Expert shares vulvovaginal candidiasis treatment pearls

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Thu, 09/02/2021 - 14:23

For patients who present with pesky vulvovaginal candidiasis, consider a course of ibrexafungerp, a first-in-class oral triterpenoid antifungal drug that was approved in June 2021, Aruna Venkatesan, MD, recommends.

Dr. Aruna Venkatesan

Ibrexafungerp, an inhibitor of beta (1-3)–glucan synthase, is important for many reasons,” Dr. Venkatesan, chief of dermatology and director of the genital dermatology clinic at Santa Clara Valley Medical Center, San Jose, Calif., said during the annual meeting of the Pacific Dermatologic Association. “It’s one of the few drugs that can be used to treat Candida glabrata when C. glabrata is resistant to azoles and echinocandins. As the second-most common Candida species after C. albicans, C. glabrata is more common in immunosuppressed patients and it can cause mucosal and invasive disease, so ibrexafungerp is a welcome addition to our treatment armamentarium,” said Dr. Venkatesan, clinical professor of dermatology (affiliated) at Stanford (Calif.) Hospital and Clinics, adding that that vulvovaginal candidiasis can be tricky to diagnose. “In medical school, we learned that yeast infection in a woman presents as white, curd-like discharge, but that’s actually a minority of patients.”

For a patient who is being treated with topical steroids or estrogen for a genital condition, but is experiencing worsening itch, redness, or thick white discharge, she recommends performing a KOH exam.



“Instead of using a 15-blade scalpel, as we are used to performing on the skin for tinea, take a sterile [cotton swab], and swab the affected area. You can then apply it to a slide and perform a KOH exam as you normally would. Then look for yeast elements under the microscope. I also find it helpful to send for fungal culture to get speciation, especially in someone who’s not responding to therapy. This is because non-albicans yeast can be more resistant to azoles and require a different treatment plan.”

Often, patients with vulvovaginal candidiasis who present to her clinic are referred from an ob.gyn. and other general practitioners because they have failed a topical or oral azole. “I tend to avoid the topicals,” said Dr. Venkatesan, who is also president-elect of the North American chapter of the International Society for the Study of Vulvovaginal Disease. “If the culture shows C. albicans, I usually treat with oral fluconazole, 150 mg or 200 mg once, and consider repeat weekly dosing. Many patients come to me because they have recurrent refractory disease, so giving it once weekly for 6-8 weeks while they work on their potential risk factors such as diabetic blood sugar control is sensible.”

Non-albicans yeast can be resistant to azoles. If the fungal culture shows C. glabrata in such patients, “consider a course of intravaginal boric acid suppositories,” she advised. “These used to be difficult to give patients, because you would either have to send the prescription to a compounding pharmacy, or have the patients buy the capsules and boric acid crystals separately and make them themselves. That always made me nervous because of the chance of errors. The safety and the concern of taking it by mouth is an issue.” But now, intravaginal boric acid suppositories are available on Amazon and other web sites, and are relatively affordable, she said, adding, “just make sure the patient doesn’t take it by mouth as this is very toxic.”

Dr. Venkatesan reported having no financial disclosures.

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For patients who present with pesky vulvovaginal candidiasis, consider a course of ibrexafungerp, a first-in-class oral triterpenoid antifungal drug that was approved in June 2021, Aruna Venkatesan, MD, recommends.

Dr. Aruna Venkatesan

Ibrexafungerp, an inhibitor of beta (1-3)–glucan synthase, is important for many reasons,” Dr. Venkatesan, chief of dermatology and director of the genital dermatology clinic at Santa Clara Valley Medical Center, San Jose, Calif., said during the annual meeting of the Pacific Dermatologic Association. “It’s one of the few drugs that can be used to treat Candida glabrata when C. glabrata is resistant to azoles and echinocandins. As the second-most common Candida species after C. albicans, C. glabrata is more common in immunosuppressed patients and it can cause mucosal and invasive disease, so ibrexafungerp is a welcome addition to our treatment armamentarium,” said Dr. Venkatesan, clinical professor of dermatology (affiliated) at Stanford (Calif.) Hospital and Clinics, adding that that vulvovaginal candidiasis can be tricky to diagnose. “In medical school, we learned that yeast infection in a woman presents as white, curd-like discharge, but that’s actually a minority of patients.”

For a patient who is being treated with topical steroids or estrogen for a genital condition, but is experiencing worsening itch, redness, or thick white discharge, she recommends performing a KOH exam.



“Instead of using a 15-blade scalpel, as we are used to performing on the skin for tinea, take a sterile [cotton swab], and swab the affected area. You can then apply it to a slide and perform a KOH exam as you normally would. Then look for yeast elements under the microscope. I also find it helpful to send for fungal culture to get speciation, especially in someone who’s not responding to therapy. This is because non-albicans yeast can be more resistant to azoles and require a different treatment plan.”

Often, patients with vulvovaginal candidiasis who present to her clinic are referred from an ob.gyn. and other general practitioners because they have failed a topical or oral azole. “I tend to avoid the topicals,” said Dr. Venkatesan, who is also president-elect of the North American chapter of the International Society for the Study of Vulvovaginal Disease. “If the culture shows C. albicans, I usually treat with oral fluconazole, 150 mg or 200 mg once, and consider repeat weekly dosing. Many patients come to me because they have recurrent refractory disease, so giving it once weekly for 6-8 weeks while they work on their potential risk factors such as diabetic blood sugar control is sensible.”

Non-albicans yeast can be resistant to azoles. If the fungal culture shows C. glabrata in such patients, “consider a course of intravaginal boric acid suppositories,” she advised. “These used to be difficult to give patients, because you would either have to send the prescription to a compounding pharmacy, or have the patients buy the capsules and boric acid crystals separately and make them themselves. That always made me nervous because of the chance of errors. The safety and the concern of taking it by mouth is an issue.” But now, intravaginal boric acid suppositories are available on Amazon and other web sites, and are relatively affordable, she said, adding, “just make sure the patient doesn’t take it by mouth as this is very toxic.”

Dr. Venkatesan reported having no financial disclosures.

For patients who present with pesky vulvovaginal candidiasis, consider a course of ibrexafungerp, a first-in-class oral triterpenoid antifungal drug that was approved in June 2021, Aruna Venkatesan, MD, recommends.

Dr. Aruna Venkatesan

Ibrexafungerp, an inhibitor of beta (1-3)–glucan synthase, is important for many reasons,” Dr. Venkatesan, chief of dermatology and director of the genital dermatology clinic at Santa Clara Valley Medical Center, San Jose, Calif., said during the annual meeting of the Pacific Dermatologic Association. “It’s one of the few drugs that can be used to treat Candida glabrata when C. glabrata is resistant to azoles and echinocandins. As the second-most common Candida species after C. albicans, C. glabrata is more common in immunosuppressed patients and it can cause mucosal and invasive disease, so ibrexafungerp is a welcome addition to our treatment armamentarium,” said Dr. Venkatesan, clinical professor of dermatology (affiliated) at Stanford (Calif.) Hospital and Clinics, adding that that vulvovaginal candidiasis can be tricky to diagnose. “In medical school, we learned that yeast infection in a woman presents as white, curd-like discharge, but that’s actually a minority of patients.”

For a patient who is being treated with topical steroids or estrogen for a genital condition, but is experiencing worsening itch, redness, or thick white discharge, she recommends performing a KOH exam.



“Instead of using a 15-blade scalpel, as we are used to performing on the skin for tinea, take a sterile [cotton swab], and swab the affected area. You can then apply it to a slide and perform a KOH exam as you normally would. Then look for yeast elements under the microscope. I also find it helpful to send for fungal culture to get speciation, especially in someone who’s not responding to therapy. This is because non-albicans yeast can be more resistant to azoles and require a different treatment plan.”

Often, patients with vulvovaginal candidiasis who present to her clinic are referred from an ob.gyn. and other general practitioners because they have failed a topical or oral azole. “I tend to avoid the topicals,” said Dr. Venkatesan, who is also president-elect of the North American chapter of the International Society for the Study of Vulvovaginal Disease. “If the culture shows C. albicans, I usually treat with oral fluconazole, 150 mg or 200 mg once, and consider repeat weekly dosing. Many patients come to me because they have recurrent refractory disease, so giving it once weekly for 6-8 weeks while they work on their potential risk factors such as diabetic blood sugar control is sensible.”

Non-albicans yeast can be resistant to azoles. If the fungal culture shows C. glabrata in such patients, “consider a course of intravaginal boric acid suppositories,” she advised. “These used to be difficult to give patients, because you would either have to send the prescription to a compounding pharmacy, or have the patients buy the capsules and boric acid crystals separately and make them themselves. That always made me nervous because of the chance of errors. The safety and the concern of taking it by mouth is an issue.” But now, intravaginal boric acid suppositories are available on Amazon and other web sites, and are relatively affordable, she said, adding, “just make sure the patient doesn’t take it by mouth as this is very toxic.”

Dr. Venkatesan reported having no financial disclosures.

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COVID-19 linked to baby bust in high-income countries

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If COVID-19 has caused millions of deaths, it may also have prevented or at least led to a postponement of many births.

In an assessment of the pandemic’s early effects, Arnstein Aassve, PhD, and colleagues found a significant COVID-19–related decline in crude birth rates (CBRs) in 7 of 22 high-income countries, particularly in Southwestern Europe.

Dr. Aassve, an economist at the Carlo F. Dondena Center for Research on Social Dynamics and Public Policy at the Università Commerciale Luigi Bocconi, Milan, and colleagues report the results in an article published online August 30 in the Proceedings of the National Academy of Sciences.

Defining the start of the COVID-19 pandemic as February 2020, the study identifies strong declines in Italy (-9.1%), Hungary (-8.5%), Spain (-8.4%), and Portugal (-6.6%) beyond those predicted by past trends. In the United States, CBRs fell by 7.1% relative to 2019 for births occurring in Nov. and Dec. 2020 following conceptions in February and March of that year.

Significant declines in CBR also occurred in Belgium, Austria, and Singapore.

A year-to-year comparison of the mean for monthly CBRs per 1,000 population before and during the pandemic suggests a negative difference for all countries studied except for Denmark, Finland, Germany, and the Netherlands, Dr. Aassve and colleagues write. These findings may have policy implications for childcare, housing, and the labor market.

The Milan researchers compared monthly vital statistics data on live births from the international Human Fertility Database for the period of Jan. 2016 to March 2021. These figures reflect conceptions carried to term between April 2015 and June 2020. The 22 countries in the analysis represent 37% of the total reported COVID-19 cases and 34% of deaths worldwide.

The study findings align with surveys on “fertility intentions” collected early in the first COVID-19 wave in Germany, France, Spain, and the United Kingdom. These surveys indicated that 73% of people who were planning pregnancies in 2020 either decided to delay the pregnancy or they abandoned their plans.

“The popular media speculated that the lockdown would lead to a baby boom, as couples spent more time together,” Dr. Aassve told this news organization. “There’s very little evidence of this when you look to previous disasters and shocks, and the first data suggest more of an immediate collapse than a boom. But as you also see from the paper, the collapse is not seen everywhere.” Other current studies suggest the fertility drop is immediate but temporary, says Dr. Aassve, who is also a professor of demography.

Interestingly, Dr. Aassve and colleagues found that CBRs were relatively stable in Northern Europe. The authors point to supportive social and family policies in that region that might have reduced the effect of the pandemic on births. “These factors are likely to affect CBRs in the subsequent pandemic waves,” they write. They call for future studies to assess the full population implications of the pandemic, the moderating impact of policy interventions, and the nexus between short- and long-run effects in relation to the various waves of the COVID-19 pandemic.
 

 

 

Rebounds

Some regions have already reported a rebound from the COVID-19 fertility trough. Molly J. Stout, MD, director of maternal fetal medicine at the University of Michigan, Ann Arbor, and colleagues used electronic medical records to predict a surge in births after the initial decline.

“The surge we’ve seen at the end of this summer is exceeding the usual annual birth rate, as predicted,” she said in an interview. “But I think there’ll be a return to normal after this transient escalation. I don’t think birth rates will stay elevated above the normal because the birth surge is a temporary response to an event, although there will likely be regional differences.”

Looking ahead, Dr. Stout, who was not involved in Dr. Aassve’s analysis, is not certain how a fourth pandemic wave might ultimately modify a couple’s overall family size. But the toll the health crisis has taken on working women who have been forced to withdraw from the economy because of a lack of childcare points to a societal need that should be addressed.

According to Philip N. Cohen, PhD, a professor of sociology at the University of Maryland, College Park, who’s been tracking fertility trends since the onset of the COVID-19 emergency, the pandemic has combined a health crisis with an economic crisis, along with “the additional factor of social distancing and isolation, which all contributed to the decline in birth rates. Some people changed their plans to hold off on having children, while others didn’t get pregnant because they weren’t socializing and meeting people as much.”

Dr. Cohen, who was not involved in the study by Dr. Aassve and associates, said his provisional data show that although in many places, birth rates have rebounded more or less to prepandemic levels after a nadir around Jan. 2021, some areas of the United States still show substantially lower rates, including California, Hawaii, and Oregon.

As to the duration of the pandemic effect, Dr. Aassve cautions that his group’s estimates refer to the first wave only. “We then have the second, third, and currently the fourth wave. We can’t be sure about the impact of these waves on fertility since the data are not there yet, but I’d be surprised if they didn’t continue to have an impact on fertility rates,” he said.

Dr. Cohen agreed: “Some people who delayed childbearing will make up the delay. However, whenever there’s a delay, there’s inevitably some portion of the decline that’s not recouped.”

As for the wider effect across the world, Dr. Aassve said his team’s figures derive from high-income countries where data are readily available. For middle- and low-income countries, fewer data exist, and the quality of those data is not as good.

The lessons from this and other upheavals teach us that unforeseen shocks almost always have a negative impact on fertility, says Dr. Aassve. “[B]ut these effects may be separate from existing declining trends. The issue here is that those overall declining trends may be driven by other factors. In contrast, the shock of the pandemic is short-lived, and we may return to normal rather quickly. But if the pandemic also impacts other societal structures, such as the occupational and industrial sectors, then the pandemic might exacerbate the negative trend.”

The study was supported by funding from the European Research Council for funding under the European Union’s Horizon 2020 Research and Innovation Programme. The study authors, Dr. Stout, and Dr. Cohen have disclosed no relevant financial relationships.

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

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If COVID-19 has caused millions of deaths, it may also have prevented or at least led to a postponement of many births.

In an assessment of the pandemic’s early effects, Arnstein Aassve, PhD, and colleagues found a significant COVID-19–related decline in crude birth rates (CBRs) in 7 of 22 high-income countries, particularly in Southwestern Europe.

Dr. Aassve, an economist at the Carlo F. Dondena Center for Research on Social Dynamics and Public Policy at the Università Commerciale Luigi Bocconi, Milan, and colleagues report the results in an article published online August 30 in the Proceedings of the National Academy of Sciences.

