Women who experienced severe complications during pregnancy were more than twice as likely to die at any time after their last pregnancy, including post partum and beyond, based on data from more than 1 million women.

“Current data suggest that up to 88% of maternal deaths are preceded by severe maternal morbidity,” but the long-term risk of mortality and the effect of severe maternal morbidity has not been well studied, wrote U. Vivian Ukah, MPH, PhD, of McGill University, Montreal, and colleagues.

In a longitudinal cohort study published in Obstetrics & Gynecology, the researchers identified 1,229,306 pregnant women who delivered in Quebec between 1989 and 2016.

The primary outcome of in-hospital mortality after the last pregnancy, either post partum (within 42 days of delivery) or long term (43 days to 29 years after delivery).

Overall, 2.9% of the study population experienced severe maternal morbidity, with an associated mortality rate of 0.86 per 1,000 person-years versus 0.41 per 1,000 person-years in women without severe maternal morbidity. The median time to death for women with severe maternal mortality was 6.8 years, compared with 151 years for those without severe maternal morbidity.

The death rate at any time after delivery, post partum and beyond, was twice as high among women with severe maternal morbidity. The morbidities most often associated with long-term mortality after 42 days were severe cardiac complications (hazard ratio, 7.00), acute renal failure (HR, 4.35), and cerebrovascular accidents (HR, 4.03).

However, the mortality risk following severe maternal morbidity decreased over time, the researchers noted. Severe maternal morbidity was associated with 6.73 times the mortality risk, compared with no morbidity, during the period from 43 days to 11 months, but this difference dropped to 1.91, 1.77, and 1.18 times the risk, compared with no comorbidity, at 1-4 years, 5-9 years, and 10-29 years, respectively.

The study findings were limited by several factors, including the inability to prove causality, the use of only in-hospital mortality data, and the potential for missed cases that fell outside the Canadian Perinatal Surveillance System definition of severe maternal morbidity, the researchers noted.

However, the results suggest that identifying severe maternal morbidity may help identify women at risk for postpartum and long-term premature mortality. “Women with severe maternal morbidity may benefit from continued surveillance and preventative interventions to reduce the risk of premature mortality,” they concluded.

Increased morbidity rates drive need for research

“In this retrospective longitudinal cohort study of over 1.2 million women delivering in Quebec between 1989 and 2016, Dr. Ukah and her colleagues demonstrated the association between severe maternal morbidity [SMM] and an accelerated risk of mortality beyond the postpartum period, compared with women who do not experience SMM,” Rachel Humphrey, MD, a maternal-fetal medicine specialist at Advent Health in Orlando, said in an interview. “This study is important as there has been a steady increase in SMM in recent years. In the United States, the CDC reports that SMM affected more than 50,000 women in 2014 alone. Across multiple countries the decline in overall health of women giving birth is felt to contribute to SMM. As the rates of preexisting conditions such as maternal obesity, hypertension, diabetes, and advanced age increases, we can assume that SMM will increase as well. This study clearly depicts the association between SMM and maternal death at 43 days to years after the complicated delivery. We can assume that, as SMM increases, so will the risk of mortality beyond the postpartum period for these women who initially survive their serious pregnancy complication.”

Dr. Humphrey said that, in some respects, the study results are to be expected. “It is logical to assume that a patient with a life-threatening issue at delivery such as severe cardiac complications, acute renal failure and cerebrovascular accident would be at higher risk for long-term morbidity and mortality. This study also adds to the large body of evidence linking socioeconomic deprivation with SMM. But there were unexpected findings in this study. I did not expect certain types of SMM to be associated with an increased risk of death years after the event.For example, hysterectomy at delivery carried a hazard ratio of 3.54 for death at 5-9 years after the event. The association between severe hemorrhage and fully adjusted hazard ratio was similarly increased at 2.96 [2.37-3.71].”

 

More screening and prospective studies needed

“Recognizing the association between SMM and accelerated long-term risk of mortality is a first step in determining what interventions might improve health and longevity in women who experience SMM,” said Dr. Humphrey. “With the absence of prospective studies, it still is logical to assume that close medical follow-up and lifestyle interventions are appropriate in this population. Screening for and actively managing chronic conditions such as diabetes, dyslipidemia, and hypertension seems appropriate for these patients.”

As for further research, “I am interested to know through prospective clinical trials if specific health maintenance screens and interventions would have a positive impact on the life expectancy of survivors of SMM,” said Dr. Humphrey. “I applaud this team for providing data up to 27 years after an obstetric complication, and I am interested to see if Dr. Ukah and her team will continue their research to determine if there is a ‘second peak’ in mortality in the survivors of SMM when they are elderly. Finally, I would be interested to see more detailed data from this team on the associations between socioeconomic deprivation and short- and long-term mortality for women in their study. This information may help further fuel the movement toward social changes to maximize the health of the women and families we serve.”

The study was supported by the Heart & Stroke Foundation of Canada and awards to the lead author and others from the Fonds de recherche du Québec-Santé. The researchers and Dr. Humphrey had no financial conflicts to disclose.

Women who experienced severe complications during pregnancy were more than twice as likely to die at any time after their last pregnancy, including post partum and beyond, based on data from more than 1 million women.

“Current data suggest that up to 88% of maternal deaths are preceded by severe maternal morbidity,” but the long-term risk of mortality and the effect of severe maternal morbidity has not been well studied, wrote U. Vivian Ukah, MPH, PhD, of McGill University, Montreal, and colleagues.

In a longitudinal cohort study published in Obstetrics & Gynecology, the researchers identified 1,229,306 pregnant women who delivered in Quebec between 1989 and 2016.

The primary outcome of in-hospital mortality after the last pregnancy, either post partum (within 42 days of delivery) or long term (43 days to 29 years after delivery).

Overall, 2.9% of the study population experienced severe maternal morbidity, with an associated mortality rate of 0.86 per 1,000 person-years versus 0.41 per 1,000 person-years in women without severe maternal morbidity. The median time to death for women with severe maternal mortality was 6.8 years, compared with 151 years for those without severe maternal morbidity.

The death rate at any time after delivery, post partum and beyond, was twice as high among women with severe maternal morbidity. The morbidities most often associated with long-term mortality after 42 days were severe cardiac complications (hazard ratio, 7.00), acute renal failure (HR, 4.35), and cerebrovascular accidents (HR, 4.03).

However, the mortality risk following severe maternal morbidity decreased over time, the researchers noted. Severe maternal morbidity was associated with 6.73 times the mortality risk, compared with no morbidity, during the period from 43 days to 11 months, but this difference dropped to 1.91, 1.77, and 1.18 times the risk, compared with no comorbidity, at 1-4 years, 5-9 years, and 10-29 years, respectively.

The study findings were limited by several factors, including the inability to prove causality, the use of only in-hospital mortality data, and the potential for missed cases that fell outside the Canadian Perinatal Surveillance System definition of severe maternal morbidity, the researchers noted.

However, the results suggest that identifying severe maternal morbidity may help identify women at risk for postpartum and long-term premature mortality. “Women with severe maternal morbidity may benefit from continued surveillance and preventative interventions to reduce the risk of premature mortality,” they concluded.

Increased morbidity rates drive need for research

“In this retrospective longitudinal cohort study of over 1.2 million women delivering in Quebec between 1989 and 2016, Dr. Ukah and her colleagues demonstrated the association between severe maternal morbidity [SMM] and an accelerated risk of mortality beyond the postpartum period, compared with women who do not experience SMM,” Rachel Humphrey, MD, a maternal-fetal medicine specialist at Advent Health in Orlando, said in an interview. “This study is important as there has been a steady increase in SMM in recent years. In the United States, the CDC reports that SMM affected more than 50,000 women in 2014 alone. Across multiple countries the decline in overall health of women giving birth is felt to contribute to SMM. As the rates of preexisting conditions such as maternal obesity, hypertension, diabetes, and advanced age increases, we can assume that SMM will increase as well. This study clearly depicts the association between SMM and maternal death at 43 days to years after the complicated delivery. We can assume that, as SMM increases, so will the risk of mortality beyond the postpartum period for these women who initially survive their serious pregnancy complication.”

Dr. Humphrey said that, in some respects, the study results are to be expected. “It is logical to assume that a patient with a life-threatening issue at delivery such as severe cardiac complications, acute renal failure and cerebrovascular accident would be at higher risk for long-term morbidity and mortality. This study also adds to the large body of evidence linking socioeconomic deprivation with SMM. But there were unexpected findings in this study. I did not expect certain types of SMM to be associated with an increased risk of death years after the event.For example, hysterectomy at delivery carried a hazard ratio of 3.54 for death at 5-9 years after the event. The association between severe hemorrhage and fully adjusted hazard ratio was similarly increased at 2.96 [2.37-3.71].”

 

More screening and prospective studies needed

“Recognizing the association between SMM and accelerated long-term risk of mortality is a first step in determining what interventions might improve health and longevity in women who experience SMM,” said Dr. Humphrey. “With the absence of prospective studies, it still is logical to assume that close medical follow-up and lifestyle interventions are appropriate in this population. Screening for and actively managing chronic conditions such as diabetes, dyslipidemia, and hypertension seems appropriate for these patients.”

As for further research, “I am interested to know through prospective clinical trials if specific health maintenance screens and interventions would have a positive impact on the life expectancy of survivors of SMM,” said Dr. Humphrey. “I applaud this team for providing data up to 27 years after an obstetric complication, and I am interested to see if Dr. Ukah and her team will continue their research to determine if there is a ‘second peak’ in mortality in the survivors of SMM when they are elderly. Finally, I would be interested to see more detailed data from this team on the associations between socioeconomic deprivation and short- and long-term mortality for women in their study. This information may help further fuel the movement toward social changes to maximize the health of the women and families we serve.”

The study was supported by the Heart & Stroke Foundation of Canada and awards to the lead author and others from the Fonds de recherche du Québec-Santé. The researchers and Dr. Humphrey had no financial conflicts to disclose.

Women who experienced severe complications during pregnancy were more than twice as likely to die at any time after their last pregnancy, including post partum and beyond, based on data from more than 1 million women.

“Current data suggest that up to 88% of maternal deaths are preceded by severe maternal morbidity,” but the long-term risk of mortality and the effect of severe maternal morbidity has not been well studied, wrote U. Vivian Ukah, MPH, PhD, of McGill University, Montreal, and colleagues.

In a longitudinal cohort study published in Obstetrics & Gynecology, the researchers identified 1,229,306 pregnant women who delivered in Quebec between 1989 and 2016.

The primary outcome of in-hospital mortality after the last pregnancy, either post partum (within 42 days of delivery) or long term (43 days to 29 years after delivery).

Overall, 2.9% of the study population experienced severe maternal morbidity, with an associated mortality rate of 0.86 per 1,000 person-years versus 0.41 per 1,000 person-years in women without severe maternal morbidity. The median time to death for women with severe maternal mortality was 6.8 years, compared with 151 years for those without severe maternal morbidity.

The death rate at any time after delivery, post partum and beyond, was twice as high among women with severe maternal morbidity. The morbidities most often associated with long-term mortality after 42 days were severe cardiac complications (hazard ratio, 7.00), acute renal failure (HR, 4.35), and cerebrovascular accidents (HR, 4.03).

However, the mortality risk following severe maternal morbidity decreased over time, the researchers noted. Severe maternal morbidity was associated with 6.73 times the mortality risk, compared with no morbidity, during the period from 43 days to 11 months, but this difference dropped to 1.91, 1.77, and 1.18 times the risk, compared with no comorbidity, at 1-4 years, 5-9 years, and 10-29 years, respectively.

The study findings were limited by several factors, including the inability to prove causality, the use of only in-hospital mortality data, and the potential for missed cases that fell outside the Canadian Perinatal Surveillance System definition of severe maternal morbidity, the researchers noted.

However, the results suggest that identifying severe maternal morbidity may help identify women at risk for postpartum and long-term premature mortality. “Women with severe maternal morbidity may benefit from continued surveillance and preventative interventions to reduce the risk of premature mortality,” they concluded.

Increased morbidity rates drive need for research

“In this retrospective longitudinal cohort study of over 1.2 million women delivering in Quebec between 1989 and 2016, Dr. Ukah and her colleagues demonstrated the association between severe maternal morbidity [SMM] and an accelerated risk of mortality beyond the postpartum period, compared with women who do not experience SMM,” Rachel Humphrey, MD, a maternal-fetal medicine specialist at Advent Health in Orlando, said in an interview. “This study is important as there has been a steady increase in SMM in recent years. In the United States, the CDC reports that SMM affected more than 50,000 women in 2014 alone. Across multiple countries the decline in overall health of women giving birth is felt to contribute to SMM. As the rates of preexisting conditions such as maternal obesity, hypertension, diabetes, and advanced age increases, we can assume that SMM will increase as well. This study clearly depicts the association between SMM and maternal death at 43 days to years after the complicated delivery. We can assume that, as SMM increases, so will the risk of mortality beyond the postpartum period for these women who initially survive their serious pregnancy complication.”

Dr. Humphrey said that, in some respects, the study results are to be expected. “It is logical to assume that a patient with a life-threatening issue at delivery such as severe cardiac complications, acute renal failure and cerebrovascular accident would be at higher risk for long-term morbidity and mortality. This study also adds to the large body of evidence linking socioeconomic deprivation with SMM. But there were unexpected findings in this study. I did not expect certain types of SMM to be associated with an increased risk of death years after the event.For example, hysterectomy at delivery carried a hazard ratio of 3.54 for death at 5-9 years after the event. The association between severe hemorrhage and fully adjusted hazard ratio was similarly increased at 2.96 [2.37-3.71].”

 

More screening and prospective studies needed

“Recognizing the association between SMM and accelerated long-term risk of mortality is a first step in determining what interventions might improve health and longevity in women who experience SMM,” said Dr. Humphrey. “With the absence of prospective studies, it still is logical to assume that close medical follow-up and lifestyle interventions are appropriate in this population. Screening for and actively managing chronic conditions such as diabetes, dyslipidemia, and hypertension seems appropriate for these patients.”

As for further research, “I am interested to know through prospective clinical trials if specific health maintenance screens and interventions would have a positive impact on the life expectancy of survivors of SMM,” said Dr. Humphrey. “I applaud this team for providing data up to 27 years after an obstetric complication, and I am interested to see if Dr. Ukah and her team will continue their research to determine if there is a ‘second peak’ in mortality in the survivors of SMM when they are elderly. Finally, I would be interested to see more detailed data from this team on the associations between socioeconomic deprivation and short- and long-term mortality for women in their study. This information may help further fuel the movement toward social changes to maximize the health of the women and families we serve.”

The study was supported by the Heart & Stroke Foundation of Canada and awards to the lead author and others from the Fonds de recherche du Québec-Santé. The researchers and Dr. Humphrey had no financial conflicts to disclose.

