Onychomycosis is the most prevalent nail condition worldwide and has a significant impact on quality of life.¹ There were 10 million physician visits for nail fungal infections in the National Ambulatory Medical Care Survey from 2007 to 2016, which was more than double the number of all other nail diagnoses combined.² Therefore, it is important for dermatologists to be familiar with the most current data on diagnosis and treatment of this extremely common nail disease as well as antifungal medication safety.

Onychomycosis Diagnosis

Diagnosis of onychomycosis using clinical examination alone has poor sensitivity and specificity and may lead to progression of disease and unwanted side effects from inappropriate therapy.^3,4 Dermoscopy is a useful adjunct but diagnostically is still inferior compared to mycologic testing.⁵ Classical methods of diagnosis include potassium hydroxide staining with microscopy, fungal culture, and histopathology. Polymerase chain reaction is a newer technique with wide accessibility and excellent sensitivity and specificity.⁶ Although these techniques have excellent diagnostic accuracy both alone and in combination, the ideal test would have 100% sensitivity and specificity and would not require nail sampling. Artificial intelligence recently has been studied for the diagnosis of onychomycosis. In a prospective study of 90 patients with onychodystrophy who had photographs of the nails taken by nonphysicians, deep neural networks showed comparable sensitivity (70.2% vs 73.0%) and specificity (72.7% vs 49.7%) for diagnosis of onychomycosis vs clinical examination by dermatologists with a mean of 5.6 years of experience.⁷ Therefore, artificial intelligence may be considered as a supplement to clinical examination for dermatology residents and junior attending dermatologists and may be superior to clinical examination by nondermatologists, but mycologic confirmation is still necessary before initiating onychomycosis treatment.

Treatment of Onychomycosis

There are 3 topical therapies (ciclopirox lacquer 8%, efinaconazole solution 10%, and tavaborole solution 5%) and 3 oral therapies (terbinafine, itraconazole, and griseofulvin) that are approved by the US Food and Drug Administration for onychomycosis therapy. Griseofulvin rarely is used due to the availability of more efficacious treatment options. Fluconazole is an off-label treatment that often is used in the United States.⁸

There are new data on the efficacy and safety of topical onychomycosis treatments in children. A phase 4 open‐label study of efinaconazole solution 10% applied once daily for 48 weeks was performed in children aged 6 to 16 years with distal lateral subungual onychomycosis (N=62).^9,10 The medication was both well tolerated and safe in children. The only treatment-related adverse event was onychocryptosis, which was reported by 2 patients. At week 52, mycologic cure was 65% and complete cure was 40% (N=50). In a pharmacokinetic assessment performed in a subset of 17 patients aged 12 to 16 years, efinaconazole was measured at very low levels in plasma.⁹

A phase 4 open-label study also was performed to evaluate the safety, pharmacokinetics, and efficacy of tavaborole for treatment of distal lateral subungual onychomycosis in children aged 6 years to under 17 years (N=55).¹¹ Tavaborole solution 5% was applied once daily for 48 weeks; at week 52, mycologic and complete cures were 36.2% and 8.5%, respectively (N=47). Systemic exposure was low (C_max=5.9 ng/mL [day 29]) in a subset of patients aged 12 years to under 17 years (N=37), and the medication demonstrated good safety and tolerability.¹¹

Fosravuconazole was approved for treatment of onychomycosis in Japan in 2018. In a randomized, double-blind, phase 3 trial of oral fosravuconazole 100 mg once daily (n=101) vs placebo (n=52) for 12 weeks in patients with onychomycosis (mean age, 58.4 years), the complete cure rate at 48 weeks was 59.4%.¹² In a small trial of 37 elderly patients (mean age, 78.1 years), complete cure rates were 5.0% in patients with a nail plate thickness of 3 mm or greater and 58.8% in those with a thickness lessthan 3 mm, and there were no severe adverse events.¹³ In addition to excellent efficacy and proven safety in elderly adults, the main advantage of fosravuconazole is less-potent inhibition of cytochrome P450 3A compared to other triazole antifungals, with no contraindicated drugs listed.

Safety of Antifungals

There are new data describing the safety of oral terbinafine in pregnant women and immunosuppressed patients. In a nationwide cohort study conducted in Denmark (1,650,649 pregnancies [942 oral terbinafine exposed, 9420 unexposed matched cohorts]), there was no association between oral or topical terbinafine exposure during pregnancy and risk of preterm birth, small-for-gestational-age birth weight, low birth weight, or stillbirth.¹⁴ In a small study of 13 kidney transplant recipients taking oral tacrolimus, cyclosporine, or everolimus who were treated with oral terbinafine, there were no severe drug interactions and no clinical consequences in renal grafts.¹⁵

There also is new information on laboratory abnormalities in adults, children, and patients with comorbidities who are taking oral terbinafine. In a retrospective study of 944 adult patients without pre-existing hepatic or hematologic conditions who were prescribed 3 months of oral terbinafine for onychomycosis, abnormal monitoring liver function tests (LFTs) and complete blood cell counts (CBCs) were uncommon (2.4% and 2.8%, respectively) and mild and resolved after treatment completion. In addition, patients with laboratory abnormalities were an average of 14.8 years older and approximately 3-times more likely to be 65 years or older compared to the overall study population.¹⁶ There were similar findings in a retrospective study of 134 children 18 years or younger who were prescribed oral terbinafine for superficial fungal infections. Abnormal monitoring LFTs and CBCs were uncommon (1.7% and 4.4%, respectively) and mild, resolving after after treatment completion.¹⁷ Finally, in a study of 255 patients with a pre-existing liver or hematologic condition who were prescribed oral terbinafine for onychomycosis, worsening of LFT or CBC values were rare, and all resolved after treatment completion or medication discontinuation.¹⁸

Final Thoughts

Mycologic confirmation is still necessary before treatment despite encouraging data on use of artificial intelligence for diagnosis of onychomycosis. Efinaconazole solution 10% and tavaborole solution 5% have shown good safety, tolerability, and efficacy in children with onychomycosis. Recent data suggest the safety of oral terbinafine in pregnant women and kidney transplant recipients, but these findings must be corroborated before its use in these populations. Fosravuconazole is a promising systemic treatment for onychomycosis with no drug-drug interactions reported to date. While baseline laboratory testing is recommended before prescribing terbinafine, interval laboratory monitoring may not be necessary in healthy adults.¹⁹ Prospective studies are necessary to corroborate these findings before formal recommendations can be made for prescribing terbinafine in the special populations discussed above, including children, and for interval laboratory monitoring.

Onychomycosis is the most prevalent nail condition worldwide and has a significant impact on quality of life.¹ There were 10 million physician visits for nail fungal infections in the National Ambulatory Medical Care Survey from 2007 to 2016, which was more than double the number of all other nail diagnoses combined.² Therefore, it is important for dermatologists to be familiar with the most current data on diagnosis and treatment of this extremely common nail disease as well as antifungal medication safety.

Onychomycosis Diagnosis

Diagnosis of onychomycosis using clinical examination alone has poor sensitivity and specificity and may lead to progression of disease and unwanted side effects from inappropriate therapy.^3,4 Dermoscopy is a useful adjunct but diagnostically is still inferior compared to mycologic testing.⁵ Classical methods of diagnosis include potassium hydroxide staining with microscopy, fungal culture, and histopathology. Polymerase chain reaction is a newer technique with wide accessibility and excellent sensitivity and specificity.⁶ Although these techniques have excellent diagnostic accuracy both alone and in combination, the ideal test would have 100% sensitivity and specificity and would not require nail sampling. Artificial intelligence recently has been studied for the diagnosis of onychomycosis. In a prospective study of 90 patients with onychodystrophy who had photographs of the nails taken by nonphysicians, deep neural networks showed comparable sensitivity (70.2% vs 73.0%) and specificity (72.7% vs 49.7%) for diagnosis of onychomycosis vs clinical examination by dermatologists with a mean of 5.6 years of experience.⁷ Therefore, artificial intelligence may be considered as a supplement to clinical examination for dermatology residents and junior attending dermatologists and may be superior to clinical examination by nondermatologists, but mycologic confirmation is still necessary before initiating onychomycosis treatment.

Treatment of Onychomycosis

There are 3 topical therapies (ciclopirox lacquer 8%, efinaconazole solution 10%, and tavaborole solution 5%) and 3 oral therapies (terbinafine, itraconazole, and griseofulvin) that are approved by the US Food and Drug Administration for onychomycosis therapy. Griseofulvin rarely is used due to the availability of more efficacious treatment options. Fluconazole is an off-label treatment that often is used in the United States.⁸

There are new data on the efficacy and safety of topical onychomycosis treatments in children. A phase 4 open‐label study of efinaconazole solution 10% applied once daily for 48 weeks was performed in children aged 6 to 16 years with distal lateral subungual onychomycosis (N=62).^9,10 The medication was both well tolerated and safe in children. The only treatment-related adverse event was onychocryptosis, which was reported by 2 patients. At week 52, mycologic cure was 65% and complete cure was 40% (N=50). In a pharmacokinetic assessment performed in a subset of 17 patients aged 12 to 16 years, efinaconazole was measured at very low levels in plasma.⁹

A phase 4 open-label study also was performed to evaluate the safety, pharmacokinetics, and efficacy of tavaborole for treatment of distal lateral subungual onychomycosis in children aged 6 years to under 17 years (N=55).¹¹ Tavaborole solution 5% was applied once daily for 48 weeks; at week 52, mycologic and complete cures were 36.2% and 8.5%, respectively (N=47). Systemic exposure was low (C_max=5.9 ng/mL [day 29]) in a subset of patients aged 12 years to under 17 years (N=37), and the medication demonstrated good safety and tolerability.¹¹

Fosravuconazole was approved for treatment of onychomycosis in Japan in 2018. In a randomized, double-blind, phase 3 trial of oral fosravuconazole 100 mg once daily (n=101) vs placebo (n=52) for 12 weeks in patients with onychomycosis (mean age, 58.4 years), the complete cure rate at 48 weeks was 59.4%.¹² In a small trial of 37 elderly patients (mean age, 78.1 years), complete cure rates were 5.0% in patients with a nail plate thickness of 3 mm or greater and 58.8% in those with a thickness lessthan 3 mm, and there were no severe adverse events.¹³ In addition to excellent efficacy and proven safety in elderly adults, the main advantage of fosravuconazole is less-potent inhibition of cytochrome P450 3A compared to other triazole antifungals, with no contraindicated drugs listed.

