Grandhi R, Shamloul N, Powell M. Purpuric bullae on the lower extremities. Cutis. 2020;105:282, 286-287.

In the article above from the June 2020 issue, the images were incorrect. The correct images appear below. The article has been corrected online at www.mdedge.com/dermatology. We apologize for the error.

Quiz Images

Discussion Images

Grandhi R, Shamloul N, Powell M. Purpuric bullae on the lower extremities. Cutis. 2020;105:282, 286-287.

In the article above from the June 2020 issue, the images were incorrect. The correct images appear below. The article has been corrected online at www.mdedge.com/dermatology. We apologize for the error.

Quiz Images

Discussion Images

Grandhi R, Shamloul N, Powell M. Purpuric bullae on the lower extremities. Cutis. 2020;105:282, 286-287.

In the article above from the June 2020 issue, the images were incorrect. The correct images appear below. The article has been corrected online at www.mdedge.com/dermatology. We apologize for the error.

Quiz Images

Discussion Images

Research on COVID-19 as it relates to rheumatic and musculoskeletal diseases (RMDs) is accumulating “at an enormously rapid pace,” but a recent review of the literature suggests that quantity should not be confused with quality.

“We are faced by the worldwide spread of a disease that was nonexistent less than a year ago,” Féline P.B. Kroon, MD, and associates said in Annals of the Rheumatic Diseases. “To date, no robust evidence is available to allow strong conclusions on the effects of COVID-19 in patients with RMDs or whether RMDs or [their] treatment impact incidence of infection or outcomes.”

When it comes to quantity of evidence, “the exponential increase in publications over time is evident,” they said. From Jan. 1, 2019 to June 24, 2020, there were 1,725 hits on PubMed for published reports combining COVID-19 with RMDs and drugs used in RMDs. At the beginning of the year, there were only 135 such publications.

The early start of the search, well before identification of the novel coronavirus in China, was meant to ensure that nothing was missed, so “citations that came up in the first months of 2019 mostly encompass papers about other coronaviruses, such as SARS and MERS,” said Dr. Kroon of Zuyderland Medical Center, Heerlen, the Netherlands, when asked for clarification.

The quality of that evidence, however, is another matter. A majority of publications (60%) are “viewpoints or (narrative) literature reviews, and only a small proportion actually presents original data in the form of case reports or case series (15%), observational cohort studies (10%), or clinical trials (<1%),” the investigators explained.

Very few of the published studies, about 10%, specifically involve COVID-19 and RMDs. Even well-regarded sources such as systematic literature reviews or meta-analyses, “which will undoubtedly appear more frequently in the next few months in response to requests by users who feel overwhelmed by a multitude of data, will not eliminate the internal bias present in individual studies,” Dr. Kroon and associates wrote.

The lack of evidence also brings into question one particular form of guidance: recommendations “issued by groups of the so-called experts and (inter)national societies, such as, among others, American College of Rheumatology and European League Against Rheumatism,” the investigators said.

“The rapid increase in research on COVID-19 is encouraging,” but at the same time it “also poses risks of ‘information overload’ or ‘fake news,’ ” they said. “As researchers and clinicians, it is our responsibility to carefully interpret study results that emerge, even more so in this ‘digital era,’ in which published data can quickly have a large societal impact.”

[email protected]

SOURCE: Kroon FPB et al. Ann Rheum Dis. 2020 Aug 12. doi: 10.1136/annrheumdis-2020-218483.

Research on COVID-19 as it relates to rheumatic and musculoskeletal diseases (RMDs) is accumulating “at an enormously rapid pace,” but a recent review of the literature suggests that quantity should not be confused with quality.

“We are faced by the worldwide spread of a disease that was nonexistent less than a year ago,” Féline P.B. Kroon, MD, and associates said in Annals of the Rheumatic Diseases. “To date, no robust evidence is available to allow strong conclusions on the effects of COVID-19 in patients with RMDs or whether RMDs or [their] treatment impact incidence of infection or outcomes.”

When it comes to quantity of evidence, “the exponential increase in publications over time is evident,” they said. From Jan. 1, 2019 to June 24, 2020, there were 1,725 hits on PubMed for published reports combining COVID-19 with RMDs and drugs used in RMDs. At the beginning of the year, there were only 135 such publications.

