Women with HIV and men with HIV who have sex with women (MSW) have substantially different experiences with treatment than men with HIV who have sex with men (MSM), according to findings presented at the HIV Glasgow 2020 Virtual Meeting. MSM had better overall health outcomes than the other two groups, the study found, suggesting that MSW and women have unmet needs that require providers’ attention.

Chinyere Okoli of ViiV Healthcare Global Medical Affairs in Brentford, England, and her associates administered a Web-based survey about HIV-related perceptions and behaviors to 2,389 adults with HIV in 25 countries. The respondents included 1,018 MSM, 479 MSW, and 696 women.

In high-income countries, MSM respondents had been diagnosed a median 9 years earlier, MSW respondents a median 4 years earlier, and women respondents a median 5 years earlier. In middle-income countries, diagnosis was a median 3 years ago for MSM respondents and a median 6 years for MSW and women respondents.

Rates of suboptimal adherence to antiretroviral therapy (ART) were lowest (15.5%) among MSM, compared with MSW (38.8%) and women (28%). Similarly, viral nonsuppression had occurred in only 10.9% of MSM, whereas it had occurred in 43.2% of MSW and 37.1% of women. A little more than one-third (36.5%) of MSM had suboptimal overall health, whereas 47.2% of MSW and 46.2% of women had suboptimal overall health (P < .05).

A similar percentage of MSM (38%) and women (38.2%) reported polypharmacy; both percentages were significantly lower than for MSW (45.1%; P = .020). Yet MSW were less likely than the other two groups to have comorbidities unrelated to HIV: 46.1%, compared with 64.6% of MSM and 56.7% of women (P < .001).

Although a higher proportion (63%) of MSW than MSM (44%) or women (55%) were receiving a multitablet ART regimen, MSW were least likely to consider the impact of side effects when they began ART and were most likely to experience side effects. Only 45% of MSW prioritized minimizing side effects when they began receiving ART, and more than half (52%) were experiencing side effects with their current regimen.

By contrast, a majority of MSM (60%) prioritized minimizing side effects at ART initiation, and only 35% currently had side effects. Women fell in the middle with 48% considering side effects when starting ART and 49% reporting current side effects.

The proportion of respondents who said ART side effects were affecting their lives was not significantly different: 69% of MSM, 73% of MSW, and 74% of women. However, 56% of MSW reported skipping at least one dose in the past month because of side effects, which was more than twice the percentage of MSM (24%; P < .001). One-third of women (33%) reported skipping at least one dose.

MSW were also least comfortable talking to their health care provider about ART side effects: 55% reported discomfort, compared with 34% of MSM and 43% of women. A high majority of MSW (87.9%) said they experienced barriers to talking to their providers about relevant health concerns. The proportion who reported barriers was lower for MSM (59%) and women (72.7%; P < .001).

The substantial differences between MSM and MSW, which were even greater than those between MSW and women, suggest this population has the greatest amount of unmet needs, the researchers concluded. “Acknowledging these differences when planning/administering care can help narrow disparities,” they wrote.
 

A version of this article originally appeared on Medscape.com.

Women with HIV and men with HIV who have sex with women (MSW) have substantially different experiences with treatment than men with HIV who have sex with men (MSM), according to findings presented at the HIV Glasgow 2020 Virtual Meeting. MSM had better overall health outcomes than the other two groups, the study found, suggesting that MSW and women have unmet needs that require providers’ attention.

Chinyere Okoli of ViiV Healthcare Global Medical Affairs in Brentford, England, and her associates administered a Web-based survey about HIV-related perceptions and behaviors to 2,389 adults with HIV in 25 countries. The respondents included 1,018 MSM, 479 MSW, and 696 women.

In high-income countries, MSM respondents had been diagnosed a median 9 years earlier, MSW respondents a median 4 years earlier, and women respondents a median 5 years earlier. In middle-income countries, diagnosis was a median 3 years ago for MSM respondents and a median 6 years for MSW and women respondents.

Rates of suboptimal adherence to antiretroviral therapy (ART) were lowest (15.5%) among MSM, compared with MSW (38.8%) and women (28%). Similarly, viral nonsuppression had occurred in only 10.9% of MSM, whereas it had occurred in 43.2% of MSW and 37.1% of women. A little more than one-third (36.5%) of MSM had suboptimal overall health, whereas 47.2% of MSW and 46.2% of women had suboptimal overall health (P < .05).

A similar percentage of MSM (38%) and women (38.2%) reported polypharmacy; both percentages were significantly lower than for MSW (45.1%; P = .020). Yet MSW were less likely than the other two groups to have comorbidities unrelated to HIV: 46.1%, compared with 64.6% of MSM and 56.7% of women (P < .001).

Although a higher proportion (63%) of MSW than MSM (44%) or women (55%) were receiving a multitablet ART regimen, MSW were least likely to consider the impact of side effects when they began ART and were most likely to experience side effects. Only 45% of MSW prioritized minimizing side effects when they began receiving ART, and more than half (52%) were experiencing side effects with their current regimen.

By contrast, a majority of MSM (60%) prioritized minimizing side effects at ART initiation, and only 35% currently had side effects. Women fell in the middle with 48% considering side effects when starting ART and 49% reporting current side effects.

The proportion of respondents who said ART side effects were affecting their lives was not significantly different: 69% of MSM, 73% of MSW, and 74% of women. However, 56% of MSW reported skipping at least one dose in the past month because of side effects, which was more than twice the percentage of MSM (24%; P < .001). One-third of women (33%) reported skipping at least one dose.

MSW were also least comfortable talking to their health care provider about ART side effects: 55% reported discomfort, compared with 34% of MSM and 43% of women. A high majority of MSW (87.9%) said they experienced barriers to talking to their providers about relevant health concerns. The proportion who reported barriers was lower for MSM (59%) and women (72.7%; P < .001).

The substantial differences between MSM and MSW, which were even greater than those between MSW and women, suggest this population has the greatest amount of unmet needs, the researchers concluded. “Acknowledging these differences when planning/administering care can help narrow disparities,” they wrote.
 

A version of this article originally appeared on Medscape.com.

Women with HIV and men with HIV who have sex with women (MSW) have substantially different experiences with treatment than men with HIV who have sex with men (MSM), according to findings presented at the HIV Glasgow 2020 Virtual Meeting. MSM had better overall health outcomes than the other two groups, the study found, suggesting that MSW and women have unmet needs that require providers’ attention.

Chinyere Okoli of ViiV Healthcare Global Medical Affairs in Brentford, England, and her associates administered a Web-based survey about HIV-related perceptions and behaviors to 2,389 adults with HIV in 25 countries. The respondents included 1,018 MSM, 479 MSW, and 696 women.

In high-income countries, MSM respondents had been diagnosed a median 9 years earlier, MSW respondents a median 4 years earlier, and women respondents a median 5 years earlier. In middle-income countries, diagnosis was a median 3 years ago for MSM respondents and a median 6 years for MSW and women respondents.

Rates of suboptimal adherence to antiretroviral therapy (ART) were lowest (15.5%) among MSM, compared with MSW (38.8%) and women (28%). Similarly, viral nonsuppression had occurred in only 10.9% of MSM, whereas it had occurred in 43.2% of MSW and 37.1% of women. A little more than one-third (36.5%) of MSM had suboptimal overall health, whereas 47.2% of MSW and 46.2% of women had suboptimal overall health (P < .05).

A similar percentage of MSM (38%) and women (38.2%) reported polypharmacy; both percentages were significantly lower than for MSW (45.1%; P = .020). Yet MSW were less likely than the other two groups to have comorbidities unrelated to HIV: 46.1%, compared with 64.6% of MSM and 56.7% of women (P < .001).

Although a higher proportion (63%) of MSW than MSM (44%) or women (55%) were receiving a multitablet ART regimen, MSW were least likely to consider the impact of side effects when they began ART and were most likely to experience side effects. Only 45% of MSW prioritized minimizing side effects when they began receiving ART, and more than half (52%) were experiencing side effects with their current regimen.

By contrast, a majority of MSM (60%) prioritized minimizing side effects at ART initiation, and only 35% currently had side effects. Women fell in the middle with 48% considering side effects when starting ART and 49% reporting current side effects.

The proportion of respondents who said ART side effects were affecting their lives was not significantly different: 69% of MSM, 73% of MSW, and 74% of women. However, 56% of MSW reported skipping at least one dose in the past month because of side effects, which was more than twice the percentage of MSM (24%; P < .001). One-third of women (33%) reported skipping at least one dose.

MSW were also least comfortable talking to their health care provider about ART side effects: 55% reported discomfort, compared with 34% of MSM and 43% of women. A high majority of MSW (87.9%) said they experienced barriers to talking to their providers about relevant health concerns. The proportion who reported barriers was lower for MSM (59%) and women (72.7%; P < .001).

The substantial differences between MSM and MSW, which were even greater than those between MSW and women, suggest this population has the greatest amount of unmet needs, the researchers concluded. “Acknowledging these differences when planning/administering care can help narrow disparities,” they wrote.
 

A version of this article originally appeared on Medscape.com.

Masks, it seems, are effective at blocking the transmission of coronavirus. They’re also pretty good at stultifying consonants. For those specialties not accustomed to wearing a mask all day, it’s frustrating: How many times have you had to repeat yourself today? Or ask your patient to say something again? (Ain’t no one got time to repeat a third time how to do that prednisone taper). Worse, we’re losing important nonverbal cues that help us connect with our patients. How can we be understood when our faces are covered and 6 feet away?

Masks muffle both verbal and nonverbal communication. For soft-spoken or high-pitched speakers, the verbal effect is significant. In particular, masks make hearing consonants more difficult. They can make the “sh,” “th,” “f,” and “s” sounds difficult to distinguish. Typically, we’d use context and lip reading to boost the signal, but this fix is blocked (and the clear mouth-window masks are kinda creepy). 

Masks also prevent us from seeing facial microexpressions, critical information when you are trying to connect with someone or to build trust. A randomized controlled trial published in 2013 indeed showed that doctors wearing a mask were perceived as less empathetic and had diminished relational continuity with patients as compared to doctors not wearing a mask. There are a few things we can do to help. 

Speak more loudly is obvious advice. Loud talking has limitations though, as it can feel rude, and it blunts inflections, which add richness and emotion. (Shouting “THIS WILL ONLY HURT A LITTLE” seems a mixed message). More important than the volume is your choice of words. Try to use simple terms and short sentences. Pause between points. Hit your consonants harder. 

It’s also important that you have their full attention and are giving yours. As much as possible, try to align squared up with patients. Facing your computer exacerbates the problem. Look them in their eyes and be sure they are connected with you before any complex or difficult conversations. Hearing-impaired patients are now sometimes leaving out their aids because it’s too uncomfortable to wear them with their mask. You might ask them to put them back in. Check in with patients and repeat back what you heard them say. This can help with clarity and with connecting. Use your face more: if you’ve ever acted on stage, this would be your on-stage face. Exaggerate your expressions so it’s a little easier for them to read you. 

Lastly, there are apps such as Ava or Google Live Translator, which can transcribe your speech real time. You could then share your screen with the patient so they can read exactly what you’ve said. 

Some of us are natural communicators. Even if you are not, you can mitigate some of our current challenges. I’ll admit, it’s been a bit easier for me than for others. Between my prominent eyebrows and Italian-American upbringing, I can express my way through pretty much any face covering.  If you’d like to learn how to use your hands better, then just watch this little girl: https://youtu.be/Z5wAWyqDrnc.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

Masks, it seems, are effective at blocking the transmission of coronavirus. They’re also pretty good at stultifying consonants. For those specialties not accustomed to wearing a mask all day, it’s frustrating: How many times have you had to repeat yourself today? Or ask your patient to say something again? (Ain’t no one got time to repeat a third time how to do that prednisone taper). Worse, we’re losing important nonverbal cues that help us connect with our patients. How can we be understood when our faces are covered and 6 feet away?

Masks muffle both verbal and nonverbal communication. For soft-spoken or high-pitched speakers, the verbal effect is significant. In particular, masks make hearing consonants more difficult. They can make the “sh,” “th,” “f,” and “s” sounds difficult to distinguish. Typically, we’d use context and lip reading to boost the signal, but this fix is blocked (and the clear mouth-window masks are kinda creepy). 

Masks also prevent us from seeing facial microexpressions, critical information when you are trying to connect with someone or to build trust. A randomized controlled trial published in 2013 indeed showed that doctors wearing a mask were perceived as less empathetic and had diminished relational continuity with patients as compared to doctors not wearing a mask. There are a few things we can do to help. 

Speak more loudly is obvious advice. Loud talking has limitations though, as it can feel rude, and it blunts inflections, which add richness and emotion. (Shouting “THIS WILL ONLY HURT A LITTLE” seems a mixed message). More important than the volume is your choice of words. Try to use simple terms and short sentences. Pause between points. Hit your consonants harder. 

It’s also important that you have their full attention and are giving yours. As much as possible, try to align squared up with patients. Facing your computer exacerbates the problem. Look them in their eyes and be sure they are connected with you before any complex or difficult conversations. Hearing-impaired patients are now sometimes leaving out their aids because it’s too uncomfortable to wear them with their mask. You might ask them to put them back in. Check in with patients and repeat back what you heard them say. This can help with clarity and with connecting. Use your face more: if you’ve ever acted on stage, this would be your on-stage face. Exaggerate your expressions so it’s a little easier for them to read you. 