Safety of Antifungals

There are new data describing the safety of oral terbinafine in pregnant women and immunosuppressed patients. In a nationwide cohort study conducted in Denmark (1,650,649 pregnancies [942 oral terbinafine exposed, 9420 unexposed matched cohorts]), there was no association between oral or topical terbinafine exposure during pregnancy and risk of preterm birth, small-for-gestational-age birth weight, low birth weight, or stillbirth.¹⁴ In a small study of 13 kidney transplant recipients taking oral tacrolimus, cyclosporine, or everolimus who were treated with oral terbinafine, there were no severe drug interactions and no clinical consequences in renal grafts.¹⁵

There also is new information on laboratory abnormalities in adults, children, and patients with comorbidities who are taking oral terbinafine. In a retrospective study of 944 adult patients without pre-existing hepatic or hematologic conditions who were prescribed 3 months of oral terbinafine for onychomycosis, abnormal monitoring liver function tests (LFTs) and complete blood cell counts (CBCs) were uncommon (2.4% and 2.8%, respectively) and mild and resolved after treatment completion. In addition, patients with laboratory abnormalities were an average of 14.8 years older and approximately 3-times more likely to be 65 years or older compared to the overall study population.¹⁶ There were similar findings in a retrospective study of 134 children 18 years or younger who were prescribed oral terbinafine for superficial fungal infections. Abnormal monitoring LFTs and CBCs were uncommon (1.7% and 4.4%, respectively) and mild, resolving after after treatment completion.¹⁷ Finally, in a study of 255 patients with a pre-existing liver or hematologic condition who were prescribed oral terbinafine for onychomycosis, worsening of LFT or CBC values were rare, and all resolved after treatment completion or medication discontinuation.¹⁸

Final Thoughts

Mycologic confirmation is still necessary before treatment despite encouraging data on use of artificial intelligence for diagnosis of onychomycosis. Efinaconazole solution 10% and tavaborole solution 5% have shown good safety, tolerability, and efficacy in children with onychomycosis. Recent data suggest the safety of oral terbinafine in pregnant women and kidney transplant recipients, but these findings must be corroborated before its use in these populations. Fosravuconazole is a promising systemic treatment for onychomycosis with no drug-drug interactions reported to date. While baseline laboratory testing is recommended before prescribing terbinafine, interval laboratory monitoring may not be necessary in healthy adults.¹⁹ Prospective studies are necessary to corroborate these findings before formal recommendations can be made for prescribing terbinafine in the special populations discussed above, including children, and for interval laboratory monitoring.

Onychomycosis is the most prevalent nail condition worldwide and has a significant impact on quality of life.¹ There were 10 million physician visits for nail fungal infections in the National Ambulatory Medical Care Survey from 2007 to 2016, which was more than double the number of all other nail diagnoses combined.² Therefore, it is important for dermatologists to be familiar with the most current data on diagnosis and treatment of this extremely common nail disease as well as antifungal medication safety.

Onychomycosis Diagnosis

Diagnosis of onychomycosis using clinical examination alone has poor sensitivity and specificity and may lead to progression of disease and unwanted side effects from inappropriate therapy.^3,4 Dermoscopy is a useful adjunct but diagnostically is still inferior compared to mycologic testing.⁵ Classical methods of diagnosis include potassium hydroxide staining with microscopy, fungal culture, and histopathology. Polymerase chain reaction is a newer technique with wide accessibility and excellent sensitivity and specificity.⁶ Although these techniques have excellent diagnostic accuracy both alone and in combination, the ideal test would have 100% sensitivity and specificity and would not require nail sampling. Artificial intelligence recently has been studied for the diagnosis of onychomycosis. In a prospective study of 90 patients with onychodystrophy who had photographs of the nails taken by nonphysicians, deep neural networks showed comparable sensitivity (70.2% vs 73.0%) and specificity (72.7% vs 49.7%) for diagnosis of onychomycosis vs clinical examination by dermatologists with a mean of 5.6 years of experience.⁷ Therefore, artificial intelligence may be considered as a supplement to clinical examination for dermatology residents and junior attending dermatologists and may be superior to clinical examination by nondermatologists, but mycologic confirmation is still necessary before initiating onychomycosis treatment.

Treatment of Onychomycosis

There are 3 topical therapies (ciclopirox lacquer 8%, efinaconazole solution 10%, and tavaborole solution 5%) and 3 oral therapies (terbinafine, itraconazole, and griseofulvin) that are approved by the US Food and Drug Administration for onychomycosis therapy. Griseofulvin rarely is used due to the availability of more efficacious treatment options. Fluconazole is an off-label treatment that often is used in the United States.⁸

There are new data on the efficacy and safety of topical onychomycosis treatments in children. A phase 4 open‐label study of efinaconazole solution 10% applied once daily for 48 weeks was performed in children aged 6 to 16 years with distal lateral subungual onychomycosis (N=62).^9,10 The medication was both well tolerated and safe in children. The only treatment-related adverse event was onychocryptosis, which was reported by 2 patients. At week 52, mycologic cure was 65% and complete cure was 40% (N=50). In a pharmacokinetic assessment performed in a subset of 17 patients aged 12 to 16 years, efinaconazole was measured at very low levels in plasma.⁹

A phase 4 open-label study also was performed to evaluate the safety, pharmacokinetics, and efficacy of tavaborole for treatment of distal lateral subungual onychomycosis in children aged 6 years to under 17 years (N=55).¹¹ Tavaborole solution 5% was applied once daily for 48 weeks; at week 52, mycologic and complete cures were 36.2% and 8.5%, respectively (N=47). Systemic exposure was low (C_max=5.9 ng/mL [day 29]) in a subset of patients aged 12 years to under 17 years (N=37), and the medication demonstrated good safety and tolerability.¹¹

Fosravuconazole was approved for treatment of onychomycosis in Japan in 2018. In a randomized, double-blind, phase 3 trial of oral fosravuconazole 100 mg once daily (n=101) vs placebo (n=52) for 12 weeks in patients with onychomycosis (mean age, 58.4 years), the complete cure rate at 48 weeks was 59.4%.¹² In a small trial of 37 elderly patients (mean age, 78.1 years), complete cure rates were 5.0% in patients with a nail plate thickness of 3 mm or greater and 58.8% in those with a thickness lessthan 3 mm, and there were no severe adverse events.¹³ In addition to excellent efficacy and proven safety in elderly adults, the main advantage of fosravuconazole is less-potent inhibition of cytochrome P450 3A compared to other triazole antifungals, with no contraindicated drugs listed.

Safety of Antifungals

There are new data describing the safety of oral terbinafine in pregnant women and immunosuppressed patients. In a nationwide cohort study conducted in Denmark (1,650,649 pregnancies [942 oral terbinafine exposed, 9420 unexposed matched cohorts]), there was no association between oral or topical terbinafine exposure during pregnancy and risk of preterm birth, small-for-gestational-age birth weight, low birth weight, or stillbirth.¹⁴ In a small study of 13 kidney transplant recipients taking oral tacrolimus, cyclosporine, or everolimus who were treated with oral terbinafine, there were no severe drug interactions and no clinical consequences in renal grafts.¹⁵

There also is new information on laboratory abnormalities in adults, children, and patients with comorbidities who are taking oral terbinafine. In a retrospective study of 944 adult patients without pre-existing hepatic or hematologic conditions who were prescribed 3 months of oral terbinafine for onychomycosis, abnormal monitoring liver function tests (LFTs) and complete blood cell counts (CBCs) were uncommon (2.4% and 2.8%, respectively) and mild and resolved after treatment completion. In addition, patients with laboratory abnormalities were an average of 14.8 years older and approximately 3-times more likely to be 65 years or older compared to the overall study population.¹⁶ There were similar findings in a retrospective study of 134 children 18 years or younger who were prescribed oral terbinafine for superficial fungal infections. Abnormal monitoring LFTs and CBCs were uncommon (1.7% and 4.4%, respectively) and mild, resolving after after treatment completion.¹⁷ Finally, in a study of 255 patients with a pre-existing liver or hematologic condition who were prescribed oral terbinafine for onychomycosis, worsening of LFT or CBC values were rare, and all resolved after treatment completion or medication discontinuation.¹⁸

Final Thoughts

Mycologic confirmation is still necessary before treatment despite encouraging data on use of artificial intelligence for diagnosis of onychomycosis. Efinaconazole solution 10% and tavaborole solution 5% have shown good safety, tolerability, and efficacy in children with onychomycosis. Recent data suggest the safety of oral terbinafine in pregnant women and kidney transplant recipients, but these findings must be corroborated before its use in these populations. Fosravuconazole is a promising systemic treatment for onychomycosis with no drug-drug interactions reported to date. While baseline laboratory testing is recommended before prescribing terbinafine, interval laboratory monitoring may not be necessary in healthy adults.¹⁹ Prospective studies are necessary to corroborate these findings before formal recommendations can be made for prescribing terbinafine in the special populations discussed above, including children, and for interval laboratory monitoring.