The early start of the search, well before identification of the novel coronavirus in China, was meant to ensure that nothing was missed, so “citations that came up in the first months of 2019 mostly encompass papers about other coronaviruses, such as SARS and MERS,” said Dr. Kroon of Zuyderland Medical Center, Heerlen, the Netherlands, when asked for clarification.

The quality of that evidence, however, is another matter. A majority of publications (60%) are “viewpoints or (narrative) literature reviews, and only a small proportion actually presents original data in the form of case reports or case series (15%), observational cohort studies (10%), or clinical trials (<1%),” the investigators explained.

Very few of the published studies, about 10%, specifically involve COVID-19 and RMDs. Even well-regarded sources such as systematic literature reviews or meta-analyses, “which will undoubtedly appear more frequently in the next few months in response to requests by users who feel overwhelmed by a multitude of data, will not eliminate the internal bias present in individual studies,” Dr. Kroon and associates wrote.

The lack of evidence also brings into question one particular form of guidance: recommendations “issued by groups of the so-called experts and (inter)national societies, such as, among others, American College of Rheumatology and European League Against Rheumatism,” the investigators said.

“The rapid increase in research on COVID-19 is encouraging,” but at the same time it “also poses risks of ‘information overload’ or ‘fake news,’ ” they said. “As researchers and clinicians, it is our responsibility to carefully interpret study results that emerge, even more so in this ‘digital era,’ in which published data can quickly have a large societal impact.”

[email protected]

SOURCE: Kroon FPB et al. Ann Rheum Dis. 2020 Aug 12. doi: 10.1136/annrheumdis-2020-218483.

Research on COVID-19 as it relates to rheumatic and musculoskeletal diseases (RMDs) is accumulating “at an enormously rapid pace,” but a recent review of the literature suggests that quantity should not be confused with quality.

“We are faced by the worldwide spread of a disease that was nonexistent less than a year ago,” Féline P.B. Kroon, MD, and associates said in Annals of the Rheumatic Diseases. “To date, no robust evidence is available to allow strong conclusions on the effects of COVID-19 in patients with RMDs or whether RMDs or [their] treatment impact incidence of infection or outcomes.”

When it comes to quantity of evidence, “the exponential increase in publications over time is evident,” they said. From Jan. 1, 2019 to June 24, 2020, there were 1,725 hits on PubMed for published reports combining COVID-19 with RMDs and drugs used in RMDs. At the beginning of the year, there were only 135 such publications.

The early start of the search, well before identification of the novel coronavirus in China, was meant to ensure that nothing was missed, so “citations that came up in the first months of 2019 mostly encompass papers about other coronaviruses, such as SARS and MERS,” said Dr. Kroon of Zuyderland Medical Center, Heerlen, the Netherlands, when asked for clarification.

The quality of that evidence, however, is another matter. A majority of publications (60%) are “viewpoints or (narrative) literature reviews, and only a small proportion actually presents original data in the form of case reports or case series (15%), observational cohort studies (10%), or clinical trials (<1%),” the investigators explained.

Very few of the published studies, about 10%, specifically involve COVID-19 and RMDs. Even well-regarded sources such as systematic literature reviews or meta-analyses, “which will undoubtedly appear more frequently in the next few months in response to requests by users who feel overwhelmed by a multitude of data, will not eliminate the internal bias present in individual studies,” Dr. Kroon and associates wrote.

The lack of evidence also brings into question one particular form of guidance: recommendations “issued by groups of the so-called experts and (inter)national societies, such as, among others, American College of Rheumatology and European League Against Rheumatism,” the investigators said.

“The rapid increase in research on COVID-19 is encouraging,” but at the same time it “also poses risks of ‘information overload’ or ‘fake news,’ ” they said. “As researchers and clinicians, it is our responsibility to carefully interpret study results that emerge, even more so in this ‘digital era,’ in which published data can quickly have a large societal impact.”

[email protected]

SOURCE: Kroon FPB et al. Ann Rheum Dis. 2020 Aug 12. doi: 10.1136/annrheumdis-2020-218483.

ANSWER

The correct answer is all the above (choice “e”).

DISCUSSION

The differential for round or annular, scaly lesions is lengthy. In addition to all 4 conditions listed above, it includes eczema, basal cell carcinoma, and irritant or contact dermatitis.