Mounting evidence suggests it’s a mistake to reject the diagnosis of drug reaction with eosinophilia and systemic symptoms, or DRESS, simply because the interval between initiating a drug and symptom onset is less than 15 days, Sarah Walsh, MD, said at the virtual annual congress of the European Academy of Dermatology and Venereology.

The standard dictum has been that diagnosis of this severe T-cell-mediated drug reaction requires more than a 2-week delay in symptom onset following initial drug intake. But this can steer physicians in the wrong direction and lead to stopping an innocent drug while the true culprit medication remains on board. This adversely affects patient prognosis, since a longer duration of drug exposure after symptom onset is associated with increased hospital length of stay and greater mortality risk, explained Dr. Walsh, clinical lead for dermatology at King’s College Hospital, London.

In addition to sharing recent data demonstrating that DRESS symptoms often occur within just a week or 2 of drug exposure, she highlighted several recent advances in the ability to predict DRESS severity. These include clues provided by rash morphology and histopathology, HLA testing, and a novel scoring system to assess DRESS severity and the risk of potentially fatal cytomegalovirus reactivation.

Short-delay DRESS onset

In a retrospective study of 41 patients with a first episode of DRESS in three French dermatology departments, 14 (34%) had onset within 15 days or less of initial exposure to the causative drug. In 6 of 14 patients in the rapid-onset group the offending drug was an antibiotic, while in another 5 the culprit was iodinated contrast media. In the delayed-onset DRESS group, the chief sensitizers were allopurinol in 8 patients, lamotrigine in 6, carbamazepine in 4, and sulfasalazine in 2; of note, none of these 4 delayed-onset DRESS drugs were implicated in any cases of rapid-onset DRESS. There were no differences in the clinical manifestations of DRESS between the rapid- and delayed-onset groups.

Similarly, dermatologists at Government Medical College in Kerala, India, reported in a retrospective study of 100 consecutive patients with DRESS, the drug reaction emerged within 2 weeks after starting the culprit medication in 36% of cases. Indeed, 11 patients became symptomatic within 3-7 days after beginning the medication; in 10 of the 11 cases, the offending agent was an antibiotic, and in 1 patient it was terbinafine. In the 25 cases of DRESS that arose on day 8-14 of drug therapy, the culprit was phenytoin in 14, antibiotics in 6, and 1 each for clopidogrel, hydroxychloroquine, sodium valproate, lamotrigine, and vitamin D₃.

Both groups of investigators concluded that a short time lag between starting a drug and development of symptoms of a drug reaction shouldn’t rule out DRESS as a possibility provided other criteria consistent with the diagnosis are present. Hallmarks of DRESS include an acute extensive rash, fever greater than 38 degrees C, enlarged lymph nodes at two or more sites, internal organ involvement, a low platelet count, elevated eosinophils, and abnormal lymphocyte levels.
 

Rash morphology and histology as prognostic indicators

Dr. Walsh was the lead investigator in a study that identified four distinct patterns of skin involvement in patients with DRESS. The most common type of rash in this single-center retrospective study of 27 consecutive patients was an urticated papular exanthem, present in 13 of the 27 patients. An erythema multiforme-like reaction was present in 8, exfoliative erythroderma in 3, and a morbilliform erythema in 3 others. The worst prognosis was in the subgroup with an erythema multiforme-like rash.

All 27 patients had hepatic involvement, which was severe in 9 cases. Six of the 9 with severe liver impairment had an erythema multiforme-like rash, compared with just 2 of the 18 with mild or moderate liver involvement; thus, an erythema multiforme-like skin eruption was associated with a fivefold increased likelihood of severe hepatic involvement.

“It is a clinical sign that we take seriously at presentation if atypical target lesions are present,” the dermatologist said.

Separately, Taiwanese investigators compared clinical and histopathologic features in a study of 32 patients with DRESS and 17 with maculopapular exanthem. Interface vacuolization, which was present in 29 of the 32 patients with DRESS, was far more prominent than in the comparator group. Moreover, severe dyskeratosis was significantly associated with more severe liver impairment in the DRESS group.
 

HLA testing

Testing for HLA haplotypes associated with severe drug reactions has a useful role as a screening tool prior to prescribing selected high-risk drugs, Dr. Walsh said. For example, it’s known that 6.8% of individuals of European ancestry carry HLA-A*32:01, an allele that was strongly associated with an increased rate of vancomycin-associated DRESS in a case-control study at Vanderbilt University, Nashville, Tenn. Indeed, 19 of 23 individuals with vancomycin-associated DRESS were HLA-A*32:01 positive, compared with none of 46 vancomycin-tolerant controls. Nineteen percent of HLA-A*32:01-positive patients developed DRESS during treatment with vancomycin, and the drug reaction occurred within 4 weeks.

The investigators noted that testing for HLA-A*32:01 is also useful in DRESS occurring in patients on vancomycin and multiple other drugs because the test’s high negative predictive value may safely allow continued therapy with this potent antibiotic for Gram-positive infections.
 

A DRESS prognostic scoring system

Japanese researchers have developed a scoring system for DRESS for use in monitoring severity of the drug reaction, predicting prognosis, and estimating the risk of developing cytomegalovirus disease and its potentially fatal complications. The scoring system incorporates patient factors, including age, duration of drug exposure after symptom onset; rash characteristics, such as percentage of body surface area involved and presence or absence of erythroderma; appetite loss; and laboratory values.

“It yields a prognostic score that can be used to determine treatment choices, such as immediate intervention with anti-CMV agents. It’s a very useful tool,” Dr. Walsh said.

She reported having no financial conflicts regarding her presentation.

[email protected]

Mounting evidence suggests it’s a mistake to reject the diagnosis of drug reaction with eosinophilia and systemic symptoms, or DRESS, simply because the interval between initiating a drug and symptom onset is less than 15 days, Sarah Walsh, MD, said at the virtual annual congress of the European Academy of Dermatology and Venereology.

The standard dictum has been that diagnosis of this severe T-cell-mediated drug reaction requires more than a 2-week delay in symptom onset following initial drug intake. But this can steer physicians in the wrong direction and lead to stopping an innocent drug while the true culprit medication remains on board. This adversely affects patient prognosis, since a longer duration of drug exposure after symptom onset is associated with increased hospital length of stay and greater mortality risk, explained Dr. Walsh, clinical lead for dermatology at King’s College Hospital, London.

In addition to sharing recent data demonstrating that DRESS symptoms often occur within just a week or 2 of drug exposure, she highlighted several recent advances in the ability to predict DRESS severity. These include clues provided by rash morphology and histopathology, HLA testing, and a novel scoring system to assess DRESS severity and the risk of potentially fatal cytomegalovirus reactivation.

Short-delay DRESS onset

In a retrospective study of 41 patients with a first episode of DRESS in three French dermatology departments, 14 (34%) had onset within 15 days or less of initial exposure to the causative drug. In 6 of 14 patients in the rapid-onset group the offending drug was an antibiotic, while in another 5 the culprit was iodinated contrast media. In the delayed-onset DRESS group, the chief sensitizers were allopurinol in 8 patients, lamotrigine in 6, carbamazepine in 4, and sulfasalazine in 2; of note, none of these 4 delayed-onset DRESS drugs were implicated in any cases of rapid-onset DRESS. There were no differences in the clinical manifestations of DRESS between the rapid- and delayed-onset groups.

Similarly, dermatologists at Government Medical College in Kerala, India, reported in a retrospective study of 100 consecutive patients with DRESS, the drug reaction emerged within 2 weeks after starting the culprit medication in 36% of cases. Indeed, 11 patients became symptomatic within 3-7 days after beginning the medication; in 10 of the 11 cases, the offending agent was an antibiotic, and in 1 patient it was terbinafine. In the 25 cases of DRESS that arose on day 8-14 of drug therapy, the culprit was phenytoin in 14, antibiotics in 6, and 1 each for clopidogrel, hydroxychloroquine, sodium valproate, lamotrigine, and vitamin D₃.

Both groups of investigators concluded that a short time lag between starting a drug and development of symptoms of a drug reaction shouldn’t rule out DRESS as a possibility provided other criteria consistent with the diagnosis are present. Hallmarks of DRESS include an acute extensive rash, fever greater than 38 degrees C, enlarged lymph nodes at two or more sites, internal organ involvement, a low platelet count, elevated eosinophils, and abnormal lymphocyte levels.
 

Rash morphology and histology as prognostic indicators

Dr. Walsh was the lead investigator in a study that identified four distinct patterns of skin involvement in patients with DRESS. The most common type of rash in this single-center retrospective study of 27 consecutive patients was an urticated papular exanthem, present in 13 of the 27 patients. An erythema multiforme-like reaction was present in 8, exfoliative erythroderma in 3, and a morbilliform erythema in 3 others. The worst prognosis was in the subgroup with an erythema multiforme-like rash.

All 27 patients had hepatic involvement, which was severe in 9 cases. Six of the 9 with severe liver impairment had an erythema multiforme-like rash, compared with just 2 of the 18 with mild or moderate liver involvement; thus, an erythema multiforme-like skin eruption was associated with a fivefold increased likelihood of severe hepatic involvement.

“It is a clinical sign that we take seriously at presentation if atypical target lesions are present,” the dermatologist said.

Separately, Taiwanese investigators compared clinical and histopathologic features in a study of 32 patients with DRESS and 17 with maculopapular exanthem. Interface vacuolization, which was present in 29 of the 32 patients with DRESS, was far more prominent than in the comparator group. Moreover, severe dyskeratosis was significantly associated with more severe liver impairment in the DRESS group.
 

HLA testing

Testing for HLA haplotypes associated with severe drug reactions has a useful role as a screening tool prior to prescribing selected high-risk drugs, Dr. Walsh said. For example, it’s known that 6.8% of individuals of European ancestry carry HLA-A*32:01, an allele that was strongly associated with an increased rate of vancomycin-associated DRESS in a case-control study at Vanderbilt University, Nashville, Tenn. Indeed, 19 of 23 individuals with vancomycin-associated DRESS were HLA-A*32:01 positive, compared with none of 46 vancomycin-tolerant controls. Nineteen percent of HLA-A*32:01-positive patients developed DRESS during treatment with vancomycin, and the drug reaction occurred within 4 weeks.

The investigators noted that testing for HLA-A*32:01 is also useful in DRESS occurring in patients on vancomycin and multiple other drugs because the test’s high negative predictive value may safely allow continued therapy with this potent antibiotic for Gram-positive infections.
 

A DRESS prognostic scoring system

Japanese researchers have developed a scoring system for DRESS for use in monitoring severity of the drug reaction, predicting prognosis, and estimating the risk of developing cytomegalovirus disease and its potentially fatal complications. The scoring system incorporates patient factors, including age, duration of drug exposure after symptom onset; rash characteristics, such as percentage of body surface area involved and presence or absence of erythroderma; appetite loss; and laboratory values.

“It yields a prognostic score that can be used to determine treatment choices, such as immediate intervention with anti-CMV agents. It’s a very useful tool,” Dr. Walsh said.

She reported having no financial conflicts regarding her presentation.

[email protected]

Mounting evidence suggests it’s a mistake to reject the diagnosis of drug reaction with eosinophilia and systemic symptoms, or DRESS, simply because the interval between initiating a drug and symptom onset is less than 15 days, Sarah Walsh, MD, said at the virtual annual congress of the European Academy of Dermatology and Venereology.

The standard dictum has been that diagnosis of this severe T-cell-mediated drug reaction requires more than a 2-week delay in symptom onset following initial drug intake. But this can steer physicians in the wrong direction and lead to stopping an innocent drug while the true culprit medication remains on board. This adversely affects patient prognosis, since a longer duration of drug exposure after symptom onset is associated with increased hospital length of stay and greater mortality risk, explained Dr. Walsh, clinical lead for dermatology at King’s College Hospital, London.

In addition to sharing recent data demonstrating that DRESS symptoms often occur within just a week or 2 of drug exposure, she highlighted several recent advances in the ability to predict DRESS severity. These include clues provided by rash morphology and histopathology, HLA testing, and a novel scoring system to assess DRESS severity and the risk of potentially fatal cytomegalovirus reactivation.

Short-delay DRESS onset

In a retrospective study of 41 patients with a first episode of DRESS in three French dermatology departments, 14 (34%) had onset within 15 days or less of initial exposure to the causative drug. In 6 of 14 patients in the rapid-onset group the offending drug was an antibiotic, while in another 5 the culprit was iodinated contrast media. In the delayed-onset DRESS group, the chief sensitizers were allopurinol in 8 patients, lamotrigine in 6, carbamazepine in 4, and sulfasalazine in 2; of note, none of these 4 delayed-onset DRESS drugs were implicated in any cases of rapid-onset DRESS. There were no differences in the clinical manifestations of DRESS between the rapid- and delayed-onset groups.

Similarly, dermatologists at Government Medical College in Kerala, India, reported in a retrospective study of 100 consecutive patients with DRESS, the drug reaction emerged within 2 weeks after starting the culprit medication in 36% of cases. Indeed, 11 patients became symptomatic within 3-7 days after beginning the medication; in 10 of the 11 cases, the offending agent was an antibiotic, and in 1 patient it was terbinafine. In the 25 cases of DRESS that arose on day 8-14 of drug therapy, the culprit was phenytoin in 14, antibiotics in 6, and 1 each for clopidogrel, hydroxychloroquine, sodium valproate, lamotrigine, and vitamin D₃.

Both groups of investigators concluded that a short time lag between starting a drug and development of symptoms of a drug reaction shouldn’t rule out DRESS as a possibility provided other criteria consistent with the diagnosis are present. Hallmarks of DRESS include an acute extensive rash, fever greater than 38 degrees C, enlarged lymph nodes at two or more sites, internal organ involvement, a low platelet count, elevated eosinophils, and abnormal lymphocyte levels.
 

Rash morphology and histology as prognostic indicators

Dr. Walsh was the lead investigator in a study that identified four distinct patterns of skin involvement in patients with DRESS. The most common type of rash in this single-center retrospective study of 27 consecutive patients was an urticated papular exanthem, present in 13 of the 27 patients. An erythema multiforme-like reaction was present in 8, exfoliative erythroderma in 3, and a morbilliform erythema in 3 others. The worst prognosis was in the subgroup with an erythema multiforme-like rash.

All 27 patients had hepatic involvement, which was severe in 9 cases. Six of the 9 with severe liver impairment had an erythema multiforme-like rash, compared with just 2 of the 18 with mild or moderate liver involvement; thus, an erythema multiforme-like skin eruption was associated with a fivefold increased likelihood of severe hepatic involvement.

“It is a clinical sign that we take seriously at presentation if atypical target lesions are present,” the dermatologist said.

Separately, Taiwanese investigators compared clinical and histopathologic features in a study of 32 patients with DRESS and 17 with maculopapular exanthem. Interface vacuolization, which was present in 29 of the 32 patients with DRESS, was far more prominent than in the comparator group. Moreover, severe dyskeratosis was significantly associated with more severe liver impairment in the DRESS group.
 