The numbers are in to back up two policies designed to restrict the spread of the COVID-19 pandemic.

Researchers at the Centers for Disease Control and Prevention) found that when states lifted restrictions on dining on premises at restaurants, rates of daily COVID-19 cases jumped 41-100 days later. COVID-19-related deaths also increased significantly after 60 days.

On the other hand, the same report demonstrates that state mask mandates slowed the spread of SARS-CoV-2 within a few weeks.

The study was published online March 5 in the CDC Morbidity and Mortality Weekly Report.

The investigators did not distinguish between outdoor and indoor restaurant dining. But they did compare COVID-19 case and death rates before and after most states banned restaurants from serving patrons on-premises in March and April 2020.

They found, for example, that COVID-19 daily cases increased by 0.9% at 41-60 days after on-premise dining was permitted. Similarly, rates jumped by 1.2% at 61-80 days, and 1.1% at 81-100 days after the restaurant restrictions were lifted. 

The differences were statistically significant, with P values of .02, <.01, and .04, respectively.

COVID-19–related death rates did not increase significantly at first – but did jump 2.2% between 61 and 80 days after the return of on-premises dining, for example. Deaths also increased by 3% at 81-100 days.

Both these differences were statistically significant (P < .01).

This is not the first report where the CDC announced reservations about in-person dining. In September 2020, CDC investigators implicated the inability to wear a mask while eating and drinking as likely contributing to the heightened risk.
 

Masks make a difference

The CDC report also provided more evidence to back mask-wearing policies for public spaces. Between March 1 and Dec. 31, 2020, 74% of U.S. counties issued mask mandates.

Investigators found that these policies had a more immediate effect, reducing daily COVID-19 cases by 0.5% in the first 20 days. Mask mandates likewise were linked to daily cases dropping 1.1% between 21 and 40 days, 1.5% between 41 and 60 days, 1.7% between 61 and 80 days, and 1.8% between 81 and 100 days.

These decreases in daily COVID-19 cases were statistically significant (P < .01) compared with a reference period before March 1, 2020.

The CDC also linked mask mandates to lower mortality. For example, these state policies were associated with 0.7% fewer deaths at 1-20 days post implementation. The effect increased thereafter – 1.0% drop at 21-40 days, 1.4% decrease at 41-60 days, 1.6% drop between 61 and 80 days, and 1.9% fewer deaths between 81 and 100 days.

The decrease in deaths was statistically significant at 1-20 days after the mask mandate (P = .03), as well as during the other periods (each P < .01) compared with the reference period.

CDC Director Rochelle Walensky, MD, reacted to the new findings at a White House press briefing. She cited how increases in COVID-19 cases and death rates “slowed significantly within 20 days of putting mask mandates into place. This is why I’m asking you to double down on prevention measures.

“We have seen this movie before,” Dr. Walensky added. “When prevention measures like mask-wearing mandates are lifted, cases go up.”

Recently, multiple states have announced plans to roll back restrictions related to the pandemic, including mask mandates, which prompted warnings from some public health officials.

These are not the first CDC data to show that mask mandates make a difference.

In February 2021, for example, the agency pointed out that state-wide mask mandates reduced COVID-19 hospitalizations by 5.5% among adults 18-64 years old within 3 weeks of implementation.

Restrictions regarding on-premises restaurant dining and implementation of state-wide mask mandates are two tactics within a more comprehensive CDC strategy to reduce the spread of SARS-CoV-2. The researchers note that “such efforts are increasingly important given the emergence of highly transmissible SARS-CoV-2 variants in the United States.”

The researchers have disclosed no relevant financial relationships.

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

The numbers are in to back up two policies designed to restrict the spread of the COVID-19 pandemic.

Researchers at the Centers for Disease Control and Prevention) found that when states lifted restrictions on dining on premises at restaurants, rates of daily COVID-19 cases jumped 41-100 days later. COVID-19-related deaths also increased significantly after 60 days.

On the other hand, the same report demonstrates that state mask mandates slowed the spread of SARS-CoV-2 within a few weeks.

The study was published online March 5 in the CDC Morbidity and Mortality Weekly Report.

The investigators did not distinguish between outdoor and indoor restaurant dining. But they did compare COVID-19 case and death rates before and after most states banned restaurants from serving patrons on-premises in March and April 2020.

They found, for example, that COVID-19 daily cases increased by 0.9% at 41-60 days after on-premise dining was permitted. Similarly, rates jumped by 1.2% at 61-80 days, and 1.1% at 81-100 days after the restaurant restrictions were lifted. 

The differences were statistically significant, with P values of .02, <.01, and .04, respectively.

COVID-19–related death rates did not increase significantly at first – but did jump 2.2% between 61 and 80 days after the return of on-premises dining, for example. Deaths also increased by 3% at 81-100 days.

Both these differences were statistically significant (P < .01).

This is not the first report where the CDC announced reservations about in-person dining. In September 2020, CDC investigators implicated the inability to wear a mask while eating and drinking as likely contributing to the heightened risk.
 

Masks make a difference

The CDC report also provided more evidence to back mask-wearing policies for public spaces. Between March 1 and Dec. 31, 2020, 74% of U.S. counties issued mask mandates.

Investigators found that these policies had a more immediate effect, reducing daily COVID-19 cases by 0.5% in the first 20 days. Mask mandates likewise were linked to daily cases dropping 1.1% between 21 and 40 days, 1.5% between 41 and 60 days, 1.7% between 61 and 80 days, and 1.8% between 81 and 100 days.

These decreases in daily COVID-19 cases were statistically significant (P < .01) compared with a reference period before March 1, 2020.

The CDC also linked mask mandates to lower mortality. For example, these state policies were associated with 0.7% fewer deaths at 1-20 days post implementation. The effect increased thereafter – 1.0% drop at 21-40 days, 1.4% decrease at 41-60 days, 1.6% drop between 61 and 80 days, and 1.9% fewer deaths between 81 and 100 days.

The decrease in deaths was statistically significant at 1-20 days after the mask mandate (P = .03), as well as during the other periods (each P < .01) compared with the reference period.

CDC Director Rochelle Walensky, MD, reacted to the new findings at a White House press briefing. She cited how increases in COVID-19 cases and death rates “slowed significantly within 20 days of putting mask mandates into place. This is why I’m asking you to double down on prevention measures.

“We have seen this movie before,” Dr. Walensky added. “When prevention measures like mask-wearing mandates are lifted, cases go up.”

Recently, multiple states have announced plans to roll back restrictions related to the pandemic, including mask mandates, which prompted warnings from some public health officials.

These are not the first CDC data to show that mask mandates make a difference.

In February 2021, for example, the agency pointed out that state-wide mask mandates reduced COVID-19 hospitalizations by 5.5% among adults 18-64 years old within 3 weeks of implementation.

Restrictions regarding on-premises restaurant dining and implementation of state-wide mask mandates are two tactics within a more comprehensive CDC strategy to reduce the spread of SARS-CoV-2. The researchers note that “such efforts are increasingly important given the emergence of highly transmissible SARS-CoV-2 variants in the United States.”

The researchers have disclosed no relevant financial relationships.

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

The numbers are in to back up two policies designed to restrict the spread of the COVID-19 pandemic.

Researchers at the Centers for Disease Control and Prevention) found that when states lifted restrictions on dining on premises at restaurants, rates of daily COVID-19 cases jumped 41-100 days later. COVID-19-related deaths also increased significantly after 60 days.

On the other hand, the same report demonstrates that state mask mandates slowed the spread of SARS-CoV-2 within a few weeks.

The study was published online March 5 in the CDC Morbidity and Mortality Weekly Report.

The investigators did not distinguish between outdoor and indoor restaurant dining. But they did compare COVID-19 case and death rates before and after most states banned restaurants from serving patrons on-premises in March and April 2020.

They found, for example, that COVID-19 daily cases increased by 0.9% at 41-60 days after on-premise dining was permitted. Similarly, rates jumped by 1.2% at 61-80 days, and 1.1% at 81-100 days after the restaurant restrictions were lifted. 

The differences were statistically significant, with P values of .02, <.01, and .04, respectively.

COVID-19–related death rates did not increase significantly at first – but did jump 2.2% between 61 and 80 days after the return of on-premises dining, for example. Deaths also increased by 3% at 81-100 days.

Both these differences were statistically significant (P < .01).

This is not the first report where the CDC announced reservations about in-person dining. In September 2020, CDC investigators implicated the inability to wear a mask while eating and drinking as likely contributing to the heightened risk.
 

Masks make a difference

The CDC report also provided more evidence to back mask-wearing policies for public spaces. Between March 1 and Dec. 31, 2020, 74% of U.S. counties issued mask mandates.