With this patient’s history, the diagnosis of fungal infection was not unreasonable. However, the total lack of response to antifungal treatment—along with a negative KOH prep—made that diagnosis questionable at best. Then there was the lack of lymphadenopathy, which would almost certainly have been present with such longstanding infection. Given her country of origin, cutaneous New World leishmaniasis (caused by a protozoan delivered to the patient by an insect vector) was a possibility.

For this patient, skin biopsy with a 4-mm punch was the only way to establish the correct diagnosis. The defect from the biopsy was closed with 5-0 nylon sutures to minimize scarring.

The pathological findings included interface dermatitis, apoptotic keratinocytes, and a brisk periadnexal lymphocytic infiltrate, which—given the morphological and historical context—were entirely consistent with discoid lupus erythematosus (DLE; otherwise known as subacute cutaneous lupus erythematosus). Subsequent bloodwork failed to show any connection with systemic lupus erythematosus (SLE), which is not surprising because only about 18% of DLE cases evolve into SLE.

DLE is more common in women, especially in those with skin of color. The associated lesions are seldom as impressive as this patient’s, manifesting as papulosquamous patches typically found on the ears, neck, face, arms, and other sun-exposed areas. Indeed, it appears that sun exposure is a major trigger for the disease—a clue that can assist with the diagnosis.

TREATMENT

In addition to proscribing excessive sun exposure, providers should encourage the use of sunscreen. DLE is often treated with topical steroids. More advanced cases, such as this patient’s, may require oral hydroxychloroquine (200 mg bid). Though these treatments are effective in most cases, DLE can leave serious scarring and/or discoloration, especially in those with darker skin.

ANSWER

The correct answer is all the above (choice “e”).

DISCUSSION

The differential for round or annular, scaly lesions is lengthy. In addition to all 4 conditions listed above, it includes eczema, basal cell carcinoma, and irritant or contact dermatitis.

With this patient’s history, the diagnosis of fungal infection was not unreasonable. However, the total lack of response to antifungal treatment—along with a negative KOH prep—made that diagnosis questionable at best. Then there was the lack of lymphadenopathy, which would almost certainly have been present with such longstanding infection. Given her country of origin, cutaneous New World leishmaniasis (caused by a protozoan delivered to the patient by an insect vector) was a possibility.

For this patient, skin biopsy with a 4-mm punch was the only way to establish the correct diagnosis. The defect from the biopsy was closed with 5-0 nylon sutures to minimize scarring.

The pathological findings included interface dermatitis, apoptotic keratinocytes, and a brisk periadnexal lymphocytic infiltrate, which—given the morphological and historical context—were entirely consistent with discoid lupus erythematosus (DLE; otherwise known as subacute cutaneous lupus erythematosus). Subsequent bloodwork failed to show any connection with systemic lupus erythematosus (SLE), which is not surprising because only about 18% of DLE cases evolve into SLE.

DLE is more common in women, especially in those with skin of color. The associated lesions are seldom as impressive as this patient’s, manifesting as papulosquamous patches typically found on the ears, neck, face, arms, and other sun-exposed areas. Indeed, it appears that sun exposure is a major trigger for the disease—a clue that can assist with the diagnosis.

TREATMENT

In addition to proscribing excessive sun exposure, providers should encourage the use of sunscreen. DLE is often treated with topical steroids. More advanced cases, such as this patient’s, may require oral hydroxychloroquine (200 mg bid). Though these treatments are effective in most cases, DLE can leave serious scarring and/or discoloration, especially in those with darker skin.

ANSWER

The correct answer is all the above (choice “e”).

DISCUSSION

The differential for round or annular, scaly lesions is lengthy. In addition to all 4 conditions listed above, it includes eczema, basal cell carcinoma, and irritant or contact dermatitis.

With this patient’s history, the diagnosis of fungal infection was not unreasonable. However, the total lack of response to antifungal treatment—along with a negative KOH prep—made that diagnosis questionable at best. Then there was the lack of lymphadenopathy, which would almost certainly have been present with such longstanding infection. Given her country of origin, cutaneous New World leishmaniasis (caused by a protozoan delivered to the patient by an insect vector) was a possibility.

For this patient, skin biopsy with a 4-mm punch was the only way to establish the correct diagnosis. The defect from the biopsy was closed with 5-0 nylon sutures to minimize scarring.

