What is the recent research behind 5-fluorouracil cream 5% combined with calcipotriol ointment 0.005% for actinic keratoses?

Cunningham et al published a randomized double-blind study in which 131 patients with actinic keratoses (AKs) were assigned to either 5-fluorouracil (5-FU) cream 5% combined with calcipotriol (calcipotriene) ointment 0.005% twice daily to the face, scalp, and arms for 4 days, or 5-FU 5% combined with petrolatum applied in the same fashion. There was an 87.8% versus 26.3% mean reduction in the number of AKs and less severe pain, crusting, and ulceration in the study cohort compared to the 5-FU plus petrolatum group.

The same study also investigated immune parameters in these patients and found that the study group preferentially displayed activated thymic stromal lymphopoietin and a CD4 T cell-mediated reaction, among other effects. In prior studies, thymic stromal lymphopoietin has been shown to be upregulated in barrier-defective skin, displays antitumor activity, and is enhanced by topical calcipotriol application based on its original indication for psoriasis.

How do these study results impact patient care?

In a perfect world, every patient could tolerate and afford chemopreventative measures such as 5-FU cream, apply it diffusely to sun-exposed skin, and experience no severe irritant reactions and/or social pariah status. We all know that this product is effective, and we all overprepare patients to use it, knowing that they will call our offices panicked and fearful that they are allergic to or are becoming infected by this cream.

Although further study clearly is needed to determine the optimal application amount, duration of use, and vehicle mix, this new compound utilizing 2 topicals that are familiar to us--5-FU cream approved for AKs and early squamous cell skin cancers and calcipotriol ointment (though available only in cream in the United States currently) for psoriasis--is an encouraging step. Home therapy for AKs and possibly early nonmelanoma skin cancers that is more tolerable, of shorter duration, and in turn more effective than the current options would lessen the burden of treating these lesions surgically or rescheduling 5-FU patients often for irritation reaction education.

How do patients respond to this regimen?

In my own anecdotal experience, this regimen has been well received by patients and often is covered by most insurances when written as 2 separate prescriptions (both in cream vehicle).  They still report some irritation, but I prefer to utilize it segmentally instead of treating all sun-exposed areas at once (ie, treat one side of the face/scalp twice daily for 4 days, then the other, or even divide it into smaller segments once the prior segment has healed). This combination, in addition to, for example, adding nicotinamide 500 mg twice daily to a patient's skin cancer chemopreventative sequence, is in my opinion a novel but safe, effective, and well-tolerated field therapy recommendation.

Suggested Readings

• Cunningham TJ, Tabacchi M, Eliane JP, et al. Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy. J Clin Invest. 2017;127:106-116.
• Demehri S, Turkoz A, Manivasagam S, et al. Elevated epidermal thymic stromal lymphopoietin levels establish an antitumor environment in the skin. Cancer Cell. 2012;22:494-505.
• Rosamilia LL. Three Cheers for B₃? Cutis. July 7, 2015. http://www.mdedge.com/cutis/article/101102/nonmelanoma-skin-cancer/three-cheers-b3. Accessed November 20, 2017.
• Sato-Deguchi E, Imafuku S, Chou B, et al. Topical vitamin D(3) analogues induce thymic stromal lymphopoietin and cathelicidin in psoriatic skin lesions. Br J Dermatol. 2012;167:77-84.

What is the recent research behind 5-fluorouracil cream 5% combined with calcipotriol ointment 0.005% for actinic keratoses?

Cunningham et al published a randomized double-blind study in which 131 patients with actinic keratoses (AKs) were assigned to either 5-fluorouracil (5-FU) cream 5% combined with calcipotriol (calcipotriene) ointment 0.005% twice daily to the face, scalp, and arms for 4 days, or 5-FU 5% combined with petrolatum applied in the same fashion. There was an 87.8% versus 26.3% mean reduction in the number of AKs and less severe pain, crusting, and ulceration in the study cohort compared to the 5-FU plus petrolatum group.

The same study also investigated immune parameters in these patients and found that the study group preferentially displayed activated thymic stromal lymphopoietin and a CD4 T cell-mediated reaction, among other effects. In prior studies, thymic stromal lymphopoietin has been shown to be upregulated in barrier-defective skin, displays antitumor activity, and is enhanced by topical calcipotriol application based on its original indication for psoriasis.

How do these study results impact patient care?

In a perfect world, every patient could tolerate and afford chemopreventative measures such as 5-FU cream, apply it diffusely to sun-exposed skin, and experience no severe irritant reactions and/or social pariah status. We all know that this product is effective, and we all overprepare patients to use it, knowing that they will call our offices panicked and fearful that they are allergic to or are becoming infected by this cream.

Although further study clearly is needed to determine the optimal application amount, duration of use, and vehicle mix, this new compound utilizing 2 topicals that are familiar to us--5-FU cream approved for AKs and early squamous cell skin cancers and calcipotriol ointment (though available only in cream in the United States currently) for psoriasis--is an encouraging step. Home therapy for AKs and possibly early nonmelanoma skin cancers that is more tolerable, of shorter duration, and in turn more effective than the current options would lessen the burden of treating these lesions surgically or rescheduling 5-FU patients often for irritation reaction education.

How do patients respond to this regimen?

In my own anecdotal experience, this regimen has been well received by patients and often is covered by most insurances when written as 2 separate prescriptions (both in cream vehicle).  They still report some irritation, but I prefer to utilize it segmentally instead of treating all sun-exposed areas at once (ie, treat one side of the face/scalp twice daily for 4 days, then the other, or even divide it into smaller segments once the prior segment has healed). This combination, in addition to, for example, adding nicotinamide 500 mg twice daily to a patient's skin cancer chemopreventative sequence, is in my opinion a novel but safe, effective, and well-tolerated field therapy recommendation.

Suggested Readings

• Cunningham TJ, Tabacchi M, Eliane JP, et al. Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy. J Clin Invest. 2017;127:106-116.
• Demehri S, Turkoz A, Manivasagam S, et al. Elevated epidermal thymic stromal lymphopoietin levels establish an antitumor environment in the skin. Cancer Cell. 2012;22:494-505.
• Rosamilia LL. Three Cheers for B₃? Cutis. July 7, 2015. http://www.mdedge.com/cutis/article/101102/nonmelanoma-skin-cancer/three-cheers-b3. Accessed November 20, 2017.
• Sato-Deguchi E, Imafuku S, Chou B, et al. Topical vitamin D(3) analogues induce thymic stromal lymphopoietin and cathelicidin in psoriatic skin lesions. Br J Dermatol. 2012;167:77-84.

What is the recent research behind 5-fluorouracil cream 5% combined with calcipotriol ointment 0.005% for actinic keratoses?

Cunningham et al published a randomized double-blind study in which 131 patients with actinic keratoses (AKs) were assigned to either 5-fluorouracil (5-FU) cream 5% combined with calcipotriol (calcipotriene) ointment 0.005% twice daily to the face, scalp, and arms for 4 days, or 5-FU 5% combined with petrolatum applied in the same fashion. There was an 87.8% versus 26.3% mean reduction in the number of AKs and less severe pain, crusting, and ulceration in the study cohort compared to the 5-FU plus petrolatum group.

The same study also investigated immune parameters in these patients and found that the study group preferentially displayed activated thymic stromal lymphopoietin and a CD4 T cell-mediated reaction, among other effects. In prior studies, thymic stromal lymphopoietin has been shown to be upregulated in barrier-defective skin, displays antitumor activity, and is enhanced by topical calcipotriol application based on its original indication for psoriasis.

How do these study results impact patient care?

In a perfect world, every patient could tolerate and afford chemopreventative measures such as 5-FU cream, apply it diffusely to sun-exposed skin, and experience no severe irritant reactions and/or social pariah status. We all know that this product is effective, and we all overprepare patients to use it, knowing that they will call our offices panicked and fearful that they are allergic to or are becoming infected by this cream.

Although further study clearly is needed to determine the optimal application amount, duration of use, and vehicle mix, this new compound utilizing 2 topicals that are familiar to us--5-FU cream approved for AKs and early squamous cell skin cancers and calcipotriol ointment (though available only in cream in the United States currently) for psoriasis--is an encouraging step. Home therapy for AKs and possibly early nonmelanoma skin cancers that is more tolerable, of shorter duration, and in turn more effective than the current options would lessen the burden of treating these lesions surgically or rescheduling 5-FU patients often for irritation reaction education.

How do patients respond to this regimen?

In my own anecdotal experience, this regimen has been well received by patients and often is covered by most insurances when written as 2 separate prescriptions (both in cream vehicle).  They still report some irritation, but I prefer to utilize it segmentally instead of treating all sun-exposed areas at once (ie, treat one side of the face/scalp twice daily for 4 days, then the other, or even divide it into smaller segments once the prior segment has healed). This combination, in addition to, for example, adding nicotinamide 500 mg twice daily to a patient's skin cancer chemopreventative sequence, is in my opinion a novel but safe, effective, and well-tolerated field therapy recommendation.