Investigators found that these policies had a more immediate effect, reducing daily COVID-19 cases by 0.5% in the first 20 days. Mask mandates likewise were linked to daily cases dropping 1.1% between 21 and 40 days, 1.5% between 41 and 60 days, 1.7% between 61 and 80 days, and 1.8% between 81 and 100 days.

These decreases in daily COVID-19 cases were statistically significant (P < .01) compared with a reference period before March 1, 2020.

The CDC also linked mask mandates to lower mortality. For example, these state policies were associated with 0.7% fewer deaths at 1-20 days post implementation. The effect increased thereafter – 1.0% drop at 21-40 days, 1.4% decrease at 41-60 days, 1.6% drop between 61 and 80 days, and 1.9% fewer deaths between 81 and 100 days.

The decrease in deaths was statistically significant at 1-20 days after the mask mandate (P = .03), as well as during the other periods (each P < .01) compared with the reference period.

CDC Director Rochelle Walensky, MD, reacted to the new findings at a White House press briefing. She cited how increases in COVID-19 cases and death rates “slowed significantly within 20 days of putting mask mandates into place. This is why I’m asking you to double down on prevention measures.

“We have seen this movie before,” Dr. Walensky added. “When prevention measures like mask-wearing mandates are lifted, cases go up.”

Recently, multiple states have announced plans to roll back restrictions related to the pandemic, including mask mandates, which prompted warnings from some public health officials.

These are not the first CDC data to show that mask mandates make a difference.

In February 2021, for example, the agency pointed out that state-wide mask mandates reduced COVID-19 hospitalizations by 5.5% among adults 18-64 years old within 3 weeks of implementation.

Restrictions regarding on-premises restaurant dining and implementation of state-wide mask mandates are two tactics within a more comprehensive CDC strategy to reduce the spread of SARS-CoV-2. The researchers note that “such efforts are increasingly important given the emergence of highly transmissible SARS-CoV-2 variants in the United States.”

The researchers have disclosed no relevant financial relationships.

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

One of the greatest challenges psychotherapists face when working with justice-involved outpatients is a lack of familiarity with the criminal legal system, according to Debra A. Pinals, MD.

“It’s certainly nothing we learned about in medical school or in our mental health training, per se,” said Dr. Pinals, director of the program in psychiatry, law, and ethics at the University of Michigan, Ann Arbor, during an annual psychopharmacology update held by the Nevada Psychiatric Association.

“Another challenge is a lack of comfort with some patient personality styles, particularly those with antisocial personality styles,” she said. “We may have countertransference issues that emerge in our work with this population. That can lead to concerns about our own safety, which may at times be reasonable but often because of stereotypes often becomes of mythical proportion. The population is a high-demand population with limited resources, usually tapping public mental health services. That becomes a challenge as well. And there can be burnout when the challenges of our patient population exceed our capacity.”

Despite such obstacles, Dr. Pinals described the outpatient treatment of individuals involved in the criminal justice system as exciting, interesting, and intellectually challenging. But she acknowledged the role that stigma and fear can play.

“Though there are some unique challenges, the benefits of working with criminal justice–involved persons with serious mental illness are often not discussed,” Dr. Pinals said. “There is a tendency to overvalue the risk they may present without really looking at the specific nuances that would be involved in conducting true risk assessments and understanding that not all of these patients will be as risky as we might believe due to stigma and fear.”

Separate from how patients with criminal histories may be perceived in clinical settings. There is much to learn about the role of mental illness in crime. In a 2014 study, researchers reviewed the records of criminal arrests in 143 people with mental illness and tried to discern whether the crime itself was completely independent or completely directly connected to the symptoms of mental illness the individual was experiencing. They found that 65% were completely independent of mental illness symptoms while 8% were directly related to mental illness symptoms.

“This means that as clinicians working with outpatients, we have to understand the whole person, and what might be going on in their lives that leads them down this criminal pathway,” said Dr. Pinals, who is also a clinical professor of psychiatry at the medical school.

According to the risk-need-responsivity (RNR) paradigm, eight criminogenic risk factors are associated with recurrent involvement in the criminal legal system (Crime & Delinquency. 2006;52:7-27). The big four include history of antisocial behavior, antisocial personality pattern, antisocial cognition, and antisocial attitudes. “These are the factors that certain cognitive-behavioral therapy approaches try to address, in an effort to reduce those antisocial cognitive tendencies,” Dr. Pinals said. The other four risk factors include family or marital discord, poor school and/or work performance, few leisure or recreation activities, and substance misuse.

“You’ll notice that mental illness is not listed,” she said. “Mental illness is not considered a major driver of crime, although it might be considered a responsivity factor within this RNR paradigm. This means it’s important to address it because it may help people better respond to criminal justice supervision and thereby have an indirect effect in reducing criminal recidivism. For example, if somebody has a social anxiety disorder or agoraphobia and therefore can’t make their probation appointment, probation won’t be able to help them adhere to the terms of their probation conditions. So, we do have to treat the illnesses underlying responsivity to how the criminal justice system operates.”

To optimally serve this population, Dr. Pinals recommends that psychotherapists become familiar with the Sequential Intercept Model, which was first published in 2006. “It takes the premise that individuals move through the criminal legal system in logical steps, and if we could identify those with mental health or substance use conditions and redirect them out of the criminal legal system and into treatment, we could reduce the overall penetration of those individuals from the criminal legal system,” she said. “We know that individuals with mental illness are overrepresented in the criminal legal system.”

By understanding what happens when a patient is arrested, mental health professionals can foster communication that could facilitate treatment for their patients.

“It’s important that we remember that these are people who are going through a challenging time,” Dr. Pinals said. “Maybe we don’t like what they did. Maybe we don’t like that they were accused of committing some kind of crime. However, it is important to realize that they are patients, and we want them to achieve the best outcome, whatever setting they’re in, that continuity of care and communication across systems might be beneficial. It might reduce their chance of returning to the criminal system and having other people victimized.”

copyright/Kuzma/iStockphoto

Mental health services vary across jails and prisons, she continued, but they are generally required to be commensurate with community standards.

“Of course, that’s often fraught with complexity and may not be available in particular jurisdictions” she said. Prisons, unlike local county jails, tend to have more levels of outpatient care, including inpatient, outpatient, and residential services. “Persons with mental illness can be moved in and out of these levels of care as needed,” Dr. Pinals said. “However, persons with mental illness can be at more risk for disciplinary infractions, especially if they’re not able to follow directions or if they’re psychotic or manic.”

Reentry creates certain risks to be mindful of, including social isolation, recurrent symptoms, problems acquiring medications and housing, suicide, violence, and a return to substance use. A reentry approach she recommended is the APIC model, which stands for Assess, Plan, Identify, and Coordinate. “That means individuals approaching release should be screened and assessed for their needs with a plan to meet the needs, identify critical periods and needed policies, and coordinate across systems,” Dr. Pinals said. “So, if you get a call as an outpatient provider from the reentry coordinator at a local jail trying to help you coordinate a patient’s reentry, that’s something to pay attention to.”

When first meeting with patients after a criminal justice experience, Dr. Pinals recommends asking them to discuss their arrest and criminal justice experience, and to address any emerging psychiatric or clinical issues, including trauma and adjustment associated with the arrests, incarceration, and legal processes. “The risks of rearrest are higher for those who have already touched the criminal justice system, so we want to help minimize that risk of rearrest,” she said.

Some clinics won’t allow patients with a criminal record to return, “which means you have to help potentially find alternative places for them to be seen,” she noted. “You may want to consult a specialist if you have doubts about your capacity to work with the patient. You also want to support staff who might have concerns about how to continue to treat this patient and you want to advocate for the patient’s needs and help them return to a stable treatment setting.”

Dr. Pinals concluded her presentation by underscoring the importance of delivering treatment services that are trauma informed. “There are high levels of trauma for those receiving care in psychiatric settings and among those who have spent time in jails and prisons,” she said. “We want to be sensitive to the fact that any of our patients who were involved in the criminal legal system might have a strong trauma history. Help instill a sense of safety and community, and hold hope for positive change.”

She reported consulting to jurisdictions and attorneys pertaining to behavioral health and justice, and forensic psychiatry. She reported having no relevant commercial financial disclosures.

dbrunk@mdedge.com

One of the greatest challenges psychotherapists face when working with justice-involved outpatients is a lack of familiarity with the criminal legal system, according to Debra A. Pinals, MD.

“It’s certainly nothing we learned about in medical school or in our mental health training, per se,” said Dr. Pinals, director of the program in psychiatry, law, and ethics at the University of Michigan, Ann Arbor, during an annual psychopharmacology update held by the Nevada Psychiatric Association.

“Another challenge is a lack of comfort with some patient personality styles, particularly those with antisocial personality styles,” she said. “We may have countertransference issues that emerge in our work with this population. That can lead to concerns about our own safety, which may at times be reasonable but often because of stereotypes often becomes of mythical proportion. The population is a high-demand population with limited resources, usually tapping public mental health services. That becomes a challenge as well. And there can be burnout when the challenges of our patient population exceed our capacity.”

Despite such obstacles, Dr. Pinals described the outpatient treatment of individuals involved in the criminal justice system as exciting, interesting, and intellectually challenging. But she acknowledged the role that stigma and fear can play.

“Though there are some unique challenges, the benefits of working with criminal justice–involved persons with serious mental illness are often not discussed,” Dr. Pinals said. “There is a tendency to overvalue the risk they may present without really looking at the specific nuances that would be involved in conducting true risk assessments and understanding that not all of these patients will be as risky as we might believe due to stigma and fear.”