The pathological findings included interface dermatitis, apoptotic keratinocytes, and a brisk periadnexal lymphocytic infiltrate, which—given the morphological and historical context—were entirely consistent with discoid lupus erythematosus (DLE; otherwise known as subacute cutaneous lupus erythematosus). Subsequent bloodwork failed to show any connection with systemic lupus erythematosus (SLE), which is not surprising because only about 18% of DLE cases evolve into SLE.

DLE is more common in women, especially in those with skin of color. The associated lesions are seldom as impressive as this patient’s, manifesting as papulosquamous patches typically found on the ears, neck, face, arms, and other sun-exposed areas. Indeed, it appears that sun exposure is a major trigger for the disease—a clue that can assist with the diagnosis.

TREATMENT

In addition to proscribing excessive sun exposure, providers should encourage the use of sunscreen. DLE is often treated with topical steroids. More advanced cases, such as this patient’s, may require oral hydroxychloroquine (200 mg bid). Though these treatments are effective in most cases, DLE can leave serious scarring and/or discoloration, especially in those with darker skin.

New data will add fuel to the ongoing debate over the age at which mammography screening for breast cancer should begin. Many guidelines recommend starting at age 50.

But yearly mammography between the ages of 40 and 49 years was associated with a “substantial and significant” 25% reduction in breast cancer mortality during the first 10 years of follow-up, according to new data from the UK Age Trial.

The researchers calculated that 1,150 women needed to undergo screening in the age group of 40-49 years to prevent 1 breast cancer death, or about 1 breast cancer death prevented per 1,000 screened.

However, they also noted that, in the years since the trial first began, there have been improvements in the treatment of breast cancer, so “there might be less scope for screening to reduce mortality in our current era.”

The study was published online August 12 in Lancet Oncology.

“Our results do indicate that screening before age 50 does indeed prevent deaths from breast cancer, with a minimal additional burden of overdiagnosis,” said lead author Stephen W. Duffy, MSc, director of the policy research unit in cancer awareness, screening and early diagnosis, at Queen Mary University, London.

That said, Dr. Duffy explained they do not expect policy makers to extend the age range on the basis of these results alone. “For one thing, they will want to consider costs, both human and financial.” “For another, at this time, the services are concentrating on recovering from the hiatus caused by the COVID-19 crisis, and, at this time, it would be impractical to try to expand the eligibility for screening.”

“I would say our results indicate that lowering the age range, although not necessarily to 40 but to some age below 50, will be at least worth considering when the current crisis is over,” he added.
 

Guideline recommendations differ

Breast cancer screening guidelines have generated debate, much of which has focused on the age at which to begin screening.

The U.S. Preventive Services Task Force and American College of Physicians recommend screening every other year, on average, for women between the ages of 50 and 74 years.

However, other organizations disagree. The American College of Radiology and Society of Breast Imaging both recommend annual mammograms starting at age 40, and continuing “as long as they are in good health.”

In the UK, where the study was conducted, a national breast cancer screening program offers mammography to women aged 50-70 years every 3 years.

Given the uncertainty that continues to exist over the optimal age for average-risk women to begin screening, the UK Age Trial set out to assess if screening should begin at a younger age and if that might lead to overdiagnosis of breast cancer.

Results from the study’s 17-year follow-up, published in 2015, showed a reduction in breast cancer mortality with annual screening, beginning at age 40 years, which was significant in the first 10 years after participants were randomized (Lancet Oncol. 2015;16:1123-32).

In the current study, Dr. Duffy and colleagues report on breast cancer incidence and mortality results in the UK Age trial after 23 years of follow-up.

The cohort included 160,921 women enrolled between Oct. 14, 1990, and Sept. 24, 1997, who were randomized to screening (n = 53,883) or the control group (n = 106,953).

Of those screened during the study period, 7,893 (18.1%) had at least one false-positive result. There were 10,439 deaths, of which 683 (7%) were attributed to breast cancer diagnosed during the study period.

At 10 years of follow-up, death from breast cancer was significantly lower among women in the screening versus control group (83 vs 219 deaths; relative risk, 0.75; P = .029).

However, no significant reduction was observed thereafter, with 126 versus 255 deaths occurring after more than 10 years of follow-up (RR, 0.98; 95% confidence interval, 0.79-1.22; P = .86), the authors note.