Defining the start of the COVID-19 pandemic as February 2020, the study identifies strong declines in Italy (-9.1%), Hungary (-8.5%), Spain (-8.4%), and Portugal (-6.6%) beyond those predicted by past trends. In the United States, CBRs fell by 7.1% relative to 2019 for births occurring in Nov. and Dec. 2020 following conceptions in February and March of that year.

Significant declines in CBR also occurred in Belgium, Austria, and Singapore.

A year-to-year comparison of the mean for monthly CBRs per 1,000 population before and during the pandemic suggests a negative difference for all countries studied except for Denmark, Finland, Germany, and the Netherlands, Dr. Aassve and colleagues write. These findings may have policy implications for childcare, housing, and the labor market.

The Milan researchers compared monthly vital statistics data on live births from the international Human Fertility Database for the period of Jan. 2016 to March 2021. These figures reflect conceptions carried to term between April 2015 and June 2020. The 22 countries in the analysis represent 37% of the total reported COVID-19 cases and 34% of deaths worldwide.

The study findings align with surveys on “fertility intentions” collected early in the first COVID-19 wave in Germany, France, Spain, and the United Kingdom. These surveys indicated that 73% of people who were planning pregnancies in 2020 either decided to delay the pregnancy or they abandoned their plans.

“The popular media speculated that the lockdown would lead to a baby boom, as couples spent more time together,” Dr. Aassve told this news organization. “There’s very little evidence of this when you look to previous disasters and shocks, and the first data suggest more of an immediate collapse than a boom. But as you also see from the paper, the collapse is not seen everywhere.” Other current studies suggest the fertility drop is immediate but temporary, says Dr. Aassve, who is also a professor of demography.

Interestingly, Dr. Aassve and colleagues found that CBRs were relatively stable in Northern Europe. The authors point to supportive social and family policies in that region that might have reduced the effect of the pandemic on births. “These factors are likely to affect CBRs in the subsequent pandemic waves,” they write. They call for future studies to assess the full population implications of the pandemic, the moderating impact of policy interventions, and the nexus between short- and long-run effects in relation to the various waves of the COVID-19 pandemic.
 

 

 

Rebounds

Some regions have already reported a rebound from the COVID-19 fertility trough. Molly J. Stout, MD, director of maternal fetal medicine at the University of Michigan, Ann Arbor, and colleagues used electronic medical records to predict a surge in births after the initial decline.

“The surge we’ve seen at the end of this summer is exceeding the usual annual birth rate, as predicted,” she said in an interview. “But I think there’ll be a return to normal after this transient escalation. I don’t think birth rates will stay elevated above the normal because the birth surge is a temporary response to an event, although there will likely be regional differences.”

Looking ahead, Dr. Stout, who was not involved in Dr. Aassve’s analysis, is not certain how a fourth pandemic wave might ultimately modify a couple’s overall family size. But the toll the health crisis has taken on working women who have been forced to withdraw from the economy because of a lack of childcare points to a societal need that should be addressed.

According to Philip N. Cohen, PhD, a professor of sociology at the University of Maryland, College Park, who’s been tracking fertility trends since the onset of the COVID-19 emergency, the pandemic has combined a health crisis with an economic crisis, along with “the additional factor of social distancing and isolation, which all contributed to the decline in birth rates. Some people changed their plans to hold off on having children, while others didn’t get pregnant because they weren’t socializing and meeting people as much.”

Dr. Cohen, who was not involved in the study by Dr. Aassve and associates, said his provisional data show that although in many places, birth rates have rebounded more or less to prepandemic levels after a nadir around Jan. 2021, some areas of the United States still show substantially lower rates, including California, Hawaii, and Oregon.

As to the duration of the pandemic effect, Dr. Aassve cautions that his group’s estimates refer to the first wave only. “We then have the second, third, and currently the fourth wave. We can’t be sure about the impact of these waves on fertility since the data are not there yet, but I’d be surprised if they didn’t continue to have an impact on fertility rates,” he said.

Dr. Cohen agreed: “Some people who delayed childbearing will make up the delay. However, whenever there’s a delay, there’s inevitably some portion of the decline that’s not recouped.”

As for the wider effect across the world, Dr. Aassve said his team’s figures derive from high-income countries where data are readily available. For middle- and low-income countries, fewer data exist, and the quality of those data is not as good.

The lessons from this and other upheavals teach us that unforeseen shocks almost always have a negative impact on fertility, says Dr. Aassve. “[B]ut these effects may be separate from existing declining trends. The issue here is that those overall declining trends may be driven by other factors. In contrast, the shock of the pandemic is short-lived, and we may return to normal rather quickly. But if the pandemic also impacts other societal structures, such as the occupational and industrial sectors, then the pandemic might exacerbate the negative trend.”

The study was supported by funding from the European Research Council for funding under the European Union’s Horizon 2020 Research and Innovation Programme. The study authors, Dr. Stout, and Dr. Cohen have disclosed no relevant financial relationships.

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

If COVID-19 has caused millions of deaths, it may also have prevented or at least led to a postponement of many births.

In an assessment of the pandemic’s early effects, Arnstein Aassve, PhD, and colleagues found a significant COVID-19–related decline in crude birth rates (CBRs) in 7 of 22 high-income countries, particularly in Southwestern Europe.

Dr. Aassve, an economist at the Carlo F. Dondena Center for Research on Social Dynamics and Public Policy at the Università Commerciale Luigi Bocconi, Milan, and colleagues report the results in an article published online August 30 in the Proceedings of the National Academy of Sciences.

Defining the start of the COVID-19 pandemic as February 2020, the study identifies strong declines in Italy (-9.1%), Hungary (-8.5%), Spain (-8.4%), and Portugal (-6.6%) beyond those predicted by past trends. In the United States, CBRs fell by 7.1% relative to 2019 for births occurring in Nov. and Dec. 2020 following conceptions in February and March of that year.

Significant declines in CBR also occurred in Belgium, Austria, and Singapore.

A year-to-year comparison of the mean for monthly CBRs per 1,000 population before and during the pandemic suggests a negative difference for all countries studied except for Denmark, Finland, Germany, and the Netherlands, Dr. Aassve and colleagues write. These findings may have policy implications for childcare, housing, and the labor market.

The Milan researchers compared monthly vital statistics data on live births from the international Human Fertility Database for the period of Jan. 2016 to March 2021. These figures reflect conceptions carried to term between April 2015 and June 2020. The 22 countries in the analysis represent 37% of the total reported COVID-19 cases and 34% of deaths worldwide.

The study findings align with surveys on “fertility intentions” collected early in the first COVID-19 wave in Germany, France, Spain, and the United Kingdom. These surveys indicated that 73% of people who were planning pregnancies in 2020 either decided to delay the pregnancy or they abandoned their plans.

“The popular media speculated that the lockdown would lead to a baby boom, as couples spent more time together,” Dr. Aassve told this news organization. “There’s very little evidence of this when you look to previous disasters and shocks, and the first data suggest more of an immediate collapse than a boom. But as you also see from the paper, the collapse is not seen everywhere.” Other current studies suggest the fertility drop is immediate but temporary, says Dr. Aassve, who is also a professor of demography.

Interestingly, Dr. Aassve and colleagues found that CBRs were relatively stable in Northern Europe. The authors point to supportive social and family policies in that region that might have reduced the effect of the pandemic on births. “These factors are likely to affect CBRs in the subsequent pandemic waves,” they write. They call for future studies to assess the full population implications of the pandemic, the moderating impact of policy interventions, and the nexus between short- and long-run effects in relation to the various waves of the COVID-19 pandemic.
 

 

 

Rebounds

Some regions have already reported a rebound from the COVID-19 fertility trough. Molly J. Stout, MD, director of maternal fetal medicine at the University of Michigan, Ann Arbor, and colleagues used electronic medical records to predict a surge in births after the initial decline.

“The surge we’ve seen at the end of this summer is exceeding the usual annual birth rate, as predicted,” she said in an interview. “But I think there’ll be a return to normal after this transient escalation. I don’t think birth rates will stay elevated above the normal because the birth surge is a temporary response to an event, although there will likely be regional differences.”

Looking ahead, Dr. Stout, who was not involved in Dr. Aassve’s analysis, is not certain how a fourth pandemic wave might ultimately modify a couple’s overall family size. But the toll the health crisis has taken on working women who have been forced to withdraw from the economy because of a lack of childcare points to a societal need that should be addressed.

According to Philip N. Cohen, PhD, a professor of sociology at the University of Maryland, College Park, who’s been tracking fertility trends since the onset of the COVID-19 emergency, the pandemic has combined a health crisis with an economic crisis, along with “the additional factor of social distancing and isolation, which all contributed to the decline in birth rates. Some people changed their plans to hold off on having children, while others didn’t get pregnant because they weren’t socializing and meeting people as much.”

Dr. Cohen, who was not involved in the study by Dr. Aassve and associates, said his provisional data show that although in many places, birth rates have rebounded more or less to prepandemic levels after a nadir around Jan. 2021, some areas of the United States still show substantially lower rates, including California, Hawaii, and Oregon.

As to the duration of the pandemic effect, Dr. Aassve cautions that his group’s estimates refer to the first wave only. “We then have the second, third, and currently the fourth wave. We can’t be sure about the impact of these waves on fertility since the data are not there yet, but I’d be surprised if they didn’t continue to have an impact on fertility rates,” he said.

Dr. Cohen agreed: “Some people who delayed childbearing will make up the delay. However, whenever there’s a delay, there’s inevitably some portion of the decline that’s not recouped.”

As for the wider effect across the world, Dr. Aassve said his team’s figures derive from high-income countries where data are readily available. For middle- and low-income countries, fewer data exist, and the quality of those data is not as good.

The lessons from this and other upheavals teach us that unforeseen shocks almost always have a negative impact on fertility, says Dr. Aassve. “[B]ut these effects may be separate from existing declining trends. The issue here is that those overall declining trends may be driven by other factors. In contrast, the shock of the pandemic is short-lived, and we may return to normal rather quickly. But if the pandemic also impacts other societal structures, such as the occupational and industrial sectors, then the pandemic might exacerbate the negative trend.”

The study was supported by funding from the European Research Council for funding under the European Union’s Horizon 2020 Research and Innovation Programme. The study authors, Dr. Stout, and Dr. Cohen have disclosed no relevant financial relationships.

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

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Malaria study shows remarkable 70% reduction in severe disease and death

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Wed, 09/01/2021 - 15:17

new study from Africa shows a remarkable 70% reduction in malaria if two treatments — a vaccine and an antimalarial medication — are combined instead of giving them individually.

Malaria is endemic in the tropics. The World Health Organization (WHO) reports that in 2019, there were 229 million cases and 409,000 deaths from this parasitic infection. Most of the burden (94%) occurs in Africa, and children younger than age 5 account for 67% of the deaths.

In the Sahel region of Africa, a broad, sub-Saharan band that stretches across the continent, high malaria transmission is seasonal. Children in some countries there are treated with monthly courses of sulfadoxine-pyrimethamine and amodiaquine chemoprophylaxis during the four higher-risk months. Such seasonal malaria chemoprophylaxis (SMC) has been shown to reduce infections by up to 88% and costs an average of $3.43 per child per year.

This double-blind, randomized controlled trial enrolled young children (5-17 months old) in Burkina Faso and Mali, where SMC is the current treatment regimen. Nearly 6,000 children received either chemoprophylaxis, the RTS,S/AS01E malaria vaccine (RTS,S), or both treatments. The study, led by investigators at the London School of Hygiene and Tropical Medicine (LSHTM), was reported in the New England Journal of Medicine.

Co-lead investigator Daniel Chandramohan, MBBS, PhD, MSc, professor of public health at LSHTM, said in an interview that SMC administration is quite labor-intensive and that “we thought we can replace these four cycles of seasonal cure prevention with one seasonal vaccination like the flu vaccine ... and that there might be some additive benefit.”

Instead, the study found the combination reduces the incidence of malaria by 62% against clinical malaria infection, 70% against severe malaria, and 73% against death from malaria compared with SMC alone. “Not in our wildest dreams would I have hypothesized that this is a possibility,” Dr. Chandramohan said. He continued that this was unlikely a “freak result” because the findings are “consistent between both countries. Two, it is consistent across the years. Three, all the malaria outcomes ... are consistently showing the protective effect at the same level.”

To maintain the blinded study design, children received injections of rabies vaccine and hepatitis A vaccine instead of a placebo for RTS,S. Both were chosen to provide additional benefits by protecting children against those infections.

With so many children followed over years, accuracy in providing the correct treatment for each study arm can be difficult. Each child was given a QR code and picture identification to facilitate drug distribution each year in this study.

Miriam K. Laufer, MD, professor and associate director for malaria research at the University of Maryland, Baltimore, who was not involved in the study, said in an interview, “This is a spectacular result, you know, decreasing disease by 60%-70% using interventions that we already have.”

RTS,S is not a new vaccine; it was developed in 2001 by GlaxoSmithKline with Path’s Malaria Vaccine Initiative, then manufactured by GSK. The Gates Foundation has supported production. Dr. Chandramohan said GSK has transferred the technology to Bharat, in India, and that it will take 2-3 years to ramp up production. Until then, enough vaccine is available to supply Kenya, Malawi, and Ghana, where the pilot studies are being done.

Dr. Laufer stressed that the “group that got RTS,S did as well as the group that received SMC.” She noted that the use of SMC is limited to specific areas of the Sahel sub-region of Africa, with a brief transmission period. In other areas of Africa where malaria has a longer transmission period, SMC isn’t as effective. “RTS,S vaccine could really have an impact” there, she added.

Asked if RTS,S might be substituted for SMC to reduce the likelihood of resistance emerging, Dr. Laufer said, “Giving RTS,S vaccine is as good as using repeated treatment of malaria drugs during the malaria season. And that’s important for two reasons. One is that the advantage of a vaccine is that you’re not producing pressure of drugs that would enable drug resistance to emerge and spread. So maybe your vaccine efficacy could last longer than drug efficacy. We don’t know the answer to that.”

Hypothesizing about the unexpectedly good trial results, Dr. Laufer explained, “We know that RTS,S decreases the number of parasites that make it into the blood when a child is bitten by an infected mosquito. When drugs like sulfadoxine-pyrimethamine and amodiaquine that have moderate efficacy only have to kill off a small number of parasites, they can work better. Maybe that explains why the combination of RTS,S and SMC created such a positive outcome.”

Dr. Laufer echoed Chandramohan, saying, “Results were much more dramatic than anybody – certainly than I anticipated.” Both physicians anticipate that WHO will give full approval for this combination this fall.

Dr. Chandramohan and Dr. Laufer have disclosed no relevant financial relationships.

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

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new study from Africa shows a remarkable 70% reduction in malaria if two treatments — a vaccine and an antimalarial medication — are combined instead of giving them individually.

Malaria is endemic in the tropics. The World Health Organization (WHO) reports that in 2019, there were 229 million cases and 409,000 deaths from this parasitic infection. Most of the burden (94%) occurs in Africa, and children younger than age 5 account for 67% of the deaths.