Separate from how patients with criminal histories may be perceived in clinical settings. There is much to learn about the role of mental illness in crime. In a 2014 study, researchers reviewed the records of criminal arrests in 143 people with mental illness and tried to discern whether the crime itself was completely independent or completely directly connected to the symptoms of mental illness the individual was experiencing. They found that 65% were completely independent of mental illness symptoms while 8% were directly related to mental illness symptoms.

“This means that as clinicians working with outpatients, we have to understand the whole person, and what might be going on in their lives that leads them down this criminal pathway,” said Dr. Pinals, who is also a clinical professor of psychiatry at the medical school.

According to the risk-need-responsivity (RNR) paradigm, eight criminogenic risk factors are associated with recurrent involvement in the criminal legal system (Crime & Delinquency. 2006;52:7-27). The big four include history of antisocial behavior, antisocial personality pattern, antisocial cognition, and antisocial attitudes. “These are the factors that certain cognitive-behavioral therapy approaches try to address, in an effort to reduce those antisocial cognitive tendencies,” Dr. Pinals said. The other four risk factors include family or marital discord, poor school and/or work performance, few leisure or recreation activities, and substance misuse.

“You’ll notice that mental illness is not listed,” she said. “Mental illness is not considered a major driver of crime, although it might be considered a responsivity factor within this RNR paradigm. This means it’s important to address it because it may help people better respond to criminal justice supervision and thereby have an indirect effect in reducing criminal recidivism. For example, if somebody has a social anxiety disorder or agoraphobia and therefore can’t make their probation appointment, probation won’t be able to help them adhere to the terms of their probation conditions. So, we do have to treat the illnesses underlying responsivity to how the criminal justice system operates.”

To optimally serve this population, Dr. Pinals recommends that psychotherapists become familiar with the Sequential Intercept Model, which was first published in 2006. “It takes the premise that individuals move through the criminal legal system in logical steps, and if we could identify those with mental health or substance use conditions and redirect them out of the criminal legal system and into treatment, we could reduce the overall penetration of those individuals from the criminal legal system,” she said. “We know that individuals with mental illness are overrepresented in the criminal legal system.”

By understanding what happens when a patient is arrested, mental health professionals can foster communication that could facilitate treatment for their patients.

“It’s important that we remember that these are people who are going through a challenging time,” Dr. Pinals said. “Maybe we don’t like what they did. Maybe we don’t like that they were accused of committing some kind of crime. However, it is important to realize that they are patients, and we want them to achieve the best outcome, whatever setting they’re in, that continuity of care and communication across systems might be beneficial. It might reduce their chance of returning to the criminal system and having other people victimized.”

copyright/Kuzma/iStockphoto

Mental health services vary across jails and prisons, she continued, but they are generally required to be commensurate with community standards.

“Of course, that’s often fraught with complexity and may not be available in particular jurisdictions” she said. Prisons, unlike local county jails, tend to have more levels of outpatient care, including inpatient, outpatient, and residential services. “Persons with mental illness can be moved in and out of these levels of care as needed,” Dr. Pinals said. “However, persons with mental illness can be at more risk for disciplinary infractions, especially if they’re not able to follow directions or if they’re psychotic or manic.”

Reentry creates certain risks to be mindful of, including social isolation, recurrent symptoms, problems acquiring medications and housing, suicide, violence, and a return to substance use. A reentry approach she recommended is the APIC model, which stands for Assess, Plan, Identify, and Coordinate. “That means individuals approaching release should be screened and assessed for their needs with a plan to meet the needs, identify critical periods and needed policies, and coordinate across systems,” Dr. Pinals said. “So, if you get a call as an outpatient provider from the reentry coordinator at a local jail trying to help you coordinate a patient’s reentry, that’s something to pay attention to.”

When first meeting with patients after a criminal justice experience, Dr. Pinals recommends asking them to discuss their arrest and criminal justice experience, and to address any emerging psychiatric or clinical issues, including trauma and adjustment associated with the arrests, incarceration, and legal processes. “The risks of rearrest are higher for those who have already touched the criminal justice system, so we want to help minimize that risk of rearrest,” she said.

Some clinics won’t allow patients with a criminal record to return, “which means you have to help potentially find alternative places for them to be seen,” she noted. “You may want to consult a specialist if you have doubts about your capacity to work with the patient. You also want to support staff who might have concerns about how to continue to treat this patient and you want to advocate for the patient’s needs and help them return to a stable treatment setting.”

Dr. Pinals concluded her presentation by underscoring the importance of delivering treatment services that are trauma informed. “There are high levels of trauma for those receiving care in psychiatric settings and among those who have spent time in jails and prisons,” she said. “We want to be sensitive to the fact that any of our patients who were involved in the criminal legal system might have a strong trauma history. Help instill a sense of safety and community, and hold hope for positive change.”

She reported consulting to jurisdictions and attorneys pertaining to behavioral health and justice, and forensic psychiatry. She reported having no relevant commercial financial disclosures.

dbrunk@mdedge.com

One of the greatest challenges psychotherapists face when working with justice-involved outpatients is a lack of familiarity with the criminal legal system, according to Debra A. Pinals, MD.

“It’s certainly nothing we learned about in medical school or in our mental health training, per se,” said Dr. Pinals, director of the program in psychiatry, law, and ethics at the University of Michigan, Ann Arbor, during an annual psychopharmacology update held by the Nevada Psychiatric Association.

“Another challenge is a lack of comfort with some patient personality styles, particularly those with antisocial personality styles,” she said. “We may have countertransference issues that emerge in our work with this population. That can lead to concerns about our own safety, which may at times be reasonable but often because of stereotypes often becomes of mythical proportion. The population is a high-demand population with limited resources, usually tapping public mental health services. That becomes a challenge as well. And there can be burnout when the challenges of our patient population exceed our capacity.”

Despite such obstacles, Dr. Pinals described the outpatient treatment of individuals involved in the criminal justice system as exciting, interesting, and intellectually challenging. But she acknowledged the role that stigma and fear can play.

“Though there are some unique challenges, the benefits of working with criminal justice–involved persons with serious mental illness are often not discussed,” Dr. Pinals said. “There is a tendency to overvalue the risk they may present without really looking at the specific nuances that would be involved in conducting true risk assessments and understanding that not all of these patients will be as risky as we might believe due to stigma and fear.”

Separate from how patients with criminal histories may be perceived in clinical settings. There is much to learn about the role of mental illness in crime. In a 2014 study, researchers reviewed the records of criminal arrests in 143 people with mental illness and tried to discern whether the crime itself was completely independent or completely directly connected to the symptoms of mental illness the individual was experiencing. They found that 65% were completely independent of mental illness symptoms while 8% were directly related to mental illness symptoms.

“This means that as clinicians working with outpatients, we have to understand the whole person, and what might be going on in their lives that leads them down this criminal pathway,” said Dr. Pinals, who is also a clinical professor of psychiatry at the medical school.

According to the risk-need-responsivity (RNR) paradigm, eight criminogenic risk factors are associated with recurrent involvement in the criminal legal system (Crime & Delinquency. 2006;52:7-27). The big four include history of antisocial behavior, antisocial personality pattern, antisocial cognition, and antisocial attitudes. “These are the factors that certain cognitive-behavioral therapy approaches try to address, in an effort to reduce those antisocial cognitive tendencies,” Dr. Pinals said. The other four risk factors include family or marital discord, poor school and/or work performance, few leisure or recreation activities, and substance misuse.

“You’ll notice that mental illness is not listed,” she said. “Mental illness is not considered a major driver of crime, although it might be considered a responsivity factor within this RNR paradigm. This means it’s important to address it because it may help people better respond to criminal justice supervision and thereby have an indirect effect in reducing criminal recidivism. For example, if somebody has a social anxiety disorder or agoraphobia and therefore can’t make their probation appointment, probation won’t be able to help them adhere to the terms of their probation conditions. So, we do have to treat the illnesses underlying responsivity to how the criminal justice system operates.”

To optimally serve this population, Dr. Pinals recommends that psychotherapists become familiar with the Sequential Intercept Model, which was first published in 2006. “It takes the premise that individuals move through the criminal legal system in logical steps, and if we could identify those with mental health or substance use conditions and redirect them out of the criminal legal system and into treatment, we could reduce the overall penetration of those individuals from the criminal legal system,” she said. “We know that individuals with mental illness are overrepresented in the criminal legal system.”

By understanding what happens when a patient is arrested, mental health professionals can foster communication that could facilitate treatment for their patients.

“It’s important that we remember that these are people who are going through a challenging time,” Dr. Pinals said. “Maybe we don’t like what they did. Maybe we don’t like that they were accused of committing some kind of crime. However, it is important to realize that they are patients, and we want them to achieve the best outcome, whatever setting they’re in, that continuity of care and communication across systems might be beneficial. It might reduce their chance of returning to the criminal system and having other people victimized.”

copyright/Kuzma/iStockphoto

Mental health services vary across jails and prisons, she continued, but they are generally required to be commensurate with community standards.

“Of course, that’s often fraught with complexity and may not be available in particular jurisdictions” she said. Prisons, unlike local county jails, tend to have more levels of outpatient care, including inpatient, outpatient, and residential services. “Persons with mental illness can be moved in and out of these levels of care as needed,” Dr. Pinals said. “However, persons with mental illness can be at more risk for disciplinary infractions, especially if they’re not able to follow directions or if they’re psychotic or manic.”