Suggested Readings

• Cunningham TJ, Tabacchi M, Eliane JP, et al. Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy. J Clin Invest. 2017;127:106-116.
• Demehri S, Turkoz A, Manivasagam S, et al. Elevated epidermal thymic stromal lymphopoietin levels establish an antitumor environment in the skin. Cancer Cell. 2012;22:494-505.
• Rosamilia LL. Three Cheers for B₃? Cutis. July 7, 2015. http://www.mdedge.com/cutis/article/101102/nonmelanoma-skin-cancer/three-cheers-b3. Accessed November 20, 2017.
• Sato-Deguchi E, Imafuku S, Chou B, et al. Topical vitamin D(3) analogues induce thymic stromal lymphopoietin and cathelicidin in psoriatic skin lesions. Br J Dermatol. 2012;167:77-84.

Physician diversity benefits patient care: Patients are more satisfied during race-concordant visits, report their physicians as more engaged and responsive to their needs, and experience notably longer visits.^1,2 Nonwhite physicians (ie, races and ethnicities that are underrepresented in medicine [URM] with respect to the general population) are more likely to care for underserved communities. Furthermore, increased diversity in the learning environment supports preparedness of all trainees to serve diverse patients.³ For these reasons, a more diverse physician workforce can contribute to better access to care in all communities, thus addressing health disparities.^1,4

Increasing diversity in the dermatology workforce has been identified as an emerging priority.⁵ Dermatology is one of the least diverse specialties,⁵ and the representation of URM dermatologists is lower compared to other medical specialties and the general US population. The proportion of specialty leaders from underrepresented backgrounds may be even smaller. The lack of diversity in academic dermatology has negative consequences for patients and communities. Increasing the diversity of resident trainees is the only way to improve the diversity gap within the dermatology workforce.⁶

Recent commentary on this topic has highlighted several priorities for addressing the dermatology diversity gap,^6-11 including the following: (1) making diversity an explicit goal in dermatology; (2) ensuring early exposure to dermatology in medical school; (3) supporting mentorship programs for minority medical students; (4) increasing medical student diversity; (5) encouraging that all dermatology program directors and leaders train in implicit bias; and (6) reviewing residency admission criteria to ensure they are objective and equitable, not biased against any applicants.

The process of reviewing residency selection criteria has begun. In 2017, Chen and Shinkai⁷ called for our specialty to rethink the selection process. The authors argued that emphasis on test scores, grades, and publications systematically disadvantages underrepresented minorities and students from lower socioeconomic statuses. The authors proposed several solutions: (1) make diversity an explicit goal of the selection process, (2) shift away from test scores for all applicants, (3) change the interview format, (4) prioritize other competencies such as observation skills, and (5) recruit and retain faculty who support URM trainees.⁷

Several dermatology leadership groups have taken action to promote programs that aim to improve diversity within dermatology. The Dermatology Diversity Champions initiative includes 6 US dermatology residency programs that are committed to increasing diversity and collaborate to evaluate pilot approaches. The American Academy of Dermatology President’s Conference on Diversity in Dermatology in Chicago, Illinois, in August 2017, as well as the focus on diversity in residency training programs at the Annual Meeting of the Association of Professors of Dermatology in Chicago, Illinois, in October 2017, are strong indicators that our specialty as a whole is aware and eager to embrace diversity as a priority. The American Academy of Dermatology President’s Conference, which was comprised of representatives from many leadership organizations and interest groups within dermatology, identified 3 action items: (1) increase the pipeline of URM students into medical school, (2) increase interest in dermatology among URM medical students, and (3) increase URM representation in residency training programs.

There are many strengths, weaknesses, opportunities, and threats/barriers (SWOT) to attaining this goal. Current strengths include strong support from dermatology leaders and activities that build on existing mentorship and diversity efforts by leaders within our specialty. SWOT analysis highlights several key opportunities of this mission, including connecting with the House of Medicine in shared efforts to improve diversity, as well as increased understanding of skin of color, health disparities, and implicit bias among physicians. Although faculty development will require time and financial investment, it will lead to tremendous benefits and opportunities for all dermatologists, including URM physicians. Other weaknesses and threats/barriers are outlined in the Figure.

Final Thoughts

We are far from reaching our goal of a diverse dermatology workforce, and the road ahead is long. We have a start and we have momentum. We can move forward by spreading the word that all types of diversity are a priority for our specialty. Making a true difference will require commitment and sustained efforts. Dermatology can lead the way as all of American medicine strives to attain workforce diversity.

Physician diversity benefits patient care: Patients are more satisfied during race-concordant visits, report their physicians as more engaged and responsive to their needs, and experience notably longer visits.^1,2 Nonwhite physicians (ie, races and ethnicities that are underrepresented in medicine [URM] with respect to the general population) are more likely to care for underserved communities. Furthermore, increased diversity in the learning environment supports preparedness of all trainees to serve diverse patients.³ For these reasons, a more diverse physician workforce can contribute to better access to care in all communities, thus addressing health disparities.^1,4

Increasing diversity in the dermatology workforce has been identified as an emerging priority.⁵ Dermatology is one of the least diverse specialties,⁵ and the representation of URM dermatologists is lower compared to other medical specialties and the general US population. The proportion of specialty leaders from underrepresented backgrounds may be even smaller. The lack of diversity in academic dermatology has negative consequences for patients and communities. Increasing the diversity of resident trainees is the only way to improve the diversity gap within the dermatology workforce.⁶

Recent commentary on this topic has highlighted several priorities for addressing the dermatology diversity gap,^6-11 including the following: (1) making diversity an explicit goal in dermatology; (2) ensuring early exposure to dermatology in medical school; (3) supporting mentorship programs for minority medical students; (4) increasing medical student diversity; (5) encouraging that all dermatology program directors and leaders train in implicit bias; and (6) reviewing residency admission criteria to ensure they are objective and equitable, not biased against any applicants.

The process of reviewing residency selection criteria has begun. In 2017, Chen and Shinkai⁷ called for our specialty to rethink the selection process. The authors argued that emphasis on test scores, grades, and publications systematically disadvantages underrepresented minorities and students from lower socioeconomic statuses. The authors proposed several solutions: (1) make diversity an explicit goal of the selection process, (2) shift away from test scores for all applicants, (3) change the interview format, (4) prioritize other competencies such as observation skills, and (5) recruit and retain faculty who support URM trainees.⁷

Several dermatology leadership groups have taken action to promote programs that aim to improve diversity within dermatology. The Dermatology Diversity Champions initiative includes 6 US dermatology residency programs that are committed to increasing diversity and collaborate to evaluate pilot approaches. The American Academy of Dermatology President’s Conference on Diversity in Dermatology in Chicago, Illinois, in August 2017, as well as the focus on diversity in residency training programs at the Annual Meeting of the Association of Professors of Dermatology in Chicago, Illinois, in October 2017, are strong indicators that our specialty as a whole is aware and eager to embrace diversity as a priority. The American Academy of Dermatology President’s Conference, which was comprised of representatives from many leadership organizations and interest groups within dermatology, identified 3 action items: (1) increase the pipeline of URM students into medical school, (2) increase interest in dermatology among URM medical students, and (3) increase URM representation in residency training programs.

There are many strengths, weaknesses, opportunities, and threats/barriers (SWOT) to attaining this goal. Current strengths include strong support from dermatology leaders and activities that build on existing mentorship and diversity efforts by leaders within our specialty. SWOT analysis highlights several key opportunities of this mission, including connecting with the House of Medicine in shared efforts to improve diversity, as well as increased understanding of skin of color, health disparities, and implicit bias among physicians. Although faculty development will require time and financial investment, it will lead to tremendous benefits and opportunities for all dermatologists, including URM physicians. Other weaknesses and threats/barriers are outlined in the Figure.

Final Thoughts

We are far from reaching our goal of a diverse dermatology workforce, and the road ahead is long. We have a start and we have momentum. We can move forward by spreading the word that all types of diversity are a priority for our specialty. Making a true difference will require commitment and sustained efforts. Dermatology can lead the way as all of American medicine strives to attain workforce diversity.

Physician diversity benefits patient care: Patients are more satisfied during race-concordant visits, report their physicians as more engaged and responsive to their needs, and experience notably longer visits.^1,2 Nonwhite physicians (ie, races and ethnicities that are underrepresented in medicine [URM] with respect to the general population) are more likely to care for underserved communities. Furthermore, increased diversity in the learning environment supports preparedness of all trainees to serve diverse patients.³ For these reasons, a more diverse physician workforce can contribute to better access to care in all communities, thus addressing health disparities.^1,4

Increasing diversity in the dermatology workforce has been identified as an emerging priority.⁵ Dermatology is one of the least diverse specialties,⁵ and the representation of URM dermatologists is lower compared to other medical specialties and the general US population. The proportion of specialty leaders from underrepresented backgrounds may be even smaller. The lack of diversity in academic dermatology has negative consequences for patients and communities. Increasing the diversity of resident trainees is the only way to improve the diversity gap within the dermatology workforce.⁶

Recent commentary on this topic has highlighted several priorities for addressing the dermatology diversity gap,^6-11 including the following: (1) making diversity an explicit goal in dermatology; (2) ensuring early exposure to dermatology in medical school; (3) supporting mentorship programs for minority medical students; (4) increasing medical student diversity; (5) encouraging that all dermatology program directors and leaders train in implicit bias; and (6) reviewing residency admission criteria to ensure they are objective and equitable, not biased against any applicants.