Lastly, there are apps such as Ava or Google Live Translator, which can transcribe your speech real time. You could then share your screen with the patient so they can read exactly what you’ve said. 

Some of us are natural communicators. Even if you are not, you can mitigate some of our current challenges. I’ll admit, it’s been a bit easier for me than for others. Between my prominent eyebrows and Italian-American upbringing, I can express my way through pretty much any face covering.  If you’d like to learn how to use your hands better, then just watch this little girl: https://youtu.be/Z5wAWyqDrnc.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

Masks, it seems, are effective at blocking the transmission of coronavirus. They’re also pretty good at stultifying consonants. For those specialties not accustomed to wearing a mask all day, it’s frustrating: How many times have you had to repeat yourself today? Or ask your patient to say something again? (Ain’t no one got time to repeat a third time how to do that prednisone taper). Worse, we’re losing important nonverbal cues that help us connect with our patients. How can we be understood when our faces are covered and 6 feet away?

Masks muffle both verbal and nonverbal communication. For soft-spoken or high-pitched speakers, the verbal effect is significant. In particular, masks make hearing consonants more difficult. They can make the “sh,” “th,” “f,” and “s” sounds difficult to distinguish. Typically, we’d use context and lip reading to boost the signal, but this fix is blocked (and the clear mouth-window masks are kinda creepy). 

Masks also prevent us from seeing facial microexpressions, critical information when you are trying to connect with someone or to build trust. A randomized controlled trial published in 2013 indeed showed that doctors wearing a mask were perceived as less empathetic and had diminished relational continuity with patients as compared to doctors not wearing a mask. There are a few things we can do to help. 

Speak more loudly is obvious advice. Loud talking has limitations though, as it can feel rude, and it blunts inflections, which add richness and emotion. (Shouting “THIS WILL ONLY HURT A LITTLE” seems a mixed message). More important than the volume is your choice of words. Try to use simple terms and short sentences. Pause between points. Hit your consonants harder. 

It’s also important that you have their full attention and are giving yours. As much as possible, try to align squared up with patients. Facing your computer exacerbates the problem. Look them in their eyes and be sure they are connected with you before any complex or difficult conversations. Hearing-impaired patients are now sometimes leaving out their aids because it’s too uncomfortable to wear them with their mask. You might ask them to put them back in. Check in with patients and repeat back what you heard them say. This can help with clarity and with connecting. Use your face more: if you’ve ever acted on stage, this would be your on-stage face. Exaggerate your expressions so it’s a little easier for them to read you. 

Lastly, there are apps such as Ava or Google Live Translator, which can transcribe your speech real time. You could then share your screen with the patient so they can read exactly what you’ve said. 

Some of us are natural communicators. Even if you are not, you can mitigate some of our current challenges. I’ll admit, it’s been a bit easier for me than for others. Between my prominent eyebrows and Italian-American upbringing, I can express my way through pretty much any face covering.  If you’d like to learn how to use your hands better, then just watch this little girl: https://youtu.be/Z5wAWyqDrnc.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

Patients with heart failure with preserved ejection fraction (HFpEF) who received sacubitril/valsartan in the PARAGON-HF trial had significant protection against progression of renal dysfunction in a prespecified secondary analysis.

The 2,419 patients with HFpEF who received sacubitril/valsartan (Entresto) had half the rate of the primary adverse renal outcome, compared with the 2,403 patients randomized to valsartan alone in the comparator group, a significant difference, according to the results published online Sept. 29 in Circulation by Finnian R. McCausland, MBBCh, and colleagues.

In absolute terms, sacubitril/valsartan treatment, an angiotensin-receptor/neprilysin inhibitor (ARNI), cut the incidence of the combined renal endpoint – renal death, end-stage renal disease, or at least a 50% drop in estimated glomerular filtration rate (eGFR) – from 2.7% in the control group to 1.4% in the sacubitril/valsartan group during a median follow-up of 35 months.

The absolute difference of 1.3% equated to a number needed to treat of 51 to prevent one of these events.

Also notable was that renal protection from sacubitril/valsartan was equally robust across the range of baseline kidney function.
 

‘An important therapeutic option’

The efficacy “across the spectrum of baseline renal function” indicates treatment with sacubitril/valsartan is “an important therapeutic option to slow renal-function decline in patients with heart failure,” wrote Dr. McCausland, a nephrologist at Brigham and Women’s Hospital in Boston, and colleagues.

The authors’ conclusion is striking because currently no drug class has produced clear evidence for efficacy in HFpEF.

On the other hand, the PARAGON-HF trial that provided the data for this new analysis was statistically neutral for its primary endpoint – a reduction in the combined rate of cardiovascular death and hospitalizations for heart failure – with a P value of .06 and 95% confidence interval of 0.75-1.01.

“Because this difference [in the primary endpoint incidence between the two study group] did not meet the predetermined level of statistical significance, subsequent analyses were considered to be exploratory,” noted the authors of the primary analysis of PARAGON-HF, as reported by Medscape Medical News.

Despite this limitation in interpreting secondary outcomes from the trial, the new report of a significant renal benefit “opens the potential to provide evidence-based treatment for patients with HFpEF,” commented Sheldon W. Tobe, MD, and Stephanie Poon, MD, in an editorial accompanying the latest analysis.

“At the very least, these results are certainly intriguing and suggest that there may be important patient subgroups with HFpEF who might benefit from using sacubitril/valsartan,” they emphasized.
 

First large trial to show renal improvement in HFpEF

The editorialists’ enthusiasm for the implications of the new findings relate in part to the fact that “PARAGON-HF is the first large trial to demonstrate improvement in renal parameters in HFpEF,” they noted.

“The finding that the composite renal outcome did not differ according to baseline eGFR is significant and suggests that the beneficial effect on renal function was indirect, possibly linked to improved cardiac function,” say Dr. Tobe, a nephrologist, and Dr. Poon, a cardiologist, both at Sunnybrook Health Sciences Centre in Toronto.

PARAGON-HF enrolled 4,822 HFpEF patients at 848 centers in 43 countries, and the efficacy analysis included 4,796 patients.

The composite renal outcome was mainly driven by the incidence of a 50% or greater drop from baseline in eGFR, which occurred in 27 patients (1.1%) in the sacubitril/valsartan group and 60 patients (2.5%) who received valsartan alone.

The annual average drop in eGFR during the study was 2.0 mL/min per 1.73m² in the sacubitril/valsartan group and 2.7 mL/min per 1.73m² in the control group.

Although the heart failure community was disappointed that sacubitril/valsartan failed to show a significant benefit for the study’s primary outcome in HFpEF, the combination has become a mainstay of treatment for patients with HFpEF based on its performance in the PARADIGM-HF trial.

And despite the unqualified support sacubitril/valsartan now receives in guidelines and its label as a foundational treatment for HFpEF, the formulation has had a hard time gaining traction in U.S. practice, often because of barriers placed by third-party payers.

PARAGON-HF was sponsored by Novartis, which markets sacubitril/valsartan (Entresto). Dr. McCausland has reported no relevant financial relationships. Dr. Tobe has reported participating on a steering committee for Bayer Fidelio/Figaro studies and being a speaker on behalf of Pfizer and Servier. Dr. Poon has reported being an adviser to Novartis, Boehringer Ingelheim, and Servier.
 

A version of this article originally appeared on Medscape.com.

Patients with heart failure with preserved ejection fraction (HFpEF) who received sacubitril/valsartan in the PARAGON-HF trial had significant protection against progression of renal dysfunction in a prespecified secondary analysis.

The 2,419 patients with HFpEF who received sacubitril/valsartan (Entresto) had half the rate of the primary adverse renal outcome, compared with the 2,403 patients randomized to valsartan alone in the comparator group, a significant difference, according to the results published online Sept. 29 in Circulation by Finnian R. McCausland, MBBCh, and colleagues.

In absolute terms, sacubitril/valsartan treatment, an angiotensin-receptor/neprilysin inhibitor (ARNI), cut the incidence of the combined renal endpoint – renal death, end-stage renal disease, or at least a 50% drop in estimated glomerular filtration rate (eGFR) – from 2.7% in the control group to 1.4% in the sacubitril/valsartan group during a median follow-up of 35 months.

The absolute difference of 1.3% equated to a number needed to treat of 51 to prevent one of these events.

Also notable was that renal protection from sacubitril/valsartan was equally robust across the range of baseline kidney function.
 

‘An important therapeutic option’

The efficacy “across the spectrum of baseline renal function” indicates treatment with sacubitril/valsartan is “an important therapeutic option to slow renal-function decline in patients with heart failure,” wrote Dr. McCausland, a nephrologist at Brigham and Women’s Hospital in Boston, and colleagues.

The authors’ conclusion is striking because currently no drug class has produced clear evidence for efficacy in HFpEF.

On the other hand, the PARAGON-HF trial that provided the data for this new analysis was statistically neutral for its primary endpoint – a reduction in the combined rate of cardiovascular death and hospitalizations for heart failure – with a P value of .06 and 95% confidence interval of 0.75-1.01.

“Because this difference [in the primary endpoint incidence between the two study group] did not meet the predetermined level of statistical significance, subsequent analyses were considered to be exploratory,” noted the authors of the primary analysis of PARAGON-HF, as reported by Medscape Medical News.

Despite this limitation in interpreting secondary outcomes from the trial, the new report of a significant renal benefit “opens the potential to provide evidence-based treatment for patients with HFpEF,” commented Sheldon W. Tobe, MD, and Stephanie Poon, MD, in an editorial accompanying the latest analysis.

“At the very least, these results are certainly intriguing and suggest that there may be important patient subgroups with HFpEF who might benefit from using sacubitril/valsartan,” they emphasized.
 

First large trial to show renal improvement in HFpEF

The editorialists’ enthusiasm for the implications of the new findings relate in part to the fact that “PARAGON-HF is the first large trial to demonstrate improvement in renal parameters in HFpEF,” they noted.

“The finding that the composite renal outcome did not differ according to baseline eGFR is significant and suggests that the beneficial effect on renal function was indirect, possibly linked to improved cardiac function,” say Dr. Tobe, a nephrologist, and Dr. Poon, a cardiologist, both at Sunnybrook Health Sciences Centre in Toronto.

PARAGON-HF enrolled 4,822 HFpEF patients at 848 centers in 43 countries, and the efficacy analysis included 4,796 patients.

The composite renal outcome was mainly driven by the incidence of a 50% or greater drop from baseline in eGFR, which occurred in 27 patients (1.1%) in the sacubitril/valsartan group and 60 patients (2.5%) who received valsartan alone.

The annual average drop in eGFR during the study was 2.0 mL/min per 1.73m² in the sacubitril/valsartan group and 2.7 mL/min per 1.73m² in the control group.

Although the heart failure community was disappointed that sacubitril/valsartan failed to show a significant benefit for the study’s primary outcome in HFpEF, the combination has become a mainstay of treatment for patients with HFpEF based on its performance in the PARADIGM-HF trial.

And despite the unqualified support sacubitril/valsartan now receives in guidelines and its label as a foundational treatment for HFpEF, the formulation has had a hard time gaining traction in U.S. practice, often because of barriers placed by third-party payers.

PARAGON-HF was sponsored by Novartis, which markets sacubitril/valsartan (Entresto). Dr. McCausland has reported no relevant financial relationships. Dr. Tobe has reported participating on a steering committee for Bayer Fidelio/Figaro studies and being a speaker on behalf of Pfizer and Servier. Dr. Poon has reported being an adviser to Novartis, Boehringer Ingelheim, and Servier.
 

A version of this article originally appeared on Medscape.com.

Patients with heart failure with preserved ejection fraction (HFpEF) who received sacubitril/valsartan in the PARAGON-HF trial had significant protection against progression of renal dysfunction in a prespecified secondary analysis.

The 2,419 patients with HFpEF who received sacubitril/valsartan (Entresto) had half the rate of the primary adverse renal outcome, compared with the 2,403 patients randomized to valsartan alone in the comparator group, a significant difference, according to the results published online Sept. 29 in Circulation by Finnian R. McCausland, MBBCh, and colleagues.

In absolute terms, sacubitril/valsartan treatment, an angiotensin-receptor/neprilysin inhibitor (ARNI), cut the incidence of the combined renal endpoint – renal death, end-stage renal disease, or at least a 50% drop in estimated glomerular filtration rate (eGFR) – from 2.7% in the control group to 1.4% in the sacubitril/valsartan group during a median follow-up of 35 months.

The absolute difference of 1.3% equated to a number needed to treat of 51 to prevent one of these events.

Also notable was that renal protection from sacubitril/valsartan was equally robust across the range of baseline kidney function.
 

‘An important therapeutic option’

The efficacy “across the spectrum of baseline renal function” indicates treatment with sacubitril/valsartan is “an important therapeutic option to slow renal-function decline in patients with heart failure,” wrote Dr. McCausland, a nephrologist at Brigham and Women’s Hospital in Boston, and colleagues.

The authors’ conclusion is striking because currently no drug class has produced clear evidence for efficacy in HFpEF.

On the other hand, the PARAGON-HF trial that provided the data for this new analysis was statistically neutral for its primary endpoint – a reduction in the combined rate of cardiovascular death and hospitalizations for heart failure – with a P value of .06 and 95% confidence interval of 0.75-1.01.