Reentry creates certain risks to be mindful of, including social isolation, recurrent symptoms, problems acquiring medications and housing, suicide, violence, and a return to substance use. A reentry approach she recommended is the APIC model, which stands for Assess, Plan, Identify, and Coordinate. “That means individuals approaching release should be screened and assessed for their needs with a plan to meet the needs, identify critical periods and needed policies, and coordinate across systems,” Dr. Pinals said. “So, if you get a call as an outpatient provider from the reentry coordinator at a local jail trying to help you coordinate a patient’s reentry, that’s something to pay attention to.”

When first meeting with patients after a criminal justice experience, Dr. Pinals recommends asking them to discuss their arrest and criminal justice experience, and to address any emerging psychiatric or clinical issues, including trauma and adjustment associated with the arrests, incarceration, and legal processes. “The risks of rearrest are higher for those who have already touched the criminal justice system, so we want to help minimize that risk of rearrest,” she said.

Some clinics won’t allow patients with a criminal record to return, “which means you have to help potentially find alternative places for them to be seen,” she noted. “You may want to consult a specialist if you have doubts about your capacity to work with the patient. You also want to support staff who might have concerns about how to continue to treat this patient and you want to advocate for the patient’s needs and help them return to a stable treatment setting.”

Dr. Pinals concluded her presentation by underscoring the importance of delivering treatment services that are trauma informed. “There are high levels of trauma for those receiving care in psychiatric settings and among those who have spent time in jails and prisons,” she said. “We want to be sensitive to the fact that any of our patients who were involved in the criminal legal system might have a strong trauma history. Help instill a sense of safety and community, and hold hope for positive change.”

She reported consulting to jurisdictions and attorneys pertaining to behavioral health and justice, and forensic psychiatry. She reported having no relevant commercial financial disclosures.

dbrunk@mdedge.com

For patients with myelodysplastic syndromes (MDS), allogeneic stem cell transplantation (SCT) is currently the only curative treatment, however, is associated with risk of transplant-related mortality, as well as relapse. Reduced intensity conditioning (RIC) regimens may decrease toxicity yet there may be increased risk of relapse compared to myeloablative conditioning (MAC) regimens. In an analysis of MDS patients enrolled on the BMT CTN 0901 study, which was a phase III randomized clinical trial comparing outcomes by conditioning intensity prior to allogeneic stem cell transplantation in adult patients with myeloid malignancy, 42% of patients had detectable mutations in a set of 10 genes prior to conditioning with RIC or MAC. Presence of mutations prior to conditioning was associated with increased risk of relapse (3 year relapse, 40% vs 11%, p=0.022) and decreased overall survival (3 year OS 55% vs 79%, p=0.045). Among those with detectable mutations, receiving RIC had higher relapse rates (3 year relapse 75% vs 17%, p=0.003) and lower relapse-free survival (3 year RFS 13% vs 49%, p=0.003) compared to receiving MAC, although there was no difference in overall survival. Further investigation is warranted given small sample size of MDS patients, however, there may be benefit of considering MAC conditioning in MDS patients with detectable mutations prior to conditioning for allogeneic SCT.

TP53 mutations are found in 10-20% of patients with MDS and confer worse outcomes. Eprenetapopt (APR-246) is a small molecule inhibitor that stabilizes mutant p53 and induces apoptosis in TP53-mutant cells. In a phase Ib/II study of eprenatapopt combined with azacitidine in patients with TP53-mutatnt MDS or acute myeloid leukemia (AML), overall response in MDS patients (n=40) was 73%, with 50% achieving complete remission and 58% achieving a cytogenetic response. Median overall survival was 10.8 months, and no dose limiting toxicities were observed. Despite the promising early trial results, the phase 3 clinical trial evaluating eprenetapopt with azacitidine compared to azacitidine in MDS patients with TP53 mutation did not meet the primary endpoint of complete remission rate (33.3% vs 22.4%, p=0.13) (Aprea Press Release, 12/28/2020). Further results including secondary endpoints from the phase 3 trial will be reported in the future. 

For patients with myelodysplastic syndromes (MDS), allogeneic stem cell transplantation (SCT) is currently the only curative treatment, however, is associated with risk of transplant-related mortality, as well as relapse. Reduced intensity conditioning (RIC) regimens may decrease toxicity yet there may be increased risk of relapse compared to myeloablative conditioning (MAC) regimens. In an analysis of MDS patients enrolled on the BMT CTN 0901 study, which was a phase III randomized clinical trial comparing outcomes by conditioning intensity prior to allogeneic stem cell transplantation in adult patients with myeloid malignancy, 42% of patients had detectable mutations in a set of 10 genes prior to conditioning with RIC or MAC. Presence of mutations prior to conditioning was associated with increased risk of relapse (3 year relapse, 40% vs 11%, p=0.022) and decreased overall survival (3 year OS 55% vs 79%, p=0.045). Among those with detectable mutations, receiving RIC had higher relapse rates (3 year relapse 75% vs 17%, p=0.003) and lower relapse-free survival (3 year RFS 13% vs 49%, p=0.003) compared to receiving MAC, although there was no difference in overall survival. Further investigation is warranted given small sample size of MDS patients, however, there may be benefit of considering MAC conditioning in MDS patients with detectable mutations prior to conditioning for allogeneic SCT.

TP53 mutations are found in 10-20% of patients with MDS and confer worse outcomes. Eprenetapopt (APR-246) is a small molecule inhibitor that stabilizes mutant p53 and induces apoptosis in TP53-mutant cells. In a phase Ib/II study of eprenatapopt combined with azacitidine in patients with TP53-mutatnt MDS or acute myeloid leukemia (AML), overall response in MDS patients (n=40) was 73%, with 50% achieving complete remission and 58% achieving a cytogenetic response. Median overall survival was 10.8 months, and no dose limiting toxicities were observed. Despite the promising early trial results, the phase 3 clinical trial evaluating eprenetapopt with azacitidine compared to azacitidine in MDS patients with TP53 mutation did not meet the primary endpoint of complete remission rate (33.3% vs 22.4%, p=0.13) (Aprea Press Release, 12/28/2020). Further results including secondary endpoints from the phase 3 trial will be reported in the future. 

For patients with myelodysplastic syndromes (MDS), allogeneic stem cell transplantation (SCT) is currently the only curative treatment, however, is associated with risk of transplant-related mortality, as well as relapse. Reduced intensity conditioning (RIC) regimens may decrease toxicity yet there may be increased risk of relapse compared to myeloablative conditioning (MAC) regimens. In an analysis of MDS patients enrolled on the BMT CTN 0901 study, which was a phase III randomized clinical trial comparing outcomes by conditioning intensity prior to allogeneic stem cell transplantation in adult patients with myeloid malignancy, 42% of patients had detectable mutations in a set of 10 genes prior to conditioning with RIC or MAC. Presence of mutations prior to conditioning was associated with increased risk of relapse (3 year relapse, 40% vs 11%, p=0.022) and decreased overall survival (3 year OS 55% vs 79%, p=0.045). Among those with detectable mutations, receiving RIC had higher relapse rates (3 year relapse 75% vs 17%, p=0.003) and lower relapse-free survival (3 year RFS 13% vs 49%, p=0.003) compared to receiving MAC, although there was no difference in overall survival. Further investigation is warranted given small sample size of MDS patients, however, there may be benefit of considering MAC conditioning in MDS patients with detectable mutations prior to conditioning for allogeneic SCT.

TP53 mutations are found in 10-20% of patients with MDS and confer worse outcomes. Eprenetapopt (APR-246) is a small molecule inhibitor that stabilizes mutant p53 and induces apoptosis in TP53-mutant cells. In a phase Ib/II study of eprenatapopt combined with azacitidine in patients with TP53-mutatnt MDS or acute myeloid leukemia (AML), overall response in MDS patients (n=40) was 73%, with 50% achieving complete remission and 58% achieving a cytogenetic response. Median overall survival was 10.8 months, and no dose limiting toxicities were observed. Despite the promising early trial results, the phase 3 clinical trial evaluating eprenetapopt with azacitidine compared to azacitidine in MDS patients with TP53 mutation did not meet the primary endpoint of complete remission rate (33.3% vs 22.4%, p=0.13) (Aprea Press Release, 12/28/2020). Further results including secondary endpoints from the phase 3 trial will be reported in the future. 

Key clinical point: High fibrinogen-albumin ratio index (FARI) is associated with shorter overall survival (OS) in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) treated with azacitidine.

Major finding: One-year OS was significantly shorter in patients with high (at or above 0.079) vs. low (less than 0.079) FARI (35.6% vs. 77.5%; P less than .001).

Study details: Findings are from a retrospective study of 99 patients with de novo MDS (n=86) and AML-MRC (n=13) treated with azacitidine between May 2011 and June 2019.

Disclosures: The authors did not report any source of funding. The authors declared no potential competing interests.

Source: Akimoto M et al. Ann Hematol. 2021 Feb 1. doi: 10.1007/s00277-021-04440-z.

Key clinical point: High fibrinogen-albumin ratio index (FARI) is associated with shorter overall survival (OS) in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) treated with azacitidine.

Major finding: One-year OS was significantly shorter in patients with high (at or above 0.079) vs. low (less than 0.079) FARI (35.6% vs. 77.5%; P less than .001).