HLA testing

Testing for HLA haplotypes associated with severe drug reactions has a useful role as a screening tool prior to prescribing selected high-risk drugs, Dr. Walsh said. For example, it’s known that 6.8% of individuals of European ancestry carry HLA-A*32:01, an allele that was strongly associated with an increased rate of vancomycin-associated DRESS in a case-control study at Vanderbilt University, Nashville, Tenn. Indeed, 19 of 23 individuals with vancomycin-associated DRESS were HLA-A*32:01 positive, compared with none of 46 vancomycin-tolerant controls. Nineteen percent of HLA-A*32:01-positive patients developed DRESS during treatment with vancomycin, and the drug reaction occurred within 4 weeks.

The investigators noted that testing for HLA-A*32:01 is also useful in DRESS occurring in patients on vancomycin and multiple other drugs because the test’s high negative predictive value may safely allow continued therapy with this potent antibiotic for Gram-positive infections.
 

A DRESS prognostic scoring system

Japanese researchers have developed a scoring system for DRESS for use in monitoring severity of the drug reaction, predicting prognosis, and estimating the risk of developing cytomegalovirus disease and its potentially fatal complications. The scoring system incorporates patient factors, including age, duration of drug exposure after symptom onset; rash characteristics, such as percentage of body surface area involved and presence or absence of erythroderma; appetite loss; and laboratory values.

“It yields a prognostic score that can be used to determine treatment choices, such as immediate intervention with anti-CMV agents. It’s a very useful tool,” Dr. Walsh said.

She reported having no financial conflicts regarding her presentation.

[email protected]

The United States is nearly 6 weeks into its historic campaign to vaccinate Americans against the virus that causes COVID-19, and so far, the two vaccines in use look remarkably low risk, according to new data presented today at a meeting of vaccine experts that advise the Centers for Disease Control and Prevention.

With 23.5 million doses of the Pfizer and Moderna vaccines now given, there have been very few serious side effects. In addition, deaths reported after people got the vaccine do not seem to be related to it.

The most common symptoms reported after vaccination were pain where people got the shot, fatigue, headache, and muscle soreness. These were more common after the second dose. In addition, about one in four people reported fever and chills after the second shot.

“On the whole, I thought it was very reassuring,” said William Schaffner, MD, an infectious disease expert with Vanderbilt University, Nashville, Tenn., who listened to the presentations.

The CDC is collecting safety information through multiple channels. These include a new smartphone-based app called V-Safe, which collects daily information from people who’ve been vaccinated; the federal Vaccine Adverse Event Reporting System, which accepts reports from anyone; and the Vaccine Safety Datalink, which is a collaboration between the CDC and nine major hospital systems. There’s also the Clinical Immunization Safety Assessment Project, a collaboration between the CDC and vaccine safety experts.

After surveying these systems, experts heading the safety committee for the CDC’s Advisory Committee on Immunization Practices said there have been few serious side effects reported.

Very rarely, severe allergic reactions – called anaphylaxis – have occurred after vaccination. There have been 50 of these cases reported after the Pfizer vaccine and 21 cases reported after the Moderna vaccine to date. Nearly all of them – 94% of the anaphylaxis cases after Pfizer vaccines and 100% of those after Moderna’s vaccine – have been in women, though it’s not clear why.

That translates to a rate of about five cases of anaphylaxis for every million doses of the Pfizer vaccine and about three for every million doses of the Moderna vaccine. Most of these occur within 15 minutes after getting a vaccine dose, with one reported as long as 20 hours after the shot.

The CDC suspects these may be related to an ingredient called polyethylene glycol (PEG). PEG is a part of the particles that slip the vaccines’ mRNA into cells with instructions to make the spike protein of the virus. Cells then express these spikes on their surfaces so the immune system can learn to recognize them and make defenses against them. PEG is a common ingredient in many drugs and occasionally triggers anaphylaxis.
 

Reported deaths seem unrelated to vaccines

Through Jan. 18, 196 people have died after getting a vaccine.

Most of these deaths (129) were in patients in long term care facilities. These deaths are still being investigated, but when they were compared with the number of deaths that might be expected over the same period because of natural causes, they seemed to be coincidental and not caused by the vaccine, said Tom Shimabukuro, MD, deputy director of the Immunization Safety Office at the CDC, who studied the data.

In fact, death rates were lower among vaccinated nursing home residents, compared with those who had not been vaccinated.

“These findings suggest that short-term mortality rates appear unrelated to vaccination for COVID-19,” Dr. Shimabukuro said.

This also appeared to be true for younger adults who died after their shots.

There were 28 people aged under 65 years who died after being vaccinated. Most of these deaths were heart related, according to autopsy reports. When investigators compared the number of sudden cardiac deaths expected to occur in this population naturally, they found people who were vaccinated had a lower rate than would have been expected without vaccination. This suggests that these deaths were also unrelated to the vaccine.
 

More vaccines on the horizon

The panel also heard an update from drug company AstraZeneca on its vaccine. It’s being used in 18 countries but has not yet been authorized in the United States.

That vaccine is currently in phase 3 of its U.S. clinical trials, and more than 26,000 people who have volunteered to get the shot had received their second dose as of Jan. 21, the company said.

The Food and Drug Administration requires at least 2 months of follow-up before it will evaluate a vaccine for an emergency-use authorization, which means the company would be ready to submit by the end of March, with a possible approval by April.

The AstraZeneca vaccine uses a more traditional method to create immunity, slipping a key part of the virus that causes COVID-19 into the shell of an adenovirus – a virus that causes cold-like symptoms – that normally infects monkeys. When the immune system sees the virus, it generates protective defenses against it.

The two-dose vaccine can be stored in a regular refrigerator for up to 6 months, which makes it easier to handle than the mRNA vaccines, which require much colder storage. Another advantage appears to be that it’s less likely to trigger severe allergic reactions. So far, there have been no cases of anaphylaxis reported after this shot.

In total, four serious side effects have been reported with the AstraZeneca vaccine, including two cases of transverse myelitis, a serious condition that causes swelling of the spinal cord, leading to pain, muscle weakness, and paralysis. One of these was in the group that got the placebo. The reports paused the trial, but it was allowed to continue after a safety review.

This vaccine also appears to be less effective than the mRNA shots. Data presented to the panel show it appears to cut the risk of developing a COVID infection that has symptoms by 62%. That’s over the 50% threshold the FDA set for approval but less than seen with the mRNA vaccines, which are more than 90% effective at preventing infections.

“Is the average person going to want to take the AstraZeneca shot? What role is this going to play in our vaccination program?” Dr. Schaffner said.

Johnson & Johnson will have enough data from its clinical trials to submit it to the FDA within the next week, the company said in a call with shareholders on Tuesday. So far, its one-dose shots looks to be about as effective as both the Pfizer and Moderna vaccines.

“It could be that we wind up with four vaccines: Three that can run very fast, and one that’s not so fast,” Dr. Schaffner said.

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

The United States is nearly 6 weeks into its historic campaign to vaccinate Americans against the virus that causes COVID-19, and so far, the two vaccines in use look remarkably low risk, according to new data presented today at a meeting of vaccine experts that advise the Centers for Disease Control and Prevention.

With 23.5 million doses of the Pfizer and Moderna vaccines now given, there have been very few serious side effects. In addition, deaths reported after people got the vaccine do not seem to be related to it.

The most common symptoms reported after vaccination were pain where people got the shot, fatigue, headache, and muscle soreness. These were more common after the second dose. In addition, about one in four people reported fever and chills after the second shot.

“On the whole, I thought it was very reassuring,” said William Schaffner, MD, an infectious disease expert with Vanderbilt University, Nashville, Tenn., who listened to the presentations.

The CDC is collecting safety information through multiple channels. These include a new smartphone-based app called V-Safe, which collects daily information from people who’ve been vaccinated; the federal Vaccine Adverse Event Reporting System, which accepts reports from anyone; and the Vaccine Safety Datalink, which is a collaboration between the CDC and nine major hospital systems. There’s also the Clinical Immunization Safety Assessment Project, a collaboration between the CDC and vaccine safety experts.

After surveying these systems, experts heading the safety committee for the CDC’s Advisory Committee on Immunization Practices said there have been few serious side effects reported.

Very rarely, severe allergic reactions – called anaphylaxis – have occurred after vaccination. There have been 50 of these cases reported after the Pfizer vaccine and 21 cases reported after the Moderna vaccine to date. Nearly all of them – 94% of the anaphylaxis cases after Pfizer vaccines and 100% of those after Moderna’s vaccine – have been in women, though it’s not clear why.

That translates to a rate of about five cases of anaphylaxis for every million doses of the Pfizer vaccine and about three for every million doses of the Moderna vaccine. Most of these occur within 15 minutes after getting a vaccine dose, with one reported as long as 20 hours after the shot.

The CDC suspects these may be related to an ingredient called polyethylene glycol (PEG). PEG is a part of the particles that slip the vaccines’ mRNA into cells with instructions to make the spike protein of the virus. Cells then express these spikes on their surfaces so the immune system can learn to recognize them and make defenses against them. PEG is a common ingredient in many drugs and occasionally triggers anaphylaxis.
 

Reported deaths seem unrelated to vaccines

Through Jan. 18, 196 people have died after getting a vaccine.

Most of these deaths (129) were in patients in long term care facilities. These deaths are still being investigated, but when they were compared with the number of deaths that might be expected over the same period because of natural causes, they seemed to be coincidental and not caused by the vaccine, said Tom Shimabukuro, MD, deputy director of the Immunization Safety Office at the CDC, who studied the data.

In fact, death rates were lower among vaccinated nursing home residents, compared with those who had not been vaccinated.

“These findings suggest that short-term mortality rates appear unrelated to vaccination for COVID-19,” Dr. Shimabukuro said.

This also appeared to be true for younger adults who died after their shots.

There were 28 people aged under 65 years who died after being vaccinated. Most of these deaths were heart related, according to autopsy reports. When investigators compared the number of sudden cardiac deaths expected to occur in this population naturally, they found people who were vaccinated had a lower rate than would have been expected without vaccination. This suggests that these deaths were also unrelated to the vaccine.
 

More vaccines on the horizon

The panel also heard an update from drug company AstraZeneca on its vaccine. It’s being used in 18 countries but has not yet been authorized in the United States.

That vaccine is currently in phase 3 of its U.S. clinical trials, and more than 26,000 people who have volunteered to get the shot had received their second dose as of Jan. 21, the company said.

The Food and Drug Administration requires at least 2 months of follow-up before it will evaluate a vaccine for an emergency-use authorization, which means the company would be ready to submit by the end of March, with a possible approval by April.

The AstraZeneca vaccine uses a more traditional method to create immunity, slipping a key part of the virus that causes COVID-19 into the shell of an adenovirus – a virus that causes cold-like symptoms – that normally infects monkeys. When the immune system sees the virus, it generates protective defenses against it.

The two-dose vaccine can be stored in a regular refrigerator for up to 6 months, which makes it easier to handle than the mRNA vaccines, which require much colder storage. Another advantage appears to be that it’s less likely to trigger severe allergic reactions. So far, there have been no cases of anaphylaxis reported after this shot.

In total, four serious side effects have been reported with the AstraZeneca vaccine, including two cases of transverse myelitis, a serious condition that causes swelling of the spinal cord, leading to pain, muscle weakness, and paralysis. One of these was in the group that got the placebo. The reports paused the trial, but it was allowed to continue after a safety review.

This vaccine also appears to be less effective than the mRNA shots. Data presented to the panel show it appears to cut the risk of developing a COVID infection that has symptoms by 62%. That’s over the 50% threshold the FDA set for approval but less than seen with the mRNA vaccines, which are more than 90% effective at preventing infections.

“Is the average person going to want to take the AstraZeneca shot? What role is this going to play in our vaccination program?” Dr. Schaffner said.

Johnson & Johnson will have enough data from its clinical trials to submit it to the FDA within the next week, the company said in a call with shareholders on Tuesday. So far, its one-dose shots looks to be about as effective as both the Pfizer and Moderna vaccines.

“It could be that we wind up with four vaccines: Three that can run very fast, and one that’s not so fast,” Dr. Schaffner said.

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

The United States is nearly 6 weeks into its historic campaign to vaccinate Americans against the virus that causes COVID-19, and so far, the two vaccines in use look remarkably low risk, according to new data presented today at a meeting of vaccine experts that advise the Centers for Disease Control and Prevention.

With 23.5 million doses of the Pfizer and Moderna vaccines now given, there have been very few serious side effects. In addition, deaths reported after people got the vaccine do not seem to be related to it.

The most common symptoms reported after vaccination were pain where people got the shot, fatigue, headache, and muscle soreness. These were more common after the second dose. In addition, about one in four people reported fever and chills after the second shot.

“On the whole, I thought it was very reassuring,” said William Schaffner, MD, an infectious disease expert with Vanderbilt University, Nashville, Tenn., who listened to the presentations.

The CDC is collecting safety information through multiple channels. These include a new smartphone-based app called V-Safe, which collects daily information from people who’ve been vaccinated; the federal Vaccine Adverse Event Reporting System, which accepts reports from anyone; and the Vaccine Safety Datalink, which is a collaboration between the CDC and nine major hospital systems. There’s also the Clinical Immunization Safety Assessment Project, a collaboration between the CDC and vaccine safety experts.

After surveying these systems, experts heading the safety committee for the CDC’s Advisory Committee on Immunization Practices said there have been few serious side effects reported.

Very rarely, severe allergic reactions – called anaphylaxis – have occurred after vaccination. There have been 50 of these cases reported after the Pfizer vaccine and 21 cases reported after the Moderna vaccine to date. Nearly all of them – 94% of the anaphylaxis cases after Pfizer vaccines and 100% of those after Moderna’s vaccine – have been in women, though it’s not clear why.

That translates to a rate of about five cases of anaphylaxis for every million doses of the Pfizer vaccine and about three for every million doses of the Moderna vaccine. Most of these occur within 15 minutes after getting a vaccine dose, with one reported as long as 20 hours after the shot.

The CDC suspects these may be related to an ingredient called polyethylene glycol (PEG). PEG is a part of the particles that slip the vaccines’ mRNA into cells with instructions to make the spike protein of the virus. Cells then express these spikes on their surfaces so the immune system can learn to recognize them and make defenses against them. PEG is a common ingredient in many drugs and occasionally triggers anaphylaxis.
 

Reported deaths seem unrelated to vaccines

Through Jan. 18, 196 people have died after getting a vaccine.

Most of these deaths (129) were in patients in long term care facilities. These deaths are still being investigated, but when they were compared with the number of deaths that might be expected over the same period because of natural causes, they seemed to be coincidental and not caused by the vaccine, said Tom Shimabukuro, MD, deputy director of the Immunization Safety Office at the CDC, who studied the data.

In fact, death rates were lower among vaccinated nursing home residents, compared with those who had not been vaccinated.

“These findings suggest that short-term mortality rates appear unrelated to vaccination for COVID-19,” Dr. Shimabukuro said.