In the Sahel region of Africa, a broad, sub-Saharan band that stretches across the continent, high malaria transmission is seasonal. Children in some countries there are treated with monthly courses of sulfadoxine-pyrimethamine and amodiaquine chemoprophylaxis during the four higher-risk months. Such seasonal malaria chemoprophylaxis (SMC) has been shown to reduce infections by up to 88% and costs an average of $3.43 per child per year.

This double-blind, randomized controlled trial enrolled young children (5-17 months old) in Burkina Faso and Mali, where SMC is the current treatment regimen. Nearly 6,000 children received either chemoprophylaxis, the RTS,S/AS01E malaria vaccine (RTS,S), or both treatments. The study, led by investigators at the London School of Hygiene and Tropical Medicine (LSHTM), was reported in the New England Journal of Medicine.

Co-lead investigator Daniel Chandramohan, MBBS, PhD, MSc, professor of public health at LSHTM, said in an interview that SMC administration is quite labor-intensive and that “we thought we can replace these four cycles of seasonal cure prevention with one seasonal vaccination like the flu vaccine ... and that there might be some additive benefit.”

Instead, the study found the combination reduces the incidence of malaria by 62% against clinical malaria infection, 70% against severe malaria, and 73% against death from malaria compared with SMC alone. “Not in our wildest dreams would I have hypothesized that this is a possibility,” Dr. Chandramohan said. He continued that this was unlikely a “freak result” because the findings are “consistent between both countries. Two, it is consistent across the years. Three, all the malaria outcomes ... are consistently showing the protective effect at the same level.”

To maintain the blinded study design, children received injections of rabies vaccine and hepatitis A vaccine instead of a placebo for RTS,S. Both were chosen to provide additional benefits by protecting children against those infections.

With so many children followed over years, accuracy in providing the correct treatment for each study arm can be difficult. Each child was given a QR code and picture identification to facilitate drug distribution each year in this study.

Miriam K. Laufer, MD, professor and associate director for malaria research at the University of Maryland, Baltimore, who was not involved in the study, said in an interview, “This is a spectacular result, you know, decreasing disease by 60%-70% using interventions that we already have.”

RTS,S is not a new vaccine; it was developed in 2001 by GlaxoSmithKline with Path’s Malaria Vaccine Initiative, then manufactured by GSK. The Gates Foundation has supported production. Dr. Chandramohan said GSK has transferred the technology to Bharat, in India, and that it will take 2-3 years to ramp up production. Until then, enough vaccine is available to supply Kenya, Malawi, and Ghana, where the pilot studies are being done.

Dr. Laufer stressed that the “group that got RTS,S did as well as the group that received SMC.” She noted that the use of SMC is limited to specific areas of the Sahel sub-region of Africa, with a brief transmission period. In other areas of Africa where malaria has a longer transmission period, SMC isn’t as effective. “RTS,S vaccine could really have an impact” there, she added.

Asked if RTS,S might be substituted for SMC to reduce the likelihood of resistance emerging, Dr. Laufer said, “Giving RTS,S vaccine is as good as using repeated treatment of malaria drugs during the malaria season. And that’s important for two reasons. One is that the advantage of a vaccine is that you’re not producing pressure of drugs that would enable drug resistance to emerge and spread. So maybe your vaccine efficacy could last longer than drug efficacy. We don’t know the answer to that.”

Hypothesizing about the unexpectedly good trial results, Dr. Laufer explained, “We know that RTS,S decreases the number of parasites that make it into the blood when a child is bitten by an infected mosquito. When drugs like sulfadoxine-pyrimethamine and amodiaquine that have moderate efficacy only have to kill off a small number of parasites, they can work better. Maybe that explains why the combination of RTS,S and SMC created such a positive outcome.”

Dr. Laufer echoed Chandramohan, saying, “Results were much more dramatic than anybody – certainly than I anticipated.” Both physicians anticipate that WHO will give full approval for this combination this fall.

Dr. Chandramohan and Dr. Laufer have disclosed no relevant financial relationships.

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

new study from Africa shows a remarkable 70% reduction in malaria if two treatments — a vaccine and an antimalarial medication — are combined instead of giving them individually.

Malaria is endemic in the tropics. The World Health Organization (WHO) reports that in 2019, there were 229 million cases and 409,000 deaths from this parasitic infection. Most of the burden (94%) occurs in Africa, and children younger than age 5 account for 67% of the deaths.

In the Sahel region of Africa, a broad, sub-Saharan band that stretches across the continent, high malaria transmission is seasonal. Children in some countries there are treated with monthly courses of sulfadoxine-pyrimethamine and amodiaquine chemoprophylaxis during the four higher-risk months. Such seasonal malaria chemoprophylaxis (SMC) has been shown to reduce infections by up to 88% and costs an average of $3.43 per child per year.

This double-blind, randomized controlled trial enrolled young children (5-17 months old) in Burkina Faso and Mali, where SMC is the current treatment regimen. Nearly 6,000 children received either chemoprophylaxis, the RTS,S/AS01E malaria vaccine (RTS,S), or both treatments. The study, led by investigators at the London School of Hygiene and Tropical Medicine (LSHTM), was reported in the New England Journal of Medicine.

Co-lead investigator Daniel Chandramohan, MBBS, PhD, MSc, professor of public health at LSHTM, said in an interview that SMC administration is quite labor-intensive and that “we thought we can replace these four cycles of seasonal cure prevention with one seasonal vaccination like the flu vaccine ... and that there might be some additive benefit.”

Instead, the study found the combination reduces the incidence of malaria by 62% against clinical malaria infection, 70% against severe malaria, and 73% against death from malaria compared with SMC alone. “Not in our wildest dreams would I have hypothesized that this is a possibility,” Dr. Chandramohan said. He continued that this was unlikely a “freak result” because the findings are “consistent between both countries. Two, it is consistent across the years. Three, all the malaria outcomes ... are consistently showing the protective effect at the same level.”

To maintain the blinded study design, children received injections of rabies vaccine and hepatitis A vaccine instead of a placebo for RTS,S. Both were chosen to provide additional benefits by protecting children against those infections.

With so many children followed over years, accuracy in providing the correct treatment for each study arm can be difficult. Each child was given a QR code and picture identification to facilitate drug distribution each year in this study.

Miriam K. Laufer, MD, professor and associate director for malaria research at the University of Maryland, Baltimore, who was not involved in the study, said in an interview, “This is a spectacular result, you know, decreasing disease by 60%-70% using interventions that we already have.”

RTS,S is not a new vaccine; it was developed in 2001 by GlaxoSmithKline with Path’s Malaria Vaccine Initiative, then manufactured by GSK. The Gates Foundation has supported production. Dr. Chandramohan said GSK has transferred the technology to Bharat, in India, and that it will take 2-3 years to ramp up production. Until then, enough vaccine is available to supply Kenya, Malawi, and Ghana, where the pilot studies are being done.

Dr. Laufer stressed that the “group that got RTS,S did as well as the group that received SMC.” She noted that the use of SMC is limited to specific areas of the Sahel sub-region of Africa, with a brief transmission period. In other areas of Africa where malaria has a longer transmission period, SMC isn’t as effective. “RTS,S vaccine could really have an impact” there, she added.

Asked if RTS,S might be substituted for SMC to reduce the likelihood of resistance emerging, Dr. Laufer said, “Giving RTS,S vaccine is as good as using repeated treatment of malaria drugs during the malaria season. And that’s important for two reasons. One is that the advantage of a vaccine is that you’re not producing pressure of drugs that would enable drug resistance to emerge and spread. So maybe your vaccine efficacy could last longer than drug efficacy. We don’t know the answer to that.”

Hypothesizing about the unexpectedly good trial results, Dr. Laufer explained, “We know that RTS,S decreases the number of parasites that make it into the blood when a child is bitten by an infected mosquito. When drugs like sulfadoxine-pyrimethamine and amodiaquine that have moderate efficacy only have to kill off a small number of parasites, they can work better. Maybe that explains why the combination of RTS,S and SMC created such a positive outcome.”

Dr. Laufer echoed Chandramohan, saying, “Results were much more dramatic than anybody – certainly than I anticipated.” Both physicians anticipate that WHO will give full approval for this combination this fall.

Dr. Chandramohan and Dr. Laufer have disclosed no relevant financial relationships.

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

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Verruca Vulgaris Arising Within the Red Portion of a Multicolored Tattoo

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To the Editor:

The art of tattooing continues to gain popularity in the 21st century, albeit with accompanying hazards.1 Reported adverse reactions to tattoos include infections, tumors, and hypersensitivity and granulomatous reactions.2 Various infectious agents may involve tattoos, including human papillomavirus (HPV), molluscum contagiosum, herpes simplex virus, hepatitis C virus, tuberculoid and nontuberculoid mycobacteria, and Staphylococcus aureus.2 Verruca vulgaris infrequently has been reported to develop in tattoos.3,4 Previously reported cases of verruca in tattoos suggest a predilection for blue or black pigment.1-5 We report a case of verruca vulgaris occurring within the red-inked areas of a tattoo that first appeared approximately 18 years after the initial tattoo placement.

A 44-year-old woman presented with erythema, induration, and irritation of a tattoo on the left leg of 2 years’ duration. The tattoo initially was inscribed more than 20 years prior. The patient had a history of type 2 diabetes mellitus and chronic obstructive pulmonary disease. She reported no prior trauma to the area, prior rash or irritation, or similar changes to her other tattoos, including those with red ink. The affected tattoo was inscribed at a separate time from the other tattoos. Physical examination of the irritated tattoo revealed hyperkeratotic papules with firm scaling in the zone of dermal red pigment (Figure 1). Notable nodularity or deep induration was not present. The clinical differential diagnosis included a hypersensitivity reaction to red tattoo ink, sarcoidosis, and an infectious process, such as an atypical mycobacterial infection. A punch biopsy demonstrated papillomatous epidermal hyperplasia with hyperkeratosis, focal parakeratosis, and frequent vacuolization of keratinocytes with enlarged keratohyalin granules, diagnostic of verruca vulgaris (Figure 2). Of note, the patient did not have clinically apparent viral warts elsewhere on physical examination. The patient was successfully managedwith a combination of 2 treatments of intralesional Candida antigen and 3 treatments of cryotherapy with resolution of most lesions over the course of 8 months. Over the following several months, the patient applied topical salicylic acid, which led to the resolution of the remaining lesions. The verrucae had not recurred 19 months after the initial presentation.

Figure 1. Scaly papules coalescing into small plaques, largely confined to the red-inked area of a tattoo with only focal involvement of the black-inked rim.

Figure 2. Histopathologic findings of verruca vulgaris. A, Verrucous epidermal changes and dermal pigment (H&E, original magnification ×40). B, Epidermal acanthosis and papillomatosis with viral cytopathic changes (H&E, original magnification ×200). C, Underlying dermal red tattoo pigment (H&E, original magnification ×400).

The development of verruca vulgaris within a tattoo may occur secondary to various mechanisms of HPV inoculation, including introduction of the virus through contaminated ink, the tattoo artist’s saliva, autoinoculation, or koebnerization of a pre-existing verruca vulgaris.4 Local immune system dysregulation secondary to tattoo ink also has been proposed as a mechanism for HPV infection in this setting.1,5 The contents of darker tattoo pigments may promote formation of reactive oxygen species inducing local immunocompromise.5

The pathogenic mechanism was elusive in our patient. Although the localization of verruca vulgaris to the zones of red pigment may be merely coincidental, this phenomenon raised suspicion for direct inoculation via contaminated red ink. The patient’s other red ink–containing tattoos that were inscribed separately were spared, compatible with contamination of the red ink used for the affected tattoo. However, the delayed onset of nearly 2 decades was exceptional, given the shorter previously reported latencies ranging from months to 10 years.4 Autoinoculation or koebnerization is plausible, though greater involvement of nonred pigments would be expected as well as a briefer latency. Finally, the possibility of local immune dysregulation seemed feasible, given the slow evolution of the lesions largely restricted to one pigment type.



We report a case of verruca vulgaris within the red area of a multicolored tattoo that occurred approximately 18 years after tattoo placement. This case highlights a rare presentation of an infectious agent that may complicate tattoos. Both predilection for red pigment rather than black or blue pigment and the long latency period raised interesting questions regarding pathogenesis. Confirmatory biopsy enables effective management of this tattoo complication.

References
  1. Huynh TN, Jackson JD, Brodell RT. Tattoo and vaccination sites: possible nest for opportunistic infections, tumors, and dysimmune reactions. Clin Dermatol. 2014;32:678-684.
  2. Wenzel SM, Rittmann I, Landthaler M, et al. Adverse reactions after tattooing: review of the literature and comparison to results of a survey. Dermatology. 2013;226:138-147.
  3. Trefzer U, Schmollack K, Stockfleth E, et al. Verrucae in a multicolored decorative tattoo. J Am Acad Dermatol. 2004;50:478-479.
  4. Wanat KA, Tyring S, Rady P, et al. Human papillomavirus type 27 associated with multiple verruca within a tattoo: report of a case and review of the literature. Int J Dermatol. 2014;53:882-884.
  5. Ramey K, Ibrahim J, Brodell RT. Verruca localization predominately in black tattoo ink: a retrospective case series. J Eur Acad Dermatol Venereol. 2016;30:E34-E36.
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Dr. Sahni is from the Department of Dermatology, University of Utah Health, Salt Lake City. Dr. Cummings is from Commonwealth Dermatology, Richmond, Virginia. Drs. Lee, Lenczowski, and Mochel are from the Department of Dermatology, Virginia Commonwealth University, Richmond.

Dr. Mochel also is from the Department of Pathology.

The authors report no conflict of interest.

Correspondence: Mark Cameron Mochel, MD, Departments of Pathology and Dermatology, Virginia Commonwealth University Health System, 1200 E Marshall St, Gateway 6, Richmond, VA 23298 ([email protected]).

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Dr. Sahni is from the Department of Dermatology, University of Utah Health, Salt Lake City. Dr. Cummings is from Commonwealth Dermatology, Richmond, Virginia. Drs. Lee, Lenczowski, and Mochel are from the Department of Dermatology, Virginia Commonwealth University, Richmond.

Dr. Mochel also is from the Department of Pathology.

The authors report no conflict of interest.

Correspondence: Mark Cameron Mochel, MD, Departments of Pathology and Dermatology, Virginia Commonwealth University Health System, 1200 E Marshall St, Gateway 6, Richmond, VA 23298 ([email protected]).

Author and Disclosure Information

Dr. Sahni is from the Department of Dermatology, University of Utah Health, Salt Lake City. Dr. Cummings is from Commonwealth Dermatology, Richmond, Virginia. Drs. Lee, Lenczowski, and Mochel are from the Department of Dermatology, Virginia Commonwealth University, Richmond.

Dr. Mochel also is from the Department of Pathology.

The authors report no conflict of interest.