Study details: Findings are from a retrospective study of 99 patients with de novo MDS (n=86) and AML-MRC (n=13) treated with azacitidine between May 2011 and June 2019.

Disclosures: The authors did not report any source of funding. The authors declared no potential competing interests.

Source: Akimoto M et al. Ann Hematol. 2021 Feb 1. doi: 10.1007/s00277-021-04440-z.

Key clinical point: High fibrinogen-albumin ratio index (FARI) is associated with shorter overall survival (OS) in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) treated with azacitidine.

Major finding: One-year OS was significantly shorter in patients with high (at or above 0.079) vs. low (less than 0.079) FARI (35.6% vs. 77.5%; P less than .001).

Study details: Findings are from a retrospective study of 99 patients with de novo MDS (n=86) and AML-MRC (n=13) treated with azacitidine between May 2011 and June 2019.

Disclosures: The authors did not report any source of funding. The authors declared no potential competing interests.

Source: Akimoto M et al. Ann Hematol. 2021 Feb 1. doi: 10.1007/s00277-021-04440-z.

Key clinical point: Reduced-dose decitabine (DAC) could have a better response than reduced-dose azacitidine (AZA) in patients with myelodysplastic syndromes (MDS) with different prognostic risks.

Major finding: Overall response rate (ORR) was higher in the DAC (62.5%) than AZA (42.1%) group (P = .007). Incidences of neutropenia (P = .016) and infections (P = .032) were higher in the DAC vs. AZA group.

Study details: Findings are from a retrospective study of 158 patients with MDS with varied prognostic risks who were administered reduced-dose of AZA (n=38) or DAC (n=120). Included patients received these hypomethylating agents for the first time between May 2006 and February 2020 and could not tolerate the standard doses.

Disclosures: The study was funded by the National Science and Technology Major Project of China. The authors declared no competing interests.

Source: Hu N et al. Med Sci Monit. 2021 Jan 30. doi: 10.12659/MSM.928454.

Key clinical point: Reduced-dose decitabine (DAC) could have a better response than reduced-dose azacitidine (AZA) in patients with myelodysplastic syndromes (MDS) with different prognostic risks.

Major finding: Overall response rate (ORR) was higher in the DAC (62.5%) than AZA (42.1%) group (P = .007). Incidences of neutropenia (P = .016) and infections (P = .032) were higher in the DAC vs. AZA group.

Study details: Findings are from a retrospective study of 158 patients with MDS with varied prognostic risks who were administered reduced-dose of AZA (n=38) or DAC (n=120). Included patients received these hypomethylating agents for the first time between May 2006 and February 2020 and could not tolerate the standard doses.

Disclosures: The study was funded by the National Science and Technology Major Project of China. The authors declared no competing interests.

Source: Hu N et al. Med Sci Monit. 2021 Jan 30. doi: 10.12659/MSM.928454.

Key clinical point: Reduced-dose decitabine (DAC) could have a better response than reduced-dose azacitidine (AZA) in patients with myelodysplastic syndromes (MDS) with different prognostic risks.

Major finding: Overall response rate (ORR) was higher in the DAC (62.5%) than AZA (42.1%) group (P = .007). Incidences of neutropenia (P = .016) and infections (P = .032) were higher in the DAC vs. AZA group.

Study details: Findings are from a retrospective study of 158 patients with MDS with varied prognostic risks who were administered reduced-dose of AZA (n=38) or DAC (n=120). Included patients received these hypomethylating agents for the first time between May 2006 and February 2020 and could not tolerate the standard doses.

Disclosures: The study was funded by the National Science and Technology Major Project of China. The authors declared no competing interests.

Source: Hu N et al. Med Sci Monit. 2021 Jan 30. doi: 10.12659/MSM.928454.

Key clinical point: Daratumumab provided some clinical activity in patients with low- to intermediate-risk myelodysplastic syndromes (MDS), who relapsed or were refractory to erythropoiesis-stimulating agents (ESA) treatment. No new safety signals were identified.

Major finding: Eight-week transfusion independence (TI) was achieved by 6.1% (95% confidence interval, 0.7%-20.2%) of patients. Time to 8-week TI was 4–5 weeks after the first daratumumab infusion. Daratumumab-related adverse events were reported by 54.5% of patients, of whom 3 patients experienced 4 serious adverse events. Infusion-related reaction was observed, but none led to treatment discontinuation.

Study details: Findings are from a phase 2, randomized, open-label study involving 34 patients with low- or intermediate-1-risk MDS, who were transfusion dependent and who relapsed or were refractory to ESA treatment. Patients received either daratumumab (n=33) or talacotuzumab (n=1); however, recruitment to talacotuzumab arm was closed after the occurrence of a serious adverse event in the first patient.

Disclosures: This study was supported by Janssen Research & Development. The lead author reported receiving research support from Johnson & Johnson. Some of the coinvestigators reported owning stocks, being an employee, serving on an advisory board, receiving support, and consulting for various pharmaceutical companies including Janssen Research & Development. Six of the coinvestigators declared no potential competing interests.

Source: Garcia‐Manero G et al. Am J Hematol. 2021 Jan 15. doi: 10.1002/ajh.26095.

Key clinical point: Daratumumab provided some clinical activity in patients with low- to intermediate-risk myelodysplastic syndromes (MDS), who relapsed or were refractory to erythropoiesis-stimulating agents (ESA) treatment. No new safety signals were identified.

Major finding: Eight-week transfusion independence (TI) was achieved by 6.1% (95% confidence interval, 0.7%-20.2%) of patients. Time to 8-week TI was 4–5 weeks after the first daratumumab infusion. Daratumumab-related adverse events were reported by 54.5% of patients, of whom 3 patients experienced 4 serious adverse events. Infusion-related reaction was observed, but none led to treatment discontinuation.

Study details: Findings are from a phase 2, randomized, open-label study involving 34 patients with low- or intermediate-1-risk MDS, who were transfusion dependent and who relapsed or were refractory to ESA treatment. Patients received either daratumumab (n=33) or talacotuzumab (n=1); however, recruitment to talacotuzumab arm was closed after the occurrence of a serious adverse event in the first patient.

Disclosures: This study was supported by Janssen Research & Development. The lead author reported receiving research support from Johnson & Johnson. Some of the coinvestigators reported owning stocks, being an employee, serving on an advisory board, receiving support, and consulting for various pharmaceutical companies including Janssen Research & Development. Six of the coinvestigators declared no potential competing interests.

Source: Garcia‐Manero G et al. Am J Hematol. 2021 Jan 15. doi: 10.1002/ajh.26095.

Key clinical point: Daratumumab provided some clinical activity in patients with low- to intermediate-risk myelodysplastic syndromes (MDS), who relapsed or were refractory to erythropoiesis-stimulating agents (ESA) treatment. No new safety signals were identified.

Major finding: Eight-week transfusion independence (TI) was achieved by 6.1% (95% confidence interval, 0.7%-20.2%) of patients. Time to 8-week TI was 4–5 weeks after the first daratumumab infusion. Daratumumab-related adverse events were reported by 54.5% of patients, of whom 3 patients experienced 4 serious adverse events. Infusion-related reaction was observed, but none led to treatment discontinuation.

Study details: Findings are from a phase 2, randomized, open-label study involving 34 patients with low- or intermediate-1-risk MDS, who were transfusion dependent and who relapsed or were refractory to ESA treatment. Patients received either daratumumab (n=33) or talacotuzumab (n=1); however, recruitment to talacotuzumab arm was closed after the occurrence of a serious adverse event in the first patient.

Disclosures: This study was supported by Janssen Research & Development. The lead author reported receiving research support from Johnson & Johnson. Some of the coinvestigators reported owning stocks, being an employee, serving on an advisory board, receiving support, and consulting for various pharmaceutical companies including Janssen Research & Development. Six of the coinvestigators declared no potential competing interests.

Source: Garcia‐Manero G et al. Am J Hematol. 2021 Jan 15. doi: 10.1002/ajh.26095.

Key clinical point: A myeloablative, fractionated busulfan (f-Bu) regimen reduces relapse and boosts survival without increasing nonrelapse mortality (NRM) in older patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).

Major finding: At 2 years, the f-Bu group had a significantly better progression-free survival than the nonfractionated, lower dose busalfan (Bu) group (45% vs 24%; hazard ratio [HR], 0.6; P = .004), attributed to a significant reduction in progression (34% vs 59%; HR, 0.5; P = .003) without an increase in NRM (21% vs 15%; HR, 1.4; P = .3). Overall survival also improved in the f-Bu group vs the Bu group (51% vs 31%, HR, 0.6; P = .01).

Study details: In an open-label, phase 2 trial, patients with AML or MDS were randomly assigned to either myeloablative f-Bu over 2 weeks (n = 84; median age, 65 years) or a standard Bu regimen over 4 days (n = 78; median age, 66 years).

Disclosures: This study was supported in part by a grant from the National Cancer Institute. Q Bashir, C Hosing, K Rezvani and UR Popat reported relationships with various pharmaceutical companies and/or research organizations. The remaining authors declared no conflicts of interest.

Source: Oran B et al. Cancer. 2021 Jan 20. doi: 10.1002/cncr.33383

Key clinical point: A myeloablative, fractionated busulfan (f-Bu) regimen reduces relapse and boosts survival without increasing nonrelapse mortality (NRM) in older patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).