This also appeared to be true for younger adults who died after their shots.

There were 28 people aged under 65 years who died after being vaccinated. Most of these deaths were heart related, according to autopsy reports. When investigators compared the number of sudden cardiac deaths expected to occur in this population naturally, they found people who were vaccinated had a lower rate than would have been expected without vaccination. This suggests that these deaths were also unrelated to the vaccine.
 

More vaccines on the horizon

The panel also heard an update from drug company AstraZeneca on its vaccine. It’s being used in 18 countries but has not yet been authorized in the United States.

That vaccine is currently in phase 3 of its U.S. clinical trials, and more than 26,000 people who have volunteered to get the shot had received their second dose as of Jan. 21, the company said.

The Food and Drug Administration requires at least 2 months of follow-up before it will evaluate a vaccine for an emergency-use authorization, which means the company would be ready to submit by the end of March, with a possible approval by April.

The AstraZeneca vaccine uses a more traditional method to create immunity, slipping a key part of the virus that causes COVID-19 into the shell of an adenovirus – a virus that causes cold-like symptoms – that normally infects monkeys. When the immune system sees the virus, it generates protective defenses against it.

The two-dose vaccine can be stored in a regular refrigerator for up to 6 months, which makes it easier to handle than the mRNA vaccines, which require much colder storage. Another advantage appears to be that it’s less likely to trigger severe allergic reactions. So far, there have been no cases of anaphylaxis reported after this shot.

In total, four serious side effects have been reported with the AstraZeneca vaccine, including two cases of transverse myelitis, a serious condition that causes swelling of the spinal cord, leading to pain, muscle weakness, and paralysis. One of these was in the group that got the placebo. The reports paused the trial, but it was allowed to continue after a safety review.

This vaccine also appears to be less effective than the mRNA shots. Data presented to the panel show it appears to cut the risk of developing a COVID infection that has symptoms by 62%. That’s over the 50% threshold the FDA set for approval but less than seen with the mRNA vaccines, which are more than 90% effective at preventing infections.

“Is the average person going to want to take the AstraZeneca shot? What role is this going to play in our vaccination program?” Dr. Schaffner said.

Johnson & Johnson will have enough data from its clinical trials to submit it to the FDA within the next week, the company said in a call with shareholders on Tuesday. So far, its one-dose shots looks to be about as effective as both the Pfizer and Moderna vaccines.

“It could be that we wind up with four vaccines: Three that can run very fast, and one that’s not so fast,” Dr. Schaffner said.

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

The Biden administration is exploring whether factories can be retrofitted to produce more of the Pfizer/BioNTech and Moderna COVID-19 mRNA vaccines to speed up vaccination of the vast majority of Americans.

The announcement comes as the nation is on track to see 479,000-514,000 deaths by the end of February, said Rochelle Walensky, MD, the director of the Centers for Disease Control and Prevention.

Dr. Walensky, speaking to reporters Wednesday in the first briefing from the White House COVID-19 Response Team, said that 1.6 million COVID-19 shots had been administered each day over the past week and that 3.4 million Americans have been fully vaccinated with two doses.

More than 500 million doses will be needed to vaccinate every American older than 16 years, Andy Slavitt, the senior advisor to the COVID-19 response team, told reporters. Pfizer and Moderna are due to deliver an additional 200 million doses near the end of March, and President Biden is seeking to purchase another 200 million doses from the companies, said Mr. Slavitt.

But it may not be enough. Whether companies can retrofit factories to produce vaccines is “something that’s under active exploration,” Mr. Slavitt said.

“This is a national emergency,” said Jeff Zients, the White House COVID-19 response coordinator. “Everything is on the table across the whole supply chain,” he said. He noted that the administration was also buying low-dead-space syringes to help extract an additional sixth dose from every Pfizer vial.

Mr. Slavitt said the team had identified 12 areas in which Mr. Biden was authorized to use the Defense Production Act to spur the manufacture of items such as masks and COVID-19 diagnostics.
 

More sequencing needed

As new variants emerge, vaccine makers and the CDC are racing to stay a step ahead. “RNA viruses mutate all the time – that’s what they do, that’s their business,” said Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases and Mr. Biden’s chief medical adviser, in the briefing.

Three concerning variants have emerged: the B117, which is circulating widely in the United Kingdom; the B1.351 in South Africa; and the P.1 in Brazil. As of Jan. 26, no cases involving the B1.351 variant have been detected in the United States; one person with the P.1 variant was identified in Minnesota. The CDC has identified 308 cases of the U.K. variant in 26 states, said Dr. Walensky.

The United States is dismally behind in surveillance and sequencing of variants, said Zients. “We are 43rd in the world at genomic sequencing,” which he said was “totally unacceptable.”

Dr. Walensky said the CDC is working on improving data collection and sequencing, but she said more money is needed to “do the amount of sequencing and surveillance that we need in order to be able to detect these when they first start to emerge.”

Both she and Mr. Zients called on Congress to pass Mr. Biden’s proposed American Rescue package, which includes more money for sequencing.

Dr. Fauci said the National Institutes of Health was collaborating with the CDC to determine whether other newly emerging variants pose any threat – such as increased transmissibility or lethality or some other functional characteristic. Scientists will also monitor “in real-time” whether current vaccines continue to make neutralizing antibodies against these mutants.

“With the U.K. variant, what we’re seeing is a very slight, if at all, impact on vaccine-induced antibodies and very little impact on anything else,” he said. With the South African variant, there is “a multifold diminution in the in vitro neutralization by vaccine-induced antibodies,” but “it still is well within the cushion of protection” for the current vaccines.

But, he added, “we have to be concerned looking forward of what the further evolution of this might be.” The anti-COVID monoclonal antibodies – bamlanivimab and the combination of casirivimab and imdevimab – are “more seriously inhibited by this South African strain,” which is spurring development of new monoclonals.

Dr. Fauci also noted that the Johnson & Johnson/Janssen vaccine that is in development – for which phase 3 data may be released within days – was tested in South Africa and Brazil in addition to the United States. The comparative data could help researchers and clinicians make better-informed decisions about what vaccine to use if the South African variant “seeds itself in the U.S.”

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

The Biden administration is exploring whether factories can be retrofitted to produce more of the Pfizer/BioNTech and Moderna COVID-19 mRNA vaccines to speed up vaccination of the vast majority of Americans.

The announcement comes as the nation is on track to see 479,000-514,000 deaths by the end of February, said Rochelle Walensky, MD, the director of the Centers for Disease Control and Prevention.

Dr. Walensky, speaking to reporters Wednesday in the first briefing from the White House COVID-19 Response Team, said that 1.6 million COVID-19 shots had been administered each day over the past week and that 3.4 million Americans have been fully vaccinated with two doses.

More than 500 million doses will be needed to vaccinate every American older than 16 years, Andy Slavitt, the senior advisor to the COVID-19 response team, told reporters. Pfizer and Moderna are due to deliver an additional 200 million doses near the end of March, and President Biden is seeking to purchase another 200 million doses from the companies, said Mr. Slavitt.

But it may not be enough. Whether companies can retrofit factories to produce vaccines is “something that’s under active exploration,” Mr. Slavitt said.

“This is a national emergency,” said Jeff Zients, the White House COVID-19 response coordinator. “Everything is on the table across the whole supply chain,” he said. He noted that the administration was also buying low-dead-space syringes to help extract an additional sixth dose from every Pfizer vial.

Mr. Slavitt said the team had identified 12 areas in which Mr. Biden was authorized to use the Defense Production Act to spur the manufacture of items such as masks and COVID-19 diagnostics.
 

More sequencing needed

As new variants emerge, vaccine makers and the CDC are racing to stay a step ahead. “RNA viruses mutate all the time – that’s what they do, that’s their business,” said Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases and Mr. Biden’s chief medical adviser, in the briefing.

Three concerning variants have emerged: the B117, which is circulating widely in the United Kingdom; the B1.351 in South Africa; and the P.1 in Brazil. As of Jan. 26, no cases involving the B1.351 variant have been detected in the United States; one person with the P.1 variant was identified in Minnesota. The CDC has identified 308 cases of the U.K. variant in 26 states, said Dr. Walensky.

The United States is dismally behind in surveillance and sequencing of variants, said Zients. “We are 43rd in the world at genomic sequencing,” which he said was “totally unacceptable.”

Dr. Walensky said the CDC is working on improving data collection and sequencing, but she said more money is needed to “do the amount of sequencing and surveillance that we need in order to be able to detect these when they first start to emerge.”

Both she and Mr. Zients called on Congress to pass Mr. Biden’s proposed American Rescue package, which includes more money for sequencing.

Dr. Fauci said the National Institutes of Health was collaborating with the CDC to determine whether other newly emerging variants pose any threat – such as increased transmissibility or lethality or some other functional characteristic. Scientists will also monitor “in real-time” whether current vaccines continue to make neutralizing antibodies against these mutants.

“With the U.K. variant, what we’re seeing is a very slight, if at all, impact on vaccine-induced antibodies and very little impact on anything else,” he said. With the South African variant, there is “a multifold diminution in the in vitro neutralization by vaccine-induced antibodies,” but “it still is well within the cushion of protection” for the current vaccines.

But, he added, “we have to be concerned looking forward of what the further evolution of this might be.” The anti-COVID monoclonal antibodies – bamlanivimab and the combination of casirivimab and imdevimab – are “more seriously inhibited by this South African strain,” which is spurring development of new monoclonals.

Dr. Fauci also noted that the Johnson & Johnson/Janssen vaccine that is in development – for which phase 3 data may be released within days – was tested in South Africa and Brazil in addition to the United States. The comparative data could help researchers and clinicians make better-informed decisions about what vaccine to use if the South African variant “seeds itself in the U.S.”

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

The Biden administration is exploring whether factories can be retrofitted to produce more of the Pfizer/BioNTech and Moderna COVID-19 mRNA vaccines to speed up vaccination of the vast majority of Americans.

The announcement comes as the nation is on track to see 479,000-514,000 deaths by the end of February, said Rochelle Walensky, MD, the director of the Centers for Disease Control and Prevention.

Dr. Walensky, speaking to reporters Wednesday in the first briefing from the White House COVID-19 Response Team, said that 1.6 million COVID-19 shots had been administered each day over the past week and that 3.4 million Americans have been fully vaccinated with two doses.

More than 500 million doses will be needed to vaccinate every American older than 16 years, Andy Slavitt, the senior advisor to the COVID-19 response team, told reporters. Pfizer and Moderna are due to deliver an additional 200 million doses near the end of March, and President Biden is seeking to purchase another 200 million doses from the companies, said Mr. Slavitt.

But it may not be enough. Whether companies can retrofit factories to produce vaccines is “something that’s under active exploration,” Mr. Slavitt said.

“This is a national emergency,” said Jeff Zients, the White House COVID-19 response coordinator. “Everything is on the table across the whole supply chain,” he said. He noted that the administration was also buying low-dead-space syringes to help extract an additional sixth dose from every Pfizer vial.

Mr. Slavitt said the team had identified 12 areas in which Mr. Biden was authorized to use the Defense Production Act to spur the manufacture of items such as masks and COVID-19 diagnostics.
 

More sequencing needed

As new variants emerge, vaccine makers and the CDC are racing to stay a step ahead. “RNA viruses mutate all the time – that’s what they do, that’s their business,” said Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases and Mr. Biden’s chief medical adviser, in the briefing.

Three concerning variants have emerged: the B117, which is circulating widely in the United Kingdom; the B1.351 in South Africa; and the P.1 in Brazil. As of Jan. 26, no cases involving the B1.351 variant have been detected in the United States; one person with the P.1 variant was identified in Minnesota. The CDC has identified 308 cases of the U.K. variant in 26 states, said Dr. Walensky.

The United States is dismally behind in surveillance and sequencing of variants, said Zients. “We are 43rd in the world at genomic sequencing,” which he said was “totally unacceptable.”

Dr. Walensky said the CDC is working on improving data collection and sequencing, but she said more money is needed to “do the amount of sequencing and surveillance that we need in order to be able to detect these when they first start to emerge.”

Both she and Mr. Zients called on Congress to pass Mr. Biden’s proposed American Rescue package, which includes more money for sequencing.

Dr. Fauci said the National Institutes of Health was collaborating with the CDC to determine whether other newly emerging variants pose any threat – such as increased transmissibility or lethality or some other functional characteristic. Scientists will also monitor “in real-time” whether current vaccines continue to make neutralizing antibodies against these mutants.

“With the U.K. variant, what we’re seeing is a very slight, if at all, impact on vaccine-induced antibodies and very little impact on anything else,” he said. With the South African variant, there is “a multifold diminution in the in vitro neutralization by vaccine-induced antibodies,” but “it still is well within the cushion of protection” for the current vaccines.

But, he added, “we have to be concerned looking forward of what the further evolution of this might be.” The anti-COVID monoclonal antibodies – bamlanivimab and the combination of casirivimab and imdevimab – are “more seriously inhibited by this South African strain,” which is spurring development of new monoclonals.

Dr. Fauci also noted that the Johnson & Johnson/Janssen vaccine that is in development – for which phase 3 data may be released within days – was tested in South Africa and Brazil in addition to the United States. The comparative data could help researchers and clinicians make better-informed decisions about what vaccine to use if the South African variant “seeds itself in the U.S.”

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

Offering a combination of colonoscopy and fecal immunochemical testing (FIT), either in sequence or by choice, may significantly increase participation in colorectal cancer (CRC) screening, according to a prospective study involving more than 12,000 individuals in Poland.

Still, greater participation did not lead to significantly higher rates of advanced disease detection, reported lead author Nastazja Dagny Pilonis, MD, of the Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, and colleagues in Gastroenterology.

According to the investigators, screening programs that offer colonoscopy and FIT are more effective than those that offer colonoscopy alone, but an optimal combination protocol has yet to be established, and some parts of the world still rely upon a single diagnostic method.

“In Europe, CRC screening programs often implement only one screening modality: colonoscopy, sigmoidoscopy, or stool testing, depending on the health care provider,” the investigators wrote in Gastroenterology. They noted, however, that national guidelines in the United States recommend strategies that include more than one screening method. “‘One-size-fits-all’ approaches to CRC screening do not result in satisfactory participation” because of behavioral, cultural, and socioeconomic variation among individuals.

To improve understanding of the best ways to improve participation, the investigators conducted a prospective randomized trial, PICCOLINO, via the Polish Colonoscopy Screening Program. In total, 12,485 eligible individuals aged between 55 and 64 years received postal invitations to participate in CRC screening. Individuals were randomized in a 1:1:1 ratio into one of three mailing protocols, each of which involved an initial invitation, and, if needed, a second invitation that offered the following:

• Control group: colonoscopy, with nonresponders receiving the same invitation again
• Sequential group: colonoscopy, with nonresponders or refusers receiving a second invitation that offered FIT
• Choice group: choice between colonoscopy or FIT, with nonresponders receiving the same invitation again

The primary outcome was participation in screening within 18 weeks of enrollment. The secondary outcome was diagnostic yield for either advanced adenoma or CRC.