“Because this difference [in the primary endpoint incidence between the two study group] did not meet the predetermined level of statistical significance, subsequent analyses were considered to be exploratory,” noted the authors of the primary analysis of PARAGON-HF, as reported by Medscape Medical News.

Despite this limitation in interpreting secondary outcomes from the trial, the new report of a significant renal benefit “opens the potential to provide evidence-based treatment for patients with HFpEF,” commented Sheldon W. Tobe, MD, and Stephanie Poon, MD, in an editorial accompanying the latest analysis.

“At the very least, these results are certainly intriguing and suggest that there may be important patient subgroups with HFpEF who might benefit from using sacubitril/valsartan,” they emphasized.
 

First large trial to show renal improvement in HFpEF

The editorialists’ enthusiasm for the implications of the new findings relate in part to the fact that “PARAGON-HF is the first large trial to demonstrate improvement in renal parameters in HFpEF,” they noted.

“The finding that the composite renal outcome did not differ according to baseline eGFR is significant and suggests that the beneficial effect on renal function was indirect, possibly linked to improved cardiac function,” say Dr. Tobe, a nephrologist, and Dr. Poon, a cardiologist, both at Sunnybrook Health Sciences Centre in Toronto.

PARAGON-HF enrolled 4,822 HFpEF patients at 848 centers in 43 countries, and the efficacy analysis included 4,796 patients.

The composite renal outcome was mainly driven by the incidence of a 50% or greater drop from baseline in eGFR, which occurred in 27 patients (1.1%) in the sacubitril/valsartan group and 60 patients (2.5%) who received valsartan alone.

The annual average drop in eGFR during the study was 2.0 mL/min per 1.73m² in the sacubitril/valsartan group and 2.7 mL/min per 1.73m² in the control group.

Although the heart failure community was disappointed that sacubitril/valsartan failed to show a significant benefit for the study’s primary outcome in HFpEF, the combination has become a mainstay of treatment for patients with HFpEF based on its performance in the PARADIGM-HF trial.

And despite the unqualified support sacubitril/valsartan now receives in guidelines and its label as a foundational treatment for HFpEF, the formulation has had a hard time gaining traction in U.S. practice, often because of barriers placed by third-party payers.

PARAGON-HF was sponsored by Novartis, which markets sacubitril/valsartan (Entresto). Dr. McCausland has reported no relevant financial relationships. Dr. Tobe has reported participating on a steering committee for Bayer Fidelio/Figaro studies and being a speaker on behalf of Pfizer and Servier. Dr. Poon has reported being an adviser to Novartis, Boehringer Ingelheim, and Servier.
 

A version of this article originally appeared on Medscape.com.

Have you been surprised and impressed by a child who says after a visit, “Thank you, Doctor [Howard]”? While it may seem antiquated to teach such manners to children these days, there are several important benefits to this education.

monkeybusinessimages/thinkstockphotos.com

Manners serve important functions in benefiting a person’s group with cohesiveness and the individuals themselves with acceptance in the group. Use of manners instantly suggests a more trustworthy person.

There are three main categories of manners: hygiene, courtesy, and cultural norm manners.

Hygiene manners, from using the toilet to refraining from picking one’s nose, have obvious health benefits of not spreading disease. Hygiene manners take time to teach, but parents are motivated and helped by natural reactions of disgust that even infants recognize.

Courtesy manners, on the other hand, are habits of self-control and good-faith behaviors that signal that one is putting the interests of others ahead of one’s own for the moment. Taking another’s comfort into account, basic to kindness and respect, does not require agreeing with or submitting to the other. Courtesy manners require a developing self-awareness (I can choose to act this way) and awareness of social status (I am not more important than everyone else) that begins in toddlerhood. Modeling manners around the child is the most important way to teach courtesy. Parents usually start actively teaching the child to say “please” and “thank you,” and show pride in this apparent “demonstration of appreciation” even when it is simply reinforced behavior at first. The delight of grandparents reinforces both the parents and children, and reflects manners as building tribe cohesiveness.
 

Good manners become a habit

Manners such as warm greetings, a firm handshake (before COVID-19), and prompt thanks are most believable when occurring promptly when appropriate – when they come from habit. This immediate reaction, a result of so-called “fast thinking,” develops when behaviors learned from “slow thinking” are instilled early and often until they are automatic. The other benefit of this overlearning is that the behavior then looks unambivalent; a lag of too many milliseconds makes the recipient doubt genuineness.

Parents often ask us how to handle their child‘s rude or disrespectful behavior. Praise for manners is a simple start. Toddlers and preschoolers are taught manners best by adult modeling, but also by reinforcement and praise for the basics: to say “Hello,” ask “Please,” and say “Thank you,” “Excuse me,” “You’re welcome,” or “Would you help me, please?” The behaviors also include avoiding raising one’s voice, suppressing interrupting, and apologizing when appropriate. Even shy children can learn eye contact by making a game of figuring out the other’s eye color. Shaming, yelling, and punishing for poor manners usually backfires because it shows disrespect of the child who will likely give this back.

Older children can be taught to offer other people the opportunity to go through a door first, to be first to select a seat, speak first and without interruption, or order first. There are daily opportunities for these manners of showing respect. Opening doors for others, or standing when a guest enters the room are more formal but still appreciated. Parents who use and expect courtesy manners with everyone – irrespective of gender, race, ethnicity, or role as a server versus professional – show that they value others and build antiracism.

School age is a time to learn to wait before speaking to consider whether what they say could be experienced as hurtful to the other person. This requires taking someone else’s point of view, an ability that emerges around age 6 years and can be promoted when parents review with their child “How would you feel if it were you?” Role playing common scenarios of how to behave and speak when seeing a person who looks or acts different is also effective. Avoiding interrupting may be more difficult for very talkative or impulsive children, especially those with ADHD. Practicing waiting for permission to speak by being handed a “talking stick” at the dinner table can be good practice for everyone.
 

Manners are a group asset

Beyond personal benefits, manners are the basis of a civil society. Manners contribute to mutual respect, effective communication, and team collaboration. Cultural norm manners are particular to groups, helping members feel affiliated, as well as identifying those with different manners as “other.”

Teens are particularly likely to use a different code of behavior to fit in with a subgroup. This may be acceptable if restricted to within their group (such as swear words) or within certain agreed-upon limits with family members. But teens need to understand the value of learning, practicing, and using manners for their own, as well as their group’s and nation’s, well-being.

As a developmental-behavioral pediatrician, I have cared for many children with intellectual disabilities and autism spectrum disorder (ASD). Deficits in social interaction skills are a basic criterion for the diagnosis of ASD. Overtraining is especially needed for children with ASD whose mirror movements, social attention, and imitation are weak. For children with these conditions, making manners a strong habit takes more effort but is even more vital than for neurotypical children. Temple Grandin, a famous adult with ASD, has described how her mother taught her manners as a survival skill. She reports incorporating manners very consciously and methodically because they did not come naturally. Children with even rote social skills are liked better by peers and teachers, their atypical behaviors is better tolerated, and they get more positive feedback that encourages integration inside and outside the classroom. Manners may make the difference between being allowed in or expelled from classrooms, libraries, clubs, teams, or religious institutions. When it is time to get a job, social skills are the key factor for employment for these individuals and a significant help for neurotypical individuals as well. Failure to signal socially appropriate behavior can make a person appear threatening and has had the rare but tragic result of rough or fatal handling by police.

Has the teaching of manners waned? Perhaps, because, for some families, the child is being socialized mostly by nonfamily caregivers who have low use of manners. Some parents have made teaching manners a low priority or even resisted using manners themselves as inauthentic. This may reflect prioritizing a “laid-back” lifestyle and speaking crudely as a sign of independence, perhaps in reaction to lack of autonomy at work. Mastering the careful interactions developed over time to avoid invoking an aggressive response depend on direct feedback from reactions of the recipient. With so much of our communication done electronically, asynchronously, even anonymously, the usual feedback has been reduced. Practicing curses, insults, and put-downs online easily extends to in-person interactions without the perpetrator even noticing and are generally reinforced and repeated without parental supervision. Disrespectful behavior from community leaders also reduces the threshold for society.

When people are ignorant of or choose not to use manners they may be perceived as “other” and hostile. This may lead to distrust, dislike, and lowered ability to find the common ground needed for making decisions that benefit the greater society. Oliver Wendell Holmes said “Under bad manners ... lies very commonly an overestimate of our special individuality, as distinguished from our generic humanity (“The Professor at the Breakfast Table,” 1858). Working for major goals that benefit all of humanity is essential to survival in our highly interconnected world. Considering all of humanity is a difficult concept for children, and even for many adults, but it starts with using civil behavior at home, in school, and in one’s community.
 

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].

Have you been surprised and impressed by a child who says after a visit, “Thank you, Doctor [Howard]”? While it may seem antiquated to teach such manners to children these days, there are several important benefits to this education.

monkeybusinessimages/thinkstockphotos.com

Manners serve important functions in benefiting a person’s group with cohesiveness and the individuals themselves with acceptance in the group. Use of manners instantly suggests a more trustworthy person.

There are three main categories of manners: hygiene, courtesy, and cultural norm manners.

Hygiene manners, from using the toilet to refraining from picking one’s nose, have obvious health benefits of not spreading disease. Hygiene manners take time to teach, but parents are motivated and helped by natural reactions of disgust that even infants recognize.

Courtesy manners, on the other hand, are habits of self-control and good-faith behaviors that signal that one is putting the interests of others ahead of one’s own for the moment. Taking another’s comfort into account, basic to kindness and respect, does not require agreeing with or submitting to the other. Courtesy manners require a developing self-awareness (I can choose to act this way) and awareness of social status (I am not more important than everyone else) that begins in toddlerhood. Modeling manners around the child is the most important way to teach courtesy. Parents usually start actively teaching the child to say “please” and “thank you,” and show pride in this apparent “demonstration of appreciation” even when it is simply reinforced behavior at first. The delight of grandparents reinforces both the parents and children, and reflects manners as building tribe cohesiveness.
 

Good manners become a habit

Manners such as warm greetings, a firm handshake (before COVID-19), and prompt thanks are most believable when occurring promptly when appropriate – when they come from habit. This immediate reaction, a result of so-called “fast thinking,” develops when behaviors learned from “slow thinking” are instilled early and often until they are automatic. The other benefit of this overlearning is that the behavior then looks unambivalent; a lag of too many milliseconds makes the recipient doubt genuineness.

Parents often ask us how to handle their child‘s rude or disrespectful behavior. Praise for manners is a simple start. Toddlers and preschoolers are taught manners best by adult modeling, but also by reinforcement and praise for the basics: to say “Hello,” ask “Please,” and say “Thank you,” “Excuse me,” “You’re welcome,” or “Would you help me, please?” The behaviors also include avoiding raising one’s voice, suppressing interrupting, and apologizing when appropriate. Even shy children can learn eye contact by making a game of figuring out the other’s eye color. Shaming, yelling, and punishing for poor manners usually backfires because it shows disrespect of the child who will likely give this back.

Older children can be taught to offer other people the opportunity to go through a door first, to be first to select a seat, speak first and without interruption, or order first. There are daily opportunities for these manners of showing respect. Opening doors for others, or standing when a guest enters the room are more formal but still appreciated. Parents who use and expect courtesy manners with everyone – irrespective of gender, race, ethnicity, or role as a server versus professional – show that they value others and build antiracism.

School age is a time to learn to wait before speaking to consider whether what they say could be experienced as hurtful to the other person. This requires taking someone else’s point of view, an ability that emerges around age 6 years and can be promoted when parents review with their child “How would you feel if it were you?” Role playing common scenarios of how to behave and speak when seeing a person who looks or acts different is also effective. Avoiding interrupting may be more difficult for very talkative or impulsive children, especially those with ADHD. Practicing waiting for permission to speak by being handed a “talking stick” at the dinner table can be good practice for everyone.
 

Manners are a group asset

Beyond personal benefits, manners are the basis of a civil society. Manners contribute to mutual respect, effective communication, and team collaboration. Cultural norm manners are particular to groups, helping members feel affiliated, as well as identifying those with different manners as “other.”

Teens are particularly likely to use a different code of behavior to fit in with a subgroup. This may be acceptable if restricted to within their group (such as swear words) or within certain agreed-upon limits with family members. But teens need to understand the value of learning, practicing, and using manners for their own, as well as their group’s and nation’s, well-being.

As a developmental-behavioral pediatrician, I have cared for many children with intellectual disabilities and autism spectrum disorder (ASD). Deficits in social interaction skills are a basic criterion for the diagnosis of ASD. Overtraining is especially needed for children with ASD whose mirror movements, social attention, and imitation are weak. For children with these conditions, making manners a strong habit takes more effort but is even more vital than for neurotypical children. Temple Grandin, a famous adult with ASD, has described how her mother taught her manners as a survival skill. She reports incorporating manners very consciously and methodically because they did not come naturally. Children with even rote social skills are liked better by peers and teachers, their atypical behaviors is better tolerated, and they get more positive feedback that encourages integration inside and outside the classroom. Manners may make the difference between being allowed in or expelled from classrooms, libraries, clubs, teams, or religious institutions. When it is time to get a job, social skills are the key factor for employment for these individuals and a significant help for neurotypical individuals as well. Failure to signal socially appropriate behavior can make a person appear threatening and has had the rare but tragic result of rough or fatal handling by police.