The process of reviewing residency selection criteria has begun. In 2017, Chen and Shinkai⁷ called for our specialty to rethink the selection process. The authors argued that emphasis on test scores, grades, and publications systematically disadvantages underrepresented minorities and students from lower socioeconomic statuses. The authors proposed several solutions: (1) make diversity an explicit goal of the selection process, (2) shift away from test scores for all applicants, (3) change the interview format, (4) prioritize other competencies such as observation skills, and (5) recruit and retain faculty who support URM trainees.⁷

Several dermatology leadership groups have taken action to promote programs that aim to improve diversity within dermatology. The Dermatology Diversity Champions initiative includes 6 US dermatology residency programs that are committed to increasing diversity and collaborate to evaluate pilot approaches. The American Academy of Dermatology President’s Conference on Diversity in Dermatology in Chicago, Illinois, in August 2017, as well as the focus on diversity in residency training programs at the Annual Meeting of the Association of Professors of Dermatology in Chicago, Illinois, in October 2017, are strong indicators that our specialty as a whole is aware and eager to embrace diversity as a priority. The American Academy of Dermatology President’s Conference, which was comprised of representatives from many leadership organizations and interest groups within dermatology, identified 3 action items: (1) increase the pipeline of URM students into medical school, (2) increase interest in dermatology among URM medical students, and (3) increase URM representation in residency training programs.

There are many strengths, weaknesses, opportunities, and threats/barriers (SWOT) to attaining this goal. Current strengths include strong support from dermatology leaders and activities that build on existing mentorship and diversity efforts by leaders within our specialty. SWOT analysis highlights several key opportunities of this mission, including connecting with the House of Medicine in shared efforts to improve diversity, as well as increased understanding of skin of color, health disparities, and implicit bias among physicians. Although faculty development will require time and financial investment, it will lead to tremendous benefits and opportunities for all dermatologists, including URM physicians. Other weaknesses and threats/barriers are outlined in the Figure.

Final Thoughts

We are far from reaching our goal of a diverse dermatology workforce, and the road ahead is long. We have a start and we have momentum. We can move forward by spreading the word that all types of diversity are a priority for our specialty. Making a true difference will require commitment and sustained efforts. Dermatology can lead the way as all of American medicine strives to attain workforce diversity.

Coastal travel accounts for 80% of all tourism worldwide, a number that continues to grow. The number of travelers to the Mediterranean Sea alone is expected to rise to 350 million individuals per year within the next 20 years.¹ As the number of tourists visiting the world’s oceans increases, the rate of sunscreen unintentionally washed into these marine environments also rises. One study estimated that approximately one-quarter of the sunscreen applied to the skin is washed off over a 20-minute period spent in the water.² Four of the most common sunscreen agents—benzophenone-3 (BP-3), 4-methylbenzylidene camphor (4-MBC), and the nanoparticles titanium dioxide and zinc oxide—have been considered to be risks to marine environments. As this topic has received increasing media scrutiny over the last few years, we summarize the general conclusions that can be drawn from current research and note the questions that still remain to better address patient concerns.

Benzophenone-3

Benzophenone-3, or oxybenzone, is a widely studied UV filter and its effects on marine ecosystems have received the media’s attention over the last few years. Benzophenone-3 is known to cause a bleaching effect to coral, which can inhibit growth and possibly kill the organism.³ Further, oxybenzone sunscreens can promote viral infections in coral, resulting in additional bleaching events.² In a recent study, exposure to BP-3 caused mobile planulae, the larval form of coral, to become clearly deformed, trapped within its own calcium carbonate skeleton.³ The concentration of BP-3 needed to induce these physiological changes is as small as 62 parts per trillion, which is the equivalent of a single drop of water in 6.5 Olympic-sized swimming pools. Levels of BP-3 contamination in the waters off of the US Virgin Islands’ beaches have been recorded as high as 1.4 parts per million, with average concentrations closer to 250 parts per billion.³ High BP-3 concentrations have also been recorded in the waters off the Canary Islands,⁴ Hawaii,³ and South Carolina.⁵

4-Methylbenzylidene Camphor

Environmental concerns have also been raised about another common chemical UV filter: 4-MBC, or enzacamene. In laboratory studies, 4-MBC has been shown to cause oxidative stress to Tetrahymena thermophila, an aquatic protozoan, which results in inhibited growth. At higher concentrations, damage to the cellular membrane was seen as soon as 4 hours after exposure.⁶ In embryonic zebrafish, elevated 4-MBC levels were correlated to improper nerve and muscular development, resulting in developmental defects.⁷ Another study demonstrated that 4-MBC was toxic to Mytilus galloprovincialis, known as the Mediterranean mussel, and Paracentrotus lividus, a species of sea urchin.⁸ Although these studies utilized highly controlled laboratory settings, further studies are needed to examine the effects of 4-MBC on these species at environmentally relevant concentrations.

Physical Sunscreens

Physical sunscreens, as compared to the chemical filters referenced above, use either zinc or titanium to protect the skin from the sun’s rays. Nanoparticles, in particular, are preferred because they do not leave a white film on the skin.⁹ Both titanium dioxide and zinc oxide nanoparticles have been found to inhibit the growth and photosynthesis of marine phytoplankton, the most abundant primary producers on Earth.^10,11 These metal contaminants can be transferred to organisms of higher trophic levels, including zooplankton,¹² and filter-feeding organisms, including marine abalone¹³ and the Mediterranean mussel.¹⁴ These nanoparticles have been shown to cause oxidative stress to these organisms, making them less fit to withstand environmental stressors. It is difficult to show their true impact, however, as it is challenging to accurately detect and quantify nanoparticle concentrations in vivo.¹⁵

Final Thoughts

A recent study showed that 7% of consumers (N=325) regarded environmental agencies’ recommendations as an important factor in their sunscreen purchase.¹⁶ When treating patients with these concerns, the ability to provide sound and informed advice will likely impact their sunscreen use and future sun protection behaviors. Although studies have shown the potential for sunscreen pollution to cause environmental harm, it is important to note that a portion of this research is not correlated to in vivo findings, and further work is required to determine the magnitude and importance of these studies.¹⁵ Regardless, legislation has already been submitted in both Hawaii and the European Union calling for a ban on oxybenzone-containing sunscreens, so knowledge of the subject is prudent when counseling patients.¹⁷ One potential solution may be to recommend sun-protective clothing during water-intensive activities to both increase skin protection and reduce the environmental impact. Furthermore, recommendations could be tailored to specific settings, such as coastal resorts and populated beaches, where these sunscreen ingredients are found in much higher concentrations. At this time, more data must be collected before making any definitive claims or recommendations, but knowledge of the current research will be an important tool in educating patients going forward.

Coastal travel accounts for 80% of all tourism worldwide, a number that continues to grow. The number of travelers to the Mediterranean Sea alone is expected to rise to 350 million individuals per year within the next 20 years.¹ As the number of tourists visiting the world’s oceans increases, the rate of sunscreen unintentionally washed into these marine environments also rises. One study estimated that approximately one-quarter of the sunscreen applied to the skin is washed off over a 20-minute period spent in the water.² Four of the most common sunscreen agents—benzophenone-3 (BP-3), 4-methylbenzylidene camphor (4-MBC), and the nanoparticles titanium dioxide and zinc oxide—have been considered to be risks to marine environments. As this topic has received increasing media scrutiny over the last few years, we summarize the general conclusions that can be drawn from current research and note the questions that still remain to better address patient concerns.

Benzophenone-3

Benzophenone-3, or oxybenzone, is a widely studied UV filter and its effects on marine ecosystems have received the media’s attention over the last few years. Benzophenone-3 is known to cause a bleaching effect to coral, which can inhibit growth and possibly kill the organism.³ Further, oxybenzone sunscreens can promote viral infections in coral, resulting in additional bleaching events.² In a recent study, exposure to BP-3 caused mobile planulae, the larval form of coral, to become clearly deformed, trapped within its own calcium carbonate skeleton.³ The concentration of BP-3 needed to induce these physiological changes is as small as 62 parts per trillion, which is the equivalent of a single drop of water in 6.5 Olympic-sized swimming pools. Levels of BP-3 contamination in the waters off of the US Virgin Islands’ beaches have been recorded as high as 1.4 parts per million, with average concentrations closer to 250 parts per billion.³ High BP-3 concentrations have also been recorded in the waters off the Canary Islands,⁴ Hawaii,³ and South Carolina.⁵

4-Methylbenzylidene Camphor

Environmental concerns have also been raised about another common chemical UV filter: 4-MBC, or enzacamene. In laboratory studies, 4-MBC has been shown to cause oxidative stress to Tetrahymena thermophila, an aquatic protozoan, which results in inhibited growth. At higher concentrations, damage to the cellular membrane was seen as soon as 4 hours after exposure.⁶ In embryonic zebrafish, elevated 4-MBC levels were correlated to improper nerve and muscular development, resulting in developmental defects.⁷ Another study demonstrated that 4-MBC was toxic to Mytilus galloprovincialis, known as the Mediterranean mussel, and Paracentrotus lividus, a species of sea urchin.⁸ Although these studies utilized highly controlled laboratory settings, further studies are needed to examine the effects of 4-MBC on these species at environmentally relevant concentrations.