Correspondence: Mark Cameron Mochel, MD, Departments of Pathology and Dermatology, Virginia Commonwealth University Health System, 1200 E Marshall St, Gateway 6, Richmond, VA 23298 ([email protected]).

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To the Editor:

The art of tattooing continues to gain popularity in the 21st century, albeit with accompanying hazards.1 Reported adverse reactions to tattoos include infections, tumors, and hypersensitivity and granulomatous reactions.2 Various infectious agents may involve tattoos, including human papillomavirus (HPV), molluscum contagiosum, herpes simplex virus, hepatitis C virus, tuberculoid and nontuberculoid mycobacteria, and Staphylococcus aureus.2 Verruca vulgaris infrequently has been reported to develop in tattoos.3,4 Previously reported cases of verruca in tattoos suggest a predilection for blue or black pigment.1-5 We report a case of verruca vulgaris occurring within the red-inked areas of a tattoo that first appeared approximately 18 years after the initial tattoo placement.

A 44-year-old woman presented with erythema, induration, and irritation of a tattoo on the left leg of 2 years’ duration. The tattoo initially was inscribed more than 20 years prior. The patient had a history of type 2 diabetes mellitus and chronic obstructive pulmonary disease. She reported no prior trauma to the area, prior rash or irritation, or similar changes to her other tattoos, including those with red ink. The affected tattoo was inscribed at a separate time from the other tattoos. Physical examination of the irritated tattoo revealed hyperkeratotic papules with firm scaling in the zone of dermal red pigment (Figure 1). Notable nodularity or deep induration was not present. The clinical differential diagnosis included a hypersensitivity reaction to red tattoo ink, sarcoidosis, and an infectious process, such as an atypical mycobacterial infection. A punch biopsy demonstrated papillomatous epidermal hyperplasia with hyperkeratosis, focal parakeratosis, and frequent vacuolization of keratinocytes with enlarged keratohyalin granules, diagnostic of verruca vulgaris (Figure 2). Of note, the patient did not have clinically apparent viral warts elsewhere on physical examination. The patient was successfully managedwith a combination of 2 treatments of intralesional Candida antigen and 3 treatments of cryotherapy with resolution of most lesions over the course of 8 months. Over the following several months, the patient applied topical salicylic acid, which led to the resolution of the remaining lesions. The verrucae had not recurred 19 months after the initial presentation.

Figure 1. Scaly papules coalescing into small plaques, largely confined to the red-inked area of a tattoo with only focal involvement of the black-inked rim.

Figure 2. Histopathologic findings of verruca vulgaris. A, Verrucous epidermal changes and dermal pigment (H&E, original magnification ×40). B, Epidermal acanthosis and papillomatosis with viral cytopathic changes (H&E, original magnification ×200). C, Underlying dermal red tattoo pigment (H&E, original magnification ×400).

The development of verruca vulgaris within a tattoo may occur secondary to various mechanisms of HPV inoculation, including introduction of the virus through contaminated ink, the tattoo artist’s saliva, autoinoculation, or koebnerization of a pre-existing verruca vulgaris.4 Local immune system dysregulation secondary to tattoo ink also has been proposed as a mechanism for HPV infection in this setting.1,5 The contents of darker tattoo pigments may promote formation of reactive oxygen species inducing local immunocompromise.5

The pathogenic mechanism was elusive in our patient. Although the localization of verruca vulgaris to the zones of red pigment may be merely coincidental, this phenomenon raised suspicion for direct inoculation via contaminated red ink. The patient’s other red ink–containing tattoos that were inscribed separately were spared, compatible with contamination of the red ink used for the affected tattoo. However, the delayed onset of nearly 2 decades was exceptional, given the shorter previously reported latencies ranging from months to 10 years.4 Autoinoculation or koebnerization is plausible, though greater involvement of nonred pigments would be expected as well as a briefer latency. Finally, the possibility of local immune dysregulation seemed feasible, given the slow evolution of the lesions largely restricted to one pigment type.



We report a case of verruca vulgaris within the red area of a multicolored tattoo that occurred approximately 18 years after tattoo placement. This case highlights a rare presentation of an infectious agent that may complicate tattoos. Both predilection for red pigment rather than black or blue pigment and the long latency period raised interesting questions regarding pathogenesis. Confirmatory biopsy enables effective management of this tattoo complication.

To the Editor:

The art of tattooing continues to gain popularity in the 21st century, albeit with accompanying hazards.1 Reported adverse reactions to tattoos include infections, tumors, and hypersensitivity and granulomatous reactions.2 Various infectious agents may involve tattoos, including human papillomavirus (HPV), molluscum contagiosum, herpes simplex virus, hepatitis C virus, tuberculoid and nontuberculoid mycobacteria, and Staphylococcus aureus.2 Verruca vulgaris infrequently has been reported to develop in tattoos.3,4 Previously reported cases of verruca in tattoos suggest a predilection for blue or black pigment.1-5 We report a case of verruca vulgaris occurring within the red-inked areas of a tattoo that first appeared approximately 18 years after the initial tattoo placement.

A 44-year-old woman presented with erythema, induration, and irritation of a tattoo on the left leg of 2 years’ duration. The tattoo initially was inscribed more than 20 years prior. The patient had a history of type 2 diabetes mellitus and chronic obstructive pulmonary disease. She reported no prior trauma to the area, prior rash or irritation, or similar changes to her other tattoos, including those with red ink. The affected tattoo was inscribed at a separate time from the other tattoos. Physical examination of the irritated tattoo revealed hyperkeratotic papules with firm scaling in the zone of dermal red pigment (Figure 1). Notable nodularity or deep induration was not present. The clinical differential diagnosis included a hypersensitivity reaction to red tattoo ink, sarcoidosis, and an infectious process, such as an atypical mycobacterial infection. A punch biopsy demonstrated papillomatous epidermal hyperplasia with hyperkeratosis, focal parakeratosis, and frequent vacuolization of keratinocytes with enlarged keratohyalin granules, diagnostic of verruca vulgaris (Figure 2). Of note, the patient did not have clinically apparent viral warts elsewhere on physical examination. The patient was successfully managedwith a combination of 2 treatments of intralesional Candida antigen and 3 treatments of cryotherapy with resolution of most lesions over the course of 8 months. Over the following several months, the patient applied topical salicylic acid, which led to the resolution of the remaining lesions. The verrucae had not recurred 19 months after the initial presentation.

Figure 1. Scaly papules coalescing into small plaques, largely confined to the red-inked area of a tattoo with only focal involvement of the black-inked rim.

Figure 2. Histopathologic findings of verruca vulgaris. A, Verrucous epidermal changes and dermal pigment (H&E, original magnification ×40). B, Epidermal acanthosis and papillomatosis with viral cytopathic changes (H&E, original magnification ×200). C, Underlying dermal red tattoo pigment (H&E, original magnification ×400).

The development of verruca vulgaris within a tattoo may occur secondary to various mechanisms of HPV inoculation, including introduction of the virus through contaminated ink, the tattoo artist’s saliva, autoinoculation, or koebnerization of a pre-existing verruca vulgaris.4 Local immune system dysregulation secondary to tattoo ink also has been proposed as a mechanism for HPV infection in this setting.1,5 The contents of darker tattoo pigments may promote formation of reactive oxygen species inducing local immunocompromise.5

The pathogenic mechanism was elusive in our patient. Although the localization of verruca vulgaris to the zones of red pigment may be merely coincidental, this phenomenon raised suspicion for direct inoculation via contaminated red ink. The patient’s other red ink–containing tattoos that were inscribed separately were spared, compatible with contamination of the red ink used for the affected tattoo. However, the delayed onset of nearly 2 decades was exceptional, given the shorter previously reported latencies ranging from months to 10 years.4 Autoinoculation or koebnerization is plausible, though greater involvement of nonred pigments would be expected as well as a briefer latency. Finally, the possibility of local immune dysregulation seemed feasible, given the slow evolution of the lesions largely restricted to one pigment type.



We report a case of verruca vulgaris within the red area of a multicolored tattoo that occurred approximately 18 years after tattoo placement. This case highlights a rare presentation of an infectious agent that may complicate tattoos. Both predilection for red pigment rather than black or blue pigment and the long latency period raised interesting questions regarding pathogenesis. Confirmatory biopsy enables effective management of this tattoo complication.

References
  1. Huynh TN, Jackson JD, Brodell RT. Tattoo and vaccination sites: possible nest for opportunistic infections, tumors, and dysimmune reactions. Clin Dermatol. 2014;32:678-684.
  2. Wenzel SM, Rittmann I, Landthaler M, et al. Adverse reactions after tattooing: review of the literature and comparison to results of a survey. Dermatology. 2013;226:138-147.
  3. Trefzer U, Schmollack K, Stockfleth E, et al. Verrucae in a multicolored decorative tattoo. J Am Acad Dermatol. 2004;50:478-479.
  4. Wanat KA, Tyring S, Rady P, et al. Human papillomavirus type 27 associated with multiple verruca within a tattoo: report of a case and review of the literature. Int J Dermatol. 2014;53:882-884.
  5. Ramey K, Ibrahim J, Brodell RT. Verruca localization predominately in black tattoo ink: a retrospective case series. J Eur Acad Dermatol Venereol. 2016;30:E34-E36.
References
  1. Huynh TN, Jackson JD, Brodell RT. Tattoo and vaccination sites: possible nest for opportunistic infections, tumors, and dysimmune reactions. Clin Dermatol. 2014;32:678-684.
  2. Wenzel SM, Rittmann I, Landthaler M, et al. Adverse reactions after tattooing: review of the literature and comparison to results of a survey. Dermatology. 2013;226:138-147.
  3. Trefzer U, Schmollack K, Stockfleth E, et al. Verrucae in a multicolored decorative tattoo. J Am Acad Dermatol. 2004;50:478-479.
  4. Wanat KA, Tyring S, Rady P, et al. Human papillomavirus type 27 associated with multiple verruca within a tattoo: report of a case and review of the literature. Int J Dermatol. 2014;53:882-884.
  5. Ramey K, Ibrahim J, Brodell RT. Verruca localization predominately in black tattoo ink: a retrospective case series. J Eur Acad Dermatol Venereol. 2016;30:E34-E36.
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Practice Points

  • Various adverse reactions and infectious agents may involve tattoos.
  • Verruca vulgaris may affect tattoos in a color-restricted manner and demonstrate latency of many years after tattoo placement.
  • Timely diagnosis of the tattoo-involving process, confirmed by biopsy, allows for appropriate management.
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‘Deeper dive’ into opioid overdose deaths during COVID pandemic

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Opioid overdose deaths were significantly higher during 2020, but occurrences were not homogeneous across nine states. Male deaths were higher than in the 2 previous years in two states, according to a new, granular examination of data collected by researchers at the Massachusetts General Hospital (Mass General), Boston.

The analysis also showed that synthetic opioids such as fentanyl played an outsized role in most of the states that were reviewed. Additional drugs of abuse found in decedents, such as cocaine and psychostimulants, were more prevalent in some states than in others.

The Centers for Disease Control and Prevention used provisional death data in its recent report. It found that opioid-related deaths substantially rose in 2020 and that synthetic opioids were a primary driver.

The current Mass General analysis provides a more timely and detailed dive, senior author Mohammad Jalali, PhD, who is a senior scientist at Mass General’s Institute for Technology Assessment, told this news organization.

The findings, which have not yet been peer reviewed, were published in MedRxiv.
 

Shifting sands of opioid use disorder

Dr. Jalali and colleagues used a decision analysis approach to study opioid data in the hopes of providing better tools for policymakers to analyze and project trends and also to be better prepared to address the shifting sands of opioid use disorder in the United States.

Dr. Mohammad Jalali

They attempted to collect data on confirmed opioid overdose deaths from all 50 states and Washington, D.C. to assess what might have changed during the COVID-19 pandemic. Only nine states provided enough data for the analysis, which has been submitted to a peer reviewed publication.

These states were Alaska, Connecticut, Indiana, Massachusetts, North Carolina, Rhode Island, Colorado, Utah, and Wyoming.

“Drug overdose data are collected and reported more slowly than COVID-19 data,” Dr. Jalali said in a press release. The data reflected a lag time of about 4 to 8 months in Massachusetts and North Carolina to more than a year in Maryland and Ohio, he noted.

The reporting lag “has clouded the understanding of the effects of the COVID-19 pandemic on opioid-related overdose deaths,” said Dr. Jalali.

Commenting on the findings, Brandon Marshall, PhD, associate professor of epidemiology at Brown University, Providence, R.I, said that “the overall pattern of what’s being reported here is not surprising,” given the national trends seen in the CDC data.

“This paper adds a deeper dive into some of the sociodemographic trends that we’re starting to observe in specific states,” Dr. Marshall said.

Also commenting for this news organization, Brian Fuehrlein, MD, PhD, director of the psychiatric emergency department at the VA Connecticut Healthcare System in West Haven, Connecticut, noted that the current study “highlights things that we are currently seeing at VA Connecticut.”
 

Decrease in heroin, rise in fentanyl

The investigators found a significant reduction in overdose deaths that involved heroin in Alaska, Connecticut, Indiana, Massachusetts, North Carolina, and Rhode Island. That was a new trend for Alaska, Indiana, and Rhode Island, although with only 3 years of data, it’s hard to say whether it will continue, Dr. Jalali noted.

Dr. Brian Fuehrlein

The decrease in heroin involvement seemed to continue a trend previously observed in Colorado, Connecticut, Massachusetts, and North Carolina.

In Connecticut, heroin was involved in 36% of deaths in 2018, 30% in 2019, and 16% in 2020, according to the study.

“We have begun seeing more and more heroin-negative, fentanyl-positive drug screens,” said Dr. Fuehrlein, who is also associate professor of psychiatry at Yale University, New Haven, Conn.

“There is a shift from fentanyl being an adulterant to fentanyl being what is sold and used exclusively,” he added.

In 2020, 92% (n = 887) of deaths in Connecticut involved synthetic opioids, continuing a trend. In Alaska, however, synthetic opioids were involved in 60% (44) of deaths, which is a big jump from 23% (9) in 2018.

Synthetic opioids were involved in the largest percentage of overdoses in all of the states studied. The fewest deaths, 17 (49%), occurred in Wyoming.

Cocaine is also increasingly found in addition to other substances in decedents. In Alaska, about 14% of individuals who overdosed in 2020 also had cocaine in their system, which was a jump from 2% in the prior year.

In Colorado, 19% (94) of those who died also had taken cocaine, up from 13% in 2019. Cocaine was also frequently found in those who died in the northeast: 39% (467) of those who died in Massachusetts, 29% (280) in Connecticut, and 47% (109) in Rhode Island.

There was also an increase in psychostimulants found in those who had died in Massachusetts in 2020.
 

More male overdoses in 2020

Results also showed that, compared to 2019, significantly more men died from overdoses in 2020 in Colorado (61% vs. 70%, P = .017) and Indiana (62% vs. 70%, P = .026).

This finding was unexpected, said Dr. Marshall, who has observed the same phenomenon in Rhode Island. He is the scientific director of PreventOverdoseRI, Rhode Island’s drug overdose surveillance and information dashboard.