Has the teaching of manners waned? Perhaps, because, for some families, the child is being socialized mostly by nonfamily caregivers who have low use of manners. Some parents have made teaching manners a low priority or even resisted using manners themselves as inauthentic. This may reflect prioritizing a “laid-back” lifestyle and speaking crudely as a sign of independence, perhaps in reaction to lack of autonomy at work. Mastering the careful interactions developed over time to avoid invoking an aggressive response depend on direct feedback from reactions of the recipient. With so much of our communication done electronically, asynchronously, even anonymously, the usual feedback has been reduced. Practicing curses, insults, and put-downs online easily extends to in-person interactions without the perpetrator even noticing and are generally reinforced and repeated without parental supervision. Disrespectful behavior from community leaders also reduces the threshold for society.

When people are ignorant of or choose not to use manners they may be perceived as “other” and hostile. This may lead to distrust, dislike, and lowered ability to find the common ground needed for making decisions that benefit the greater society. Oliver Wendell Holmes said “Under bad manners ... lies very commonly an overestimate of our special individuality, as distinguished from our generic humanity (“The Professor at the Breakfast Table,” 1858). Working for major goals that benefit all of humanity is essential to survival in our highly interconnected world. Considering all of humanity is a difficult concept for children, and even for many adults, but it starts with using civil behavior at home, in school, and in one’s community.
 

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].

Have you been surprised and impressed by a child who says after a visit, “Thank you, Doctor [Howard]”? While it may seem antiquated to teach such manners to children these days, there are several important benefits to this education.

monkeybusinessimages/thinkstockphotos.com

Manners serve important functions in benefiting a person’s group with cohesiveness and the individuals themselves with acceptance in the group. Use of manners instantly suggests a more trustworthy person.

There are three main categories of manners: hygiene, courtesy, and cultural norm manners.

Hygiene manners, from using the toilet to refraining from picking one’s nose, have obvious health benefits of not spreading disease. Hygiene manners take time to teach, but parents are motivated and helped by natural reactions of disgust that even infants recognize.

Courtesy manners, on the other hand, are habits of self-control and good-faith behaviors that signal that one is putting the interests of others ahead of one’s own for the moment. Taking another’s comfort into account, basic to kindness and respect, does not require agreeing with or submitting to the other. Courtesy manners require a developing self-awareness (I can choose to act this way) and awareness of social status (I am not more important than everyone else) that begins in toddlerhood. Modeling manners around the child is the most important way to teach courtesy. Parents usually start actively teaching the child to say “please” and “thank you,” and show pride in this apparent “demonstration of appreciation” even when it is simply reinforced behavior at first. The delight of grandparents reinforces both the parents and children, and reflects manners as building tribe cohesiveness.
 

Good manners become a habit

Manners such as warm greetings, a firm handshake (before COVID-19), and prompt thanks are most believable when occurring promptly when appropriate – when they come from habit. This immediate reaction, a result of so-called “fast thinking,” develops when behaviors learned from “slow thinking” are instilled early and often until they are automatic. The other benefit of this overlearning is that the behavior then looks unambivalent; a lag of too many milliseconds makes the recipient doubt genuineness.

Parents often ask us how to handle their child‘s rude or disrespectful behavior. Praise for manners is a simple start. Toddlers and preschoolers are taught manners best by adult modeling, but also by reinforcement and praise for the basics: to say “Hello,” ask “Please,” and say “Thank you,” “Excuse me,” “You’re welcome,” or “Would you help me, please?” The behaviors also include avoiding raising one’s voice, suppressing interrupting, and apologizing when appropriate. Even shy children can learn eye contact by making a game of figuring out the other’s eye color. Shaming, yelling, and punishing for poor manners usually backfires because it shows disrespect of the child who will likely give this back.

Older children can be taught to offer other people the opportunity to go through a door first, to be first to select a seat, speak first and without interruption, or order first. There are daily opportunities for these manners of showing respect. Opening doors for others, or standing when a guest enters the room are more formal but still appreciated. Parents who use and expect courtesy manners with everyone – irrespective of gender, race, ethnicity, or role as a server versus professional – show that they value others and build antiracism.

School age is a time to learn to wait before speaking to consider whether what they say could be experienced as hurtful to the other person. This requires taking someone else’s point of view, an ability that emerges around age 6 years and can be promoted when parents review with their child “How would you feel if it were you?” Role playing common scenarios of how to behave and speak when seeing a person who looks or acts different is also effective. Avoiding interrupting may be more difficult for very talkative or impulsive children, especially those with ADHD. Practicing waiting for permission to speak by being handed a “talking stick” at the dinner table can be good practice for everyone.
 

Manners are a group asset

Beyond personal benefits, manners are the basis of a civil society. Manners contribute to mutual respect, effective communication, and team collaboration. Cultural norm manners are particular to groups, helping members feel affiliated, as well as identifying those with different manners as “other.”

Teens are particularly likely to use a different code of behavior to fit in with a subgroup. This may be acceptable if restricted to within their group (such as swear words) or within certain agreed-upon limits with family members. But teens need to understand the value of learning, practicing, and using manners for their own, as well as their group’s and nation’s, well-being.

As a developmental-behavioral pediatrician, I have cared for many children with intellectual disabilities and autism spectrum disorder (ASD). Deficits in social interaction skills are a basic criterion for the diagnosis of ASD. Overtraining is especially needed for children with ASD whose mirror movements, social attention, and imitation are weak. For children with these conditions, making manners a strong habit takes more effort but is even more vital than for neurotypical children. Temple Grandin, a famous adult with ASD, has described how her mother taught her manners as a survival skill. She reports incorporating manners very consciously and methodically because they did not come naturally. Children with even rote social skills are liked better by peers and teachers, their atypical behaviors is better tolerated, and they get more positive feedback that encourages integration inside and outside the classroom. Manners may make the difference between being allowed in or expelled from classrooms, libraries, clubs, teams, or religious institutions. When it is time to get a job, social skills are the key factor for employment for these individuals and a significant help for neurotypical individuals as well. Failure to signal socially appropriate behavior can make a person appear threatening and has had the rare but tragic result of rough or fatal handling by police.

Has the teaching of manners waned? Perhaps, because, for some families, the child is being socialized mostly by nonfamily caregivers who have low use of manners. Some parents have made teaching manners a low priority or even resisted using manners themselves as inauthentic. This may reflect prioritizing a “laid-back” lifestyle and speaking crudely as a sign of independence, perhaps in reaction to lack of autonomy at work. Mastering the careful interactions developed over time to avoid invoking an aggressive response depend on direct feedback from reactions of the recipient. With so much of our communication done electronically, asynchronously, even anonymously, the usual feedback has been reduced. Practicing curses, insults, and put-downs online easily extends to in-person interactions without the perpetrator even noticing and are generally reinforced and repeated without parental supervision. Disrespectful behavior from community leaders also reduces the threshold for society.

When people are ignorant of or choose not to use manners they may be perceived as “other” and hostile. This may lead to distrust, dislike, and lowered ability to find the common ground needed for making decisions that benefit the greater society. Oliver Wendell Holmes said “Under bad manners ... lies very commonly an overestimate of our special individuality, as distinguished from our generic humanity (“The Professor at the Breakfast Table,” 1858). Working for major goals that benefit all of humanity is essential to survival in our highly interconnected world. Considering all of humanity is a difficult concept for children, and even for many adults, but it starts with using civil behavior at home, in school, and in one’s community.
 

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].

The MammaPrint 70-gene signature has similar prognostic performance in women with early-stage invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) and may help guide chemotherapy decisions, according to an exploratory analysis of the MINDACT trial reported at the 12th European Breast Cancer Conference.

ILC is enriched with features indicating low proliferative activity, noted investigator Otto Metzger, MD, of the Dana Farber Cancer Institute in Boston.

“Data from retrospective series have indicated no benefit with adjuvant chemotherapy for patients diagnosed with early-stage ILC,” he said. “It’s fair to say that chemotherapy decisions for patients with ILC remain controversial.”

With this in mind, Dr. Metzger and colleagues analyzed data for 5,313 women who underwent surgery for early-stage breast cancer (node-negative or up to three positive lymph nodes) and were risk-stratified to receive or skip adjuvant chemotherapy based on both clinical risk and the MammaPrint score for genomic risk. Fully 44% of women with ILC had discordant clinical and genomic risks.

With a median follow-up of 8.7 years, the 5-year rate of distant metastasis–free survival among all patients classified as genomic high risk was 92.1% in women with IDC and 88.1% in women with ILC, with overlapping 95% confidence intervals. Rates of distant metastasis–free survival for patients with genomic low risk were 96.4% in women with IDC and 96.6% in women with ILC, again with confidence intervals that overlapped.

The pattern was essentially the same for overall survival, and results carried over into 8-year outcomes as well.

“We believe that MammaPrint is a clinically useful test for patients diagnosed with ILC,” Dr. Metzger said. “There are similar survival outcomes for ILC and IDC when matched by genomic risk. This is an important message.”

It should be standard to omit chemotherapy for patients who have ILC classified as high clinical risk but low genomic risk by MammaPrint, Dr. Metzger recommended. “By contrast, MammaPrint should facilitate chemotherapy treatment decisions for patients diagnosed with ILC and high-risk MammaPrint,” he said.
 

Prognostic, but predictive?

“This is a well-designed prospective multicenter trial and provides the best evidence to date that MammaPrint is an important prognostic tool for ILC,” Todd Tuttle, MD, of University of Minnesota in Minneapolis, said in an interview.

Dr. Tuttle said he mainly uses the MammaPrint test and the OncoType 21-gene recurrence score to estimate prognosis for his patients with ILC.

These new data establish that MammaPrint is prognostic in ILC, but the value of MammaPrint’s genomic high risk result for making the decision about chemotherapy is still unclear, according to Dr. Tuttle.

“I don’t think we know whether MammaPrint can predict the benefit of chemotherapy for patients with stage I or II ILC,” he elaborated. “We need further high-quality studies such as this one to determine the best treatment strategies for ILC, which is a difficult breast cancer.”
 

Study details

Of the 5,313 patients studied, 487 had ILC (255 classic and 232 variant) and 4,826 had IDC according to central pathology assessment, Dr. Metzger reported.

MammaPrint classified 39% of the IDC group and 16% of the ILC group (10% of those with classic disease and 23% of those with variant disease) as genomically high risk for recurrence. The Adjuvant! Online tool classified 48.3% of ILC and 51.5% of IDC patients as clinically high risk.

Among the 44% of women with ILC having discordant genomic and clinical risk, discordance was usually due to the combination of low genomic risk and high clinical risk, seen in 38%.

The curves for 5-year distant metastasis–free survival stratified by genomic risk essentially overlapped for the IDC and ILC groups. Furthermore, there was no significant interaction of histologic type and genomic risk on this outcome (P = .547).

The 5-year rate of overall survival among women with genomic high risk was 95.6% in the IDC group and 93.5% in the ILC group. Among women with genomic low risk, 5-year overall survival was 98.1% in the IDC group and 97.7% in the ILC group, again with overlapping confidence intervals within each risk category.

The study was funded with support from the Breast Cancer Research Foundation. Dr. Metzger disclosed consulting fees from AbbVie, Genentech, Roche, and Pfizer. Dr. Tuttle disclosed no conflicts of interest.
 

SOURCE: Metzger O et al. EBCC-12 Virtual Conference. Abstract 6.

The MammaPrint 70-gene signature has similar prognostic performance in women with early-stage invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) and may help guide chemotherapy decisions, according to an exploratory analysis of the MINDACT trial reported at the 12th European Breast Cancer Conference.

ILC is enriched with features indicating low proliferative activity, noted investigator Otto Metzger, MD, of the Dana Farber Cancer Institute in Boston.

“Data from retrospective series have indicated no benefit with adjuvant chemotherapy for patients diagnosed with early-stage ILC,” he said. “It’s fair to say that chemotherapy decisions for patients with ILC remain controversial.”

With this in mind, Dr. Metzger and colleagues analyzed data for 5,313 women who underwent surgery for early-stage breast cancer (node-negative or up to three positive lymph nodes) and were risk-stratified to receive or skip adjuvant chemotherapy based on both clinical risk and the MammaPrint score for genomic risk. Fully 44% of women with ILC had discordant clinical and genomic risks.

With a median follow-up of 8.7 years, the 5-year rate of distant metastasis–free survival among all patients classified as genomic high risk was 92.1% in women with IDC and 88.1% in women with ILC, with overlapping 95% confidence intervals. Rates of distant metastasis–free survival for patients with genomic low risk were 96.4% in women with IDC and 96.6% in women with ILC, again with confidence intervals that overlapped.

The pattern was essentially the same for overall survival, and results carried over into 8-year outcomes as well.

“We believe that MammaPrint is a clinically useful test for patients diagnosed with ILC,” Dr. Metzger said. “There are similar survival outcomes for ILC and IDC when matched by genomic risk. This is an important message.”

It should be standard to omit chemotherapy for patients who have ILC classified as high clinical risk but low genomic risk by MammaPrint, Dr. Metzger recommended. “By contrast, MammaPrint should facilitate chemotherapy treatment decisions for patients diagnosed with ILC and high-risk MammaPrint,” he said.
 

Prognostic, but predictive?