Physical Sunscreens

Physical sunscreens, as compared to the chemical filters referenced above, use either zinc or titanium to protect the skin from the sun’s rays. Nanoparticles, in particular, are preferred because they do not leave a white film on the skin.⁹ Both titanium dioxide and zinc oxide nanoparticles have been found to inhibit the growth and photosynthesis of marine phytoplankton, the most abundant primary producers on Earth.^10,11 These metal contaminants can be transferred to organisms of higher trophic levels, including zooplankton,¹² and filter-feeding organisms, including marine abalone¹³ and the Mediterranean mussel.¹⁴ These nanoparticles have been shown to cause oxidative stress to these organisms, making them less fit to withstand environmental stressors. It is difficult to show their true impact, however, as it is challenging to accurately detect and quantify nanoparticle concentrations in vivo.¹⁵

Final Thoughts

A recent study showed that 7% of consumers (N=325) regarded environmental agencies’ recommendations as an important factor in their sunscreen purchase.¹⁶ When treating patients with these concerns, the ability to provide sound and informed advice will likely impact their sunscreen use and future sun protection behaviors. Although studies have shown the potential for sunscreen pollution to cause environmental harm, it is important to note that a portion of this research is not correlated to in vivo findings, and further work is required to determine the magnitude and importance of these studies.¹⁵ Regardless, legislation has already been submitted in both Hawaii and the European Union calling for a ban on oxybenzone-containing sunscreens, so knowledge of the subject is prudent when counseling patients.¹⁷ One potential solution may be to recommend sun-protective clothing during water-intensive activities to both increase skin protection and reduce the environmental impact. Furthermore, recommendations could be tailored to specific settings, such as coastal resorts and populated beaches, where these sunscreen ingredients are found in much higher concentrations. At this time, more data must be collected before making any definitive claims or recommendations, but knowledge of the current research will be an important tool in educating patients going forward.

Coastal travel accounts for 80% of all tourism worldwide, a number that continues to grow. The number of travelers to the Mediterranean Sea alone is expected to rise to 350 million individuals per year within the next 20 years.¹ As the number of tourists visiting the world’s oceans increases, the rate of sunscreen unintentionally washed into these marine environments also rises. One study estimated that approximately one-quarter of the sunscreen applied to the skin is washed off over a 20-minute period spent in the water.² Four of the most common sunscreen agents—benzophenone-3 (BP-3), 4-methylbenzylidene camphor (4-MBC), and the nanoparticles titanium dioxide and zinc oxide—have been considered to be risks to marine environments. As this topic has received increasing media scrutiny over the last few years, we summarize the general conclusions that can be drawn from current research and note the questions that still remain to better address patient concerns.

Benzophenone-3

Benzophenone-3, or oxybenzone, is a widely studied UV filter and its effects on marine ecosystems have received the media’s attention over the last few years. Benzophenone-3 is known to cause a bleaching effect to coral, which can inhibit growth and possibly kill the organism.³ Further, oxybenzone sunscreens can promote viral infections in coral, resulting in additional bleaching events.² In a recent study, exposure to BP-3 caused mobile planulae, the larval form of coral, to become clearly deformed, trapped within its own calcium carbonate skeleton.³ The concentration of BP-3 needed to induce these physiological changes is as small as 62 parts per trillion, which is the equivalent of a single drop of water in 6.5 Olympic-sized swimming pools. Levels of BP-3 contamination in the waters off of the US Virgin Islands’ beaches have been recorded as high as 1.4 parts per million, with average concentrations closer to 250 parts per billion.³ High BP-3 concentrations have also been recorded in the waters off the Canary Islands,⁴ Hawaii,³ and South Carolina.⁵

4-Methylbenzylidene Camphor

Environmental concerns have also been raised about another common chemical UV filter: 4-MBC, or enzacamene. In laboratory studies, 4-MBC has been shown to cause oxidative stress to Tetrahymena thermophila, an aquatic protozoan, which results in inhibited growth. At higher concentrations, damage to the cellular membrane was seen as soon as 4 hours after exposure.⁶ In embryonic zebrafish, elevated 4-MBC levels were correlated to improper nerve and muscular development, resulting in developmental defects.⁷ Another study demonstrated that 4-MBC was toxic to Mytilus galloprovincialis, known as the Mediterranean mussel, and Paracentrotus lividus, a species of sea urchin.⁸ Although these studies utilized highly controlled laboratory settings, further studies are needed to examine the effects of 4-MBC on these species at environmentally relevant concentrations.

Physical Sunscreens

Physical sunscreens, as compared to the chemical filters referenced above, use either zinc or titanium to protect the skin from the sun’s rays. Nanoparticles, in particular, are preferred because they do not leave a white film on the skin.⁹ Both titanium dioxide and zinc oxide nanoparticles have been found to inhibit the growth and photosynthesis of marine phytoplankton, the most abundant primary producers on Earth.^10,11 These metal contaminants can be transferred to organisms of higher trophic levels, including zooplankton,¹² and filter-feeding organisms, including marine abalone¹³ and the Mediterranean mussel.¹⁴ These nanoparticles have been shown to cause oxidative stress to these organisms, making them less fit to withstand environmental stressors. It is difficult to show their true impact, however, as it is challenging to accurately detect and quantify nanoparticle concentrations in vivo.¹⁵

Final Thoughts

A recent study showed that 7% of consumers (N=325) regarded environmental agencies’ recommendations as an important factor in their sunscreen purchase.¹⁶ When treating patients with these concerns, the ability to provide sound and informed advice will likely impact their sunscreen use and future sun protection behaviors. Although studies have shown the potential for sunscreen pollution to cause environmental harm, it is important to note that a portion of this research is not correlated to in vivo findings, and further work is required to determine the magnitude and importance of these studies.¹⁵ Regardless, legislation has already been submitted in both Hawaii and the European Union calling for a ban on oxybenzone-containing sunscreens, so knowledge of the subject is prudent when counseling patients.¹⁷ One potential solution may be to recommend sun-protective clothing during water-intensive activities to both increase skin protection and reduce the environmental impact. Furthermore, recommendations could be tailored to specific settings, such as coastal resorts and populated beaches, where these sunscreen ingredients are found in much higher concentrations. At this time, more data must be collected before making any definitive claims or recommendations, but knowledge of the current research will be an important tool in educating patients going forward.

Coverage for two doses of varicella vaccine among kindergarten students was highest in Mississippi and lowest in the District of Columbia, said Ranee Seither and associates at the National Center of Immunization and Respiratory Disease at the Centers for Disease Control and Prevention, Atlanta.

For the 2016-2017 school year, 99.4% of Mississippi children enrolled in kindergarten received the state-required two doses of varicella vaccine, compared with 84.6% in D.C. The median was 93.8% for the 42 states that require two doses and 96.5% for those 42 plus the 7 states that reported and only require one dose. Oklahoma and Wyoming “did not report data because of widespread problems with the quality of data reported by schools,” the CDC investigators wrote (MMWR 2017;66[40]:1073-80).

[email protected]

Coverage for two doses of varicella vaccine among kindergarten students was highest in Mississippi and lowest in the District of Columbia, said Ranee Seither and associates at the National Center of Immunization and Respiratory Disease at the Centers for Disease Control and Prevention, Atlanta.

For the 2016-2017 school year, 99.4% of Mississippi children enrolled in kindergarten received the state-required two doses of varicella vaccine, compared with 84.6% in D.C. The median was 93.8% for the 42 states that require two doses and 96.5% for those 42 plus the 7 states that reported and only require one dose. Oklahoma and Wyoming “did not report data because of widespread problems with the quality of data reported by schools,” the CDC investigators wrote (MMWR 2017;66[40]:1073-80).

[email protected]

Coverage for two doses of varicella vaccine among kindergarten students was highest in Mississippi and lowest in the District of Columbia, said Ranee Seither and associates at the National Center of Immunization and Respiratory Disease at the Centers for Disease Control and Prevention, Atlanta.

For the 2016-2017 school year, 99.4% of Mississippi children enrolled in kindergarten received the state-required two doses of varicella vaccine, compared with 84.6% in D.C. The median was 93.8% for the 42 states that require two doses and 96.5% for those 42 plus the 7 states that reported and only require one dose. Oklahoma and Wyoming “did not report data because of widespread problems with the quality of data reported by schools,” the CDC investigators wrote (MMWR 2017;66[40]:1073-80).

[email protected]

NATIONAL HARBOR, MD. – The oral, class I selective histone deacetylase (HDAC) inhibitor entinostat given in combination with pembrolizumab demonstrated antitumor activity and acceptable safety in patients with non–small cell lung cancer in the phase 1b/2 ENCORE 601 study.