Dr. Marshall and his colleagues conducted a study that also found disproportionate increases in overdoses among men. The findings of that study will be published in September.

“We’re still trying to wrap our head around why that is,” he said. He added that a deeper dive into the Rhode Island data showed that the deaths were increased especially among middle-aged men who had been diagnosed with depression and anxiety.

The same patterns were not seen among women in either Dr. Jalali’s study or his own analysis of the Rhode Island data, said Dr. Marshall.

“That suggests the COVID-19 pandemic impacted men who are at risk for overdose in some particularly severe way,” he noted.

Dr. Fuehrlein said he believes a variety of factors have led to an increase in overdose deaths during the pandemic, including the fact that many patients who would normally seek help avoided care or dropped out of treatment because of COVID fears. In addition, other support systems, such as group therapy and Narcotics Anonymous, were unavailable.

The pandemic increased stress, which can lead to worsening substance use, said Dr. Fuehrlein. He also noted that regular opioid suppliers were often not available, which led some to buy from different dealers, “which can lead to overdose if the fentanyl content is different.”
 

 

 

Identifying at-risk individuals

Dr. Jalali and colleagues note that clinicians and policymakers could use the new study to help identify and treat at-risk individuals.

“Practitioners and policy makers can use our findings to help them anticipate which groups of people might be most affected by opioid overdose and which types of policy interventions might be most effective given each state’s unique situation,” said lead study author Gian-Gabriel P. Garcia, PhD, in a press release. At the time of the study, Dr. Garcia was a postdoctoral fellow at Mass General and Harvard Medical School. He is currently an assistant professor at Georgia Tech, Atlanta.

Dr. Marshall pointed out that Dr. Jalali’s study is also relevant for emergency departments.

ED clinicians “are and will be seeing patients coming in who have no idea they were exposed to an opioid, nevermind fentanyl,” he said. ED clinicians can discuss with patients various harm reduction techniques, including the use of naloxone as well as test strips that can detect fentanyl in the drug supply, he added.

“Given the increasing use of fentanyl, which is very dangerous in overdose, clinicians need to be well versed in a harm reduction/overdose prevention approach to patient care,” Dr. Fuehrlein agreed.

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

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Opioid overdose deaths were significantly higher during 2020, but occurrences were not homogeneous across nine states. Male deaths were higher than in the 2 previous years in two states, according to a new, granular examination of data collected by researchers at the Massachusetts General Hospital (Mass General), Boston.

The analysis also showed that synthetic opioids such as fentanyl played an outsized role in most of the states that were reviewed. Additional drugs of abuse found in decedents, such as cocaine and psychostimulants, were more prevalent in some states than in others.

The Centers for Disease Control and Prevention used provisional death data in its recent report. It found that opioid-related deaths substantially rose in 2020 and that synthetic opioids were a primary driver.

The current Mass General analysis provides a more timely and detailed dive, senior author Mohammad Jalali, PhD, who is a senior scientist at Mass General’s Institute for Technology Assessment, told this news organization.

The findings, which have not yet been peer reviewed, were published in MedRxiv.
 

Shifting sands of opioid use disorder

Dr. Jalali and colleagues used a decision analysis approach to study opioid data in the hopes of providing better tools for policymakers to analyze and project trends and also to be better prepared to address the shifting sands of opioid use disorder in the United States.

Dr. Mohammad Jalali

They attempted to collect data on confirmed opioid overdose deaths from all 50 states and Washington, D.C. to assess what might have changed during the COVID-19 pandemic. Only nine states provided enough data for the analysis, which has been submitted to a peer reviewed publication.

These states were Alaska, Connecticut, Indiana, Massachusetts, North Carolina, Rhode Island, Colorado, Utah, and Wyoming.

“Drug overdose data are collected and reported more slowly than COVID-19 data,” Dr. Jalali said in a press release. The data reflected a lag time of about 4 to 8 months in Massachusetts and North Carolina to more than a year in Maryland and Ohio, he noted.

The reporting lag “has clouded the understanding of the effects of the COVID-19 pandemic on opioid-related overdose deaths,” said Dr. Jalali.

Commenting on the findings, Brandon Marshall, PhD, associate professor of epidemiology at Brown University, Providence, R.I, said that “the overall pattern of what’s being reported here is not surprising,” given the national trends seen in the CDC data.

“This paper adds a deeper dive into some of the sociodemographic trends that we’re starting to observe in specific states,” Dr. Marshall said.

Also commenting for this news organization, Brian Fuehrlein, MD, PhD, director of the psychiatric emergency department at the VA Connecticut Healthcare System in West Haven, Connecticut, noted that the current study “highlights things that we are currently seeing at VA Connecticut.”
 

Decrease in heroin, rise in fentanyl

The investigators found a significant reduction in overdose deaths that involved heroin in Alaska, Connecticut, Indiana, Massachusetts, North Carolina, and Rhode Island. That was a new trend for Alaska, Indiana, and Rhode Island, although with only 3 years of data, it’s hard to say whether it will continue, Dr. Jalali noted.

Dr. Brian Fuehrlein

The decrease in heroin involvement seemed to continue a trend previously observed in Colorado, Connecticut, Massachusetts, and North Carolina.

In Connecticut, heroin was involved in 36% of deaths in 2018, 30% in 2019, and 16% in 2020, according to the study.

“We have begun seeing more and more heroin-negative, fentanyl-positive drug screens,” said Dr. Fuehrlein, who is also associate professor of psychiatry at Yale University, New Haven, Conn.

“There is a shift from fentanyl being an adulterant to fentanyl being what is sold and used exclusively,” he added.

In 2020, 92% (n = 887) of deaths in Connecticut involved synthetic opioids, continuing a trend. In Alaska, however, synthetic opioids were involved in 60% (44) of deaths, which is a big jump from 23% (9) in 2018.

Synthetic opioids were involved in the largest percentage of overdoses in all of the states studied. The fewest deaths, 17 (49%), occurred in Wyoming.

Cocaine is also increasingly found in addition to other substances in decedents. In Alaska, about 14% of individuals who overdosed in 2020 also had cocaine in their system, which was a jump from 2% in the prior year.

In Colorado, 19% (94) of those who died also had taken cocaine, up from 13% in 2019. Cocaine was also frequently found in those who died in the northeast: 39% (467) of those who died in Massachusetts, 29% (280) in Connecticut, and 47% (109) in Rhode Island.

There was also an increase in psychostimulants found in those who had died in Massachusetts in 2020.
 

More male overdoses in 2020

Results also showed that, compared to 2019, significantly more men died from overdoses in 2020 in Colorado (61% vs. 70%, P = .017) and Indiana (62% vs. 70%, P = .026).

This finding was unexpected, said Dr. Marshall, who has observed the same phenomenon in Rhode Island. He is the scientific director of PreventOverdoseRI, Rhode Island’s drug overdose surveillance and information dashboard.

Dr. Marshall and his colleagues conducted a study that also found disproportionate increases in overdoses among men. The findings of that study will be published in September.

“We’re still trying to wrap our head around why that is,” he said. He added that a deeper dive into the Rhode Island data showed that the deaths were increased especially among middle-aged men who had been diagnosed with depression and anxiety.

The same patterns were not seen among women in either Dr. Jalali’s study or his own analysis of the Rhode Island data, said Dr. Marshall.

“That suggests the COVID-19 pandemic impacted men who are at risk for overdose in some particularly severe way,” he noted.

Dr. Fuehrlein said he believes a variety of factors have led to an increase in overdose deaths during the pandemic, including the fact that many patients who would normally seek help avoided care or dropped out of treatment because of COVID fears. In addition, other support systems, such as group therapy and Narcotics Anonymous, were unavailable.

The pandemic increased stress, which can lead to worsening substance use, said Dr. Fuehrlein. He also noted that regular opioid suppliers were often not available, which led some to buy from different dealers, “which can lead to overdose if the fentanyl content is different.”
 

 

 

Identifying at-risk individuals

Dr. Jalali and colleagues note that clinicians and policymakers could use the new study to help identify and treat at-risk individuals.

“Practitioners and policy makers can use our findings to help them anticipate which groups of people might be most affected by opioid overdose and which types of policy interventions might be most effective given each state’s unique situation,” said lead study author Gian-Gabriel P. Garcia, PhD, in a press release. At the time of the study, Dr. Garcia was a postdoctoral fellow at Mass General and Harvard Medical School. He is currently an assistant professor at Georgia Tech, Atlanta.

Dr. Marshall pointed out that Dr. Jalali’s study is also relevant for emergency departments.

ED clinicians “are and will be seeing patients coming in who have no idea they were exposed to an opioid, nevermind fentanyl,” he said. ED clinicians can discuss with patients various harm reduction techniques, including the use of naloxone as well as test strips that can detect fentanyl in the drug supply, he added.

“Given the increasing use of fentanyl, which is very dangerous in overdose, clinicians need to be well versed in a harm reduction/overdose prevention approach to patient care,” Dr. Fuehrlein agreed.

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

Opioid overdose deaths were significantly higher during 2020, but occurrences were not homogeneous across nine states. Male deaths were higher than in the 2 previous years in two states, according to a new, granular examination of data collected by researchers at the Massachusetts General Hospital (Mass General), Boston.

The analysis also showed that synthetic opioids such as fentanyl played an outsized role in most of the states that were reviewed. Additional drugs of abuse found in decedents, such as cocaine and psychostimulants, were more prevalent in some states than in others.

The Centers for Disease Control and Prevention used provisional death data in its recent report. It found that opioid-related deaths substantially rose in 2020 and that synthetic opioids were a primary driver.

The current Mass General analysis provides a more timely and detailed dive, senior author Mohammad Jalali, PhD, who is a senior scientist at Mass General’s Institute for Technology Assessment, told this news organization.

The findings, which have not yet been peer reviewed, were published in MedRxiv.
 

Shifting sands of opioid use disorder

Dr. Jalali and colleagues used a decision analysis approach to study opioid data in the hopes of providing better tools for policymakers to analyze and project trends and also to be better prepared to address the shifting sands of opioid use disorder in the United States.

Dr. Mohammad Jalali

They attempted to collect data on confirmed opioid overdose deaths from all 50 states and Washington, D.C. to assess what might have changed during the COVID-19 pandemic. Only nine states provided enough data for the analysis, which has been submitted to a peer reviewed publication.

These states were Alaska, Connecticut, Indiana, Massachusetts, North Carolina, Rhode Island, Colorado, Utah, and Wyoming.

“Drug overdose data are collected and reported more slowly than COVID-19 data,” Dr. Jalali said in a press release. The data reflected a lag time of about 4 to 8 months in Massachusetts and North Carolina to more than a year in Maryland and Ohio, he noted.

The reporting lag “has clouded the understanding of the effects of the COVID-19 pandemic on opioid-related overdose deaths,” said Dr. Jalali.

Commenting on the findings, Brandon Marshall, PhD, associate professor of epidemiology at Brown University, Providence, R.I, said that “the overall pattern of what’s being reported here is not surprising,” given the national trends seen in the CDC data.

“This paper adds a deeper dive into some of the sociodemographic trends that we’re starting to observe in specific states,” Dr. Marshall said.

Also commenting for this news organization, Brian Fuehrlein, MD, PhD, director of the psychiatric emergency department at the VA Connecticut Healthcare System in West Haven, Connecticut, noted that the current study “highlights things that we are currently seeing at VA Connecticut.”
 

Decrease in heroin, rise in fentanyl

The investigators found a significant reduction in overdose deaths that involved heroin in Alaska, Connecticut, Indiana, Massachusetts, North Carolina, and Rhode Island. That was a new trend for Alaska, Indiana, and Rhode Island, although with only 3 years of data, it’s hard to say whether it will continue, Dr. Jalali noted.

Dr. Brian Fuehrlein

The decrease in heroin involvement seemed to continue a trend previously observed in Colorado, Connecticut, Massachusetts, and North Carolina.

In Connecticut, heroin was involved in 36% of deaths in 2018, 30% in 2019, and 16% in 2020, according to the study.

“We have begun seeing more and more heroin-negative, fentanyl-positive drug screens,” said Dr. Fuehrlein, who is also associate professor of psychiatry at Yale University, New Haven, Conn.

“There is a shift from fentanyl being an adulterant to fentanyl being what is sold and used exclusively,” he added.

In 2020, 92% (n = 887) of deaths in Connecticut involved synthetic opioids, continuing a trend. In Alaska, however, synthetic opioids were involved in 60% (44) of deaths, which is a big jump from 23% (9) in 2018.

Synthetic opioids were involved in the largest percentage of overdoses in all of the states studied. The fewest deaths, 17 (49%), occurred in Wyoming.

Cocaine is also increasingly found in addition to other substances in decedents. In Alaska, about 14% of individuals who overdosed in 2020 also had cocaine in their system, which was a jump from 2% in the prior year.

In Colorado, 19% (94) of those who died also had taken cocaine, up from 13% in 2019. Cocaine was also frequently found in those who died in the northeast: 39% (467) of those who died in Massachusetts, 29% (280) in Connecticut, and 47% (109) in Rhode Island.

There was also an increase in psychostimulants found in those who had died in Massachusetts in 2020.
 

More male overdoses in 2020

Results also showed that, compared to 2019, significantly more men died from overdoses in 2020 in Colorado (61% vs. 70%, P = .017) and Indiana (62% vs. 70%, P = .026).

This finding was unexpected, said Dr. Marshall, who has observed the same phenomenon in Rhode Island. He is the scientific director of PreventOverdoseRI, Rhode Island’s drug overdose surveillance and information dashboard.

Dr. Marshall and his colleagues conducted a study that also found disproportionate increases in overdoses among men. The findings of that study will be published in September.

“We’re still trying to wrap our head around why that is,” he said. He added that a deeper dive into the Rhode Island data showed that the deaths were increased especially among middle-aged men who had been diagnosed with depression and anxiety.

The same patterns were not seen among women in either Dr. Jalali’s study or his own analysis of the Rhode Island data, said Dr. Marshall.

“That suggests the COVID-19 pandemic impacted men who are at risk for overdose in some particularly severe way,” he noted.

Dr. Fuehrlein said he believes a variety of factors have led to an increase in overdose deaths during the pandemic, including the fact that many patients who would normally seek help avoided care or dropped out of treatment because of COVID fears. In addition, other support systems, such as group therapy and Narcotics Anonymous, were unavailable.

The pandemic increased stress, which can lead to worsening substance use, said Dr. Fuehrlein. He also noted that regular opioid suppliers were often not available, which led some to buy from different dealers, “which can lead to overdose if the fentanyl content is different.”
 

 

 

Identifying at-risk individuals

Dr. Jalali and colleagues note that clinicians and policymakers could use the new study to help identify and treat at-risk individuals.