“This is a well-designed prospective multicenter trial and provides the best evidence to date that MammaPrint is an important prognostic tool for ILC,” Todd Tuttle, MD, of University of Minnesota in Minneapolis, said in an interview.

Dr. Tuttle said he mainly uses the MammaPrint test and the OncoType 21-gene recurrence score to estimate prognosis for his patients with ILC.

These new data establish that MammaPrint is prognostic in ILC, but the value of MammaPrint’s genomic high risk result for making the decision about chemotherapy is still unclear, according to Dr. Tuttle.

“I don’t think we know whether MammaPrint can predict the benefit of chemotherapy for patients with stage I or II ILC,” he elaborated. “We need further high-quality studies such as this one to determine the best treatment strategies for ILC, which is a difficult breast cancer.”
 

Study details

Of the 5,313 patients studied, 487 had ILC (255 classic and 232 variant) and 4,826 had IDC according to central pathology assessment, Dr. Metzger reported.

MammaPrint classified 39% of the IDC group and 16% of the ILC group (10% of those with classic disease and 23% of those with variant disease) as genomically high risk for recurrence. The Adjuvant! Online tool classified 48.3% of ILC and 51.5% of IDC patients as clinically high risk.

Among the 44% of women with ILC having discordant genomic and clinical risk, discordance was usually due to the combination of low genomic risk and high clinical risk, seen in 38%.

The curves for 5-year distant metastasis–free survival stratified by genomic risk essentially overlapped for the IDC and ILC groups. Furthermore, there was no significant interaction of histologic type and genomic risk on this outcome (P = .547).

The 5-year rate of overall survival among women with genomic high risk was 95.6% in the IDC group and 93.5% in the ILC group. Among women with genomic low risk, 5-year overall survival was 98.1% in the IDC group and 97.7% in the ILC group, again with overlapping confidence intervals within each risk category.

The study was funded with support from the Breast Cancer Research Foundation. Dr. Metzger disclosed consulting fees from AbbVie, Genentech, Roche, and Pfizer. Dr. Tuttle disclosed no conflicts of interest.
 

SOURCE: Metzger O et al. EBCC-12 Virtual Conference. Abstract 6.

The MammaPrint 70-gene signature has similar prognostic performance in women with early-stage invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) and may help guide chemotherapy decisions, according to an exploratory analysis of the MINDACT trial reported at the 12th European Breast Cancer Conference.

ILC is enriched with features indicating low proliferative activity, noted investigator Otto Metzger, MD, of the Dana Farber Cancer Institute in Boston.

“Data from retrospective series have indicated no benefit with adjuvant chemotherapy for patients diagnosed with early-stage ILC,” he said. “It’s fair to say that chemotherapy decisions for patients with ILC remain controversial.”

With this in mind, Dr. Metzger and colleagues analyzed data for 5,313 women who underwent surgery for early-stage breast cancer (node-negative or up to three positive lymph nodes) and were risk-stratified to receive or skip adjuvant chemotherapy based on both clinical risk and the MammaPrint score for genomic risk. Fully 44% of women with ILC had discordant clinical and genomic risks.

With a median follow-up of 8.7 years, the 5-year rate of distant metastasis–free survival among all patients classified as genomic high risk was 92.1% in women with IDC and 88.1% in women with ILC, with overlapping 95% confidence intervals. Rates of distant metastasis–free survival for patients with genomic low risk were 96.4% in women with IDC and 96.6% in women with ILC, again with confidence intervals that overlapped.

The pattern was essentially the same for overall survival, and results carried over into 8-year outcomes as well.

“We believe that MammaPrint is a clinically useful test for patients diagnosed with ILC,” Dr. Metzger said. “There are similar survival outcomes for ILC and IDC when matched by genomic risk. This is an important message.”

It should be standard to omit chemotherapy for patients who have ILC classified as high clinical risk but low genomic risk by MammaPrint, Dr. Metzger recommended. “By contrast, MammaPrint should facilitate chemotherapy treatment decisions for patients diagnosed with ILC and high-risk MammaPrint,” he said.
 

Prognostic, but predictive?

“This is a well-designed prospective multicenter trial and provides the best evidence to date that MammaPrint is an important prognostic tool for ILC,” Todd Tuttle, MD, of University of Minnesota in Minneapolis, said in an interview.

Dr. Tuttle said he mainly uses the MammaPrint test and the OncoType 21-gene recurrence score to estimate prognosis for his patients with ILC.

These new data establish that MammaPrint is prognostic in ILC, but the value of MammaPrint’s genomic high risk result for making the decision about chemotherapy is still unclear, according to Dr. Tuttle.

“I don’t think we know whether MammaPrint can predict the benefit of chemotherapy for patients with stage I or II ILC,” he elaborated. “We need further high-quality studies such as this one to determine the best treatment strategies for ILC, which is a difficult breast cancer.”
 

Study details

Of the 5,313 patients studied, 487 had ILC (255 classic and 232 variant) and 4,826 had IDC according to central pathology assessment, Dr. Metzger reported.

MammaPrint classified 39% of the IDC group and 16% of the ILC group (10% of those with classic disease and 23% of those with variant disease) as genomically high risk for recurrence. The Adjuvant! Online tool classified 48.3% of ILC and 51.5% of IDC patients as clinically high risk.

Among the 44% of women with ILC having discordant genomic and clinical risk, discordance was usually due to the combination of low genomic risk and high clinical risk, seen in 38%.

The curves for 5-year distant metastasis–free survival stratified by genomic risk essentially overlapped for the IDC and ILC groups. Furthermore, there was no significant interaction of histologic type and genomic risk on this outcome (P = .547).

The 5-year rate of overall survival among women with genomic high risk was 95.6% in the IDC group and 93.5% in the ILC group. Among women with genomic low risk, 5-year overall survival was 98.1% in the IDC group and 97.7% in the ILC group, again with overlapping confidence intervals within each risk category.

The study was funded with support from the Breast Cancer Research Foundation. Dr. Metzger disclosed consulting fees from AbbVie, Genentech, Roche, and Pfizer. Dr. Tuttle disclosed no conflicts of interest.
 

SOURCE: Metzger O et al. EBCC-12 Virtual Conference. Abstract 6.

Adults with active psoriatic arthritis (PsA) treated with guselkumab (Tremfya) showed significant improvement in American College of Rheumatology response criteria and disease activity after 1 year, based on data from the phase 3 DISCOVER-2 trial.

The findings, published in Arthritis & Rheumatology, extend the previously published 24-week, primary endpoint results of the trial, which tested guselkumab for adults with PsA who had not previously taken a biologic drug. Guselkumab was approved in July 2020 in the United States.

Iain B. McInnes, MD, PhD, of the University of Glasgow and his colleagues described guselkumab as “a fully-human monoclonal antibody specific to interleukin (IL)-23’s p19-subunit” that offers a potential alternative for PsA patients who discontinue their index tumor necrosis factor inhibitor because of insufficient efficacy.

The study enrolled 739 PsA patients at 118 sites worldwide. Participants were randomized to receive subcutaneous injections of 100 mg guselkumab every 4 weeks; 100 mg guselkumab at week 0 and 4, then every 8 weeks; or a placebo; 238 placebo-treated patients crossed over at 24 weeks to receive 100 mg guselkumab every 4 weeks. Patients on nonbiologic disease-modifying antirheumatic drugs at baseline were allowed to continue stable doses. Overall, about 93% of patients originally randomized to the three groups remained on guselkumab at 52 weeks.

Overall, 71% and 75% of 4-week and 8-week guselkumab patients, respectively, showed an improvement of at least 20% from baseline in ACR response criteria components at 52 weeks, which was up from 64% of patients seen at 24 weeks in both groups.

The study participants had an average disease duration of more than 5 years with no biologic treatment, and an average of 12-13 swollen joints and 20-22 tender joints at baseline. Approximately half were male, half had psoriasis or dactylitis, and two-thirds had enthesitis. Skin disease severity was assessed using the Investigator’s Global Assessment and Psoriasis Area Severity Index (PASI).

At 52 weeks, 75% and 58% of patients in the guselkumab groups had resolution of dactylitis and enthesitis, respectively. In addition, 86% of patients in both guselkumab groups achieved PASI 75 at 52 weeks, and 58% and 53% of the 4-week and 8-week groups, respectively, achieved PASI 100.

In addition, patients treated with guselkumab showed low levels of radiographic progression and significant improvements from baseline in measures of physical function and quality of life.

The most frequently reported adverse events in guselkumab patients were upper respiratory tract infections, nasopharyngitis, bronchitis, and investigator-reported laboratory values of increased alanine aminotransferase and aspartate aminotransferase; these rates were similar to those seen in the previously published 24-week data. Approximately 2% of guselkumab and placebo patients discontinued their treatments because of adverse events.

No patient developed an opportunistic infection or died during the study period.

The study findings were limited by several factors including the relatively short 1-year duration, the shorter duration of placebo, compared with guselkumab, and by potential confounding from missing data on patients who discontinued, the researchers noted. However, the results support the effectiveness of guselkumab for improving a range of manifestations of active PsA, and the overall treatment and safety profiles seen at 24 weeks were maintained, they said.

“Data obtained during the second year of DISCOVER-2 will augment current knowledge of the guselkumab benefit-risk profile and further our understanding of longer-term radiographic outcomes with both guselkumab dosing regimens,” they concluded.

The study was supported by Janssen. Many authors reported financial relationships with Janssen and other pharmaceutical companies. Nine of the 15 authors are employees of Janssen (a subsidiary of Johnson & Johnson) and own Johnson & Johnson stock or stock options.

SOURCE: McInnes IB et al. Arthritis Rheumatol. 2020 Oct 11. doi: 10.1002/art.41553.

Adults with active psoriatic arthritis (PsA) treated with guselkumab (Tremfya) showed significant improvement in American College of Rheumatology response criteria and disease activity after 1 year, based on data from the phase 3 DISCOVER-2 trial.

The findings, published in Arthritis & Rheumatology, extend the previously published 24-week, primary endpoint results of the trial, which tested guselkumab for adults with PsA who had not previously taken a biologic drug. Guselkumab was approved in July 2020 in the United States.

Iain B. McInnes, MD, PhD, of the University of Glasgow and his colleagues described guselkumab as “a fully-human monoclonal antibody specific to interleukin (IL)-23’s p19-subunit” that offers a potential alternative for PsA patients who discontinue their index tumor necrosis factor inhibitor because of insufficient efficacy.

The study enrolled 739 PsA patients at 118 sites worldwide. Participants were randomized to receive subcutaneous injections of 100 mg guselkumab every 4 weeks; 100 mg guselkumab at week 0 and 4, then every 8 weeks; or a placebo; 238 placebo-treated patients crossed over at 24 weeks to receive 100 mg guselkumab every 4 weeks. Patients on nonbiologic disease-modifying antirheumatic drugs at baseline were allowed to continue stable doses. Overall, about 93% of patients originally randomized to the three groups remained on guselkumab at 52 weeks.

Overall, 71% and 75% of 4-week and 8-week guselkumab patients, respectively, showed an improvement of at least 20% from baseline in ACR response criteria components at 52 weeks, which was up from 64% of patients seen at 24 weeks in both groups.

The study participants had an average disease duration of more than 5 years with no biologic treatment, and an average of 12-13 swollen joints and 20-22 tender joints at baseline. Approximately half were male, half had psoriasis or dactylitis, and two-thirds had enthesitis. Skin disease severity was assessed using the Investigator’s Global Assessment and Psoriasis Area Severity Index (PASI).

At 52 weeks, 75% and 58% of patients in the guselkumab groups had resolution of dactylitis and enthesitis, respectively. In addition, 86% of patients in both guselkumab groups achieved PASI 75 at 52 weeks, and 58% and 53% of the 4-week and 8-week groups, respectively, achieved PASI 100.

In addition, patients treated with guselkumab showed low levels of radiographic progression and significant improvements from baseline in measures of physical function and quality of life.

The most frequently reported adverse events in guselkumab patients were upper respiratory tract infections, nasopharyngitis, bronchitis, and investigator-reported laboratory values of increased alanine aminotransferase and aspartate aminotransferase; these rates were similar to those seen in the previously published 24-week data. Approximately 2% of guselkumab and placebo patients discontinued their treatments because of adverse events.

No patient developed an opportunistic infection or died during the study period.

The study findings were limited by several factors including the relatively short 1-year duration, the shorter duration of placebo, compared with guselkumab, and by potential confounding from missing data on patients who discontinued, the researchers noted. However, the results support the effectiveness of guselkumab for improving a range of manifestations of active PsA, and the overall treatment and safety profiles seen at 24 weeks were maintained, they said.

“Data obtained during the second year of DISCOVER-2 will augment current knowledge of the guselkumab benefit-risk profile and further our understanding of longer-term radiographic outcomes with both guselkumab dosing regimens,” they concluded.

The study was supported by Janssen. Many authors reported financial relationships with Janssen and other pharmaceutical companies. Nine of the 15 authors are employees of Janssen (a subsidiary of Johnson & Johnson) and own Johnson & Johnson stock or stock options.

SOURCE: McInnes IB et al. Arthritis Rheumatol. 2020 Oct 11. doi: 10.1002/art.41553.

Adults with active psoriatic arthritis (PsA) treated with guselkumab (Tremfya) showed significant improvement in American College of Rheumatology response criteria and disease activity after 1 year, based on data from the phase 3 DISCOVER-2 trial.