Entinostat, which has been shown in preclinical models to enhance suppressor cells in the tumor microenvironment, was evaluated in ENCORE 601 as a treatment for non–small cell lung cancer (NSCLC), melanoma, and colorectal cancer. Previously reported phase 1 results showed that an oral dose of 5 mg weekly plus 200 mg of pembrolizumab given intravenously every 3 weeks deserved further exploration for these indications, according to Leena Gandhi, MD, who reported phase 2, stage 1 results from the lung cancer arm of the Simon two-stage study at the annual meeting of the Society for Immunotherapy of Cancer.

Treatment at that dose was studied in both anti-PD-L1–naive patients with advanced NSCLC, and in NSCLC patients who progressed on anti-PD-L1 treatment, said Dr. Gandhi of New York University Langone Medical Center.

The primary objective of stage 1 was objective response rate, and criteria for advancement were 4 or more responses out of 17 evaluable anti-PD-L1–naive patients (cohort 1), and at least 3 responses out of 31 patients who progressed on anti-PD-L1 therapy (cohort 2).

Both cohorts met the endpoint, with 4 of 17 evaluable cohort 1 patients (24%) achieving a partial response, and 3 of 31 evaluable cohort 2 patients (10%) achieving a partial response.

In cohort 1, two responses were confirmed and two were unconfirmed. One of the unconfirmed patients had malignant pericardial effusion, but remains on study with continued clinical benefit, Dr. Gandhi said, noting that three patients remain on study in all.

“The other notable thing I’d like to point out here … is that the majority of these were patients who did not have high levels of expression of PD-L1,” she said.

In cohort 2 patients, two responses were confirmed and one was unconfirmed. Three patients remain on study.

“In both of these cohorts there are a couple of patients who’ve had quite durable responses,” she said.

The best response to prior anti-PD-1therapy in the cohort 2 patients who had a response was stable disease (two patients). The response to prior therapy was unknown in one patient, she noted.

“All of them had clear regressions, after that initial PD-1 therapy, with this combination,” she said, noting that two had “essentially negative PD-L1 expression, and none had high levels of expression.”

Treatment was associated with grade 3/4 adverse events deemed drug related in 31% of patients; the most common of these events, occurring in at least 10% of patients in cohort 1, were hypophosphatemia and neutropenia, and in cohort 2 were fatigue, anemia, anorexia, and pneumonitis; 13% of patients discontinued treatment due to an adverse event, Dr. Gandhi said.

Of note, there were reductions in circulating myeloid derived suppressor cells in both cohorts following treatment.

Based on the responses seen in this first stage of the study, cohort 2 has advanced to stage 2 and has completed enrollment. Additional patients have not been enrolled in cohort 1, but that is still under consideration, she said.

Dr. Gandhi reported having no disclosures.

[email protected]

NATIONAL HARBOR, MD. – The oral, class I selective histone deacetylase (HDAC) inhibitor entinostat given in combination with pembrolizumab demonstrated antitumor activity and acceptable safety in patients with non–small cell lung cancer in the phase 1b/2 ENCORE 601 study.

Entinostat, which has been shown in preclinical models to enhance suppressor cells in the tumor microenvironment, was evaluated in ENCORE 601 as a treatment for non–small cell lung cancer (NSCLC), melanoma, and colorectal cancer. Previously reported phase 1 results showed that an oral dose of 5 mg weekly plus 200 mg of pembrolizumab given intravenously every 3 weeks deserved further exploration for these indications, according to Leena Gandhi, MD, who reported phase 2, stage 1 results from the lung cancer arm of the Simon two-stage study at the annual meeting of the Society for Immunotherapy of Cancer.

Treatment at that dose was studied in both anti-PD-L1–naive patients with advanced NSCLC, and in NSCLC patients who progressed on anti-PD-L1 treatment, said Dr. Gandhi of New York University Langone Medical Center.

The primary objective of stage 1 was objective response rate, and criteria for advancement were 4 or more responses out of 17 evaluable anti-PD-L1–naive patients (cohort 1), and at least 3 responses out of 31 patients who progressed on anti-PD-L1 therapy (cohort 2).

Both cohorts met the endpoint, with 4 of 17 evaluable cohort 1 patients (24%) achieving a partial response, and 3 of 31 evaluable cohort 2 patients (10%) achieving a partial response.

In cohort 1, two responses were confirmed and two were unconfirmed. One of the unconfirmed patients had malignant pericardial effusion, but remains on study with continued clinical benefit, Dr. Gandhi said, noting that three patients remain on study in all.

“The other notable thing I’d like to point out here … is that the majority of these were patients who did not have high levels of expression of PD-L1,” she said.

In cohort 2 patients, two responses were confirmed and one was unconfirmed. Three patients remain on study.

“In both of these cohorts there are a couple of patients who’ve had quite durable responses,” she said.

The best response to prior anti-PD-1therapy in the cohort 2 patients who had a response was stable disease (two patients). The response to prior therapy was unknown in one patient, she noted.

“All of them had clear regressions, after that initial PD-1 therapy, with this combination,” she said, noting that two had “essentially negative PD-L1 expression, and none had high levels of expression.”

Treatment was associated with grade 3/4 adverse events deemed drug related in 31% of patients; the most common of these events, occurring in at least 10% of patients in cohort 1, were hypophosphatemia and neutropenia, and in cohort 2 were fatigue, anemia, anorexia, and pneumonitis; 13% of patients discontinued treatment due to an adverse event, Dr. Gandhi said.

Of note, there were reductions in circulating myeloid derived suppressor cells in both cohorts following treatment.

Based on the responses seen in this first stage of the study, cohort 2 has advanced to stage 2 and has completed enrollment. Additional patients have not been enrolled in cohort 1, but that is still under consideration, she said.

Dr. Gandhi reported having no disclosures.

[email protected]

NATIONAL HARBOR, MD. – The oral, class I selective histone deacetylase (HDAC) inhibitor entinostat given in combination with pembrolizumab demonstrated antitumor activity and acceptable safety in patients with non–small cell lung cancer in the phase 1b/2 ENCORE 601 study.

Entinostat, which has been shown in preclinical models to enhance suppressor cells in the tumor microenvironment, was evaluated in ENCORE 601 as a treatment for non–small cell lung cancer (NSCLC), melanoma, and colorectal cancer. Previously reported phase 1 results showed that an oral dose of 5 mg weekly plus 200 mg of pembrolizumab given intravenously every 3 weeks deserved further exploration for these indications, according to Leena Gandhi, MD, who reported phase 2, stage 1 results from the lung cancer arm of the Simon two-stage study at the annual meeting of the Society for Immunotherapy of Cancer.

Treatment at that dose was studied in both anti-PD-L1–naive patients with advanced NSCLC, and in NSCLC patients who progressed on anti-PD-L1 treatment, said Dr. Gandhi of New York University Langone Medical Center.

The primary objective of stage 1 was objective response rate, and criteria for advancement were 4 or more responses out of 17 evaluable anti-PD-L1–naive patients (cohort 1), and at least 3 responses out of 31 patients who progressed on anti-PD-L1 therapy (cohort 2).

Both cohorts met the endpoint, with 4 of 17 evaluable cohort 1 patients (24%) achieving a partial response, and 3 of 31 evaluable cohort 2 patients (10%) achieving a partial response.

In cohort 1, two responses were confirmed and two were unconfirmed. One of the unconfirmed patients had malignant pericardial effusion, but remains on study with continued clinical benefit, Dr. Gandhi said, noting that three patients remain on study in all.

“The other notable thing I’d like to point out here … is that the majority of these were patients who did not have high levels of expression of PD-L1,” she said.

In cohort 2 patients, two responses were confirmed and one was unconfirmed. Three patients remain on study.

“In both of these cohorts there are a couple of patients who’ve had quite durable responses,” she said.

The best response to prior anti-PD-1therapy in the cohort 2 patients who had a response was stable disease (two patients). The response to prior therapy was unknown in one patient, she noted.

“All of them had clear regressions, after that initial PD-1 therapy, with this combination,” she said, noting that two had “essentially negative PD-L1 expression, and none had high levels of expression.”

Treatment was associated with grade 3/4 adverse events deemed drug related in 31% of patients; the most common of these events, occurring in at least 10% of patients in cohort 1, were hypophosphatemia and neutropenia, and in cohort 2 were fatigue, anemia, anorexia, and pneumonitis; 13% of patients discontinued treatment due to an adverse event, Dr. Gandhi said.

Of note, there were reductions in circulating myeloid derived suppressor cells in both cohorts following treatment.

Based on the responses seen in this first stage of the study, cohort 2 has advanced to stage 2 and has completed enrollment. Additional patients have not been enrolled in cohort 1, but that is still under consideration, she said.

Dr. Gandhi reported having no disclosures.

[email protected]

Clinical question

What are the differences in rates of treatment failure, duration of hospitalization, and cost between nonoperative treatment (NOT) for acute uncomplicated appendicitis versus urgent appendectomy?

Background

Acute appendicitis is found in around 5% of children presenting for urgent or emergent evaluation of abdominal pain. It is the most common illness prompting emergency abdominal surgery in children.

Study design

Meta-analysis.