“Practitioners and policy makers can use our findings to help them anticipate which groups of people might be most affected by opioid overdose and which types of policy interventions might be most effective given each state’s unique situation,” said lead study author Gian-Gabriel P. Garcia, PhD, in a press release. At the time of the study, Dr. Garcia was a postdoctoral fellow at Mass General and Harvard Medical School. He is currently an assistant professor at Georgia Tech, Atlanta.

Dr. Marshall pointed out that Dr. Jalali’s study is also relevant for emergency departments.

ED clinicians “are and will be seeing patients coming in who have no idea they were exposed to an opioid, nevermind fentanyl,” he said. ED clinicians can discuss with patients various harm reduction techniques, including the use of naloxone as well as test strips that can detect fentanyl in the drug supply, he added.

“Given the increasing use of fentanyl, which is very dangerous in overdose, clinicians need to be well versed in a harm reduction/overdose prevention approach to patient care,” Dr. Fuehrlein agreed.

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

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Children and COVID: Weekly cases top 200,000, vaccinations down

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Thu, 09/09/2021 - 16:17

Weekly pediatric cases of COVID-19 exceeded 200,000 for just the second time during the pandemic, while new vaccinations in children continued to decline.

There were almost 204,000 new cases reported in children during the week of Aug. 20-26, the highest 1-week total since the peak of 211,000 in mid-January. The weekly count has now increased for 9 consecutive weeks, during which time it has risen by over 2,300%, the American Academy of Pediatrics and the Children’s Hospital Association said in their weekly COVID-19 report. Total cases in children number almost 4.8 million since the pandemic started.

Vaccinations in children are following a different trend. Vaccine initiation has dropped 3 weeks in a row for both of the eligible age groups: First doses administered were down by 29% among 12- to 15-year-olds over that span and by 32% in 16- to 17-year-olds, according to data from the Centers for Disease Control and Prevention.

Since vaccination for children aged 12-15 years started in May, 49% had received at least one dose, and just over 36% were fully vaccinated as of Aug. 30. Among children aged 16-17 years, who have been eligible since December, 57.5% had gotten at least one dose of the vaccine and 46% have completed the two-dose regimen. The total number of children with at least one dose, including those under age 12 who are involved in clinical trials, was about 12 million, the CDC said on its COVID Data Tracker.
 

Hospitalizations are higher than ever

The recent rise in new child cases has been accompanied by an unprecedented increase in hospitalizations. The daily rate in children aged 0-17 years, which did not surpass 0.30 new admissions per 100,000 population during the worst of the winter surge, had risen to 0.45 per 100,000 by Aug. 26. Since July 4, when the new-admission rate was at its low point of 0.07 per 100,000, hospitalizations in children have jumped by 543%, based on data reported to the CDC by 5,251 hospitals.

A total of 52,245 children were admitted with confirmed COVID-19 from Aug. 1, 2020, when the CDC dataset begins, to Aug. 28, 2021. Those children represent 1.9% of all COVID admissions (2.7 million) in the United States over that period, the CDC said.



Total COVID-related deaths in children are up to 425 in the 48 jurisdictions (45 states, New York City, Puerto Rico, and Guam) that provide mortality data by age, the AAP and the CHA said.

Record-high numbers for the previous 2 reporting weeks – 23 deaths during Aug. 20-26 and 24 deaths during Aug. 13-19, when the previous weekly high was 16 – at least partially reflect the recent addition of South Carolina and New Mexico to the AAP/CHA database, as the two states just started reporting age-related data.

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Weekly pediatric cases of COVID-19 exceeded 200,000 for just the second time during the pandemic, while new vaccinations in children continued to decline.

There were almost 204,000 new cases reported in children during the week of Aug. 20-26, the highest 1-week total since the peak of 211,000 in mid-January. The weekly count has now increased for 9 consecutive weeks, during which time it has risen by over 2,300%, the American Academy of Pediatrics and the Children’s Hospital Association said in their weekly COVID-19 report. Total cases in children number almost 4.8 million since the pandemic started.

Vaccinations in children are following a different trend. Vaccine initiation has dropped 3 weeks in a row for both of the eligible age groups: First doses administered were down by 29% among 12- to 15-year-olds over that span and by 32% in 16- to 17-year-olds, according to data from the Centers for Disease Control and Prevention.

Since vaccination for children aged 12-15 years started in May, 49% had received at least one dose, and just over 36% were fully vaccinated as of Aug. 30. Among children aged 16-17 years, who have been eligible since December, 57.5% had gotten at least one dose of the vaccine and 46% have completed the two-dose regimen. The total number of children with at least one dose, including those under age 12 who are involved in clinical trials, was about 12 million, the CDC said on its COVID Data Tracker.
 

Hospitalizations are higher than ever

The recent rise in new child cases has been accompanied by an unprecedented increase in hospitalizations. The daily rate in children aged 0-17 years, which did not surpass 0.30 new admissions per 100,000 population during the worst of the winter surge, had risen to 0.45 per 100,000 by Aug. 26. Since July 4, when the new-admission rate was at its low point of 0.07 per 100,000, hospitalizations in children have jumped by 543%, based on data reported to the CDC by 5,251 hospitals.

A total of 52,245 children were admitted with confirmed COVID-19 from Aug. 1, 2020, when the CDC dataset begins, to Aug. 28, 2021. Those children represent 1.9% of all COVID admissions (2.7 million) in the United States over that period, the CDC said.



Total COVID-related deaths in children are up to 425 in the 48 jurisdictions (45 states, New York City, Puerto Rico, and Guam) that provide mortality data by age, the AAP and the CHA said.

Record-high numbers for the previous 2 reporting weeks – 23 deaths during Aug. 20-26 and 24 deaths during Aug. 13-19, when the previous weekly high was 16 – at least partially reflect the recent addition of South Carolina and New Mexico to the AAP/CHA database, as the two states just started reporting age-related data.

Weekly pediatric cases of COVID-19 exceeded 200,000 for just the second time during the pandemic, while new vaccinations in children continued to decline.

There were almost 204,000 new cases reported in children during the week of Aug. 20-26, the highest 1-week total since the peak of 211,000 in mid-January. The weekly count has now increased for 9 consecutive weeks, during which time it has risen by over 2,300%, the American Academy of Pediatrics and the Children’s Hospital Association said in their weekly COVID-19 report. Total cases in children number almost 4.8 million since the pandemic started.

Vaccinations in children are following a different trend. Vaccine initiation has dropped 3 weeks in a row for both of the eligible age groups: First doses administered were down by 29% among 12- to 15-year-olds over that span and by 32% in 16- to 17-year-olds, according to data from the Centers for Disease Control and Prevention.

Since vaccination for children aged 12-15 years started in May, 49% had received at least one dose, and just over 36% were fully vaccinated as of Aug. 30. Among children aged 16-17 years, who have been eligible since December, 57.5% had gotten at least one dose of the vaccine and 46% have completed the two-dose regimen. The total number of children with at least one dose, including those under age 12 who are involved in clinical trials, was about 12 million, the CDC said on its COVID Data Tracker.
 

Hospitalizations are higher than ever

The recent rise in new child cases has been accompanied by an unprecedented increase in hospitalizations. The daily rate in children aged 0-17 years, which did not surpass 0.30 new admissions per 100,000 population during the worst of the winter surge, had risen to 0.45 per 100,000 by Aug. 26. Since July 4, when the new-admission rate was at its low point of 0.07 per 100,000, hospitalizations in children have jumped by 543%, based on data reported to the CDC by 5,251 hospitals.

A total of 52,245 children were admitted with confirmed COVID-19 from Aug. 1, 2020, when the CDC dataset begins, to Aug. 28, 2021. Those children represent 1.9% of all COVID admissions (2.7 million) in the United States over that period, the CDC said.



Total COVID-related deaths in children are up to 425 in the 48 jurisdictions (45 states, New York City, Puerto Rico, and Guam) that provide mortality data by age, the AAP and the CHA said.

Record-high numbers for the previous 2 reporting weeks – 23 deaths during Aug. 20-26 and 24 deaths during Aug. 13-19, when the previous weekly high was 16 – at least partially reflect the recent addition of South Carolina and New Mexico to the AAP/CHA database, as the two states just started reporting age-related data.

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ICU infections and all-cause hospital mortality rate

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Mon, 08/30/2021 - 13:48

Background: Many articles have been published on sepsis and mortality in ICUs, but there are not many analyzing outcomes in patients with infections, nor types of infections. More information on the infection rate, types of infection, and possible impact on mortality should heighten awareness of infection effects, as well as guide resource allocation and help direct policy development for diagnosis and treatment.

Dr. Anna Rogozinska

Study design: 24-hour point-prevalence study with longitudinal follow-up.

Setting: ICUs in 1,150 centers in 88 countries.

Synopsis: The study included 15,202 patients who were aged 18 or older (mean, 61.6) within a 24-hour time period on Sept. 13, 2017, who were admitted to the ICU in participating centers and had documented, confirmed, or suspected infection. The investigators looked at prevalence of infection and antibiotic exposure on the study day and the main outcome measure was all cause in-hospital mortality, which was compiled 60 days later. The prevalence of suspected or proven infection in ICUs was 54% (8,135) and that of ICU-acquired infection was 22%. Of confirmed or suspected infection, 65% (5,259) had at least one positive microbiology culture. Of those cultures, 67% were gram-negative and 37% gram-positive bacteria, and 16% were fungal. 70% of ICU patients received at least one antibiotic. The in-hospital mortality rate with proven or suspected infection was 30% (2,404 of 7,936). Multilevel analysis disclosed two independent risk factors for mortality, which were ICU-acquired infections and antibiotic-resistant organisms, specifically, vancomycin-resistant Enterococcus, Klebsiella resistant to beta-lactam antibiotics, and carbapenem-resistant Acinetobacter.

Despite limitations related to being an observational study, 24-hour point evaluation, a centrally controlled database, and different geographic locations, this study elucidated the world-wide prevalence of ICU infection and high hospital-in mortality in those patients.

Bottom line: There is a high prevalence of infection in ICUs: 43%-60% depending on location. This is associated with 30% in-hospital mortality.

Citation: Vincent J-L et al. Prevalance and outcomes of infection among patients in intensive care units in 2017. JAMA. 2020 Mar 24;323(15):1478-87.

Dr. Rogozinska is a hospitalist and assistant professor of medicine at UK HealthCare, Lexington, Ky.

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Background: Many articles have been published on sepsis and mortality in ICUs, but there are not many analyzing outcomes in patients with infections, nor types of infections. More information on the infection rate, types of infection, and possible impact on mortality should heighten awareness of infection effects, as well as guide resource allocation and help direct policy development for diagnosis and treatment.

Dr. Anna Rogozinska

Study design: 24-hour point-prevalence study with longitudinal follow-up.

Setting: ICUs in 1,150 centers in 88 countries.

Synopsis: The study included 15,202 patients who were aged 18 or older (mean, 61.6) within a 24-hour time period on Sept. 13, 2017, who were admitted to the ICU in participating centers and had documented, confirmed, or suspected infection. The investigators looked at prevalence of infection and antibiotic exposure on the study day and the main outcome measure was all cause in-hospital mortality, which was compiled 60 days later. The prevalence of suspected or proven infection in ICUs was 54% (8,135) and that of ICU-acquired infection was 22%. Of confirmed or suspected infection, 65% (5,259) had at least one positive microbiology culture. Of those cultures, 67% were gram-negative and 37% gram-positive bacteria, and 16% were fungal. 70% of ICU patients received at least one antibiotic. The in-hospital mortality rate with proven or suspected infection was 30% (2,404 of 7,936). Multilevel analysis disclosed two independent risk factors for mortality, which were ICU-acquired infections and antibiotic-resistant organisms, specifically, vancomycin-resistant Enterococcus, Klebsiella resistant to beta-lactam antibiotics, and carbapenem-resistant Acinetobacter.

Despite limitations related to being an observational study, 24-hour point evaluation, a centrally controlled database, and different geographic locations, this study elucidated the world-wide prevalence of ICU infection and high hospital-in mortality in those patients.

Bottom line: There is a high prevalence of infection in ICUs: 43%-60% depending on location. This is associated with 30% in-hospital mortality.

Citation: Vincent J-L et al. Prevalance and outcomes of infection among patients in intensive care units in 2017. JAMA. 2020 Mar 24;323(15):1478-87.

Dr. Rogozinska is a hospitalist and assistant professor of medicine at UK HealthCare, Lexington, Ky.

Background: Many articles have been published on sepsis and mortality in ICUs, but there are not many analyzing outcomes in patients with infections, nor types of infections. More information on the infection rate, types of infection, and possible impact on mortality should heighten awareness of infection effects, as well as guide resource allocation and help direct policy development for diagnosis and treatment.

Dr. Anna Rogozinska

Study design: 24-hour point-prevalence study with longitudinal follow-up.

Setting: ICUs in 1,150 centers in 88 countries.

Synopsis: The study included 15,202 patients who were aged 18 or older (mean, 61.6) within a 24-hour time period on Sept. 13, 2017, who were admitted to the ICU in participating centers and had documented, confirmed, or suspected infection. The investigators looked at prevalence of infection and antibiotic exposure on the study day and the main outcome measure was all cause in-hospital mortality, which was compiled 60 days later. The prevalence of suspected or proven infection in ICUs was 54% (8,135) and that of ICU-acquired infection was 22%. Of confirmed or suspected infection, 65% (5,259) had at least one positive microbiology culture. Of those cultures, 67% were gram-negative and 37% gram-positive bacteria, and 16% were fungal. 70% of ICU patients received at least one antibiotic. The in-hospital mortality rate with proven or suspected infection was 30% (2,404 of 7,936). Multilevel analysis disclosed two independent risk factors for mortality, which were ICU-acquired infections and antibiotic-resistant organisms, specifically, vancomycin-resistant Enterococcus, Klebsiella resistant to beta-lactam antibiotics, and carbapenem-resistant Acinetobacter.

Despite limitations related to being an observational study, 24-hour point evaluation, a centrally controlled database, and different geographic locations, this study elucidated the world-wide prevalence of ICU infection and high hospital-in mortality in those patients.

Bottom line: There is a high prevalence of infection in ICUs: 43%-60% depending on location. This is associated with 30% in-hospital mortality.

Citation: Vincent J-L et al. Prevalance and outcomes of infection among patients in intensive care units in 2017. JAMA. 2020 Mar 24;323(15):1478-87.

Dr. Rogozinska is a hospitalist and assistant professor of medicine at UK HealthCare, Lexington, Ky.

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Study evaluates OTC treatments for molluscum contagiosum

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Mon, 08/30/2021 - 07:41

Most over-the-counter (OTC) products for molluscum contagiosum (MC) do not include sufficient information about their plant-based ingredients or appropriate dosing, according to an analysis of eight such products available to U.S. consumers

“It’s important for clinicians who see children with molluscum to be aware of the many products marketed to patients and to be able to provide objective information about them,” senior author Elaine Siegfried, MD, said in an interview following the annual meeting of the Society for Pediatric Dermatology, where the abstract was presented during a poster session.