Major finding: At 2 years, the f-Bu group had a significantly better progression-free survival than the nonfractionated, lower dose busalfan (Bu) group (45% vs 24%; hazard ratio [HR], 0.6; P = .004), attributed to a significant reduction in progression (34% vs 59%; HR, 0.5; P = .003) without an increase in NRM (21% vs 15%; HR, 1.4; P = .3). Overall survival also improved in the f-Bu group vs the Bu group (51% vs 31%, HR, 0.6; P = .01).

Study details: In an open-label, phase 2 trial, patients with AML or MDS were randomly assigned to either myeloablative f-Bu over 2 weeks (n = 84; median age, 65 years) or a standard Bu regimen over 4 days (n = 78; median age, 66 years).

Disclosures: This study was supported in part by a grant from the National Cancer Institute. Q Bashir, C Hosing, K Rezvani and UR Popat reported relationships with various pharmaceutical companies and/or research organizations. The remaining authors declared no conflicts of interest.

Source: Oran B et al. Cancer. 2021 Jan 20. doi: 10.1002/cncr.33383

Key clinical point: A myeloablative, fractionated busulfan (f-Bu) regimen reduces relapse and boosts survival without increasing nonrelapse mortality (NRM) in older patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).

Major finding: At 2 years, the f-Bu group had a significantly better progression-free survival than the nonfractionated, lower dose busalfan (Bu) group (45% vs 24%; hazard ratio [HR], 0.6; P = .004), attributed to a significant reduction in progression (34% vs 59%; HR, 0.5; P = .003) without an increase in NRM (21% vs 15%; HR, 1.4; P = .3). Overall survival also improved in the f-Bu group vs the Bu group (51% vs 31%, HR, 0.6; P = .01).

Study details: In an open-label, phase 2 trial, patients with AML or MDS were randomly assigned to either myeloablative f-Bu over 2 weeks (n = 84; median age, 65 years) or a standard Bu regimen over 4 days (n = 78; median age, 66 years).

Disclosures: This study was supported in part by a grant from the National Cancer Institute. Q Bashir, C Hosing, K Rezvani and UR Popat reported relationships with various pharmaceutical companies and/or research organizations. The remaining authors declared no conflicts of interest.

Source: Oran B et al. Cancer. 2021 Jan 20. doi: 10.1002/cncr.33383

Key clinical point: Baseline and serial molecular profiling by next-generation sequencing (NGS) can predict outcomes with hypomethylating agents (HMAs) in myelodysplastic syndromes (MDS). Serial molecular profiling during therapy of patients with mutant TP53 can identify patients who may benefit from allogeneic transplantation.

Major finding: Mutations in TET2 and ASXL1 genes emerged as the most informative variables associated with response to HMA therapy (overall response rate, 62.1%; complete remission rate, 34.5%). The number of mutations detected by NGS (hazard ratio [HR], 1.22; P = .02) and mutations in TP53 (HR, 2.33; P = .001) and EZH2 (HR, 2.41; P = .04) were independent covariates associated with inferior overall survival (OS). Serial molecular profiling demonstrated that clearance of TP53 mutations during HMA therapy was associated with superior OS (HR, 0.28; P = .001) and improved outcome in patients proceeding to allogeneic transplantation.

Study details: This study evaluated response and OS in 247 patients molecularly profiled by NGS before first-line HMA therapy; a subset of 108 patients were sequenced serially during treatment.

Disclosures: This study was supported in part by the S Foundation Young Investigator Grant, the Early Career Award of the Dresner Foundation, and the Edward P. Evans Foundation Award. DA Sallman, E Padron, and AF List received research funding from Celgene. The remaining authors declared no conflicts of interest.

Source: Hunter AM et al. Blood Adv. 2021 Feb 23. doi: 10.1182/bloodadvances.2020003508.

Key clinical point: Baseline and serial molecular profiling by next-generation sequencing (NGS) can predict outcomes with hypomethylating agents (HMAs) in myelodysplastic syndromes (MDS). Serial molecular profiling during therapy of patients with mutant TP53 can identify patients who may benefit from allogeneic transplantation.

Major finding: Mutations in TET2 and ASXL1 genes emerged as the most informative variables associated with response to HMA therapy (overall response rate, 62.1%; complete remission rate, 34.5%). The number of mutations detected by NGS (hazard ratio [HR], 1.22; P = .02) and mutations in TP53 (HR, 2.33; P = .001) and EZH2 (HR, 2.41; P = .04) were independent covariates associated with inferior overall survival (OS). Serial molecular profiling demonstrated that clearance of TP53 mutations during HMA therapy was associated with superior OS (HR, 0.28; P = .001) and improved outcome in patients proceeding to allogeneic transplantation.

Study details: This study evaluated response and OS in 247 patients molecularly profiled by NGS before first-line HMA therapy; a subset of 108 patients were sequenced serially during treatment.

Disclosures: This study was supported in part by the S Foundation Young Investigator Grant, the Early Career Award of the Dresner Foundation, and the Edward P. Evans Foundation Award. DA Sallman, E Padron, and AF List received research funding from Celgene. The remaining authors declared no conflicts of interest.

Source: Hunter AM et al. Blood Adv. 2021 Feb 23. doi: 10.1182/bloodadvances.2020003508.

Key clinical point: Baseline and serial molecular profiling by next-generation sequencing (NGS) can predict outcomes with hypomethylating agents (HMAs) in myelodysplastic syndromes (MDS). Serial molecular profiling during therapy of patients with mutant TP53 can identify patients who may benefit from allogeneic transplantation.

Major finding: Mutations in TET2 and ASXL1 genes emerged as the most informative variables associated with response to HMA therapy (overall response rate, 62.1%; complete remission rate, 34.5%). The number of mutations detected by NGS (hazard ratio [HR], 1.22; P = .02) and mutations in TP53 (HR, 2.33; P = .001) and EZH2 (HR, 2.41; P = .04) were independent covariates associated with inferior overall survival (OS). Serial molecular profiling demonstrated that clearance of TP53 mutations during HMA therapy was associated with superior OS (HR, 0.28; P = .001) and improved outcome in patients proceeding to allogeneic transplantation.

Study details: This study evaluated response and OS in 247 patients molecularly profiled by NGS before first-line HMA therapy; a subset of 108 patients were sequenced serially during treatment.

Disclosures: This study was supported in part by the S Foundation Young Investigator Grant, the Early Career Award of the Dresner Foundation, and the Edward P. Evans Foundation Award. DA Sallman, E Padron, and AF List received research funding from Celgene. The remaining authors declared no conflicts of interest.

Source: Hunter AM et al. Blood Adv. 2021 Feb 23. doi: 10.1182/bloodadvances.2020003508.

Key clinical point: Dysregulated erythroferrone (ERFE) expression in CD71⁺ erythroid progenitors is associated with myelodysplastic syndromes (MDS) outcome and predicts patient survival independently of International Prognostic Scoring System (IPSS) stratification.

Major finding: The expression of ERFE was significantly higher in CD71⁺ cells of MDS patients vs. healthy donors group (median normalized mean fold change, 2.42 vs. 0.78). Elevated expression of ERFE in erythroid progenitors was associated with superior survival (hazard ratio, 0.35; P = .0017) independently of IPSS stratification. For growth/differentiation factor 15, the result was similar, but not statistically significant (P = .0543).

Study details: The data come from a study of 111 patients with MDS (median age, 73 years; 66.7% males).

Disclosures: This study was supported by funds of the Deutsche Forschungsgemeinschaft. The authors declared no conflicts of interest.

Source: Riabov V et al. Br J Haematol. 2021 Jan 24. doi: 10.1111/bjh.17314.

Key clinical point: Dysregulated erythroferrone (ERFE) expression in CD71⁺ erythroid progenitors is associated with myelodysplastic syndromes (MDS) outcome and predicts patient survival independently of International Prognostic Scoring System (IPSS) stratification.

Major finding: The expression of ERFE was significantly higher in CD71⁺ cells of MDS patients vs. healthy donors group (median normalized mean fold change, 2.42 vs. 0.78). Elevated expression of ERFE in erythroid progenitors was associated with superior survival (hazard ratio, 0.35; P = .0017) independently of IPSS stratification. For growth/differentiation factor 15, the result was similar, but not statistically significant (P = .0543).

Study details: The data come from a study of 111 patients with MDS (median age, 73 years; 66.7% males).

Disclosures: This study was supported by funds of the Deutsche Forschungsgemeinschaft. The authors declared no conflicts of interest.

Source: Riabov V et al. Br J Haematol. 2021 Jan 24. doi: 10.1111/bjh.17314.

Key clinical point: Dysregulated erythroferrone (ERFE) expression in CD71⁺ erythroid progenitors is associated with myelodysplastic syndromes (MDS) outcome and predicts patient survival independently of International Prognostic Scoring System (IPSS) stratification.

Major finding: The expression of ERFE was significantly higher in CD71⁺ cells of MDS patients vs. healthy donors group (median normalized mean fold change, 2.42 vs. 0.78). Elevated expression of ERFE in erythroid progenitors was associated with superior survival (hazard ratio, 0.35; P = .0017) independently of IPSS stratification. For growth/differentiation factor 15, the result was similar, but not statistically significant (P = .0543).

Study details: The data come from a study of 111 patients with MDS (median age, 73 years; 66.7% males).

Disclosures: This study was supported by funds of the Deutsche Forschungsgemeinschaft. The authors declared no conflicts of interest.

Source: Riabov V et al. Br J Haematol. 2021 Jan 24. doi: 10.1111/bjh.17314.