The findings, published in Arthritis & Rheumatology, extend the previously published 24-week, primary endpoint results of the trial, which tested guselkumab for adults with PsA who had not previously taken a biologic drug. Guselkumab was approved in July 2020 in the United States.

Iain B. McInnes, MD, PhD, of the University of Glasgow and his colleagues described guselkumab as “a fully-human monoclonal antibody specific to interleukin (IL)-23’s p19-subunit” that offers a potential alternative for PsA patients who discontinue their index tumor necrosis factor inhibitor because of insufficient efficacy.

The study enrolled 739 PsA patients at 118 sites worldwide. Participants were randomized to receive subcutaneous injections of 100 mg guselkumab every 4 weeks; 100 mg guselkumab at week 0 and 4, then every 8 weeks; or a placebo; 238 placebo-treated patients crossed over at 24 weeks to receive 100 mg guselkumab every 4 weeks. Patients on nonbiologic disease-modifying antirheumatic drugs at baseline were allowed to continue stable doses. Overall, about 93% of patients originally randomized to the three groups remained on guselkumab at 52 weeks.

Overall, 71% and 75% of 4-week and 8-week guselkumab patients, respectively, showed an improvement of at least 20% from baseline in ACR response criteria components at 52 weeks, which was up from 64% of patients seen at 24 weeks in both groups.

The study participants had an average disease duration of more than 5 years with no biologic treatment, and an average of 12-13 swollen joints and 20-22 tender joints at baseline. Approximately half were male, half had psoriasis or dactylitis, and two-thirds had enthesitis. Skin disease severity was assessed using the Investigator’s Global Assessment and Psoriasis Area Severity Index (PASI).

At 52 weeks, 75% and 58% of patients in the guselkumab groups had resolution of dactylitis and enthesitis, respectively. In addition, 86% of patients in both guselkumab groups achieved PASI 75 at 52 weeks, and 58% and 53% of the 4-week and 8-week groups, respectively, achieved PASI 100.

In addition, patients treated with guselkumab showed low levels of radiographic progression and significant improvements from baseline in measures of physical function and quality of life.

The most frequently reported adverse events in guselkumab patients were upper respiratory tract infections, nasopharyngitis, bronchitis, and investigator-reported laboratory values of increased alanine aminotransferase and aspartate aminotransferase; these rates were similar to those seen in the previously published 24-week data. Approximately 2% of guselkumab and placebo patients discontinued their treatments because of adverse events.

No patient developed an opportunistic infection or died during the study period.

The study findings were limited by several factors including the relatively short 1-year duration, the shorter duration of placebo, compared with guselkumab, and by potential confounding from missing data on patients who discontinued, the researchers noted. However, the results support the effectiveness of guselkumab for improving a range of manifestations of active PsA, and the overall treatment and safety profiles seen at 24 weeks were maintained, they said.

“Data obtained during the second year of DISCOVER-2 will augment current knowledge of the guselkumab benefit-risk profile and further our understanding of longer-term radiographic outcomes with both guselkumab dosing regimens,” they concluded.

The study was supported by Janssen. Many authors reported financial relationships with Janssen and other pharmaceutical companies. Nine of the 15 authors are employees of Janssen (a subsidiary of Johnson & Johnson) and own Johnson & Johnson stock or stock options.

SOURCE: McInnes IB et al. Arthritis Rheumatol. 2020 Oct 11. doi: 10.1002/art.41553.

Use of febuxostat (Uloric) decreased among patients with gout in the United States following a Food and Drug Administration–mandated black-box warning that cited cardiovascular concerns, but overall use of urate-lowering therapy remained stable, according to data from a study of commercial insurance enrollees in the United States between 2009 and 2019.

Initiation of urate-lowering therapy (ULT) is recommended for gout patients, and allopurinol remains the first-line treatment, but it is not effective in all patients, and febuxostat was developed as an alternative, wrote Seoyoung C. Kim, MD, ScD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues.

However, based on data from a postmarketing safety trial (the CARES trial) mandated by the FDA, the agency first issued a safety announcement about an increased risk of cardiovascular mortality with febuxostat in November 2017, followed in February 2019 with a black-box warning after full CARES trial results were published in March 2018 showing a greater risk of cardiovascular and all-cause mortality in febuxostat versus allopurinol.

In a study published in Arthritis & Rheumatology, the researchers examined trends in the use of ULT before and after the FDA warning. They analyzed claims data from a national commercial health database that included 838,432 adult ULT users and 633,229 gout patients.

Overall, allopurinol accounted for the majority of ULT use between 2009 (95% in the first quarter) and 2019 (92% in the fourth quarter).

Febuxostat use peaked at 10% of all ULT use in 2013 and 2014, after a gradual increase following its introduction into the market in 2009, the researchers noted, but decreased to 6% of all ULT use in the fourth quarter of 2019. Other medications, including probenecid, lesinurad (Zurampic), and pegloticase (Krystexxa), accounted for no more than 5% of ULT use.

When the researchers examined gout patients in particular, they found a slight increase in any ULT use from 567 per 1,000 patients in the first quarter of 2009 to 656 per 1,000 patients in the fourth quarter of 2019.

The study findings were limited by several factors, including potential lack of generalizability to other health plans and lack of adjustment for comorbid conditions, the researchers noted.

However, the results highlight the suboptimal use of ULT as a class and the need to address the treatment gap in gout patients “with appropriate ULT prescribing and monitoring,” they said. “While the decrease in febuxostat use was accompanied by a compensatory increase in allopurinol use, the proportion of patients with gout without any ULT remained high throughout the study period,” they concluded.

The study was supported by the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital. Dr. Kim disclosed receiving research grants to Brigham and Women’s Hospital from Pfizer, AbbVie, Roche, and Bristol-Myers Squibb for research unrelated to the current study.

SOURCE: Kim SC et al. Arthritis Rheumatol. 2020 Oct 7. doi: 10.1002/art.41550.

Use of febuxostat (Uloric) decreased among patients with gout in the United States following a Food and Drug Administration–mandated black-box warning that cited cardiovascular concerns, but overall use of urate-lowering therapy remained stable, according to data from a study of commercial insurance enrollees in the United States between 2009 and 2019.

Initiation of urate-lowering therapy (ULT) is recommended for gout patients, and allopurinol remains the first-line treatment, but it is not effective in all patients, and febuxostat was developed as an alternative, wrote Seoyoung C. Kim, MD, ScD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues.

However, based on data from a postmarketing safety trial (the CARES trial) mandated by the FDA, the agency first issued a safety announcement about an increased risk of cardiovascular mortality with febuxostat in November 2017, followed in February 2019 with a black-box warning after full CARES trial results were published in March 2018 showing a greater risk of cardiovascular and all-cause mortality in febuxostat versus allopurinol.

In a study published in Arthritis & Rheumatology, the researchers examined trends in the use of ULT before and after the FDA warning. They analyzed claims data from a national commercial health database that included 838,432 adult ULT users and 633,229 gout patients.

Overall, allopurinol accounted for the majority of ULT use between 2009 (95% in the first quarter) and 2019 (92% in the fourth quarter).

Febuxostat use peaked at 10% of all ULT use in 2013 and 2014, after a gradual increase following its introduction into the market in 2009, the researchers noted, but decreased to 6% of all ULT use in the fourth quarter of 2019. Other medications, including probenecid, lesinurad (Zurampic), and pegloticase (Krystexxa), accounted for no more than 5% of ULT use.

When the researchers examined gout patients in particular, they found a slight increase in any ULT use from 567 per 1,000 patients in the first quarter of 2009 to 656 per 1,000 patients in the fourth quarter of 2019.

The study findings were limited by several factors, including potential lack of generalizability to other health plans and lack of adjustment for comorbid conditions, the researchers noted.

However, the results highlight the suboptimal use of ULT as a class and the need to address the treatment gap in gout patients “with appropriate ULT prescribing and monitoring,” they said. “While the decrease in febuxostat use was accompanied by a compensatory increase in allopurinol use, the proportion of patients with gout without any ULT remained high throughout the study period,” they concluded.

The study was supported by the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital. Dr. Kim disclosed receiving research grants to Brigham and Women’s Hospital from Pfizer, AbbVie, Roche, and Bristol-Myers Squibb for research unrelated to the current study.

SOURCE: Kim SC et al. Arthritis Rheumatol. 2020 Oct 7. doi: 10.1002/art.41550.

Use of febuxostat (Uloric) decreased among patients with gout in the United States following a Food and Drug Administration–mandated black-box warning that cited cardiovascular concerns, but overall use of urate-lowering therapy remained stable, according to data from a study of commercial insurance enrollees in the United States between 2009 and 2019.

Initiation of urate-lowering therapy (ULT) is recommended for gout patients, and allopurinol remains the first-line treatment, but it is not effective in all patients, and febuxostat was developed as an alternative, wrote Seoyoung C. Kim, MD, ScD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues.

However, based on data from a postmarketing safety trial (the CARES trial) mandated by the FDA, the agency first issued a safety announcement about an increased risk of cardiovascular mortality with febuxostat in November 2017, followed in February 2019 with a black-box warning after full CARES trial results were published in March 2018 showing a greater risk of cardiovascular and all-cause mortality in febuxostat versus allopurinol.

In a study published in Arthritis & Rheumatology, the researchers examined trends in the use of ULT before and after the FDA warning. They analyzed claims data from a national commercial health database that included 838,432 adult ULT users and 633,229 gout patients.

Overall, allopurinol accounted for the majority of ULT use between 2009 (95% in the first quarter) and 2019 (92% in the fourth quarter).

Febuxostat use peaked at 10% of all ULT use in 2013 and 2014, after a gradual increase following its introduction into the market in 2009, the researchers noted, but decreased to 6% of all ULT use in the fourth quarter of 2019. Other medications, including probenecid, lesinurad (Zurampic), and pegloticase (Krystexxa), accounted for no more than 5% of ULT use.

When the researchers examined gout patients in particular, they found a slight increase in any ULT use from 567 per 1,000 patients in the first quarter of 2009 to 656 per 1,000 patients in the fourth quarter of 2019.

The study findings were limited by several factors, including potential lack of generalizability to other health plans and lack of adjustment for comorbid conditions, the researchers noted.

However, the results highlight the suboptimal use of ULT as a class and the need to address the treatment gap in gout patients “with appropriate ULT prescribing and monitoring,” they said. “While the decrease in febuxostat use was accompanied by a compensatory increase in allopurinol use, the proportion of patients with gout without any ULT remained high throughout the study period,” they concluded.

The study was supported by the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital. Dr. Kim disclosed receiving research grants to Brigham and Women’s Hospital from Pfizer, AbbVie, Roche, and Bristol-Myers Squibb for research unrelated to the current study.

SOURCE: Kim SC et al. Arthritis Rheumatol. 2020 Oct 7. doi: 10.1002/art.41550.

Blood group O was associated with a decreased risk for contracting SARS-CoV-2 infection, according to the results of large retrospective analysis of the Danish population.

Researchers Mike Bogetofte Barnkob, MD, of the Department of Clinical Immunology, Odense (Denmark) University Hospital, and colleagues performed a retrospective cohort analysis of all Danish individuals with a known ABO blood group who were tested for SARS-CoV-2 between Feb. 27, 2020, and July 30, 2020.

Of the 841,327 people tested, ABO and RhD blood groups could be identified for 473,654 individuals. ABO and RhD data from 2,204,742 (38% of the entire Danish population) were used as a reference, according to the online report in Blood Advances.

The primary outcome was status of ABO and RhD blood groups and test results for SARS-CoV-2. The secondary outcomes followed were hospitalization and death from COVID-19.
 

Reduced prevalence

The study found that ABO blood groups varied significantly between patients and the reference group, with only 38.41% (95% confidence interval, 37.30%-39.50%) of the patients belonging to blood group O, compared with 41.70% (95% CI, 41.60%-41.80%) in the controls, corresponding to a relative risk of 0.87 (95% CI, 0.83-0.91) for acquiring COVID-19.

There was a slight, but statistically significant, difference in blood group distribution between the SARS-CoV-22 individuals and the reference population (P < .001), according to the authors.

Among the SARS-CoV-2 individuals, fewer group O individuals were found (P < .001); while more A, B, and AB individuals were seen (P < .001, P = .011, and P = .091, respectively). There was no significant difference seen among A, B, and AB blood groups (P = .30). The RR for contracting SARS-CoV-2 were 1.09 (95% CI, 1.04-1.14) for A group individuals; 1.06 (95% CI, 0.99-1.14) for B group; and 1.15 (95% CI, 1.03-1.27) for AB group, respectively.

There was no difference found in the RhD group between positive test cases and the reference population (P = .15). In addition, there was no statistical difference (all P > .40) between ABO blood groups and clinical severity of COVID-19 for nonhospitalized patients versus hospitalized patients or for deceased patients versus living patients, the researchers added.
 

Possible causes

The authors speculated on two possible causes of the lower prevalence of SARS-CoV-2 infection in the blood group O population. The first is that anti-A and anti-B antibodies may have an effect on neutralizing SARS-CoV viruses and that anti-A and anti-B are present on mucosal surfaces in some individuals lacking the corresponding ABO blood group. The second is that the association between ABO blood groups and levels of von Willebrand factor, which is higher in non-O individuals and is tied to an increased likelihood of arterial and venous thrombosis, could have an indirect or unknown impact on susceptibility to infection, according to the authors.