“This follow-up indicates that the gain in survival was concentrated in the first 10 years after the women began to be screened,” commented Kevin McConway, PhD, emeritus professor of applied statistics at the Open University, Milton Keynes, England.

“In those first 10 years, out of every 10,000 women invited for screening, on average, about 16 died of breast cancer, while in every 10,000 women in the control group who did not get the screening, on average, 21 died. These numbers indicate that lives were saved,” he said.

“But they also indicate that death from breast cancer was pretty rare in women of that age,” he pointed out.

“Because breast cancer deaths in younger women are not common, the estimates of breast cancer death rates are not very precise, despite the fact that the trial involved 160,000 women,” he said.

“Over the whole follow-up period so far, the difference in numbers of deaths between those who were screened in their 40s and those who were not is 6 deaths for every 10,000 women, but because of the statistical uncertainty, this figure could plausibly be larger, at 13 per 10,000. Or, in fact, the data are also consistent with a very slightly higher death rate [1 death per 10,000 women] in those who had the screening,” Dr. McConway explained.

“But none of those numbers is very large, out of 10,000 women. Allowing for the fact that not every woman invited for screening will actually attend the screening, the researchers estimate that 1,150 women would have to be screened in their 40s to prevent one breast cancer death,” he noted.
 

U.S. experts support starting screening at 40

“The American Society of Breast Surgeons has continued to recommend screening women at the age of 40,” said Stephanie Bernik, MD, FACS, chief of breast surgery, Mount Sinai West, and associate professor of surgery at the Icahn School of Medicine at Mount Sinai, New York. “There is no question that screening earlier saves more lives, and this study adds to the body of evidence already available.”

She pointed out that the argument against early screening was that there were many false positives, which, in turn, increased cost and anxiety. “Because women in their 40s are in the prime of their lives, often with young children, it seems as though screening would be paramount. Furthermore, it is well known that the sooner you find a cancer, the better, as the treatment needed to cure the cancer is less toxic and less dramatic.”

Catherine Tuite, MD, section chief, breast radiology, Fox Chase Cancer Center, Philadelphia, echoed a similar viewpoint. “There is no real debate on this issue. The USPSTF recommends beginning screening mammography at age 50, and it is no secret that this is a recommendation based on cost, not on saving women’s lives.”

She emphasized that these recommendations were made without the input of expert physicians. “The data, reaffirmed by this publication, have always been clear that the most years of life saved from deaths due to breast cancer are achieved in women who begin screening mammography at age 40. We know that one-sixth of all breast cancers are diagnosed before age 50, and many of these cancers are the most aggressive types of breast cancer.

“The guidelines from every organization representing health care professionals who actually diagnose and care for women with breast cancer recommend that all women of average risk begin annual screening mammography at age 40 and continue as long as the woman is in good health, with life expectancy of 10 years,” she continued.

As for screening intervals, annual mammogram is also recommended for all age groups in the United States. At her institutions, she explained that they are currently enrolling women into the TMIST screening mammogram trial, which is, among other endpoints, evaluating a biannual screening interval for postmenopausal women of lower than average risk, but again, outside of a trial setting, yearly screening for all women is recommended.

Dr. Duffy commented that, in the United Kingdom, the current screening protocol for mammograms is every 3 years, which he said “works well in women over the age of 50 years.” But for younger women, more frequent screening would be need – in this study, screening was done annually.

“The results not only from our study but from others around the world suggest that this [3-year screening interval] would not be very effective in women under 50, due partly to the denser breast tissue of younger women and partly to the faster progression on average of cancers diagnosed in younger women,” he said. “Some counties in Sweden, for example, offer screening to women under 50 at 18-month intervals, which seems more realistic.”

The study was funded by the Health Technology Assessment program of the National Institute for Health Research. Dr. Duffy reported also receiving grants from the NIHR outside this trial. Dr. Bernik, Dr. Tuite, and Dr. Hodgson reported no relevant financial relationships.

This article first appeared on Medscape.com.

New data will add fuel to the ongoing debate over the age at which mammography screening for breast cancer should begin. Many guidelines recommend starting at age 50.

But yearly mammography between the ages of 40 and 49 years was associated with a “substantial and significant” 25% reduction in breast cancer mortality during the first 10 years of follow-up, according to new data from the UK Age Trial.