Search strategy

PubMed, MEDLINE, EMBASE, and Cochrane Library were searched for relevant studies. This search identified 527 potential articles, of which the authors examined the full text of 68 and ultimately identified 5 single-center trials for analysis (4 prospective cohort trials and 1 randomized, controlled trial).

Synopsis

A total of 404 patients with uncomplicated appendicitis were seen in all trials: 168 received NOT and 236 received standard surgical care (urgent appendectomy). In the single randomized, controlled trial, patients were assigned NOT or surgical care randomly. In the other trials parental preference directed therapy.

The heterogeneity of the design, populations, definitions of illness, duration of follow-up, and NOT treatment regimens made the meta-analysis challenging. Antibiotic options for NOT varied by center but included a course of IV antibiotics followed by 7-10 days of oral antibiotics. NOT success was defined as no need for surgery within 48 hours and no recurrence of appendicitis within 1 month. Of the 236 patients who received standard surgical care, all had appendicitis and 1 had a complication requiring repeat operation. Of the NOT group, 16 (9.5%) had treatment failures, including 3 with perforated appendicitis, and 45 (27%) went on to have an appendectomy within the following year, yielding a risk ratio of failure versus standard treatment of 8.9 (95% confidence interval, 2.7-29.8). A subgroup analysis of patients with appendicoliths who received NOT found that these patients experienced a substantially increased risk of treatment failures and recurrent appendicitis with the risk ratio versus NOT without appendicolith of 10.4 (95% CI, 1.5-74). Of the 30 patients who experienced treatment failure with NOT, 15 had appendicoliths. NOT lengthened hospital stays by 14.3 hours (95% CI, 7.5-21.1) but led to lower total costs by $1,310 (95% CI, $920-$1,690).
 

Bottom line

NOT may be a reasonable alternative to standard surgical management for acute uncomplicated appendicitis without appendicolith in children, with a success rate of greater than 90%. Further larger, randomized prospective studies are required to establish its safety and efficacy.

Citation

Huang L et al. Comparison of antibiotic therapy and appendectomy for acute uncomplicated appendicitis in children: A meta-analysis. JAMA Pediatr. 2017;171(5):426-34.

Dr. Stubblefield is a pediatric hospitalist at Nemours/Alfred I. duPont Hospital for Children in Wilmington, Del., and a clinical assistant professor of pediatrics at Jefferson Medical College in Philadelphia.

Clinical question

What are the differences in rates of treatment failure, duration of hospitalization, and cost between nonoperative treatment (NOT) for acute uncomplicated appendicitis versus urgent appendectomy?

Background

Acute appendicitis is found in around 5% of children presenting for urgent or emergent evaluation of abdominal pain. It is the most common illness prompting emergency abdominal surgery in children.

Study design

Meta-analysis.

Search strategy

PubMed, MEDLINE, EMBASE, and Cochrane Library were searched for relevant studies. This search identified 527 potential articles, of which the authors examined the full text of 68 and ultimately identified 5 single-center trials for analysis (4 prospective cohort trials and 1 randomized, controlled trial).

Synopsis

A total of 404 patients with uncomplicated appendicitis were seen in all trials: 168 received NOT and 236 received standard surgical care (urgent appendectomy). In the single randomized, controlled trial, patients were assigned NOT or surgical care randomly. In the other trials parental preference directed therapy.

The heterogeneity of the design, populations, definitions of illness, duration of follow-up, and NOT treatment regimens made the meta-analysis challenging. Antibiotic options for NOT varied by center but included a course of IV antibiotics followed by 7-10 days of oral antibiotics. NOT success was defined as no need for surgery within 48 hours and no recurrence of appendicitis within 1 month. Of the 236 patients who received standard surgical care, all had appendicitis and 1 had a complication requiring repeat operation. Of the NOT group, 16 (9.5%) had treatment failures, including 3 with perforated appendicitis, and 45 (27%) went on to have an appendectomy within the following year, yielding a risk ratio of failure versus standard treatment of 8.9 (95% confidence interval, 2.7-29.8). A subgroup analysis of patients with appendicoliths who received NOT found that these patients experienced a substantially increased risk of treatment failures and recurrent appendicitis with the risk ratio versus NOT without appendicolith of 10.4 (95% CI, 1.5-74). Of the 30 patients who experienced treatment failure with NOT, 15 had appendicoliths. NOT lengthened hospital stays by 14.3 hours (95% CI, 7.5-21.1) but led to lower total costs by $1,310 (95% CI, $920-$1,690).
 

Bottom line

NOT may be a reasonable alternative to standard surgical management for acute uncomplicated appendicitis without appendicolith in children, with a success rate of greater than 90%. Further larger, randomized prospective studies are required to establish its safety and efficacy.

Citation

Huang L et al. Comparison of antibiotic therapy and appendectomy for acute uncomplicated appendicitis in children: A meta-analysis. JAMA Pediatr. 2017;171(5):426-34.

Dr. Stubblefield is a pediatric hospitalist at Nemours/Alfred I. duPont Hospital for Children in Wilmington, Del., and a clinical assistant professor of pediatrics at Jefferson Medical College in Philadelphia.

Clinical question

What are the differences in rates of treatment failure, duration of hospitalization, and cost between nonoperative treatment (NOT) for acute uncomplicated appendicitis versus urgent appendectomy?

Background

Acute appendicitis is found in around 5% of children presenting for urgent or emergent evaluation of abdominal pain. It is the most common illness prompting emergency abdominal surgery in children.

Study design

Meta-analysis.

Search strategy

PubMed, MEDLINE, EMBASE, and Cochrane Library were searched for relevant studies. This search identified 527 potential articles, of which the authors examined the full text of 68 and ultimately identified 5 single-center trials for analysis (4 prospective cohort trials and 1 randomized, controlled trial).

Synopsis

A total of 404 patients with uncomplicated appendicitis were seen in all trials: 168 received NOT and 236 received standard surgical care (urgent appendectomy). In the single randomized, controlled trial, patients were assigned NOT or surgical care randomly. In the other trials parental preference directed therapy.

The heterogeneity of the design, populations, definitions of illness, duration of follow-up, and NOT treatment regimens made the meta-analysis challenging. Antibiotic options for NOT varied by center but included a course of IV antibiotics followed by 7-10 days of oral antibiotics. NOT success was defined as no need for surgery within 48 hours and no recurrence of appendicitis within 1 month. Of the 236 patients who received standard surgical care, all had appendicitis and 1 had a complication requiring repeat operation. Of the NOT group, 16 (9.5%) had treatment failures, including 3 with perforated appendicitis, and 45 (27%) went on to have an appendectomy within the following year, yielding a risk ratio of failure versus standard treatment of 8.9 (95% confidence interval, 2.7-29.8). A subgroup analysis of patients with appendicoliths who received NOT found that these patients experienced a substantially increased risk of treatment failures and recurrent appendicitis with the risk ratio versus NOT without appendicolith of 10.4 (95% CI, 1.5-74). Of the 30 patients who experienced treatment failure with NOT, 15 had appendicoliths. NOT lengthened hospital stays by 14.3 hours (95% CI, 7.5-21.1) but led to lower total costs by $1,310 (95% CI, $920-$1,690).
 

Bottom line

NOT may be a reasonable alternative to standard surgical management for acute uncomplicated appendicitis without appendicolith in children, with a success rate of greater than 90%. Further larger, randomized prospective studies are required to establish its safety and efficacy.

Citation

Huang L et al. Comparison of antibiotic therapy and appendectomy for acute uncomplicated appendicitis in children: A meta-analysis. JAMA Pediatr. 2017;171(5):426-34.

Dr. Stubblefield is a pediatric hospitalist at Nemours/Alfred I. duPont Hospital for Children in Wilmington, Del., and a clinical assistant professor of pediatrics at Jefferson Medical College in Philadelphia.

The use of JAK inhibitors is not the only notable development in the treatment of hair loss; light-based options show potential as well, according to Maria Hordinsky, MD.

“Although the precise mechanism remains unclear, it has been postulated that photobiomodulation acts through oxidative metabolism and transcription factor stimulation,” Dr. Hordinsky said in a presentation at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.

The use of JAK inhibitors is not the only notable development in the treatment of hair loss; light-based options show potential as well, according to Maria Hordinsky, MD.

“Although the precise mechanism remains unclear, it has been postulated that photobiomodulation acts through oxidative metabolism and transcription factor stimulation,” Dr. Hordinsky said in a presentation at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.

The use of JAK inhibitors is not the only notable development in the treatment of hair loss; light-based options show potential as well, according to Maria Hordinsky, MD.

“Although the precise mechanism remains unclear, it has been postulated that photobiomodulation acts through oxidative metabolism and transcription factor stimulation,” Dr. Hordinsky said in a presentation at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.

Food and Drug Administration officials are warning of continued medical supply shortages in Puerto Rico in the aftermath of Hurricane Maria.

“In addition to our ongoing concerns related to IV saline products, we also are particularly focused on the shortage of amino acids for injection,” FDA Commissioner Scott Gottlieb, MD, said in a statement.

Wikimedia Commons/FitzColinGerald/Creative Commons License

[email protected]

Food and Drug Administration officials are warning of continued medical supply shortages in Puerto Rico in the aftermath of Hurricane Maria.