“Given the known increased risk of thrombosis in non-O individuals and the evolving central role for thrombosis in the pathogenesis of COVID-19, it is important to explore this aspect more closely in larger patient cohorts (e.g., by examining ABO blood type and viral load, the severity of symptoms, and the long-term effects following COVID-19),” the researchers concluded.

One author reported receiving fees from Bristol Myers Squibb, Novartis, and Roche. The remaining authors reported they had no competing financial interests.

[email protected]

SOURCE: Barnkob MB et al. Blood Adv. 2020 Oct 14. doi: 10.1182/bloodadvances.2020002657.

Blood group O was associated with a decreased risk for contracting SARS-CoV-2 infection, according to the results of large retrospective analysis of the Danish population.

Researchers Mike Bogetofte Barnkob, MD, of the Department of Clinical Immunology, Odense (Denmark) University Hospital, and colleagues performed a retrospective cohort analysis of all Danish individuals with a known ABO blood group who were tested for SARS-CoV-2 between Feb. 27, 2020, and July 30, 2020.

Of the 841,327 people tested, ABO and RhD blood groups could be identified for 473,654 individuals. ABO and RhD data from 2,204,742 (38% of the entire Danish population) were used as a reference, according to the online report in Blood Advances.

The primary outcome was status of ABO and RhD blood groups and test results for SARS-CoV-2. The secondary outcomes followed were hospitalization and death from COVID-19.
 

Reduced prevalence

The study found that ABO blood groups varied significantly between patients and the reference group, with only 38.41% (95% confidence interval, 37.30%-39.50%) of the patients belonging to blood group O, compared with 41.70% (95% CI, 41.60%-41.80%) in the controls, corresponding to a relative risk of 0.87 (95% CI, 0.83-0.91) for acquiring COVID-19.

There was a slight, but statistically significant, difference in blood group distribution between the SARS-CoV-22 individuals and the reference population (P < .001), according to the authors.

Among the SARS-CoV-2 individuals, fewer group O individuals were found (P < .001); while more A, B, and AB individuals were seen (P < .001, P = .011, and P = .091, respectively). There was no significant difference seen among A, B, and AB blood groups (P = .30). The RR for contracting SARS-CoV-2 were 1.09 (95% CI, 1.04-1.14) for A group individuals; 1.06 (95% CI, 0.99-1.14) for B group; and 1.15 (95% CI, 1.03-1.27) for AB group, respectively.

There was no difference found in the RhD group between positive test cases and the reference population (P = .15). In addition, there was no statistical difference (all P > .40) between ABO blood groups and clinical severity of COVID-19 for nonhospitalized patients versus hospitalized patients or for deceased patients versus living patients, the researchers added.
 

Possible causes

The authors speculated on two possible causes of the lower prevalence of SARS-CoV-2 infection in the blood group O population. The first is that anti-A and anti-B antibodies may have an effect on neutralizing SARS-CoV viruses and that anti-A and anti-B are present on mucosal surfaces in some individuals lacking the corresponding ABO blood group. The second is that the association between ABO blood groups and levels of von Willebrand factor, which is higher in non-O individuals and is tied to an increased likelihood of arterial and venous thrombosis, could have an indirect or unknown impact on susceptibility to infection, according to the authors.

“Given the known increased risk of thrombosis in non-O individuals and the evolving central role for thrombosis in the pathogenesis of COVID-19, it is important to explore this aspect more closely in larger patient cohorts (e.g., by examining ABO blood type and viral load, the severity of symptoms, and the long-term effects following COVID-19),” the researchers concluded.

One author reported receiving fees from Bristol Myers Squibb, Novartis, and Roche. The remaining authors reported they had no competing financial interests.

[email protected]

SOURCE: Barnkob MB et al. Blood Adv. 2020 Oct 14. doi: 10.1182/bloodadvances.2020002657.

Blood group O was associated with a decreased risk for contracting SARS-CoV-2 infection, according to the results of large retrospective analysis of the Danish population.

Researchers Mike Bogetofte Barnkob, MD, of the Department of Clinical Immunology, Odense (Denmark) University Hospital, and colleagues performed a retrospective cohort analysis of all Danish individuals with a known ABO blood group who were tested for SARS-CoV-2 between Feb. 27, 2020, and July 30, 2020.

Of the 841,327 people tested, ABO and RhD blood groups could be identified for 473,654 individuals. ABO and RhD data from 2,204,742 (38% of the entire Danish population) were used as a reference, according to the online report in Blood Advances.

The primary outcome was status of ABO and RhD blood groups and test results for SARS-CoV-2. The secondary outcomes followed were hospitalization and death from COVID-19.
 

Reduced prevalence

The study found that ABO blood groups varied significantly between patients and the reference group, with only 38.41% (95% confidence interval, 37.30%-39.50%) of the patients belonging to blood group O, compared with 41.70% (95% CI, 41.60%-41.80%) in the controls, corresponding to a relative risk of 0.87 (95% CI, 0.83-0.91) for acquiring COVID-19.

There was a slight, but statistically significant, difference in blood group distribution between the SARS-CoV-22 individuals and the reference population (P < .001), according to the authors.

Among the SARS-CoV-2 individuals, fewer group O individuals were found (P < .001); while more A, B, and AB individuals were seen (P < .001, P = .011, and P = .091, respectively). There was no significant difference seen among A, B, and AB blood groups (P = .30). The RR for contracting SARS-CoV-2 were 1.09 (95% CI, 1.04-1.14) for A group individuals; 1.06 (95% CI, 0.99-1.14) for B group; and 1.15 (95% CI, 1.03-1.27) for AB group, respectively.

There was no difference found in the RhD group between positive test cases and the reference population (P = .15). In addition, there was no statistical difference (all P > .40) between ABO blood groups and clinical severity of COVID-19 for nonhospitalized patients versus hospitalized patients or for deceased patients versus living patients, the researchers added.
 

Possible causes

The authors speculated on two possible causes of the lower prevalence of SARS-CoV-2 infection in the blood group O population. The first is that anti-A and anti-B antibodies may have an effect on neutralizing SARS-CoV viruses and that anti-A and anti-B are present on mucosal surfaces in some individuals lacking the corresponding ABO blood group. The second is that the association between ABO blood groups and levels of von Willebrand factor, which is higher in non-O individuals and is tied to an increased likelihood of arterial and venous thrombosis, could have an indirect or unknown impact on susceptibility to infection, according to the authors.

“Given the known increased risk of thrombosis in non-O individuals and the evolving central role for thrombosis in the pathogenesis of COVID-19, it is important to explore this aspect more closely in larger patient cohorts (e.g., by examining ABO blood type and viral load, the severity of symptoms, and the long-term effects following COVID-19),” the researchers concluded.

One author reported receiving fees from Bristol Myers Squibb, Novartis, and Roche. The remaining authors reported they had no competing financial interests.

[email protected]

SOURCE: Barnkob MB et al. Blood Adv. 2020 Oct 14. doi: 10.1182/bloodadvances.2020002657.

Ticagrelor monotherapy after just 3 months of dual-antiplatelet therapy (DAPT) in patients with ST-elevation myocardial infarction treated with drug-eluting stents proved a winning strategy in TICO-STEMI, a major randomized trial.

“This is the first report assessing the feasibility of ticagrelor monotherapy after short-term DAPT for STEMI patients with drug-eluting stents,” Byeong-Keuk Kim, MD, PhD, noted at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.

The positive results were consistent with the earlier TWILIGHT study (Ticagrelor with Aspirin or Alone in High-Risk Patients after Coronary Intervention), which also showed clinical benefit at 1 year for 3 months of DAPT followed by ticagrelor (Brilinta) monotherapy, albeit only in PCI patients without an acute coronary syndrome (ACS) or with non-STEMI ACS (N Engl J Med. 2019 Nov 21;381[21]:2032-42).

TICO-STEMI was a prespecified substudy involving the 1,103 STEMI patients included in the previously reported parent 38-center South Korean TICO (Ticagrelor With or Without Aspirin in Acute Coronary Syndrome After PCI) study of 3,056 ACS patients treated with a second-generation ultrathin biodegradable polymer-coated sirolimus-eluting stent (JAMA. 2020 Jun 16;323[23]:2407-16).

The primary outcome in TICO-STEMI was the 12-month composite rate of net adverse clinical events, composed of major bleeding, all-cause mortality, acute MI, stroke, stent thrombosis, or target vessel revascularization. In an intention-to-treat analysis, the rate was 5.0% in the 12-month DAPT group and 3.7% with ticagrelor monotherapy after 3 months of DAPT, for a 27% relative risk reduction which didn’t achieve statistical significance. However, in an as-treated analysis, the between-group difference in the primary endpoint was stronger: a 5.2% incidence with 12 months of DAPT and 2.3% with ticagrelor monotherapy, for a relative risk reduction of 56%, which was statistically significant.

Major bleeding, one of two key secondary endpoints, was a different story: The incidence within 12 months by intention-to-treat was 2.9% with 12 months of DAPT compared to 0.9% with ticagrelor monotherapy, for a statistically significant 68% relative risk reduction in favor of ticagrelor monotherapy. In contrast, there was no between-group difference in the other secondary endpoint composed of major adverse cardio- and cerebrovascular events: 2.7% with ticagrelor monotherapy, 2.5% with 12 months of DAPT.

In the subgroup of TICO-STEMI patients at high bleeding risk, ticagrelor monotherapy was associated with a 12-month major bleeding rate of 1.8%, compared to 6.3% with a full year of DAPT. Conversely, in patients who underwent complex PCI, ticagrelor monotherapy was associated with a 4.9% rate of major adverse cardio- and cerebrovascular events through 1 year, numerically greater than but not statistically significantly different from the 2.7% rate with 12 months of DAPT.

Dr. Kim noted that the study had several limitations: It was open label, had no placebo control, and was underpowered to draw definite conclusions regarding the merits of dropping aspirin and continuing ticagrelor after 3 months in STEMI patients.

“Our findings should be interpreted with caution and call for confirmatory randomized trials,” he stressed.

Session comoderator Roxana Mehran, MD, said she “wholeheartedly” agrees with that assessment.

“We really do need a future trial, and we’re working to design TWILIGHT-STEMI,” a large randomized follow-up to the TWILIGHT trial, which she directed.

“I often imagine that we can have an even shorter duration of aspirin and ticagrelor and go to monotherapy sooner than 3 months in this very, very important subgroup,” added Dr. Mehran, professor of medicine, professor of population science and policy, and director of interventional cardiovascular research and clinical trials at the Icahn School of Medicine at Mount Sinai, New York.

Discussant Marco Valgimigli, MD, PhD, of University Hospital in Bern, Switzerland, calculated that the number-needed-to-treat with ticagrelor monotherapy rather than 12 months of DAPT in order to prevent one additional major bleeding event in TICO-STEMI participants at high bleeding risk was 22, as compared to an NNT of 77 in those without high bleeding risk.

MDedge News

[email protected]

Ticagrelor monotherapy after just 3 months of dual-antiplatelet therapy (DAPT) in patients with ST-elevation myocardial infarction treated with drug-eluting stents proved a winning strategy in TICO-STEMI, a major randomized trial.

“This is the first report assessing the feasibility of ticagrelor monotherapy after short-term DAPT for STEMI patients with drug-eluting stents,” Byeong-Keuk Kim, MD, PhD, noted at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.

The positive results were consistent with the earlier TWILIGHT study (Ticagrelor with Aspirin or Alone in High-Risk Patients after Coronary Intervention), which also showed clinical benefit at 1 year for 3 months of DAPT followed by ticagrelor (Brilinta) monotherapy, albeit only in PCI patients without an acute coronary syndrome (ACS) or with non-STEMI ACS (N Engl J Med. 2019 Nov 21;381[21]:2032-42).

TICO-STEMI was a prespecified substudy involving the 1,103 STEMI patients included in the previously reported parent 38-center South Korean TICO (Ticagrelor With or Without Aspirin in Acute Coronary Syndrome After PCI) study of 3,056 ACS patients treated with a second-generation ultrathin biodegradable polymer-coated sirolimus-eluting stent (JAMA. 2020 Jun 16;323[23]:2407-16).

The primary outcome in TICO-STEMI was the 12-month composite rate of net adverse clinical events, composed of major bleeding, all-cause mortality, acute MI, stroke, stent thrombosis, or target vessel revascularization. In an intention-to-treat analysis, the rate was 5.0% in the 12-month DAPT group and 3.7% with ticagrelor monotherapy after 3 months of DAPT, for a 27% relative risk reduction which didn’t achieve statistical significance. However, in an as-treated analysis, the between-group difference in the primary endpoint was stronger: a 5.2% incidence with 12 months of DAPT and 2.3% with ticagrelor monotherapy, for a relative risk reduction of 56%, which was statistically significant.

Major bleeding, one of two key secondary endpoints, was a different story: The incidence within 12 months by intention-to-treat was 2.9% with 12 months of DAPT compared to 0.9% with ticagrelor monotherapy, for a statistically significant 68% relative risk reduction in favor of ticagrelor monotherapy. In contrast, there was no between-group difference in the other secondary endpoint composed of major adverse cardio- and cerebrovascular events: 2.7% with ticagrelor monotherapy, 2.5% with 12 months of DAPT.