The researchers calculated that 1,150 women needed to undergo screening in the age group of 40-49 years to prevent 1 breast cancer death, or about 1 breast cancer death prevented per 1,000 screened.

However, they also noted that, in the years since the trial first began, there have been improvements in the treatment of breast cancer, so “there might be less scope for screening to reduce mortality in our current era.”

The study was published online August 12 in Lancet Oncology.

“Our results do indicate that screening before age 50 does indeed prevent deaths from breast cancer, with a minimal additional burden of overdiagnosis,” said lead author Stephen W. Duffy, MSc, director of the policy research unit in cancer awareness, screening and early diagnosis, at Queen Mary University, London.

That said, Dr. Duffy explained they do not expect policy makers to extend the age range on the basis of these results alone. “For one thing, they will want to consider costs, both human and financial.” “For another, at this time, the services are concentrating on recovering from the hiatus caused by the COVID-19 crisis, and, at this time, it would be impractical to try to expand the eligibility for screening.”

“I would say our results indicate that lowering the age range, although not necessarily to 40 but to some age below 50, will be at least worth considering when the current crisis is over,” he added.
 

Guideline recommendations differ

Breast cancer screening guidelines have generated debate, much of which has focused on the age at which to begin screening.

The U.S. Preventive Services Task Force and American College of Physicians recommend screening every other year, on average, for women between the ages of 50 and 74 years.

However, other organizations disagree. The American College of Radiology and Society of Breast Imaging both recommend annual mammograms starting at age 40, and continuing “as long as they are in good health.”

In the UK, where the study was conducted, a national breast cancer screening program offers mammography to women aged 50-70 years every 3 years.

Given the uncertainty that continues to exist over the optimal age for average-risk women to begin screening, the UK Age Trial set out to assess if screening should begin at a younger age and if that might lead to overdiagnosis of breast cancer.

Results from the study’s 17-year follow-up, published in 2015, showed a reduction in breast cancer mortality with annual screening, beginning at age 40 years, which was significant in the first 10 years after participants were randomized (Lancet Oncol. 2015;16:1123-32).

In the current study, Dr. Duffy and colleagues report on breast cancer incidence and mortality results in the UK Age trial after 23 years of follow-up.

The cohort included 160,921 women enrolled between Oct. 14, 1990, and Sept. 24, 1997, who were randomized to screening (n = 53,883) or the control group (n = 106,953).

Of those screened during the study period, 7,893 (18.1%) had at least one false-positive result. There were 10,439 deaths, of which 683 (7%) were attributed to breast cancer diagnosed during the study period.

At 10 years of follow-up, death from breast cancer was significantly lower among women in the screening versus control group (83 vs 219 deaths; relative risk, 0.75; P = .029).

However, no significant reduction was observed thereafter, with 126 versus 255 deaths occurring after more than 10 years of follow-up (RR, 0.98; 95% confidence interval, 0.79-1.22; P = .86), the authors note.

“This follow-up indicates that the gain in survival was concentrated in the first 10 years after the women began to be screened,” commented Kevin McConway, PhD, emeritus professor of applied statistics at the Open University, Milton Keynes, England.

“In those first 10 years, out of every 10,000 women invited for screening, on average, about 16 died of breast cancer, while in every 10,000 women in the control group who did not get the screening, on average, 21 died. These numbers indicate that lives were saved,” he said.

“But they also indicate that death from breast cancer was pretty rare in women of that age,” he pointed out.

“Because breast cancer deaths in younger women are not common, the estimates of breast cancer death rates are not very precise, despite the fact that the trial involved 160,000 women,” he said.

“Over the whole follow-up period so far, the difference in numbers of deaths between those who were screened in their 40s and those who were not is 6 deaths for every 10,000 women, but because of the statistical uncertainty, this figure could plausibly be larger, at 13 per 10,000. Or, in fact, the data are also consistent with a very slightly higher death rate [1 death per 10,000 women] in those who had the screening,” Dr. McConway explained.

“But none of those numbers is very large, out of 10,000 women. Allowing for the fact that not every woman invited for screening will actually attend the screening, the researchers estimate that 1,150 women would have to be screened in their 40s to prevent one breast cancer death,” he noted.
 