Out of the three groups, the control group had the lowest participation rate, at 17.5%, compared with 25.8% for the sequential group and 26.5% for the choice group. Multivariable logistic regression showed that individuals in the sequential and choice groups had 64% and 70% higher rates of participation, respectively. Across all groups, age of 60 years or older predicted 12% higher likelihood of participation; in contrast, location more than 40 kilometers from a testing center was associated with an 18% decrease in participation, compared with individuals who lived less than 20 kilometers away.

While the control and sequential groups had similar rates of colonoscopy participation, at 17.5% and 15.9%, respectively (P = .788), this rate was significantly lower, at 8.5%, in the choice group (P = .001). Conversely, the sequential group had a significantly lower rate of FITs than the choice group, at 9.9% versus 17.9%, respectively (P = .001). Among participants with a positive FIT, diagnostic work-up colonoscopies were performed in 70.0% of those in the sequential group and 73.3% in the choice group, “despite active call-recall efforts.”

Across all invited individuals, advanced disease detection rates were similar across groups, at 1.1% for both the control and the sequential group and 1.2% for the choice group. Among those who were actually screened, the control group had a slightly higher diagnostic yield for advanced neoplasia, at 6.5%, compared with 4.2% in the sequential group and 4.4% in the choice group; however, these differences were not statistically significant. In contrast, significantly more adenomas of any kind were detected in the control and sequential groups (5.6% for both) than the choice group (3.9%) (P < .001).

“Although the strategies which included FIT showed higher participation rates than the strategy of offering colonoscopy alone, these strategies did not result in increased detection rates of advanced neoplasia in the intention to screen analysis,” the investigators wrote. “An absolute increase in participation rates of 8%-10% seems insufficient to translate into higher advanced neoplasia detection at the population level.”

Dr. Pilonis and colleagues also suggested that the relatively low rate of diagnostic colonoscopy after positive FIT contributed to the suboptimal diagnostic yield.

“These rates are unsatisfactory taking into account significant call-recall efforts, but are within the range reported in other studies,” they wrote.

They also wrote that their study compared participation and detection between one-time colonoscopy and one-time screening strategies combining colonoscopy and FIT. In acknowledging this, they noted that these approaches have different screening intervals and uptake over time: “FIT has been shown to achieve higher participation rates than colonoscopy for one time screening, but its uptake over several rounds may not be superior to one time colonoscopy.” Furthermore, detection rates of the sequential or choice strategies for advanced disease may rise over time with further implementation, so the one-time screening may not be sufficient to reveal what could become significant differences.

The study was funded by the Polish Ministry of Health, the Polish Foundation of Gastroenterology, and the Centre of Postgraduate Medical Education in Warsaw. FITs, materials, and reagents were provided by Eiken Chemical. The investigators disclosed relationships with Boston Scientific, AbbVie, Olympus, and others.

Offering a combination of colonoscopy and fecal immunochemical testing (FIT), either in sequence or by choice, may significantly increase participation in colorectal cancer (CRC) screening, according to a prospective study involving more than 12,000 individuals in Poland.

Still, greater participation did not lead to significantly higher rates of advanced disease detection, reported lead author Nastazja Dagny Pilonis, MD, of the Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, and colleagues in Gastroenterology.

According to the investigators, screening programs that offer colonoscopy and FIT are more effective than those that offer colonoscopy alone, but an optimal combination protocol has yet to be established, and some parts of the world still rely upon a single diagnostic method.

“In Europe, CRC screening programs often implement only one screening modality: colonoscopy, sigmoidoscopy, or stool testing, depending on the health care provider,” the investigators wrote in Gastroenterology. They noted, however, that national guidelines in the United States recommend strategies that include more than one screening method. “‘One-size-fits-all’ approaches to CRC screening do not result in satisfactory participation” because of behavioral, cultural, and socioeconomic variation among individuals.

To improve understanding of the best ways to improve participation, the investigators conducted a prospective randomized trial, PICCOLINO, via the Polish Colonoscopy Screening Program. In total, 12,485 eligible individuals aged between 55 and 64 years received postal invitations to participate in CRC screening. Individuals were randomized in a 1:1:1 ratio into one of three mailing protocols, each of which involved an initial invitation, and, if needed, a second invitation that offered the following:

• Control group: colonoscopy, with nonresponders receiving the same invitation again
• Sequential group: colonoscopy, with nonresponders or refusers receiving a second invitation that offered FIT
• Choice group: choice between colonoscopy or FIT, with nonresponders receiving the same invitation again

The primary outcome was participation in screening within 18 weeks of enrollment. The secondary outcome was diagnostic yield for either advanced adenoma or CRC.

Out of the three groups, the control group had the lowest participation rate, at 17.5%, compared with 25.8% for the sequential group and 26.5% for the choice group. Multivariable logistic regression showed that individuals in the sequential and choice groups had 64% and 70% higher rates of participation, respectively. Across all groups, age of 60 years or older predicted 12% higher likelihood of participation; in contrast, location more than 40 kilometers from a testing center was associated with an 18% decrease in participation, compared with individuals who lived less than 20 kilometers away.

While the control and sequential groups had similar rates of colonoscopy participation, at 17.5% and 15.9%, respectively (P = .788), this rate was significantly lower, at 8.5%, in the choice group (P = .001). Conversely, the sequential group had a significantly lower rate of FITs than the choice group, at 9.9% versus 17.9%, respectively (P = .001). Among participants with a positive FIT, diagnostic work-up colonoscopies were performed in 70.0% of those in the sequential group and 73.3% in the choice group, “despite active call-recall efforts.”

Across all invited individuals, advanced disease detection rates were similar across groups, at 1.1% for both the control and the sequential group and 1.2% for the choice group. Among those who were actually screened, the control group had a slightly higher diagnostic yield for advanced neoplasia, at 6.5%, compared with 4.2% in the sequential group and 4.4% in the choice group; however, these differences were not statistically significant. In contrast, significantly more adenomas of any kind were detected in the control and sequential groups (5.6% for both) than the choice group (3.9%) (P < .001).

“Although the strategies which included FIT showed higher participation rates than the strategy of offering colonoscopy alone, these strategies did not result in increased detection rates of advanced neoplasia in the intention to screen analysis,” the investigators wrote. “An absolute increase in participation rates of 8%-10% seems insufficient to translate into higher advanced neoplasia detection at the population level.”

Dr. Pilonis and colleagues also suggested that the relatively low rate of diagnostic colonoscopy after positive FIT contributed to the suboptimal diagnostic yield.

“These rates are unsatisfactory taking into account significant call-recall efforts, but are within the range reported in other studies,” they wrote.

They also wrote that their study compared participation and detection between one-time colonoscopy and one-time screening strategies combining colonoscopy and FIT. In acknowledging this, they noted that these approaches have different screening intervals and uptake over time: “FIT has been shown to achieve higher participation rates than colonoscopy for one time screening, but its uptake over several rounds may not be superior to one time colonoscopy.” Furthermore, detection rates of the sequential or choice strategies for advanced disease may rise over time with further implementation, so the one-time screening may not be sufficient to reveal what could become significant differences.

The study was funded by the Polish Ministry of Health, the Polish Foundation of Gastroenterology, and the Centre of Postgraduate Medical Education in Warsaw. FITs, materials, and reagents were provided by Eiken Chemical. The investigators disclosed relationships with Boston Scientific, AbbVie, Olympus, and others.

Offering a combination of colonoscopy and fecal immunochemical testing (FIT), either in sequence or by choice, may significantly increase participation in colorectal cancer (CRC) screening, according to a prospective study involving more than 12,000 individuals in Poland.

Still, greater participation did not lead to significantly higher rates of advanced disease detection, reported lead author Nastazja Dagny Pilonis, MD, of the Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, and colleagues in Gastroenterology.

According to the investigators, screening programs that offer colonoscopy and FIT are more effective than those that offer colonoscopy alone, but an optimal combination protocol has yet to be established, and some parts of the world still rely upon a single diagnostic method.

“In Europe, CRC screening programs often implement only one screening modality: colonoscopy, sigmoidoscopy, or stool testing, depending on the health care provider,” the investigators wrote in Gastroenterology. They noted, however, that national guidelines in the United States recommend strategies that include more than one screening method. “‘One-size-fits-all’ approaches to CRC screening do not result in satisfactory participation” because of behavioral, cultural, and socioeconomic variation among individuals.

To improve understanding of the best ways to improve participation, the investigators conducted a prospective randomized trial, PICCOLINO, via the Polish Colonoscopy Screening Program. In total, 12,485 eligible individuals aged between 55 and 64 years received postal invitations to participate in CRC screening. Individuals were randomized in a 1:1:1 ratio into one of three mailing protocols, each of which involved an initial invitation, and, if needed, a second invitation that offered the following:

• Control group: colonoscopy, with nonresponders receiving the same invitation again
• Sequential group: colonoscopy, with nonresponders or refusers receiving a second invitation that offered FIT
• Choice group: choice between colonoscopy or FIT, with nonresponders receiving the same invitation again

The primary outcome was participation in screening within 18 weeks of enrollment. The secondary outcome was diagnostic yield for either advanced adenoma or CRC.

Out of the three groups, the control group had the lowest participation rate, at 17.5%, compared with 25.8% for the sequential group and 26.5% for the choice group. Multivariable logistic regression showed that individuals in the sequential and choice groups had 64% and 70% higher rates of participation, respectively. Across all groups, age of 60 years or older predicted 12% higher likelihood of participation; in contrast, location more than 40 kilometers from a testing center was associated with an 18% decrease in participation, compared with individuals who lived less than 20 kilometers away.

While the control and sequential groups had similar rates of colonoscopy participation, at 17.5% and 15.9%, respectively (P = .788), this rate was significantly lower, at 8.5%, in the choice group (P = .001). Conversely, the sequential group had a significantly lower rate of FITs than the choice group, at 9.9% versus 17.9%, respectively (P = .001). Among participants with a positive FIT, diagnostic work-up colonoscopies were performed in 70.0% of those in the sequential group and 73.3% in the choice group, “despite active call-recall efforts.”

Across all invited individuals, advanced disease detection rates were similar across groups, at 1.1% for both the control and the sequential group and 1.2% for the choice group. Among those who were actually screened, the control group had a slightly higher diagnostic yield for advanced neoplasia, at 6.5%, compared with 4.2% in the sequential group and 4.4% in the choice group; however, these differences were not statistically significant. In contrast, significantly more adenomas of any kind were detected in the control and sequential groups (5.6% for both) than the choice group (3.9%) (P < .001).

“Although the strategies which included FIT showed higher participation rates than the strategy of offering colonoscopy alone, these strategies did not result in increased detection rates of advanced neoplasia in the intention to screen analysis,” the investigators wrote. “An absolute increase in participation rates of 8%-10% seems insufficient to translate into higher advanced neoplasia detection at the population level.”

Dr. Pilonis and colleagues also suggested that the relatively low rate of diagnostic colonoscopy after positive FIT contributed to the suboptimal diagnostic yield.

“These rates are unsatisfactory taking into account significant call-recall efforts, but are within the range reported in other studies,” they wrote.

They also wrote that their study compared participation and detection between one-time colonoscopy and one-time screening strategies combining colonoscopy and FIT. In acknowledging this, they noted that these approaches have different screening intervals and uptake over time: “FIT has been shown to achieve higher participation rates than colonoscopy for one time screening, but its uptake over several rounds may not be superior to one time colonoscopy.” Furthermore, detection rates of the sequential or choice strategies for advanced disease may rise over time with further implementation, so the one-time screening may not be sufficient to reveal what could become significant differences.

The study was funded by the Polish Ministry of Health, the Polish Foundation of Gastroenterology, and the Centre of Postgraduate Medical Education in Warsaw. FITs, materials, and reagents were provided by Eiken Chemical. The investigators disclosed relationships with Boston Scientific, AbbVie, Olympus, and others.

Cosmetic procedures continued to increase in popularity in 2019, and body sculpting and laser/light/energy-based procedures led the way, according to a survey by the American Society of Dermatologic Surgery.

The number of cosmetic procedures performed by dermatologic surgeons increased by 14% from 2018 to 2019, with body-sculpting procedures jumping by almost 62%, the largest proportional rise among the major categories of cosmetic procedures, the ASDS reported in its annual member survey.

Use of laser/light/energy-based devices was up by a much lower 18%, but the increase in the actual number of procedures – nearly 637,000 more than 2018 – was larger than any other category, the ASDS said.

Procedures categorized as “other rejuvenation” – microneedling, platelet-rich plasma, hair rejuvenation, and thread lifts – were another bright spot in the cosmetic lineup in 2019, rising 38% over their 2018 volume. Injectable neuromodulator treatments, which were second in overall volume with almost 2.4 million procedures, were up by 12.5% in 2019, compared with 2018, the ASDS said.

The injectable soft-tissue fillers, however, did not produce any noteworthy gain in the volume of procedures for the second consecutive year. Meanwhile, the number of chemical peel procedures dropped by almost 16% in 2019 after rising for the last 2 years, the ASDS reported.

A closer look at the body-sculpting sector also shows some declines in 2019, despite the overall success: Cryolipolysis procedures were down by 10.3% and deoxycholic acid procedures slipped 13.7%. The biggest addition – over 157,000 procedures – came from muscle-toning devices, which were new to the survey last year, the ASDS noted.

The survey was conducted among the society’s members from May 7 to July 31, 2020, and the 514 responses were generalized to the entire ASDS membership of over 6,400 physicians.

[email protected]

Cosmetic procedures continued to increase in popularity in 2019, and body sculpting and laser/light/energy-based procedures led the way, according to a survey by the American Society of Dermatologic Surgery.

The number of cosmetic procedures performed by dermatologic surgeons increased by 14% from 2018 to 2019, with body-sculpting procedures jumping by almost 62%, the largest proportional rise among the major categories of cosmetic procedures, the ASDS reported in its annual member survey.

Use of laser/light/energy-based devices was up by a much lower 18%, but the increase in the actual number of procedures – nearly 637,000 more than 2018 – was larger than any other category, the ASDS said.

Procedures categorized as “other rejuvenation” – microneedling, platelet-rich plasma, hair rejuvenation, and thread lifts – were another bright spot in the cosmetic lineup in 2019, rising 38% over their 2018 volume. Injectable neuromodulator treatments, which were second in overall volume with almost 2.4 million procedures, were up by 12.5% in 2019, compared with 2018, the ASDS said.

The injectable soft-tissue fillers, however, did not produce any noteworthy gain in the volume of procedures for the second consecutive year. Meanwhile, the number of chemical peel procedures dropped by almost 16% in 2019 after rising for the last 2 years, the ASDS reported.

A closer look at the body-sculpting sector also shows some declines in 2019, despite the overall success: Cryolipolysis procedures were down by 10.3% and deoxycholic acid procedures slipped 13.7%. The biggest addition – over 157,000 procedures – came from muscle-toning devices, which were new to the survey last year, the ASDS noted.