In the text of their abstract, Dr. Siegfried, professor of pediatrics and dermatology at Saint Louis University, and coauthors Isaac Hoft, of Open Mind Holistics in Ft. Collins, Colo., and Samantha K. Ong, BA, a student at SLU, noted that MC primarily infects children, with an annual incidence of 8%. “Although the disease is self-limited, associated symptoms, contagion and an average 1-year duration prompt concern and frequent medical visits,” they wrote.

The optimal treatment for MC has not been defined and there is currently no approved medication approved for the condition, although three products are in development: VP-102 (cantharidin) by Verrica Pharmaceuticals; SB206, a topical antiviral by Novan; and 10%-15% KOH formulation by the Gurina Foundation.

But many OTC products have been marketed to treat the condition. To identify the OTC products and to assess accompanying information related to safety, efficacy, and cost, the researchers performed an internet search using the terms “molluscum” plus “treatment,” “treatment at home,” “relief,” and “medication.” Eight products were identified for analysis: Conzerol (Elroselabs), Molleave (Innovative Med), Mollenol (Jeva Laboratories), MolluscumBLAST (Revitalize Life Organics), Molluscum Away Patches (Molluscum Away), Naturasil (Nature’s Innovation), Terrasil (Advanced Skincare % Topical Solutions), and Zymaderm (Naturopathix). Package sizes ranged from 0.78 to 1.5 ounces, and prices ranged from about $19 to almost $55.



Dr. Siegfried and colleagues found that all products provided instructions on application and use but most package labels did not include sufficient information about their plant-based ingredients or appropriate dosing. Six of the eight products contained Thuja occidentalis (Arbor vitae), a coniferous cedar whose essential oil has been used in homeopathic products for its anti-inflammatory and antiviral properties. Lemon extract, tea tree oil, and other botanicals were present in no more than three products each. Only two of the products provided information about the number of lesions that could be treated per package.

“The lack of national oversight as well as robust methods for high-level data analysis make safety and efficacy unclear for a Thuja extract marketed to treat MC,” the researchers wrote. “Numerous adverse drug events and positive intradermal skin tests related to Thuja have been reported.”

Dr. Siegfried added that many OTC products offer a money-back guarantee, “so when seeing a patient who failed to respond to one of these products, encourage them, at least, to request a refund, but to also submit a comment about lack of efficacy, in order to provide more balanced Internet information.”

Dr. Siegfried disclosed that she has served as an investigator and consultant for Verrica Pharmaceuticals, and as a consultant and Data Safety Monitoring board member for Novan, two of the companies currently developing drugs to treat molluscum. Her coauthors had no conflicts of interest to disclose.

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Most over-the-counter (OTC) products for molluscum contagiosum (MC) do not include sufficient information about their plant-based ingredients or appropriate dosing, according to an analysis of eight such products available to U.S. consumers

“It’s important for clinicians who see children with molluscum to be aware of the many products marketed to patients and to be able to provide objective information about them,” senior author Elaine Siegfried, MD, said in an interview following the annual meeting of the Society for Pediatric Dermatology, where the abstract was presented during a poster session.

In the text of their abstract, Dr. Siegfried, professor of pediatrics and dermatology at Saint Louis University, and coauthors Isaac Hoft, of Open Mind Holistics in Ft. Collins, Colo., and Samantha K. Ong, BA, a student at SLU, noted that MC primarily infects children, with an annual incidence of 8%. “Although the disease is self-limited, associated symptoms, contagion and an average 1-year duration prompt concern and frequent medical visits,” they wrote.

The optimal treatment for MC has not been defined and there is currently no approved medication approved for the condition, although three products are in development: VP-102 (cantharidin) by Verrica Pharmaceuticals; SB206, a topical antiviral by Novan; and 10%-15% KOH formulation by the Gurina Foundation.

But many OTC products have been marketed to treat the condition. To identify the OTC products and to assess accompanying information related to safety, efficacy, and cost, the researchers performed an internet search using the terms “molluscum” plus “treatment,” “treatment at home,” “relief,” and “medication.” Eight products were identified for analysis: Conzerol (Elroselabs), Molleave (Innovative Med), Mollenol (Jeva Laboratories), MolluscumBLAST (Revitalize Life Organics), Molluscum Away Patches (Molluscum Away), Naturasil (Nature’s Innovation), Terrasil (Advanced Skincare % Topical Solutions), and Zymaderm (Naturopathix). Package sizes ranged from 0.78 to 1.5 ounces, and prices ranged from about $19 to almost $55.



Dr. Siegfried and colleagues found that all products provided instructions on application and use but most package labels did not include sufficient information about their plant-based ingredients or appropriate dosing. Six of the eight products contained Thuja occidentalis (Arbor vitae), a coniferous cedar whose essential oil has been used in homeopathic products for its anti-inflammatory and antiviral properties. Lemon extract, tea tree oil, and other botanicals were present in no more than three products each. Only two of the products provided information about the number of lesions that could be treated per package.

“The lack of national oversight as well as robust methods for high-level data analysis make safety and efficacy unclear for a Thuja extract marketed to treat MC,” the researchers wrote. “Numerous adverse drug events and positive intradermal skin tests related to Thuja have been reported.”

Dr. Siegfried added that many OTC products offer a money-back guarantee, “so when seeing a patient who failed to respond to one of these products, encourage them, at least, to request a refund, but to also submit a comment about lack of efficacy, in order to provide more balanced Internet information.”

Dr. Siegfried disclosed that she has served as an investigator and consultant for Verrica Pharmaceuticals, and as a consultant and Data Safety Monitoring board member for Novan, two of the companies currently developing drugs to treat molluscum. Her coauthors had no conflicts of interest to disclose.

Most over-the-counter (OTC) products for molluscum contagiosum (MC) do not include sufficient information about their plant-based ingredients or appropriate dosing, according to an analysis of eight such products available to U.S. consumers

“It’s important for clinicians who see children with molluscum to be aware of the many products marketed to patients and to be able to provide objective information about them,” senior author Elaine Siegfried, MD, said in an interview following the annual meeting of the Society for Pediatric Dermatology, where the abstract was presented during a poster session.

In the text of their abstract, Dr. Siegfried, professor of pediatrics and dermatology at Saint Louis University, and coauthors Isaac Hoft, of Open Mind Holistics in Ft. Collins, Colo., and Samantha K. Ong, BA, a student at SLU, noted that MC primarily infects children, with an annual incidence of 8%. “Although the disease is self-limited, associated symptoms, contagion and an average 1-year duration prompt concern and frequent medical visits,” they wrote.

The optimal treatment for MC has not been defined and there is currently no approved medication approved for the condition, although three products are in development: VP-102 (cantharidin) by Verrica Pharmaceuticals; SB206, a topical antiviral by Novan; and 10%-15% KOH formulation by the Gurina Foundation.

But many OTC products have been marketed to treat the condition. To identify the OTC products and to assess accompanying information related to safety, efficacy, and cost, the researchers performed an internet search using the terms “molluscum” plus “treatment,” “treatment at home,” “relief,” and “medication.” Eight products were identified for analysis: Conzerol (Elroselabs), Molleave (Innovative Med), Mollenol (Jeva Laboratories), MolluscumBLAST (Revitalize Life Organics), Molluscum Away Patches (Molluscum Away), Naturasil (Nature’s Innovation), Terrasil (Advanced Skincare % Topical Solutions), and Zymaderm (Naturopathix). Package sizes ranged from 0.78 to 1.5 ounces, and prices ranged from about $19 to almost $55.



Dr. Siegfried and colleagues found that all products provided instructions on application and use but most package labels did not include sufficient information about their plant-based ingredients or appropriate dosing. Six of the eight products contained Thuja occidentalis (Arbor vitae), a coniferous cedar whose essential oil has been used in homeopathic products for its anti-inflammatory and antiviral properties. Lemon extract, tea tree oil, and other botanicals were present in no more than three products each. Only two of the products provided information about the number of lesions that could be treated per package.

“The lack of national oversight as well as robust methods for high-level data analysis make safety and efficacy unclear for a Thuja extract marketed to treat MC,” the researchers wrote. “Numerous adverse drug events and positive intradermal skin tests related to Thuja have been reported.”

Dr. Siegfried added that many OTC products offer a money-back guarantee, “so when seeing a patient who failed to respond to one of these products, encourage them, at least, to request a refund, but to also submit a comment about lack of efficacy, in order to provide more balanced Internet information.”

Dr. Siegfried disclosed that she has served as an investigator and consultant for Verrica Pharmaceuticals, and as a consultant and Data Safety Monitoring board member for Novan, two of the companies currently developing drugs to treat molluscum. Her coauthors had no conflicts of interest to disclose.

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TB prevention in people with HIV: How short can we go?

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Fri, 08/27/2021 - 14:29

 

A 3-month, 12-dose regimen of rifapentine and isoniazid (INH) was less toxic, had better compliance, and showed similar efficacy as 6 months of INH alone in preventing tuberculosis (TB) in people with HIV, according to the results of a clinical trial reported in Annals of Internal Medicine.

The study, a randomized pragmatic trial in South Africa, Ethiopia, and Mozambique, was called WHIP3TB (Weekly High Dose Isoniazid and Rifapentine [P] Periodic Prophylaxis for TB).

Investigators randomized patients to three groups, comparing a 3-month course of weekly rifapentine-INH, given either once or repeated in a year, with daily isoniazid for 6 months. At 1 year, 90% of the rifapentine-INH group (3HP) were still on therapy, compared with only 50.5% in the INH group.

In the study, patients were initially assessed for TB using the World Health Organization four-symptom screen, but the sensitivity in HIV patients on antiretrovirals (ARVs) was only 53%. In addition to symptoms, screening at 12 months included a chest x-ray and sputum culture.

Of the 30 patients at month 12 with confirmed TB, 26 were asymptomatic, suggesting physicians should do further evaluation prior to initiating preventive TB treatment (which was not part of the WHO recommendation when the study was initiated).

Another unexpected finding was that 10.2% of the TB cases detected in the combined 3HP groups in South Africa, along with 18% of the cases in Mozambique, had rifampin resistance.

Investigator Gavin Churchyard, MBBCh, PhD, CEO of the Aurum Institute in Johannesburg, South Africa, said in an interview: “It appeared that taking this potent short course regimen – they’re just taking a single course – provided the same level of protection as taking repeat courses of the antibiotics. So that’s good news.” He noted, too, that TB transmission rates have been declining in sub-Saharan Africa because of ARV, and “so it may just be that a single course is now adequate because the risk of exposure and reinfection” is decreasing.

But Madhu Pai, MD, PhD, associate director, McGill International TB Centre, Montreal, who was not involved in the study, shared a more cautious interpretation. He said in an interview that the 2020 WHO Consolidated Guidelines on Tuberculosis state: “In settings with high TB transmission, adults and adolescents living with HIV ... should receive at least 36 months of daily isoniazid preventive therapy (IPT) ... whether or not the person is on ART.” The problem is that almost no one can tolerate prolonged therapy with INH because of side effects, as has been shown in numerous studies.

For successful TB treatment, Dr. Pai said, “Even 3HP is not going to cut it; they’re going to get reinfected again. So that shortening of that 36 months is what this trial is really all about, in terms of new information ... and they were not successful.” But because this is still the most practical course, Dr. Pai suggests that follow-up monitoring for reinfection will be the most likely path forward.

Dr. Churchyard concluded: “If we wanted to end the global TB epidemic, we need to continue to find ways to further reduce the risk of TB overall at a population level, and then amongst high-risk groups such as people with HIV, including those on ARVs, and who have had a course of preventive therapy. ... We need to look for other strategies to further reduce that risk. Part of those strategies may be doing a more intensive screen. But also, it may be adding another intervention, particularly TB vaccines. ... No single intervention by itself will adequately address the risk of TB in people with HIV in these high TB transmission settings.”

Dr. Pai reported no relevant financial relationships. Dr. Churchyard has reported participation in a Sanofi advisory committee on the prevention of TB. Judy Stone, MD, is an infectious disease specialist and author of “Resilience: One Family’s Story of Hope and Triumph Over Evil” and of “Conducting Clinical Research.”

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

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A 3-month, 12-dose regimen of rifapentine and isoniazid (INH) was less toxic, had better compliance, and showed similar efficacy as 6 months of INH alone in preventing tuberculosis (TB) in people with HIV, according to the results of a clinical trial reported in Annals of Internal Medicine.

The study, a randomized pragmatic trial in South Africa, Ethiopia, and Mozambique, was called WHIP3TB (Weekly High Dose Isoniazid and Rifapentine [P] Periodic Prophylaxis for TB).

Investigators randomized patients to three groups, comparing a 3-month course of weekly rifapentine-INH, given either once or repeated in a year, with daily isoniazid for 6 months. At 1 year, 90% of the rifapentine-INH group (3HP) were still on therapy, compared with only 50.5% in the INH group.

In the study, patients were initially assessed for TB using the World Health Organization four-symptom screen, but the sensitivity in HIV patients on antiretrovirals (ARVs) was only 53%. In addition to symptoms, screening at 12 months included a chest x-ray and sputum culture.

Of the 30 patients at month 12 with confirmed TB, 26 were asymptomatic, suggesting physicians should do further evaluation prior to initiating preventive TB treatment (which was not part of the WHO recommendation when the study was initiated).

Another unexpected finding was that 10.2% of the TB cases detected in the combined 3HP groups in South Africa, along with 18% of the cases in Mozambique, had rifampin resistance.

Investigator Gavin Churchyard, MBBCh, PhD, CEO of the Aurum Institute in Johannesburg, South Africa, said in an interview: “It appeared that taking this potent short course regimen – they’re just taking a single course – provided the same level of protection as taking repeat courses of the antibiotics. So that’s good news.” He noted, too, that TB transmission rates have been declining in sub-Saharan Africa because of ARV, and “so it may just be that a single course is now adequate because the risk of exposure and reinfection” is decreasing.

But Madhu Pai, MD, PhD, associate director, McGill International TB Centre, Montreal, who was not involved in the study, shared a more cautious interpretation. He said in an interview that the 2020 WHO Consolidated Guidelines on Tuberculosis state: “In settings with high TB transmission, adults and adolescents living with HIV ... should receive at least 36 months of daily isoniazid preventive therapy (IPT) ... whether or not the person is on ART.” The problem is that almost no one can tolerate prolonged therapy with INH because of side effects, as has been shown in numerous studies.

For successful TB treatment, Dr. Pai said, “Even 3HP is not going to cut it; they’re going to get reinfected again. So that shortening of that 36 months is what this trial is really all about, in terms of new information ... and they were not successful.” But because this is still the most practical course, Dr. Pai suggests that follow-up monitoring for reinfection will be the most likely path forward.

Dr. Churchyard concluded: “If we wanted to end the global TB epidemic, we need to continue to find ways to further reduce the risk of TB overall at a population level, and then amongst high-risk groups such as people with HIV, including those on ARVs, and who have had a course of preventive therapy. ... We need to look for other strategies to further reduce that risk. Part of those strategies may be doing a more intensive screen. But also, it may be adding another intervention, particularly TB vaccines. ... No single intervention by itself will adequately address the risk of TB in people with HIV in these high TB transmission settings.”