In the subgroup of TICO-STEMI patients at high bleeding risk, ticagrelor monotherapy was associated with a 12-month major bleeding rate of 1.8%, compared to 6.3% with a full year of DAPT. Conversely, in patients who underwent complex PCI, ticagrelor monotherapy was associated with a 4.9% rate of major adverse cardio- and cerebrovascular events through 1 year, numerically greater than but not statistically significantly different from the 2.7% rate with 12 months of DAPT.

Dr. Kim noted that the study had several limitations: It was open label, had no placebo control, and was underpowered to draw definite conclusions regarding the merits of dropping aspirin and continuing ticagrelor after 3 months in STEMI patients.

“Our findings should be interpreted with caution and call for confirmatory randomized trials,” he stressed.

Session comoderator Roxana Mehran, MD, said she “wholeheartedly” agrees with that assessment.

“We really do need a future trial, and we’re working to design TWILIGHT-STEMI,” a large randomized follow-up to the TWILIGHT trial, which she directed.

“I often imagine that we can have an even shorter duration of aspirin and ticagrelor and go to monotherapy sooner than 3 months in this very, very important subgroup,” added Dr. Mehran, professor of medicine, professor of population science and policy, and director of interventional cardiovascular research and clinical trials at the Icahn School of Medicine at Mount Sinai, New York.

Discussant Marco Valgimigli, MD, PhD, of University Hospital in Bern, Switzerland, calculated that the number-needed-to-treat with ticagrelor monotherapy rather than 12 months of DAPT in order to prevent one additional major bleeding event in TICO-STEMI participants at high bleeding risk was 22, as compared to an NNT of 77 in those without high bleeding risk.

MDedge News

[email protected]

Ticagrelor monotherapy after just 3 months of dual-antiplatelet therapy (DAPT) in patients with ST-elevation myocardial infarction treated with drug-eluting stents proved a winning strategy in TICO-STEMI, a major randomized trial.

“This is the first report assessing the feasibility of ticagrelor monotherapy after short-term DAPT for STEMI patients with drug-eluting stents,” Byeong-Keuk Kim, MD, PhD, noted at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.

The positive results were consistent with the earlier TWILIGHT study (Ticagrelor with Aspirin or Alone in High-Risk Patients after Coronary Intervention), which also showed clinical benefit at 1 year for 3 months of DAPT followed by ticagrelor (Brilinta) monotherapy, albeit only in PCI patients without an acute coronary syndrome (ACS) or with non-STEMI ACS (N Engl J Med. 2019 Nov 21;381[21]:2032-42).

TICO-STEMI was a prespecified substudy involving the 1,103 STEMI patients included in the previously reported parent 38-center South Korean TICO (Ticagrelor With or Without Aspirin in Acute Coronary Syndrome After PCI) study of 3,056 ACS patients treated with a second-generation ultrathin biodegradable polymer-coated sirolimus-eluting stent (JAMA. 2020 Jun 16;323[23]:2407-16).

The primary outcome in TICO-STEMI was the 12-month composite rate of net adverse clinical events, composed of major bleeding, all-cause mortality, acute MI, stroke, stent thrombosis, or target vessel revascularization. In an intention-to-treat analysis, the rate was 5.0% in the 12-month DAPT group and 3.7% with ticagrelor monotherapy after 3 months of DAPT, for a 27% relative risk reduction which didn’t achieve statistical significance. However, in an as-treated analysis, the between-group difference in the primary endpoint was stronger: a 5.2% incidence with 12 months of DAPT and 2.3% with ticagrelor monotherapy, for a relative risk reduction of 56%, which was statistically significant.

Major bleeding, one of two key secondary endpoints, was a different story: The incidence within 12 months by intention-to-treat was 2.9% with 12 months of DAPT compared to 0.9% with ticagrelor monotherapy, for a statistically significant 68% relative risk reduction in favor of ticagrelor monotherapy. In contrast, there was no between-group difference in the other secondary endpoint composed of major adverse cardio- and cerebrovascular events: 2.7% with ticagrelor monotherapy, 2.5% with 12 months of DAPT.

In the subgroup of TICO-STEMI patients at high bleeding risk, ticagrelor monotherapy was associated with a 12-month major bleeding rate of 1.8%, compared to 6.3% with a full year of DAPT. Conversely, in patients who underwent complex PCI, ticagrelor monotherapy was associated with a 4.9% rate of major adverse cardio- and cerebrovascular events through 1 year, numerically greater than but not statistically significantly different from the 2.7% rate with 12 months of DAPT.

Dr. Kim noted that the study had several limitations: It was open label, had no placebo control, and was underpowered to draw definite conclusions regarding the merits of dropping aspirin and continuing ticagrelor after 3 months in STEMI patients.

“Our findings should be interpreted with caution and call for confirmatory randomized trials,” he stressed.

Session comoderator Roxana Mehran, MD, said she “wholeheartedly” agrees with that assessment.

“We really do need a future trial, and we’re working to design TWILIGHT-STEMI,” a large randomized follow-up to the TWILIGHT trial, which she directed.

“I often imagine that we can have an even shorter duration of aspirin and ticagrelor and go to monotherapy sooner than 3 months in this very, very important subgroup,” added Dr. Mehran, professor of medicine, professor of population science and policy, and director of interventional cardiovascular research and clinical trials at the Icahn School of Medicine at Mount Sinai, New York.

Discussant Marco Valgimigli, MD, PhD, of University Hospital in Bern, Switzerland, calculated that the number-needed-to-treat with ticagrelor monotherapy rather than 12 months of DAPT in order to prevent one additional major bleeding event in TICO-STEMI participants at high bleeding risk was 22, as compared to an NNT of 77 in those without high bleeding risk.

MDedge News

[email protected]

Despite survival after treatment of acute lymphoblastic leukemia (ALL), a high percentage of children suffered acute complications, even without relapse, according to a report published online in Clinical Lymphoma, Myeloma & Leukemia.

In a retrospective study of 110 children with acute lymphoblastic leukemia (ALL), Ayse Pınar Öztürk, MD, and colleagues at Istanbul University, Cerrahpasa Faculty of Medicine, evaluated the acute complications that occurred during the treatment of childhood ALL and documented their survival rates. The 110 patients, comprising 65 boys and 45 girls, were all treated with the Children’s Oncology Group protocol from 1999 to 2014.

The mean age at admission was 8.3 years and 97 patients (88.2%) were diagnosed with pre–B-cell ALL, 11 (10%) with T-cell ALL, 1 (0.9%) with mixed phenotype acute leukemia, and 1 (0.9%) with mature B-cell acute leukemia. A total of 36.3% were evaluated to be in the standard-risk group and the rest were in the high-risk group. Regular follow-up and evaluation for acute complications was available for 105 of the patients.
 

Survival and complications

Of the 110 patients, 98 were assessed in the survival analyses. The 5- and 10-year overall survival rates were both 85.9%, while the relapse-free survival rates at 1, 3, and 5 years were 97.9%, 91.3%, and 86.3%, respectively. These results are favorable and in line with good results reported in the literature, according to the researchers.

In terms of acute complications, infection was the most common (88.5%), followed by gastrointestinal (27.6%), neurologic (26.6%), metabolic/endocrine (15.2%), drug-related hypersensitivity (15.2%), avascular necrosis (12.3%), thrombotic (10.4%), severe psychiatric (1.9%), and various other complications (11.4%).

In the present study, 13 of the 98 patients (13.3%) died. All 13 patients had been in the high-risk group and 9 had had relapsed ALL. Of the 13 deaths, 8 (8.2%) had resulted from treatment resistance and toxicity and 5 (5.1%) from severe infection (sepsis).

During ALL treatment, various complications can occur related to the disease itself or the treatment, according to the authors. However, they added that in regularly and closely monitored patients, complications can be effectively prevented, treated, and eliminated by aggressive observation and prompt intervention.

“In our study, the short hospitalization period, prompt implementation of protocol updates, rapid analysis of laboratory tests, continuous supportive care, efficient education given to the parents of children, and consistently undertaking patient care and treatment management by the same expert team increased the success of the therapy and ensured low complication rates,” the researchers concluded.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Öztürk AP et al. Clin Lymphoma Myeloma Leuk. 2020 Sep 17. doi: 10.1016/j.clml.2020.08.025.

Despite survival after treatment of acute lymphoblastic leukemia (ALL), a high percentage of children suffered acute complications, even without relapse, according to a report published online in Clinical Lymphoma, Myeloma & Leukemia.

In a retrospective study of 110 children with acute lymphoblastic leukemia (ALL), Ayse Pınar Öztürk, MD, and colleagues at Istanbul University, Cerrahpasa Faculty of Medicine, evaluated the acute complications that occurred during the treatment of childhood ALL and documented their survival rates. The 110 patients, comprising 65 boys and 45 girls, were all treated with the Children’s Oncology Group protocol from 1999 to 2014.

The mean age at admission was 8.3 years and 97 patients (88.2%) were diagnosed with pre–B-cell ALL, 11 (10%) with T-cell ALL, 1 (0.9%) with mixed phenotype acute leukemia, and 1 (0.9%) with mature B-cell acute leukemia. A total of 36.3% were evaluated to be in the standard-risk group and the rest were in the high-risk group. Regular follow-up and evaluation for acute complications was available for 105 of the patients.
 

Survival and complications

Of the 110 patients, 98 were assessed in the survival analyses. The 5- and 10-year overall survival rates were both 85.9%, while the relapse-free survival rates at 1, 3, and 5 years were 97.9%, 91.3%, and 86.3%, respectively. These results are favorable and in line with good results reported in the literature, according to the researchers.

In terms of acute complications, infection was the most common (88.5%), followed by gastrointestinal (27.6%), neurologic (26.6%), metabolic/endocrine (15.2%), drug-related hypersensitivity (15.2%), avascular necrosis (12.3%), thrombotic (10.4%), severe psychiatric (1.9%), and various other complications (11.4%).

In the present study, 13 of the 98 patients (13.3%) died. All 13 patients had been in the high-risk group and 9 had had relapsed ALL. Of the 13 deaths, 8 (8.2%) had resulted from treatment resistance and toxicity and 5 (5.1%) from severe infection (sepsis).

During ALL treatment, various complications can occur related to the disease itself or the treatment, according to the authors. However, they added that in regularly and closely monitored patients, complications can be effectively prevented, treated, and eliminated by aggressive observation and prompt intervention.

“In our study, the short hospitalization period, prompt implementation of protocol updates, rapid analysis of laboratory tests, continuous supportive care, efficient education given to the parents of children, and consistently undertaking patient care and treatment management by the same expert team increased the success of the therapy and ensured low complication rates,” the researchers concluded.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Öztürk AP et al. Clin Lymphoma Myeloma Leuk. 2020 Sep 17. doi: 10.1016/j.clml.2020.08.025.

Despite survival after treatment of acute lymphoblastic leukemia (ALL), a high percentage of children suffered acute complications, even without relapse, according to a report published online in Clinical Lymphoma, Myeloma & Leukemia.

In a retrospective study of 110 children with acute lymphoblastic leukemia (ALL), Ayse Pınar Öztürk, MD, and colleagues at Istanbul University, Cerrahpasa Faculty of Medicine, evaluated the acute complications that occurred during the treatment of childhood ALL and documented their survival rates. The 110 patients, comprising 65 boys and 45 girls, were all treated with the Children’s Oncology Group protocol from 1999 to 2014.

The mean age at admission was 8.3 years and 97 patients (88.2%) were diagnosed with pre–B-cell ALL, 11 (10%) with T-cell ALL, 1 (0.9%) with mixed phenotype acute leukemia, and 1 (0.9%) with mature B-cell acute leukemia. A total of 36.3% were evaluated to be in the standard-risk group and the rest were in the high-risk group. Regular follow-up and evaluation for acute complications was available for 105 of the patients.
 

Survival and complications

Of the 110 patients, 98 were assessed in the survival analyses. The 5- and 10-year overall survival rates were both 85.9%, while the relapse-free survival rates at 1, 3, and 5 years were 97.9%, 91.3%, and 86.3%, respectively. These results are favorable and in line with good results reported in the literature, according to the researchers.

In terms of acute complications, infection was the most common (88.5%), followed by gastrointestinal (27.6%), neurologic (26.6%), metabolic/endocrine (15.2%), drug-related hypersensitivity (15.2%), avascular necrosis (12.3%), thrombotic (10.4%), severe psychiatric (1.9%), and various other complications (11.4%).

In the present study, 13 of the 98 patients (13.3%) died. All 13 patients had been in the high-risk group and 9 had had relapsed ALL. Of the 13 deaths, 8 (8.2%) had resulted from treatment resistance and toxicity and 5 (5.1%) from severe infection (sepsis).

During ALL treatment, various complications can occur related to the disease itself or the treatment, according to the authors. However, they added that in regularly and closely monitored patients, complications can be effectively prevented, treated, and eliminated by aggressive observation and prompt intervention.

“In our study, the short hospitalization period, prompt implementation of protocol updates, rapid analysis of laboratory tests, continuous supportive care, efficient education given to the parents of children, and consistently undertaking patient care and treatment management by the same expert team increased the success of the therapy and ensured low complication rates,” the researchers concluded.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Öztürk AP et al. Clin Lymphoma Myeloma Leuk. 2020 Sep 17. doi: 10.1016/j.clml.2020.08.025.