The survey was conducted among the society’s members from May 7 to July 31, 2020, and the 514 responses were generalized to the entire ASDS membership of over 6,400 physicians.

[email protected]

Cosmetic procedures continued to increase in popularity in 2019, and body sculpting and laser/light/energy-based procedures led the way, according to a survey by the American Society of Dermatologic Surgery.

The number of cosmetic procedures performed by dermatologic surgeons increased by 14% from 2018 to 2019, with body-sculpting procedures jumping by almost 62%, the largest proportional rise among the major categories of cosmetic procedures, the ASDS reported in its annual member survey.

Use of laser/light/energy-based devices was up by a much lower 18%, but the increase in the actual number of procedures – nearly 637,000 more than 2018 – was larger than any other category, the ASDS said.

Procedures categorized as “other rejuvenation” – microneedling, platelet-rich plasma, hair rejuvenation, and thread lifts – were another bright spot in the cosmetic lineup in 2019, rising 38% over their 2018 volume. Injectable neuromodulator treatments, which were second in overall volume with almost 2.4 million procedures, were up by 12.5% in 2019, compared with 2018, the ASDS said.

The injectable soft-tissue fillers, however, did not produce any noteworthy gain in the volume of procedures for the second consecutive year. Meanwhile, the number of chemical peel procedures dropped by almost 16% in 2019 after rising for the last 2 years, the ASDS reported.

A closer look at the body-sculpting sector also shows some declines in 2019, despite the overall success: Cryolipolysis procedures were down by 10.3% and deoxycholic acid procedures slipped 13.7%. The biggest addition – over 157,000 procedures – came from muscle-toning devices, which were new to the survey last year, the ASDS noted.

The survey was conducted among the society’s members from May 7 to July 31, 2020, and the 514 responses were generalized to the entire ASDS membership of over 6,400 physicians.

[email protected]

A follow-up look at an international registry suggests that some people may have persistent, long-lasting dermatologic manifestations – especially so-called “COVID toes” – as a result of infection with or exposure to the SARS-CoV-2 virus, but some dermatologists question if the skin signs and symptoms are truly related.

In their commentary in the Lancet Infectious Diseases, Esther P. Freeman, MD, PhD, and colleagues who lead and participate in the American Academy of Dermatology’s international registry said their analysis “revealed a previously unreported subset of patients who experience long-haul symptoms in dermatology-dominant COVID-19.”

Some of the data was presented at the 29th European Academy of Dermatology and Venereology in late October 2020, but has since been updated with more cases.

Dermatologists who spoke with this news organization said it has not been settled that some skin manifestations – such as pernio/chilblains rashes, seen primarily in nonhospitalized patients, and described in the registry – are definitively caused by COVID. They also noted that in some cases, patients who initially test negative for COVID-19 by polymerase chain reaction (PCR) sometimes do not ever develop antibodies, which could mean they were never actually exposed to SARS-CoV-2.

M. Alexander Otto/MDedge News

“I still question whether the perniosis is directly related to infection with SARS-CoV-2 or not,” said Anthony Fernandez, MD, PhD, director of medical and inpatient dermatology and assistant professor of dermatopathology at the Cleveland Clinic. His uncertainty is driven by the lack of seroconversion and that few cases were seen over the summer in the United States – suggesting that it may still be a result of cold temperatures.

“I’m not sure there is a definitive correct answer, definitely not that everyone would agree on,” said Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn.

Dr. Freeman, however, believed that pernio and especially persistent lesions are caused by an immune response to COVID.

In an interview, she noted the multiple cases of patients in the registry who did seroconvert and that, while a registry is not a perfect means of getting an answer, it is good for generating questions. Taken collectively, the cases in the registry can “tell a story for further hypotheses,” said Dr. Freeman, who is director of global health dermatology at Massachusetts General Hospital and assistant professor of dermatology at Harvard University, both in Boston.

“We were noticing this signal across the world” that patients “developed these toe lesions and they never got better,” said Dr. Freeman. Generally, people who experience pernio, also described as COVID toes or “COVID fingers,” recover in 4-8 weeks. But in the registry, “we did have this subset of patients who really were experiencing these very longstanding symptoms,” she added.

Two patients with lab-confirmed COVID have had long-lasting pernio of 133 days and 150 days. “I’m caring for a cohort in Boston who have had long COVID of the skin and symptoms for over 10 months,” Dr. Freeman said.
 

Pernio dominates

The registry – a collaboration between the AAD and the International League of Dermatological Societies – was launched in April 2020. Any medical professional can enter case information. From April to October, 1,030 total cases and 331 laboratory-confirmed or suspected COVID-19 cases with dermatological manifestations were entered from 41 countries.

Most of the cases were just recorded at a single time point, which is an acknowledged limitation of the study.

Dr. Freeman and colleagues reached out to registry participants in June and August to get updates on COVID lab test results and sign and symptom duration. Overall, 234 total and 96 lab-confirmed COVID infections had more lengthy data about sign and symptom duration.

Pernio lasted a median of 15 days in patients with suspected disease and 12 days for those with lab-confirmed COVID, compared with a median of 7 days for morbilliform eruptions, 4 days for urticarial eruptions, and 20 days for papulosquamous eruptions – all in patients with lab-confirmed disease.

Of the 103 cases of pernio, 7 had symptoms lasting more than 60 days. Only two of those seven patients had lab-confirmed COVID. Initially, the one patient tested negative with nasopharyngeal PCR, and serum IgM and IgG. Six weeks after pernio onset, the patient – still experiencing fatigue and pernio – seroconverted to anti–SARS-CoV-2 IgM positivity.

The other long-haul patient, after a negative PCR, tested positive for SARS-CoV-2 serum IgG 1 month after pernio onset.

Robust immune response?

Dr. Freeman said these patients might have a very high interferon response initially to the virus, which makes for a mild to nonexistent disease, but could create inflammation elsewhere. “I almost view the toes as an innocent bystander of a robust immune response to SARS-CoV-2.”

Although he has not seen extended pernio or other skin manifestations in his patients, Dr. Fernandez said the interferon hypothesis is “fair,” and “the best that’s out there.” Dr. Fernandez is currently studying cutaneous manifestations of COVID-19 as a principal investigator of a trial sponsored by the Clinical and Translational Science Collaborative of Cleveland.

Dr. Ko said in an interview that she has not observed long-haul skin issues in her patients, but Yale colleagues have.

In a study, she and Yale colleagues published in September, SARS-CoV-2 spike protein was detected in perniotic lesions, but not nuclear protein or viral RNA. The test they used – immunohistochemistry – can be nonspecific, which muddied results.

She does not think there is replicating virus in the skin or the lesions. Instead, said Dr. Ko, “either there is viral spike protein that has somehow become disassociated from actively replicating virus that somehow got deposited in endothelial cells,” or the staining “was spurious,” or some other protein is cross-reacting. “And the people who are unlucky enough to have that protein in their endothelial cells can manifest this COVID-toe, COVID-finger phenomenon.”

To her, it’s an unsolved mystery. “The weird thing is, we’ve never before had this much perniosis,” Dr. Ko said.

Dr. Fernandez is not convinced yet, noting that, in Cleveland, more pernio cases were observed in March and April than in the summer. “If it is a manifestation of the infection then you also need the right environment, the cold weather for this manifestation to present,” he said. “Or, it really isn’t a direct manifestation of COVID-19 but may be more related to other factors,” such as lifestyle changes related to limitations implemented to help mitigate the spread of the disease.

“To me the jury is still out whether or not the perniotic lesions really can tell us something about a patient’s exposure and infection with SARS-CoV-2,” he said.

Dr. Freeman reported receiving a grant from the International League of Dermatological Societies and nonfinancial support from the AAD for the study. Dr. Ko reported no conflicts. Dr. Fernadnez had no disclosures.

A follow-up look at an international registry suggests that some people may have persistent, long-lasting dermatologic manifestations – especially so-called “COVID toes” – as a result of infection with or exposure to the SARS-CoV-2 virus, but some dermatologists question if the skin signs and symptoms are truly related.

In their commentary in the Lancet Infectious Diseases, Esther P. Freeman, MD, PhD, and colleagues who lead and participate in the American Academy of Dermatology’s international registry said their analysis “revealed a previously unreported subset of patients who experience long-haul symptoms in dermatology-dominant COVID-19.”

Some of the data was presented at the 29th European Academy of Dermatology and Venereology in late October 2020, but has since been updated with more cases.

Dermatologists who spoke with this news organization said it has not been settled that some skin manifestations – such as pernio/chilblains rashes, seen primarily in nonhospitalized patients, and described in the registry – are definitively caused by COVID. They also noted that in some cases, patients who initially test negative for COVID-19 by polymerase chain reaction (PCR) sometimes do not ever develop antibodies, which could mean they were never actually exposed to SARS-CoV-2.

M. Alexander Otto/MDedge News

“I still question whether the perniosis is directly related to infection with SARS-CoV-2 or not,” said Anthony Fernandez, MD, PhD, director of medical and inpatient dermatology and assistant professor of dermatopathology at the Cleveland Clinic. His uncertainty is driven by the lack of seroconversion and that few cases were seen over the summer in the United States – suggesting that it may still be a result of cold temperatures.

“I’m not sure there is a definitive correct answer, definitely not that everyone would agree on,” said Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn.

Dr. Freeman, however, believed that pernio and especially persistent lesions are caused by an immune response to COVID.

In an interview, she noted the multiple cases of patients in the registry who did seroconvert and that, while a registry is not a perfect means of getting an answer, it is good for generating questions. Taken collectively, the cases in the registry can “tell a story for further hypotheses,” said Dr. Freeman, who is director of global health dermatology at Massachusetts General Hospital and assistant professor of dermatology at Harvard University, both in Boston.

“We were noticing this signal across the world” that patients “developed these toe lesions and they never got better,” said Dr. Freeman. Generally, people who experience pernio, also described as COVID toes or “COVID fingers,” recover in 4-8 weeks. But in the registry, “we did have this subset of patients who really were experiencing these very longstanding symptoms,” she added.

Two patients with lab-confirmed COVID have had long-lasting pernio of 133 days and 150 days. “I’m caring for a cohort in Boston who have had long COVID of the skin and symptoms for over 10 months,” Dr. Freeman said.
 

Pernio dominates

The registry – a collaboration between the AAD and the International League of Dermatological Societies – was launched in April 2020. Any medical professional can enter case information. From April to October, 1,030 total cases and 331 laboratory-confirmed or suspected COVID-19 cases with dermatological manifestations were entered from 41 countries.

Most of the cases were just recorded at a single time point, which is an acknowledged limitation of the study.

Dr. Freeman and colleagues reached out to registry participants in June and August to get updates on COVID lab test results and sign and symptom duration. Overall, 234 total and 96 lab-confirmed COVID infections had more lengthy data about sign and symptom duration.

Pernio lasted a median of 15 days in patients with suspected disease and 12 days for those with lab-confirmed COVID, compared with a median of 7 days for morbilliform eruptions, 4 days for urticarial eruptions, and 20 days for papulosquamous eruptions – all in patients with lab-confirmed disease.

Of the 103 cases of pernio, 7 had symptoms lasting more than 60 days. Only two of those seven patients had lab-confirmed COVID. Initially, the one patient tested negative with nasopharyngeal PCR, and serum IgM and IgG. Six weeks after pernio onset, the patient – still experiencing fatigue and pernio – seroconverted to anti–SARS-CoV-2 IgM positivity.

The other long-haul patient, after a negative PCR, tested positive for SARS-CoV-2 serum IgG 1 month after pernio onset.

Robust immune response?

Dr. Freeman said these patients might have a very high interferon response initially to the virus, which makes for a mild to nonexistent disease, but could create inflammation elsewhere. “I almost view the toes as an innocent bystander of a robust immune response to SARS-CoV-2.”

Although he has not seen extended pernio or other skin manifestations in his patients, Dr. Fernandez said the interferon hypothesis is “fair,” and “the best that’s out there.” Dr. Fernandez is currently studying cutaneous manifestations of COVID-19 as a principal investigator of a trial sponsored by the Clinical and Translational Science Collaborative of Cleveland.

Dr. Ko said in an interview that she has not observed long-haul skin issues in her patients, but Yale colleagues have.

In a study, she and Yale colleagues published in September, SARS-CoV-2 spike protein was detected in perniotic lesions, but not nuclear protein or viral RNA. The test they used – immunohistochemistry – can be nonspecific, which muddied results.

She does not think there is replicating virus in the skin or the lesions. Instead, said Dr. Ko, “either there is viral spike protein that has somehow become disassociated from actively replicating virus that somehow got deposited in endothelial cells,” or the staining “was spurious,” or some other protein is cross-reacting. “And the people who are unlucky enough to have that protein in their endothelial cells can manifest this COVID-toe, COVID-finger phenomenon.”

To her, it’s an unsolved mystery. “The weird thing is, we’ve never before had this much perniosis,” Dr. Ko said.

Dr. Fernandez is not convinced yet, noting that, in Cleveland, more pernio cases were observed in March and April than in the summer. “If it is a manifestation of the infection then you also need the right environment, the cold weather for this manifestation to present,” he said. “Or, it really isn’t a direct manifestation of COVID-19 but may be more related to other factors,” such as lifestyle changes related to limitations implemented to help mitigate the spread of the disease.

“To me the jury is still out whether or not the perniotic lesions really can tell us something about a patient’s exposure and infection with SARS-CoV-2,” he said.

Dr. Freeman reported receiving a grant from the International League of Dermatological Societies and nonfinancial support from the AAD for the study. Dr. Ko reported no conflicts. Dr. Fernadnez had no disclosures.

A follow-up look at an international registry suggests that some people may have persistent, long-lasting dermatologic manifestations – especially so-called “COVID toes” – as a result of infection with or exposure to the SARS-CoV-2 virus, but some dermatologists question if the skin signs and symptoms are truly related.

In their commentary in the Lancet Infectious Diseases, Esther P. Freeman, MD, PhD, and colleagues who lead and participate in the American Academy of Dermatology’s international registry said their analysis “revealed a previously unreported subset of patients who experience long-haul symptoms in dermatology-dominant COVID-19.”

Some of the data was presented at the 29th European Academy of Dermatology and Venereology in late October 2020, but has since been updated with more cases.

Dermatologists who spoke with this news organization said it has not been settled that some skin manifestations – such as pernio/chilblains rashes, seen primarily in nonhospitalized patients, and described in the registry – are definitively caused by COVID. They also noted that in some cases, patients who initially test negative for COVID-19 by polymerase chain reaction (PCR) sometimes do not ever develop antibodies, which could mean they were never actually exposed to SARS-CoV-2.

M. Alexander Otto/MDedge News

“I still question whether the perniosis is directly related to infection with SARS-CoV-2 or not,” said Anthony Fernandez, MD, PhD, director of medical and inpatient dermatology and assistant professor of dermatopathology at the Cleveland Clinic. His uncertainty is driven by the lack of seroconversion and that few cases were seen over the summer in the United States – suggesting that it may still be a result of cold temperatures.