Dr. Pai reported no relevant financial relationships. Dr. Churchyard has reported participation in a Sanofi advisory committee on the prevention of TB. Judy Stone, MD, is an infectious disease specialist and author of “Resilience: One Family’s Story of Hope and Triumph Over Evil” and of “Conducting Clinical Research.”

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

 

A 3-month, 12-dose regimen of rifapentine and isoniazid (INH) was less toxic, had better compliance, and showed similar efficacy as 6 months of INH alone in preventing tuberculosis (TB) in people with HIV, according to the results of a clinical trial reported in Annals of Internal Medicine.

The study, a randomized pragmatic trial in South Africa, Ethiopia, and Mozambique, was called WHIP3TB (Weekly High Dose Isoniazid and Rifapentine [P] Periodic Prophylaxis for TB).

Investigators randomized patients to three groups, comparing a 3-month course of weekly rifapentine-INH, given either once or repeated in a year, with daily isoniazid for 6 months. At 1 year, 90% of the rifapentine-INH group (3HP) were still on therapy, compared with only 50.5% in the INH group.

In the study, patients were initially assessed for TB using the World Health Organization four-symptom screen, but the sensitivity in HIV patients on antiretrovirals (ARVs) was only 53%. In addition to symptoms, screening at 12 months included a chest x-ray and sputum culture.

Of the 30 patients at month 12 with confirmed TB, 26 were asymptomatic, suggesting physicians should do further evaluation prior to initiating preventive TB treatment (which was not part of the WHO recommendation when the study was initiated).

Another unexpected finding was that 10.2% of the TB cases detected in the combined 3HP groups in South Africa, along with 18% of the cases in Mozambique, had rifampin resistance.

Investigator Gavin Churchyard, MBBCh, PhD, CEO of the Aurum Institute in Johannesburg, South Africa, said in an interview: “It appeared that taking this potent short course regimen – they’re just taking a single course – provided the same level of protection as taking repeat courses of the antibiotics. So that’s good news.” He noted, too, that TB transmission rates have been declining in sub-Saharan Africa because of ARV, and “so it may just be that a single course is now adequate because the risk of exposure and reinfection” is decreasing.

But Madhu Pai, MD, PhD, associate director, McGill International TB Centre, Montreal, who was not involved in the study, shared a more cautious interpretation. He said in an interview that the 2020 WHO Consolidated Guidelines on Tuberculosis state: “In settings with high TB transmission, adults and adolescents living with HIV ... should receive at least 36 months of daily isoniazid preventive therapy (IPT) ... whether or not the person is on ART.” The problem is that almost no one can tolerate prolonged therapy with INH because of side effects, as has been shown in numerous studies.

For successful TB treatment, Dr. Pai said, “Even 3HP is not going to cut it; they’re going to get reinfected again. So that shortening of that 36 months is what this trial is really all about, in terms of new information ... and they were not successful.” But because this is still the most practical course, Dr. Pai suggests that follow-up monitoring for reinfection will be the most likely path forward.

Dr. Churchyard concluded: “If we wanted to end the global TB epidemic, we need to continue to find ways to further reduce the risk of TB overall at a population level, and then amongst high-risk groups such as people with HIV, including those on ARVs, and who have had a course of preventive therapy. ... We need to look for other strategies to further reduce that risk. Part of those strategies may be doing a more intensive screen. But also, it may be adding another intervention, particularly TB vaccines. ... No single intervention by itself will adequately address the risk of TB in people with HIV in these high TB transmission settings.”

Dr. Pai reported no relevant financial relationships. Dr. Churchyard has reported participation in a Sanofi advisory committee on the prevention of TB. Judy Stone, MD, is an infectious disease specialist and author of “Resilience: One Family’s Story of Hope and Triumph Over Evil” and of “Conducting Clinical Research.”

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

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Genetic link may tie cannabis use disorder to severe COVID-19

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Thu, 09/09/2021 - 16:17

The same genetic variations may boost susceptibility to both severe COVID-19 and cannabis use disorder (CUD), a new study suggests. The research does not confirm a genetic link, but the lead author said the signs of an association are still “troubling.”

Dr. Alexander S. Hatoum

“Reducing cannabis use among heavy users may potentially provide protection against severe COVID-19 presentations,” Alexander S. Hatoum, PhD, a postdoctoral scholar at Washington University, St. Louis, said in an interview. “Outside of individual risk, these data also have important implications for policy regarding vaccination as well as treatment prioritization in an overly taxed medical system.”

The study was published in the journal Biological Psychiatry Global Open Science.

Dr. Hatoum and colleagues launched the study to gain insight into whether CUD might be a risk factor for severe COVID-19 presentations.

As defined by the DSM-5, people with CUD suffer from impairment or distress because of their cannabis use and meet at least 2 of 11 criteria over a 12-month period, such as cravings, cannabis tolerance, and withdrawal symptoms. According to a 2020 study that examined 2008-2016 data, 2.72% of children aged 12-17 showed signs of CUD, as did 1.23% of those aged over 26.

The primary reasons for hospitalization and death related to COVID-19 are respiratory symptoms. “And we have observed that genetic vulnerability to CUD is shared with respiratory disease, even after tobacco use is considered,” Dr. Hatoum said.

He and his colleagues examined data from genomewide association studies and searched for genetic correlations between CUD (14,080 cases, 343,726 controls) and COVID-19 hospitalization (9,373 cases, 1,197,256 controls). “Genetic vulnerability to COVID-19 was correlated with genetic liability to CUD (P = 1.33e–6),” the researchers wrote. “This association remained when accounting for genetic liability to related risk factors and covariates (P = .012-.049).”

According to Dr. Hatoum, the researchers found inconclusive evidence that CUD might worsen COVID-19 cases. “We applied statistical causal models, which found an effect consistent with causality, but it was nonsignificant,” he said.

Despite the absence of causality, the study findings could prove useful for clinicians and policy makers.

“Those struggling with CUD may be prioritized for vaccination and vaccination boosters to mitigate their higher likelihood of a severe COVID-19 presentation,” Dr. Hatoum said. “When testing positive for COVID-19, they may also be prioritized for earlier treatment.”

The study authors also added that the findings “urge caution” in regard to the wave of U.S. states legalizing cannabis. “Our data suggest that heavy cannabis use, but not lifetime cannabis use, represents a risk factor for severe COVID-19 presentations,” Dr. Hatoum said.

Dr. Danielle Dick

In an interview, Danielle Dick, PhD, who was not involved with the study, said it applies “cutting-edge methods to an important research question” and offers a “hint” of a genetic risk factor that makes some people more likely to be hospitalized for COVID-19. However, “the study does not tell us what those underlying genetically influenced processes might be,” added Dr. Dick, professor of psychology, and human and molecular genetics at Virginia Commonwealth University, Richmond. “And it’s an important caveat to point out that the results from this study are limited in that they are based on data from people from European descent – so they can’t necessarily be applied to address the harm experienced by so many people of color from the COVID pandemic. That’s an unfortunate limitation.”

As for the idea that the study findings should prompt caution about marijuana legalization, Dr. Dick said it’s true that increased acceptability of drug use “increases the likelihood that individuals who are genetically vulnerable will develop problems. There is robust evidence of this.”

However, Dr. Dick said, “the legalization of marijuana is a complex topic because the health consequences aren’t the only consideration when it comes to legalization. The other side of the coin is the huge harm that has been caused to communities of color through marijuana criminalization. Legalization will hopefully lead to decreased harm on that front. So it’s a double-edged sword.”

Dr. Hatoum, his colleagues, and Dr. Dick reported no relevant disclosures.

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The same genetic variations may boost susceptibility to both severe COVID-19 and cannabis use disorder (CUD), a new study suggests. The research does not confirm a genetic link, but the lead author said the signs of an association are still “troubling.”

Dr. Alexander S. Hatoum

“Reducing cannabis use among heavy users may potentially provide protection against severe COVID-19 presentations,” Alexander S. Hatoum, PhD, a postdoctoral scholar at Washington University, St. Louis, said in an interview. “Outside of individual risk, these data also have important implications for policy regarding vaccination as well as treatment prioritization in an overly taxed medical system.”

The study was published in the journal Biological Psychiatry Global Open Science.

Dr. Hatoum and colleagues launched the study to gain insight into whether CUD might be a risk factor for severe COVID-19 presentations.

As defined by the DSM-5, people with CUD suffer from impairment or distress because of their cannabis use and meet at least 2 of 11 criteria over a 12-month period, such as cravings, cannabis tolerance, and withdrawal symptoms. According to a 2020 study that examined 2008-2016 data, 2.72% of children aged 12-17 showed signs of CUD, as did 1.23% of those aged over 26.

The primary reasons for hospitalization and death related to COVID-19 are respiratory symptoms. “And we have observed that genetic vulnerability to CUD is shared with respiratory disease, even after tobacco use is considered,” Dr. Hatoum said.

He and his colleagues examined data from genomewide association studies and searched for genetic correlations between CUD (14,080 cases, 343,726 controls) and COVID-19 hospitalization (9,373 cases, 1,197,256 controls). “Genetic vulnerability to COVID-19 was correlated with genetic liability to CUD (P = 1.33e–6),” the researchers wrote. “This association remained when accounting for genetic liability to related risk factors and covariates (P = .012-.049).”

According to Dr. Hatoum, the researchers found inconclusive evidence that CUD might worsen COVID-19 cases. “We applied statistical causal models, which found an effect consistent with causality, but it was nonsignificant,” he said.

Despite the absence of causality, the study findings could prove useful for clinicians and policy makers.

“Those struggling with CUD may be prioritized for vaccination and vaccination boosters to mitigate their higher likelihood of a severe COVID-19 presentation,” Dr. Hatoum said. “When testing positive for COVID-19, they may also be prioritized for earlier treatment.”

The study authors also added that the findings “urge caution” in regard to the wave of U.S. states legalizing cannabis. “Our data suggest that heavy cannabis use, but not lifetime cannabis use, represents a risk factor for severe COVID-19 presentations,” Dr. Hatoum said.

Dr. Danielle Dick

In an interview, Danielle Dick, PhD, who was not involved with the study, said it applies “cutting-edge methods to an important research question” and offers a “hint” of a genetic risk factor that makes some people more likely to be hospitalized for COVID-19. However, “the study does not tell us what those underlying genetically influenced processes might be,” added Dr. Dick, professor of psychology, and human and molecular genetics at Virginia Commonwealth University, Richmond. “And it’s an important caveat to point out that the results from this study are limited in that they are based on data from people from European descent – so they can’t necessarily be applied to address the harm experienced by so many people of color from the COVID pandemic. That’s an unfortunate limitation.”

As for the idea that the study findings should prompt caution about marijuana legalization, Dr. Dick said it’s true that increased acceptability of drug use “increases the likelihood that individuals who are genetically vulnerable will develop problems. There is robust evidence of this.”

However, Dr. Dick said, “the legalization of marijuana is a complex topic because the health consequences aren’t the only consideration when it comes to legalization. The other side of the coin is the huge harm that has been caused to communities of color through marijuana criminalization. Legalization will hopefully lead to decreased harm on that front. So it’s a double-edged sword.”

Dr. Hatoum, his colleagues, and Dr. Dick reported no relevant disclosures.

The same genetic variations may boost susceptibility to both severe COVID-19 and cannabis use disorder (CUD), a new study suggests. The research does not confirm a genetic link, but the lead author said the signs of an association are still “troubling.”

Dr. Alexander S. Hatoum

“Reducing cannabis use among heavy users may potentially provide protection against severe COVID-19 presentations,” Alexander S. Hatoum, PhD, a postdoctoral scholar at Washington University, St. Louis, said in an interview. “Outside of individual risk, these data also have important implications for policy regarding vaccination as well as treatment prioritization in an overly taxed medical system.”

The study was published in the journal Biological Psychiatry Global Open Science.

Dr. Hatoum and colleagues launched the study to gain insight into whether CUD might be a risk factor for severe COVID-19 presentations.

As defined by the DSM-5, people with CUD suffer from impairment or distress because of their cannabis use and meet at least 2 of 11 criteria over a 12-month period, such as cravings, cannabis tolerance, and withdrawal symptoms. According to a 2020 study that examined 2008-2016 data, 2.72% of children aged 12-17 showed signs of CUD, as did 1.23% of those aged over 26.

The primary reasons for hospitalization and death related to COVID-19 are respiratory symptoms. “And we have observed that genetic vulnerability to CUD is shared with respiratory disease, even after tobacco use is considered,” Dr. Hatoum said.

He and his colleagues examined data from genomewide association studies and searched for genetic correlations between CUD (14,080 cases, 343,726 controls) and COVID-19 hospitalization (9,373 cases, 1,197,256 controls). “Genetic vulnerability to COVID-19 was correlated with genetic liability to CUD (P = 1.33e–6),” the researchers wrote. “This association remained when accounting for genetic liability to related risk factors and covariates (P = .012-.049).”

According to Dr. Hatoum, the researchers found inconclusive evidence that CUD might worsen COVID-19 cases. “We applied statistical causal models, which found an effect consistent with causality, but it was nonsignificant,” he said.

Despite the absence of causality, the study findings could prove useful for clinicians and policy makers.

“Those struggling with CUD may be prioritized for vaccination and vaccination boosters to mitigate their higher likelihood of a severe COVID-19 presentation,” Dr. Hatoum said. “When testing positive for COVID-19, they may also be prioritized for earlier treatment.”

The study authors also added that the findings “urge caution” in regard to the wave of U.S. states legalizing cannabis. “Our data suggest that heavy cannabis use, but not lifetime cannabis use, represents a risk factor for severe COVID-19 presentations,” Dr. Hatoum said.

Dr. Danielle Dick

In an interview, Danielle Dick, PhD, who was not involved with the study, said it applies “cutting-edge methods to an important research question” and offers a “hint” of a genetic risk factor that makes some people more likely to be hospitalized for COVID-19. However, “the study does not tell us what those underlying genetically influenced processes might be,” added Dr. Dick, professor of psychology, and human and molecular genetics at Virginia Commonwealth University, Richmond. “And it’s an important caveat to point out that the results from this study are limited in that they are based on data from people from European descent – so they can’t necessarily be applied to address the harm experienced by so many people of color from the COVID pandemic. That’s an unfortunate limitation.”

As for the idea that the study findings should prompt caution about marijuana legalization, Dr. Dick said it’s true that increased acceptability of drug use “increases the likelihood that individuals who are genetically vulnerable will develop problems. There is robust evidence of this.”

However, Dr. Dick said, “the legalization of marijuana is a complex topic because the health consequences aren’t the only consideration when it comes to legalization. The other side of the coin is the huge harm that has been caused to communities of color through marijuana criminalization. Legalization will hopefully lead to decreased harm on that front. So it’s a double-edged sword.”

Dr. Hatoum, his colleagues, and Dr. Dick reported no relevant disclosures.

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