“In addition to our ongoing concerns related to IV saline products, we also are particularly focused on the shortage of amino acids for injection,” FDA Commissioner Scott Gottlieb, MD, said in a statement.

Wikimedia Commons/FitzColinGerald/Creative Commons License

[email protected]

Food and Drug Administration officials are warning of continued medical supply shortages in Puerto Rico in the aftermath of Hurricane Maria.

“In addition to our ongoing concerns related to IV saline products, we also are particularly focused on the shortage of amino acids for injection,” FDA Commissioner Scott Gottlieb, MD, said in a statement.

Wikimedia Commons/FitzColinGerald/Creative Commons License

[email protected]

When evaluating lumps and bumps in infants, categorizing them can help determine whether they need immediate attention, said James R. Treat, MD, a pediatric dermatologist at Children’s Hospital of Philadelphia, Pennsylvania.

“Divide ‘birthmarks’ based on appearance, “then decide when to worry,” he said in a presentation at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.

For example, Spitz nevi occur in patients younger than 20 years, most often on the face and lower extremities, but most are benign, Dr. Treat said. However, he recommends a biopsy if the patient is pubertal or older, or if the lesions are larger than 8 mm, amelanotic, or show asymmetry, ulceration, or excessive growth.

By contrast, neurocutaneous melanosis is a rare but serious skin condition that occurs in children and can be fatal if it progresses to melanoma, he pointed out. The condition involves the migration of melanocytes into the spinal canal and cerebrospinal fluid during development. Symptoms may include headache, seizures, and paralysis, and clinicians should keep them in mind when seeing children with melanocytic nevi, he noted. The highest risk for melanoma transformation is increased for individuals with more than 20 congenital moles, and “the second-highest risk is having a giant nevus lying overtop of the midline spine or scalp,” he said.

In some cases, yellow or tan lesions in children are benign and will resolve on their own, Dr. Treat said.

Juvenile xanthogranuloma (JXG), characterized by yellow-brown asymptomatic papules and nodules, develops most often within the first year of life, but the lesions usually resolve spontaneously by school age, he added.

Mastocytosis, localized collections of mast cells, presents as yellow/tan lesions that develop within the first 2 years of life. The condition can be systemic; patients may experience flushing and diarrhea because of localized release of histamines, and those with a history of weight loss, easy bruising or bleeding, hepatosplenomegaly, or lymphadenopathy may have systemic disease, Dr. Treat explained.

Subcutaneous fat necrosis can present within the first 2 weeks of life as firm, red-purple tender nodules that may be disturbing to parents. These lesions are most likely to appear on the cheeks, arms, back, and thighs, and are related to hypoxia or trauma, he added. The lesions usually resolve spontaneously within a period of weeks to months, although they may heal with some atrophy and scarring, he said. Subcutaneous fat necrosis is associated with hypercalcemia, so “it is important to check frequently, as hypercalcemia can occur weeks after the nodules resolve,” he commented.

Dr. Treat disclosed serving as a consultant to Procter & Gamble. SDEF and this news organization are owned by Frontline Medical Communications.

When evaluating lumps and bumps in infants, categorizing them can help determine whether they need immediate attention, said James R. Treat, MD, a pediatric dermatologist at Children’s Hospital of Philadelphia, Pennsylvania.

“Divide ‘birthmarks’ based on appearance, “then decide when to worry,” he said in a presentation at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.

For example, Spitz nevi occur in patients younger than 20 years, most often on the face and lower extremities, but most are benign, Dr. Treat said. However, he recommends a biopsy if the patient is pubertal or older, or if the lesions are larger than 8 mm, amelanotic, or show asymmetry, ulceration, or excessive growth.

By contrast, neurocutaneous melanosis is a rare but serious skin condition that occurs in children and can be fatal if it progresses to melanoma, he pointed out. The condition involves the migration of melanocytes into the spinal canal and cerebrospinal fluid during development. Symptoms may include headache, seizures, and paralysis, and clinicians should keep them in mind when seeing children with melanocytic nevi, he noted. The highest risk for melanoma transformation is increased for individuals with more than 20 congenital moles, and “the second-highest risk is having a giant nevus lying overtop of the midline spine or scalp,” he said.

In some cases, yellow or tan lesions in children are benign and will resolve on their own, Dr. Treat said.

Juvenile xanthogranuloma (JXG), characterized by yellow-brown asymptomatic papules and nodules, develops most often within the first year of life, but the lesions usually resolve spontaneously by school age, he added.

Mastocytosis, localized collections of mast cells, presents as yellow/tan lesions that develop within the first 2 years of life. The condition can be systemic; patients may experience flushing and diarrhea because of localized release of histamines, and those with a history of weight loss, easy bruising or bleeding, hepatosplenomegaly, or lymphadenopathy may have systemic disease, Dr. Treat explained.

Subcutaneous fat necrosis can present within the first 2 weeks of life as firm, red-purple tender nodules that may be disturbing to parents. These lesions are most likely to appear on the cheeks, arms, back, and thighs, and are related to hypoxia or trauma, he added. The lesions usually resolve spontaneously within a period of weeks to months, although they may heal with some atrophy and scarring, he said. Subcutaneous fat necrosis is associated with hypercalcemia, so “it is important to check frequently, as hypercalcemia can occur weeks after the nodules resolve,” he commented.

Dr. Treat disclosed serving as a consultant to Procter & Gamble. SDEF and this news organization are owned by Frontline Medical Communications.

When evaluating lumps and bumps in infants, categorizing them can help determine whether they need immediate attention, said James R. Treat, MD, a pediatric dermatologist at Children’s Hospital of Philadelphia, Pennsylvania.

“Divide ‘birthmarks’ based on appearance, “then decide when to worry,” he said in a presentation at Skin Disease Education Foundation’s Women’s & Pediatric Dermatology Seminar.

For example, Spitz nevi occur in patients younger than 20 years, most often on the face and lower extremities, but most are benign, Dr. Treat said. However, he recommends a biopsy if the patient is pubertal or older, or if the lesions are larger than 8 mm, amelanotic, or show asymmetry, ulceration, or excessive growth.

By contrast, neurocutaneous melanosis is a rare but serious skin condition that occurs in children and can be fatal if it progresses to melanoma, he pointed out. The condition involves the migration of melanocytes into the spinal canal and cerebrospinal fluid during development. Symptoms may include headache, seizures, and paralysis, and clinicians should keep them in mind when seeing children with melanocytic nevi, he noted. The highest risk for melanoma transformation is increased for individuals with more than 20 congenital moles, and “the second-highest risk is having a giant nevus lying overtop of the midline spine or scalp,” he said.

In some cases, yellow or tan lesions in children are benign and will resolve on their own, Dr. Treat said.

Juvenile xanthogranuloma (JXG), characterized by yellow-brown asymptomatic papules and nodules, develops most often within the first year of life, but the lesions usually resolve spontaneously by school age, he added.

Mastocytosis, localized collections of mast cells, presents as yellow/tan lesions that develop within the first 2 years of life. The condition can be systemic; patients may experience flushing and diarrhea because of localized release of histamines, and those with a history of weight loss, easy bruising or bleeding, hepatosplenomegaly, or lymphadenopathy may have systemic disease, Dr. Treat explained.

Subcutaneous fat necrosis can present within the first 2 weeks of life as firm, red-purple tender nodules that may be disturbing to parents. These lesions are most likely to appear on the cheeks, arms, back, and thighs, and are related to hypoxia or trauma, he added. The lesions usually resolve spontaneously within a period of weeks to months, although they may heal with some atrophy and scarring, he said. Subcutaneous fat necrosis is associated with hypercalcemia, so “it is important to check frequently, as hypercalcemia can occur weeks after the nodules resolve,” he commented.

Dr. Treat disclosed serving as a consultant to Procter & Gamble. SDEF and this news organization are owned by Frontline Medical Communications.

Pediatric hospitalist Patrick Conway, MD, has been named president and chief executive officer of Blue Cross and Blue Shield of North Carolina. Dr. Conway will take over for the retiring Brad Wilson on Oct. 1.

Dr. Conway is currently the deputy administrator for Innovation and Quality, and the director of the Center for Medicare and Medicaid Innovation for the Centers for Medicare and Medicaid Services (CMS). Previously, he was CMO at CMS, having served both the Obama and Trump administrations.

Hossam Hafez, MD, recently claimed the role of chief of Hospitalist Service with Health Quest Medical Practice (LaGrangeville, N.Y.). Dr. Hafez will be based out of Health Quest’s Vassar Brothers Medical Center in Poughkeepsie, N.Y., coordinating care in that hospital and throughout the Health Quest system.

Dr. Hafez has served full-time hospitalist stints with MidMichigan Health’s Physician Hospitalist Group, as well as with RiteMed Urgent Care. A native of Egypt, Dr. Hafez is fluent in both English and Arabic.
 

Caldwell UNC Healthcare (Lenoir, N.C.) has promoted David Lowry, MD, to chief medical officer as of Aug. 1, 2017.