“I’m not sure there is a definitive correct answer, definitely not that everyone would agree on,” said Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn.

Dr. Freeman, however, believed that pernio and especially persistent lesions are caused by an immune response to COVID.

In an interview, she noted the multiple cases of patients in the registry who did seroconvert and that, while a registry is not a perfect means of getting an answer, it is good for generating questions. Taken collectively, the cases in the registry can “tell a story for further hypotheses,” said Dr. Freeman, who is director of global health dermatology at Massachusetts General Hospital and assistant professor of dermatology at Harvard University, both in Boston.

“We were noticing this signal across the world” that patients “developed these toe lesions and they never got better,” said Dr. Freeman. Generally, people who experience pernio, also described as COVID toes or “COVID fingers,” recover in 4-8 weeks. But in the registry, “we did have this subset of patients who really were experiencing these very longstanding symptoms,” she added.

Two patients with lab-confirmed COVID have had long-lasting pernio of 133 days and 150 days. “I’m caring for a cohort in Boston who have had long COVID of the skin and symptoms for over 10 months,” Dr. Freeman said.
 

Pernio dominates

The registry – a collaboration between the AAD and the International League of Dermatological Societies – was launched in April 2020. Any medical professional can enter case information. From April to October, 1,030 total cases and 331 laboratory-confirmed or suspected COVID-19 cases with dermatological manifestations were entered from 41 countries.

Most of the cases were just recorded at a single time point, which is an acknowledged limitation of the study.

Dr. Freeman and colleagues reached out to registry participants in June and August to get updates on COVID lab test results and sign and symptom duration. Overall, 234 total and 96 lab-confirmed COVID infections had more lengthy data about sign and symptom duration.

Pernio lasted a median of 15 days in patients with suspected disease and 12 days for those with lab-confirmed COVID, compared with a median of 7 days for morbilliform eruptions, 4 days for urticarial eruptions, and 20 days for papulosquamous eruptions – all in patients with lab-confirmed disease.

Of the 103 cases of pernio, 7 had symptoms lasting more than 60 days. Only two of those seven patients had lab-confirmed COVID. Initially, the one patient tested negative with nasopharyngeal PCR, and serum IgM and IgG. Six weeks after pernio onset, the patient – still experiencing fatigue and pernio – seroconverted to anti–SARS-CoV-2 IgM positivity.

The other long-haul patient, after a negative PCR, tested positive for SARS-CoV-2 serum IgG 1 month after pernio onset.

Robust immune response?

Dr. Freeman said these patients might have a very high interferon response initially to the virus, which makes for a mild to nonexistent disease, but could create inflammation elsewhere. “I almost view the toes as an innocent bystander of a robust immune response to SARS-CoV-2.”

Although he has not seen extended pernio or other skin manifestations in his patients, Dr. Fernandez said the interferon hypothesis is “fair,” and “the best that’s out there.” Dr. Fernandez is currently studying cutaneous manifestations of COVID-19 as a principal investigator of a trial sponsored by the Clinical and Translational Science Collaborative of Cleveland.

Dr. Ko said in an interview that she has not observed long-haul skin issues in her patients, but Yale colleagues have.

In a study, she and Yale colleagues published in September, SARS-CoV-2 spike protein was detected in perniotic lesions, but not nuclear protein or viral RNA. The test they used – immunohistochemistry – can be nonspecific, which muddied results.

She does not think there is replicating virus in the skin or the lesions. Instead, said Dr. Ko, “either there is viral spike protein that has somehow become disassociated from actively replicating virus that somehow got deposited in endothelial cells,” or the staining “was spurious,” or some other protein is cross-reacting. “And the people who are unlucky enough to have that protein in their endothelial cells can manifest this COVID-toe, COVID-finger phenomenon.”

To her, it’s an unsolved mystery. “The weird thing is, we’ve never before had this much perniosis,” Dr. Ko said.

Dr. Fernandez is not convinced yet, noting that, in Cleveland, more pernio cases were observed in March and April than in the summer. “If it is a manifestation of the infection then you also need the right environment, the cold weather for this manifestation to present,” he said. “Or, it really isn’t a direct manifestation of COVID-19 but may be more related to other factors,” such as lifestyle changes related to limitations implemented to help mitigate the spread of the disease.

“To me the jury is still out whether or not the perniotic lesions really can tell us something about a patient’s exposure and infection with SARS-CoV-2,” he said.

Dr. Freeman reported receiving a grant from the International League of Dermatological Societies and nonfinancial support from the AAD for the study. Dr. Ko reported no conflicts. Dr. Fernadnez had no disclosures.

Naltrexone reduces the risk for hospitalization for alcohol use disorder (AUD), regardless of whether it is used alone or in conjunction with disulfiram or acamprosate, research suggests.

Katarzyna Bialasiewicz/Thinkstock

Investigators analyzed 10-year data on more than 125,000 Swedish residents with AUD and found that naltrexone, used as monotherapy or combined with acamprosate or disulfiram, was associated with significantly lower risk for AUD hospitalization or all-cause hospitalization in comparison with patients who did not use AUD medication. The patients ranged in age from 16 to 64 years.

By contrast, benzodiazepines and acamprosate monotherapy were associated with increased risk for AUD hospitalization.

“The take-home message for practicing clinicians would be that especially naltrexone use is associated with favorable treatment outcomes and should be utilized as part of the treatment protocol for AUD,” study investigator Milja Heikkinen, MD, specialist in forensic psychiatry and addiction medicine, University of Eastern Finland, Kuopio, told this news organization.

On the other hand, “benzodiazepines should be avoided and should not be administered other than for alcohol withdrawal symptoms,” she said.

The study was published online Jan. 4 in Addiction.
 

Real-world data

Previous research has shown that disulfiram, acamprosate, naltrexone, and nalmefene are efficacious in treating AUD, but most studies have been randomized controlled trials or meta-analyses, the authors write.

“Very little is known about overall health outcomes (such as risks of hospitalization and mortality) associated with specific treatments in real-world circumstances,” they write.

“The study was motivated by the fact that, although AUD is a significant public health concern, very little is known, especially about the comparative effectiveness of medications indicated in AUD,” said Dr. Heikkinen.

To investigate, the researchers drew on data from several large nationwide Swedish registers that encompassed 125,556 patients who had been diagnosed with AUD (62.5% men; mean [standard deviation] age, 38.1 [15.9] years). They followed the cohort over a median of 4.6 years (interquartile range, 2.1-.2 years).

During the follow-up period, roughly one-fourth of patients (25.6) underwent treatment with one or more drugs.

AUD pharmacotherapy ‘underutilized’

Close to one-fourth of patients (23.9%) experienced the main outcome event (AUD-related hospitalization) during the follow-up period.

The within-individual analysis showed that naltrexone – whether used as monotherapy or adjunctively with disulfiram or acamprosate – “was associated with a significantly lower risk of AUD-related hospitalization, compared to those time periods in which the same individual did not use any AUD medication,” the authors report.

By contrast, they state, acamprosate monotherapy and benzodiazepines were associated with a significantly higher risk for AUD-related hospitalization.

‘Ravages’ of benzodiazepines

Commenting on the study in an interview, John Krystal, MD, professor and chair of psychiatry and director of the Center for the Translational Neuroscience of Alcoholism, Yale University, New Haven, Conn., said, “The main message from the study for practicing clinicians is that treatment works.”

Dr. Krystal, who was not involved with the study, noted that “many practicing clinicians are discouraged by the course of their patients with AUD, and this study highlights that naltrexone, perhaps in combination with other medications, may be effective in preventing hospitalization and, presumably, other hospitalization-related complications of AUD.”

Also commenting on the study, Raymond Anton, MD, professor, department of psychiatry and behavioral sciences, Medical University of South Carolina, Charleston, suggested that the “clinical knowledge of the harm of benzodiazepines in those with AUD is reinforced by these findings.”

In fact, the harm of benzodiazepines might be the study’s “most important message ... [a message that was] recently highlighted by the Netflix series “The Queen’s Gambit”, which shows the ravages of using both together, or how one leads to potential addiction with the other,” said Dr. Anton, who was not involved with the study.

The other “big take-home message is that naltrexone should be used more frequently,” said Dr. Anton, distinguished professor of psychiatry at the university and scientific director of the Charleston Alcohol Research Center. He noted that there are “recent data suggesting some clinical and genetic indicators that predict responsiveness to these medications, improving efficacy.”

The study was funded by the Finnish Ministry of Social Affairs and Health. Dr. Heikkinen reports no relevant financial relationships. The other authors’ disclosures are listed on the original article. Dr. Krystal consults for companies currently developing other treatments for AUDs and receives medications to test from AstraZeneca and Novartis for NIAAA-funded research programs. Dr. Anton has consulted for Alkermes, Lipha, and Lundbeck in the past. He is also chair of the Alcohol Clinical Trials Initiative, which is a public-private partnership partially sponsored by several companies and has received grant funding from the National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism to study pharmacotherapies, including naltrexone, nalmefene, and acamprosate.

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

Naltrexone reduces the risk for hospitalization for alcohol use disorder (AUD), regardless of whether it is used alone or in conjunction with disulfiram or acamprosate, research suggests.

Katarzyna Bialasiewicz/Thinkstock

Investigators analyzed 10-year data on more than 125,000 Swedish residents with AUD and found that naltrexone, used as monotherapy or combined with acamprosate or disulfiram, was associated with significantly lower risk for AUD hospitalization or all-cause hospitalization in comparison with patients who did not use AUD medication. The patients ranged in age from 16 to 64 years.

By contrast, benzodiazepines and acamprosate monotherapy were associated with increased risk for AUD hospitalization.

“The take-home message for practicing clinicians would be that especially naltrexone use is associated with favorable treatment outcomes and should be utilized as part of the treatment protocol for AUD,” study investigator Milja Heikkinen, MD, specialist in forensic psychiatry and addiction medicine, University of Eastern Finland, Kuopio, told this news organization.

On the other hand, “benzodiazepines should be avoided and should not be administered other than for alcohol withdrawal symptoms,” she said.

The study was published online Jan. 4 in Addiction.
 

Real-world data

Previous research has shown that disulfiram, acamprosate, naltrexone, and nalmefene are efficacious in treating AUD, but most studies have been randomized controlled trials or meta-analyses, the authors write.

“Very little is known about overall health outcomes (such as risks of hospitalization and mortality) associated with specific treatments in real-world circumstances,” they write.

“The study was motivated by the fact that, although AUD is a significant public health concern, very little is known, especially about the comparative effectiveness of medications indicated in AUD,” said Dr. Heikkinen.

To investigate, the researchers drew on data from several large nationwide Swedish registers that encompassed 125,556 patients who had been diagnosed with AUD (62.5% men; mean [standard deviation] age, 38.1 [15.9] years). They followed the cohort over a median of 4.6 years (interquartile range, 2.1-.2 years).

During the follow-up period, roughly one-fourth of patients (25.6) underwent treatment with one or more drugs.

AUD pharmacotherapy ‘underutilized’

Close to one-fourth of patients (23.9%) experienced the main outcome event (AUD-related hospitalization) during the follow-up period.

The within-individual analysis showed that naltrexone – whether used as monotherapy or adjunctively with disulfiram or acamprosate – “was associated with a significantly lower risk of AUD-related hospitalization, compared to those time periods in which the same individual did not use any AUD medication,” the authors report.

By contrast, they state, acamprosate monotherapy and benzodiazepines were associated with a significantly higher risk for AUD-related hospitalization.

‘Ravages’ of benzodiazepines

Commenting on the study in an interview, John Krystal, MD, professor and chair of psychiatry and director of the Center for the Translational Neuroscience of Alcoholism, Yale University, New Haven, Conn., said, “The main message from the study for practicing clinicians is that treatment works.”

Dr. Krystal, who was not involved with the study, noted that “many practicing clinicians are discouraged by the course of their patients with AUD, and this study highlights that naltrexone, perhaps in combination with other medications, may be effective in preventing hospitalization and, presumably, other hospitalization-related complications of AUD.”

Also commenting on the study, Raymond Anton, MD, professor, department of psychiatry and behavioral sciences, Medical University of South Carolina, Charleston, suggested that the “clinical knowledge of the harm of benzodiazepines in those with AUD is reinforced by these findings.”

In fact, the harm of benzodiazepines might be the study’s “most important message ... [a message that was] recently highlighted by the Netflix series “The Queen’s Gambit”, which shows the ravages of using both together, or how one leads to potential addiction with the other,” said Dr. Anton, who was not involved with the study.

The other “big take-home message is that naltrexone should be used more frequently,” said Dr. Anton, distinguished professor of psychiatry at the university and scientific director of the Charleston Alcohol Research Center. He noted that there are “recent data suggesting some clinical and genetic indicators that predict responsiveness to these medications, improving efficacy.”

The study was funded by the Finnish Ministry of Social Affairs and Health. Dr. Heikkinen reports no relevant financial relationships. The other authors’ disclosures are listed on the original article. Dr. Krystal consults for companies currently developing other treatments for AUDs and receives medications to test from AstraZeneca and Novartis for NIAAA-funded research programs. Dr. Anton has consulted for Alkermes, Lipha, and Lundbeck in the past. He is also chair of the Alcohol Clinical Trials Initiative, which is a public-private partnership partially sponsored by several companies and has received grant funding from the National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism to study pharmacotherapies, including naltrexone, nalmefene, and acamprosate.

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

Naltrexone reduces the risk for hospitalization for alcohol use disorder (AUD), regardless of whether it is used alone or in conjunction with disulfiram or acamprosate, research suggests.

Katarzyna Bialasiewicz/Thinkstock

Investigators analyzed 10-year data on more than 125,000 Swedish residents with AUD and found that naltrexone, used as monotherapy or combined with acamprosate or disulfiram, was associated with significantly lower risk for AUD hospitalization or all-cause hospitalization in comparison with patients who did not use AUD medication. The patients ranged in age from 16 to 64 years.

By contrast, benzodiazepines and acamprosate monotherapy were associated with increased risk for AUD hospitalization.

“The take-home message for practicing clinicians would be that especially naltrexone use is associated with favorable treatment outcomes and should be utilized as part of the treatment protocol for AUD,” study investigator Milja Heikkinen, MD, specialist in forensic psychiatry and addiction medicine, University of Eastern Finland, Kuopio, told this news organization.

On the other hand, “benzodiazepines should be avoided and should not be administered other than for alcohol withdrawal symptoms,” she said.

The study was published online Jan. 4 in Addiction.
 

Real-world data

Previous research has shown that disulfiram, acamprosate, naltrexone, and nalmefene are efficacious in treating AUD, but most studies have been randomized controlled trials or meta-analyses, the authors write.

“Very little is known about overall health outcomes (such as risks of hospitalization and mortality) associated with specific treatments in real-world circumstances,” they write.

