and were robust across age, sex, and intervention duration.
These results suggest that psychosocial interventions – particularly CBT and multiple or combined psychotherapeutic modalities – may play an important role in improving immune-related health outcomes.
Such interventions may not only be effective, they may also prove to be affordable alternatives to current therapeutic options. The mean length of a CBT intervention in the meta-analysis was 10.4 weeks, which the investigators equated with a total cost of $1,560 per patient.
“By comparison, the cost of using infliximab to reduce inflammation in persons with an autoimmune disorder is approximately $25,000 per patient per year,” they wrote.
“The results suggest the possibility that psychotherapy may be helpful for reducing inflammation and improving immune-related health in certain circumstances,” Dr. Slavich concluded. “However, the studies that we examined differed in terms of their quality, and we did not examine health outcomes in the present investigation.
“Therefore, more research needs to be done to determine how the present findings might be translated into treatment options or public policy.”
A path to better health
In an accompanying editorial, Veronika Engert, PhD, Joshua A. Grant, PhD, and Bernhard Strauss, PhD, noted that although infectious disease was once the primary cause of death in society, it has been supplanted by other complex and chronic illnesses, which often do not follow simple cause-and-effect associations.
“Rather,” they wrote, “these illnesses develop from a complex milieu of biological, psychological, and social factors that may also influence the disease progress and its prognosis. Against this backdrop, the meta-analysis by Shields and colleagues is an important confirmation of the biopsychosocial model.”
The editorialists explained that recent psychophysiological, neurobiological, and epigenetic research offers a glimpse into the relationship between psychological and social factors in pathogenesis. Nevertheless, the authors noted that a comprehensive examination of the potential effects of psychosocial interventions on immune parameters in various physical health conditions has been lacking.
“The evidence provided by Shields et al. is exactly what is needed to more fully shift treatment from an illness-centered to a patient-centered approach,” they wrote. “To that end, this meta-analysis may serve as a guide for policy makers aiming to improve immune-associated health.”
The research was supported by a Society in Science–Branco Weiss Fellowship, Brain and Behavior Research, and the National Institutes of Health. Dr. Slavich, Dr. Engert, Dr. Grant, and Dr. Strauss have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.