Dr. Lowry, a longtime hospitalist and veteran in hospital medicine in general, will lead the building’s hospitalist program, support the chief of staff, and provide direct patient care, as well. He will serve as physician advisor for Caldwell’s Clinical Documentation, Utilization Review, Respiratory Care, and Rehabilitation departments.

Dr. Lowry boasts more than 25 years experience in hospital medicine and led in the creation of Caldwell’s hospitalist program. Since joining Caldwell, he has held leadership positions including chief of medicine. He received the hospital’s Donald D. McNeill Jr. Award for Outstanding Physician Leadership in 2014, as voted by his peers.
 

Joahd Toure, MD, recently was hired by Adirondack Health (Saranac Lake, N.Y.) as its new chief medical officer. He started his new position in late June 2017.

Longtime employee Emily Chapman, MD, has been promoted to chief medical officer and vice president of medical affairs at Children’s Minnesota Hospital (Minneapolis). The former vice CMO took on her new role on July 5, 2017.

Mark Sockell, MD, is the new chief medical officer at Meritage Medical Network in Novato, Calif. Meritage is a physician-run network that includes more than 700 board-certified physicians in both primary care and specialist fields.

Dr. Sockell has been a member of Meritage’s Board of Directors since 2014, and he specializes in risk adjustment and quality measures. His career has focused on medical education, headed by a stint as director of medical education at St. Mary’s Medical Center (San Francisco). There, he created and ran the inpatient hospitalist program.
 

Business Moves

Hammond-Henry Hospital (Geneseo, Ill.) recently announced the creation of a hospitalist program, utilizing the facility’s own emergency room physicians. Hammond-Henry will staff one emergency room doctor available for rounds outside of their ER work throughout the day.

The center’s hospitalist program will be led by medical director Kevin Jeffries, MD, who also will serve as one of the hospital’s ER physicians/hospitalists.
 

Avera Queen of Peace Hospital (Mitchell, S.D.) started its own hospitalist program on Aug. 1, 2017, launching with the goal of improving patient experience within the building. Avera’s hospitalists will be on-site for 12 hours each day, assisting specialists and working with patients who do not have a local primary care physician.

Queen of Peace is the regional referral center for an 11-county area, part of Avera Health System’s 330 facilities across North and South Dakota, Minnesota, Iowa, and Nebraska.
 

Pediatric hospitalist Patrick Conway, MD, has been named president and chief executive officer of Blue Cross and Blue Shield of North Carolina. Dr. Conway will take over for the retiring Brad Wilson on Oct. 1.

Dr. Conway is currently the deputy administrator for Innovation and Quality, and the director of the Center for Medicare and Medicaid Innovation for the Centers for Medicare and Medicaid Services (CMS). Previously, he was CMO at CMS, having served both the Obama and Trump administrations.

Hossam Hafez, MD, recently claimed the role of chief of Hospitalist Service with Health Quest Medical Practice (LaGrangeville, N.Y.). Dr. Hafez will be based out of Health Quest’s Vassar Brothers Medical Center in Poughkeepsie, N.Y., coordinating care in that hospital and throughout the Health Quest system.

Dr. Hafez has served full-time hospitalist stints with MidMichigan Health’s Physician Hospitalist Group, as well as with RiteMed Urgent Care. A native of Egypt, Dr. Hafez is fluent in both English and Arabic.
 

Caldwell UNC Healthcare (Lenoir, N.C.) has promoted David Lowry, MD, to chief medical officer as of Aug. 1, 2017.

Dr. Lowry, a longtime hospitalist and veteran in hospital medicine in general, will lead the building’s hospitalist program, support the chief of staff, and provide direct patient care, as well. He will serve as physician advisor for Caldwell’s Clinical Documentation, Utilization Review, Respiratory Care, and Rehabilitation departments.

Dr. Lowry boasts more than 25 years experience in hospital medicine and led in the creation of Caldwell’s hospitalist program. Since joining Caldwell, he has held leadership positions including chief of medicine. He received the hospital’s Donald D. McNeill Jr. Award for Outstanding Physician Leadership in 2014, as voted by his peers.
 

Joahd Toure, MD, recently was hired by Adirondack Health (Saranac Lake, N.Y.) as its new chief medical officer. He started his new position in late June 2017.

Longtime employee Emily Chapman, MD, has been promoted to chief medical officer and vice president of medical affairs at Children’s Minnesota Hospital (Minneapolis). The former vice CMO took on her new role on July 5, 2017.

Mark Sockell, MD, is the new chief medical officer at Meritage Medical Network in Novato, Calif. Meritage is a physician-run network that includes more than 700 board-certified physicians in both primary care and specialist fields.

Dr. Sockell has been a member of Meritage’s Board of Directors since 2014, and he specializes in risk adjustment and quality measures. His career has focused on medical education, headed by a stint as director of medical education at St. Mary’s Medical Center (San Francisco). There, he created and ran the inpatient hospitalist program.
 

Business Moves

Hammond-Henry Hospital (Geneseo, Ill.) recently announced the creation of a hospitalist program, utilizing the facility’s own emergency room physicians. Hammond-Henry will staff one emergency room doctor available for rounds outside of their ER work throughout the day.

The center’s hospitalist program will be led by medical director Kevin Jeffries, MD, who also will serve as one of the hospital’s ER physicians/hospitalists.
 

Avera Queen of Peace Hospital (Mitchell, S.D.) started its own hospitalist program on Aug. 1, 2017, launching with the goal of improving patient experience within the building. Avera’s hospitalists will be on-site for 12 hours each day, assisting specialists and working with patients who do not have a local primary care physician.

Queen of Peace is the regional referral center for an 11-county area, part of Avera Health System’s 330 facilities across North and South Dakota, Minnesota, Iowa, and Nebraska.
 

Pediatric hospitalist Patrick Conway, MD, has been named president and chief executive officer of Blue Cross and Blue Shield of North Carolina. Dr. Conway will take over for the retiring Brad Wilson on Oct. 1.

Dr. Conway is currently the deputy administrator for Innovation and Quality, and the director of the Center for Medicare and Medicaid Innovation for the Centers for Medicare and Medicaid Services (CMS). Previously, he was CMO at CMS, having served both the Obama and Trump administrations.

Hossam Hafez, MD, recently claimed the role of chief of Hospitalist Service with Health Quest Medical Practice (LaGrangeville, N.Y.). Dr. Hafez will be based out of Health Quest’s Vassar Brothers Medical Center in Poughkeepsie, N.Y., coordinating care in that hospital and throughout the Health Quest system.

Dr. Hafez has served full-time hospitalist stints with MidMichigan Health’s Physician Hospitalist Group, as well as with RiteMed Urgent Care. A native of Egypt, Dr. Hafez is fluent in both English and Arabic.
 

Caldwell UNC Healthcare (Lenoir, N.C.) has promoted David Lowry, MD, to chief medical officer as of Aug. 1, 2017.

Dr. Lowry, a longtime hospitalist and veteran in hospital medicine in general, will lead the building’s hospitalist program, support the chief of staff, and provide direct patient care, as well. He will serve as physician advisor for Caldwell’s Clinical Documentation, Utilization Review, Respiratory Care, and Rehabilitation departments.

Dr. Lowry boasts more than 25 years experience in hospital medicine and led in the creation of Caldwell’s hospitalist program. Since joining Caldwell, he has held leadership positions including chief of medicine. He received the hospital’s Donald D. McNeill Jr. Award for Outstanding Physician Leadership in 2014, as voted by his peers.
 

Joahd Toure, MD, recently was hired by Adirondack Health (Saranac Lake, N.Y.) as its new chief medical officer. He started his new position in late June 2017.

Longtime employee Emily Chapman, MD, has been promoted to chief medical officer and vice president of medical affairs at Children’s Minnesota Hospital (Minneapolis). The former vice CMO took on her new role on July 5, 2017.

Mark Sockell, MD, is the new chief medical officer at Meritage Medical Network in Novato, Calif. Meritage is a physician-run network that includes more than 700 board-certified physicians in both primary care and specialist fields.

Dr. Sockell has been a member of Meritage’s Board of Directors since 2014, and he specializes in risk adjustment and quality measures. His career has focused on medical education, headed by a stint as director of medical education at St. Mary’s Medical Center (San Francisco). There, he created and ran the inpatient hospitalist program.
 

Business Moves

Hammond-Henry Hospital (Geneseo, Ill.) recently announced the creation of a hospitalist program, utilizing the facility’s own emergency room physicians. Hammond-Henry will staff one emergency room doctor available for rounds outside of their ER work throughout the day.

The center’s hospitalist program will be led by medical director Kevin Jeffries, MD, who also will serve as one of the hospital’s ER physicians/hospitalists.
 

Avera Queen of Peace Hospital (Mitchell, S.D.) started its own hospitalist program on Aug. 1, 2017, launching with the goal of improving patient experience within the building. Avera’s hospitalists will be on-site for 12 hours each day, assisting specialists and working with patients who do not have a local primary care physician.

Queen of Peace is the regional referral center for an 11-county area, part of Avera Health System’s 330 facilities across North and South Dakota, Minnesota, Iowa, and Nebraska.