“The study was motivated by the fact that, although AUD is a significant public health concern, very little is known, especially about the comparative effectiveness of medications indicated in AUD,” said Dr. Heikkinen.

To investigate, the researchers drew on data from several large nationwide Swedish registers that encompassed 125,556 patients who had been diagnosed with AUD (62.5% men; mean [standard deviation] age, 38.1 [15.9] years). They followed the cohort over a median of 4.6 years (interquartile range, 2.1-.2 years).

During the follow-up period, roughly one-fourth of patients (25.6) underwent treatment with one or more drugs.

AUD pharmacotherapy ‘underutilized’

Close to one-fourth of patients (23.9%) experienced the main outcome event (AUD-related hospitalization) during the follow-up period.

The within-individual analysis showed that naltrexone – whether used as monotherapy or adjunctively with disulfiram or acamprosate – “was associated with a significantly lower risk of AUD-related hospitalization, compared to those time periods in which the same individual did not use any AUD medication,” the authors report.

By contrast, they state, acamprosate monotherapy and benzodiazepines were associated with a significantly higher risk for AUD-related hospitalization.

‘Ravages’ of benzodiazepines

Commenting on the study in an interview, John Krystal, MD, professor and chair of psychiatry and director of the Center for the Translational Neuroscience of Alcoholism, Yale University, New Haven, Conn., said, “The main message from the study for practicing clinicians is that treatment works.”

Dr. Krystal, who was not involved with the study, noted that “many practicing clinicians are discouraged by the course of their patients with AUD, and this study highlights that naltrexone, perhaps in combination with other medications, may be effective in preventing hospitalization and, presumably, other hospitalization-related complications of AUD.”

Also commenting on the study, Raymond Anton, MD, professor, department of psychiatry and behavioral sciences, Medical University of South Carolina, Charleston, suggested that the “clinical knowledge of the harm of benzodiazepines in those with AUD is reinforced by these findings.”

In fact, the harm of benzodiazepines might be the study’s “most important message ... [a message that was] recently highlighted by the Netflix series “The Queen’s Gambit”, which shows the ravages of using both together, or how one leads to potential addiction with the other,” said Dr. Anton, who was not involved with the study.

The other “big take-home message is that naltrexone should be used more frequently,” said Dr. Anton, distinguished professor of psychiatry at the university and scientific director of the Charleston Alcohol Research Center. He noted that there are “recent data suggesting some clinical and genetic indicators that predict responsiveness to these medications, improving efficacy.”

The study was funded by the Finnish Ministry of Social Affairs and Health. Dr. Heikkinen reports no relevant financial relationships. The other authors’ disclosures are listed on the original article. Dr. Krystal consults for companies currently developing other treatments for AUDs and receives medications to test from AstraZeneca and Novartis for NIAAA-funded research programs. Dr. Anton has consulted for Alkermes, Lipha, and Lundbeck in the past. He is also chair of the Alcohol Clinical Trials Initiative, which is a public-private partnership partially sponsored by several companies and has received grant funding from the National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism to study pharmacotherapies, including naltrexone, nalmefene, and acamprosate.

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

The history and exam were all suspicious for basal cell carcinoma (BCC), the most common of all cancers in the United States. (In African Americans, the most common skin cancer is squamous cell carcinoma). The suspicious lesion in this case was in a crevice, making it difficult to obtain a shave or punch biopsy.

As a result, a 4-mm disposable sterile curette was used (Figure). After informed consent was obtained, the lesion was cleansed with alcohol and marked with a surgical marker. Then, buffered lidocaine 1% with epinephrine was injected with a small syringe. Using a firm scraping motion with gentle rotation, a 4-mm sample of the lesion was quickly obtained and placed in standard formalin. Hemostasis was immediately obtained with firm application of 70% aluminum chloride in water using a cotton-tipped applicator. Heavy petrolatum was applied as a dressing.

The patient was confirmed to have a BCC and underwent Mohs surgery with clear margins after 1 stage. This case demonstrates the utility of a curette as a biopsy instrument for patients presenting with suspicious lesions in hard-to-reach places.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

The history and exam were all suspicious for basal cell carcinoma (BCC), the most common of all cancers in the United States. (In African Americans, the most common skin cancer is squamous cell carcinoma). The suspicious lesion in this case was in a crevice, making it difficult to obtain a shave or punch biopsy.

As a result, a 4-mm disposable sterile curette was used (Figure). After informed consent was obtained, the lesion was cleansed with alcohol and marked with a surgical marker. Then, buffered lidocaine 1% with epinephrine was injected with a small syringe. Using a firm scraping motion with gentle rotation, a 4-mm sample of the lesion was quickly obtained and placed in standard formalin. Hemostasis was immediately obtained with firm application of 70% aluminum chloride in water using a cotton-tipped applicator. Heavy petrolatum was applied as a dressing.

The patient was confirmed to have a BCC and underwent Mohs surgery with clear margins after 1 stage. This case demonstrates the utility of a curette as a biopsy instrument for patients presenting with suspicious lesions in hard-to-reach places.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

The history and exam were all suspicious for basal cell carcinoma (BCC), the most common of all cancers in the United States. (In African Americans, the most common skin cancer is squamous cell carcinoma). The suspicious lesion in this case was in a crevice, making it difficult to obtain a shave or punch biopsy.

As a result, a 4-mm disposable sterile curette was used (Figure). After informed consent was obtained, the lesion was cleansed with alcohol and marked with a surgical marker. Then, buffered lidocaine 1% with epinephrine was injected with a small syringe. Using a firm scraping motion with gentle rotation, a 4-mm sample of the lesion was quickly obtained and placed in standard formalin. Hemostasis was immediately obtained with firm application of 70% aluminum chloride in water using a cotton-tipped applicator. Heavy petrolatum was applied as a dressing.

The patient was confirmed to have a BCC and underwent Mohs surgery with clear margins after 1 stage. This case demonstrates the utility of a curette as a biopsy instrument for patients presenting with suspicious lesions in hard-to-reach places.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

Nonalcoholic fatty liver disease (NAFLD) in patients with inflammatory bowel disease (IBD) is associated with worse outcomes, and that relationship may be influenced by nonmetabolic factors. That is the conclusion of a new nationwide database analysis. NAFLD is common in IBD, with an estimated prevalence of 27%-32%.

Previous, smaller studies showed possible links between NAFLD and a history of IBD surgery, IBD disease activity, and metabolic factors, “but none of the studies looked at it on the scale that we did, and our study was more focused on outcomes than simply examining factors associated with both NAFLD and IBD,” Shaya Noorian, MD, of UCLA Medical Center in Los Angeles, said in an interview. Dr. Noorian presented the research at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

Dr. Noorian and colleagues found higher rates of hospital readmission, longer hospitalization, and higher costs, but not higher rates of death among patients with both Crohn’s disease or ulcerative colitis and NAFLD. The researchers analyzed data from patients in the Nationwide Readmissions Database (2016-2017), using ICD-10 codes to identify patients with IBD and NAFLD, along with propensity-matched controls. The study included 3,655 with Crohn’s disease and NAFLD and 7,482 without, and there were 2,026 with ulcerative colitis and NAFLD 4,094 without.

IBD hospital readmission rates were higher with comorbid NAFLD in Crohn’s disease (hazard ratio, 1.98; 95% confidence interval, 1.8-2.17; P < .001) and ulcerative colitis (HR, 1.97; 95% CI, 1.67-2.32; P < .001). Comorbid NAFLD was associated with additional length of stay Crohn’s disease (0.74 days; 95% CI, 0.29-1.18; P < .01) and ulcerative colitis (0.84 days; 0.32-1.35, respectively; P < .01), and there was additional cost of care with both Crohn’s disease ($7,766; 95% CI, $2,693-$12,839; P < .01) and ulcerative colitis ($11,496; 95% CI, $4,361-$18,631; P < .01).

Kaplan Meier curves for IBD readmission-free survival versus days since discharge showed clear separation in both Crohn’s disease and ulcerative colitis among patients with versus those without NAFLD.

Although evidence points to nonmetabolic factors being involved, metabolic factors such as obesity and diabetes are likely important as well. “We still do recognize that it’s very likely that these metabolic factors play a role in developing NAFLD in IBD. I think the fact that there are worse outcomes in patients with NAFLD supports the fact that we should do our best to control the metabolic factors like diabetes, obesity, et cetera. We don’t want to minimize that aspect of it. But I think the fact that there were still worse outcomes after adjusting for metabolic factors emphasizes the importance of researching these factors further to see which ones are the main contributors. If we can find the main contributor, whether that’s medication, IBD disease burden, or history of surgery, perhaps we can use that information to prevent development or progression of NAFLD,” said Dr. Noorian.

“Historical reports have examined the relationship between Crohn’s disease and NAFLD. The currently study included both Crohn’s and ulcerative colitis, thus impressively demonstrating the importance of this interaction across IBD,” said Matthew Ciorba, MD, director of the IBD Center at Washington University in St. Louis, who attended the session.

Nonalcoholic fatty liver disease (NAFLD) in patients with inflammatory bowel disease (IBD) is associated with worse outcomes, and that relationship may be influenced by nonmetabolic factors. That is the conclusion of a new nationwide database analysis. NAFLD is common in IBD, with an estimated prevalence of 27%-32%.

Previous, smaller studies showed possible links between NAFLD and a history of IBD surgery, IBD disease activity, and metabolic factors, “but none of the studies looked at it on the scale that we did, and our study was more focused on outcomes than simply examining factors associated with both NAFLD and IBD,” Shaya Noorian, MD, of UCLA Medical Center in Los Angeles, said in an interview. Dr. Noorian presented the research at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

Dr. Noorian and colleagues found higher rates of hospital readmission, longer hospitalization, and higher costs, but not higher rates of death among patients with both Crohn’s disease or ulcerative colitis and NAFLD. The researchers analyzed data from patients in the Nationwide Readmissions Database (2016-2017), using ICD-10 codes to identify patients with IBD and NAFLD, along with propensity-matched controls. The study included 3,655 with Crohn’s disease and NAFLD and 7,482 without, and there were 2,026 with ulcerative colitis and NAFLD 4,094 without.

IBD hospital readmission rates were higher with comorbid NAFLD in Crohn’s disease (hazard ratio, 1.98; 95% confidence interval, 1.8-2.17; P < .001) and ulcerative colitis (HR, 1.97; 95% CI, 1.67-2.32; P < .001). Comorbid NAFLD was associated with additional length of stay Crohn’s disease (0.74 days; 95% CI, 0.29-1.18; P < .01) and ulcerative colitis (0.84 days; 0.32-1.35, respectively; P < .01), and there was additional cost of care with both Crohn’s disease ($7,766; 95% CI, $2,693-$12,839; P < .01) and ulcerative colitis ($11,496; 95% CI, $4,361-$18,631; P < .01).

Kaplan Meier curves for IBD readmission-free survival versus days since discharge showed clear separation in both Crohn’s disease and ulcerative colitis among patients with versus those without NAFLD.

Although evidence points to nonmetabolic factors being involved, metabolic factors such as obesity and diabetes are likely important as well. “We still do recognize that it’s very likely that these metabolic factors play a role in developing NAFLD in IBD. I think the fact that there are worse outcomes in patients with NAFLD supports the fact that we should do our best to control the metabolic factors like diabetes, obesity, et cetera. We don’t want to minimize that aspect of it. But I think the fact that there were still worse outcomes after adjusting for metabolic factors emphasizes the importance of researching these factors further to see which ones are the main contributors. If we can find the main contributor, whether that’s medication, IBD disease burden, or history of surgery, perhaps we can use that information to prevent development or progression of NAFLD,” said Dr. Noorian.

“Historical reports have examined the relationship between Crohn’s disease and NAFLD. The currently study included both Crohn’s and ulcerative colitis, thus impressively demonstrating the importance of this interaction across IBD,” said Matthew Ciorba, MD, director of the IBD Center at Washington University in St. Louis, who attended the session.

Nonalcoholic fatty liver disease (NAFLD) in patients with inflammatory bowel disease (IBD) is associated with worse outcomes, and that relationship may be influenced by nonmetabolic factors. That is the conclusion of a new nationwide database analysis. NAFLD is common in IBD, with an estimated prevalence of 27%-32%.

Previous, smaller studies showed possible links between NAFLD and a history of IBD surgery, IBD disease activity, and metabolic factors, “but none of the studies looked at it on the scale that we did, and our study was more focused on outcomes than simply examining factors associated with both NAFLD and IBD,” Shaya Noorian, MD, of UCLA Medical Center in Los Angeles, said in an interview. Dr. Noorian presented the research at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

Dr. Noorian and colleagues found higher rates of hospital readmission, longer hospitalization, and higher costs, but not higher rates of death among patients with both Crohn’s disease or ulcerative colitis and NAFLD. The researchers analyzed data from patients in the Nationwide Readmissions Database (2016-2017), using ICD-10 codes to identify patients with IBD and NAFLD, along with propensity-matched controls. The study included 3,655 with Crohn’s disease and NAFLD and 7,482 without, and there were 2,026 with ulcerative colitis and NAFLD 4,094 without.

IBD hospital readmission rates were higher with comorbid NAFLD in Crohn’s disease (hazard ratio, 1.98; 95% confidence interval, 1.8-2.17; P < .001) and ulcerative colitis (HR, 1.97; 95% CI, 1.67-2.32; P < .001). Comorbid NAFLD was associated with additional length of stay Crohn’s disease (0.74 days; 95% CI, 0.29-1.18; P < .01) and ulcerative colitis (0.84 days; 0.32-1.35, respectively; P < .01), and there was additional cost of care with both Crohn’s disease ($7,766; 95% CI, $2,693-$12,839; P < .01) and ulcerative colitis ($11,496; 95% CI, $4,361-$18,631; P < .01).

Kaplan Meier curves for IBD readmission-free survival versus days since discharge showed clear separation in both Crohn’s disease and ulcerative colitis among patients with versus those without NAFLD.

Although evidence points to nonmetabolic factors being involved, metabolic factors such as obesity and diabetes are likely important as well. “We still do recognize that it’s very likely that these metabolic factors play a role in developing NAFLD in IBD. I think the fact that there are worse outcomes in patients with NAFLD supports the fact that we should do our best to control the metabolic factors like diabetes, obesity, et cetera. We don’t want to minimize that aspect of it. But I think the fact that there were still worse outcomes after adjusting for metabolic factors emphasizes the importance of researching these factors further to see which ones are the main contributors. If we can find the main contributor, whether that’s medication, IBD disease burden, or history of surgery, perhaps we can use that information to prevent development or progression of NAFLD,” said Dr. Noorian.

“Historical reports have examined the relationship between Crohn’s disease and NAFLD. The currently study included both Crohn’s and ulcerative colitis, thus impressively demonstrating the importance of this interaction across IBD,” said Matthew Ciorba, MD, director of the IBD Center at Washington University in St. Louis, who attended the session.