U.S. experts support starting screening at 40

“The American Society of Breast Surgeons has continued to recommend screening women at the age of 40,” said Stephanie Bernik, MD, FACS, chief of breast surgery, Mount Sinai West, and associate professor of surgery at the Icahn School of Medicine at Mount Sinai, New York. “There is no question that screening earlier saves more lives, and this study adds to the body of evidence already available.”

She pointed out that the argument against early screening was that there were many false positives, which, in turn, increased cost and anxiety. “Because women in their 40s are in the prime of their lives, often with young children, it seems as though screening would be paramount. Furthermore, it is well known that the sooner you find a cancer, the better, as the treatment needed to cure the cancer is less toxic and less dramatic.”

Catherine Tuite, MD, section chief, breast radiology, Fox Chase Cancer Center, Philadelphia, echoed a similar viewpoint. “There is no real debate on this issue. The USPSTF recommends beginning screening mammography at age 50, and it is no secret that this is a recommendation based on cost, not on saving women’s lives.”

She emphasized that these recommendations were made without the input of expert physicians. “The data, reaffirmed by this publication, have always been clear that the most years of life saved from deaths due to breast cancer are achieved in women who begin screening mammography at age 40. We know that one-sixth of all breast cancers are diagnosed before age 50, and many of these cancers are the most aggressive types of breast cancer.

“The guidelines from every organization representing health care professionals who actually diagnose and care for women with breast cancer recommend that all women of average risk begin annual screening mammography at age 40 and continue as long as the woman is in good health, with life expectancy of 10 years,” she continued.

As for screening intervals, annual mammogram is also recommended for all age groups in the United States. At her institutions, she explained that they are currently enrolling women into the TMIST screening mammogram trial, which is, among other endpoints, evaluating a biannual screening interval for postmenopausal women of lower than average risk, but again, outside of a trial setting, yearly screening for all women is recommended.

Dr. Duffy commented that, in the United Kingdom, the current screening protocol for mammograms is every 3 years, which he said “works well in women over the age of 50 years.” But for younger women, more frequent screening would be need – in this study, screening was done annually.

“The results not only from our study but from others around the world suggest that this [3-year screening interval] would not be very effective in women under 50, due partly to the denser breast tissue of younger women and partly to the faster progression on average of cancers diagnosed in younger women,” he said. “Some counties in Sweden, for example, offer screening to women under 50 at 18-month intervals, which seems more realistic.”

The study was funded by the Health Technology Assessment program of the National Institute for Health Research. Dr. Duffy reported also receiving grants from the NIHR outside this trial. Dr. Bernik, Dr. Tuite, and Dr. Hodgson reported no relevant financial relationships.

This article first appeared on Medscape.com.

New data will add fuel to the ongoing debate over the age at which mammography screening for breast cancer should begin. Many guidelines recommend starting at age 50.

But yearly mammography between the ages of 40 and 49 years was associated with a “substantial and significant” 25% reduction in breast cancer mortality during the first 10 years of follow-up, according to new data from the UK Age Trial.

The researchers calculated that 1,150 women needed to undergo screening in the age group of 40-49 years to prevent 1 breast cancer death, or about 1 breast cancer death prevented per 1,000 screened.

However, they also noted that, in the years since the trial first began, there have been improvements in the treatment of breast cancer, so “there might be less scope for screening to reduce mortality in our current era.”

The study was published online August 12 in Lancet Oncology.

“Our results do indicate that screening before age 50 does indeed prevent deaths from breast cancer, with a minimal additional burden of overdiagnosis,” said lead author Stephen W. Duffy, MSc, director of the policy research unit in cancer awareness, screening and early diagnosis, at Queen Mary University, London.

That said, Dr. Duffy explained they do not expect policy makers to extend the age range on the basis of these results alone. “For one thing, they will want to consider costs, both human and financial.” “For another, at this time, the services are concentrating on recovering from the hiatus caused by the COVID-19 crisis, and, at this time, it would be impractical to try to expand the eligibility for screening.”

“I would say our results indicate that lowering the age range, although not necessarily to 40 but to some age below 50, will be at least worth considering when the current crisis is over,” he added.
 

Guideline recommendations differ

Breast cancer screening guidelines have generated debate, much of which has focused on the age at which to begin screening.

The U.S. Preventive Services Task Force and American College of Physicians recommend screening every other year, on average, for women between the ages of 50 and 74 years.

However, other organizations disagree. The American College of Radiology and Society of Breast Imaging both recommend annual mammograms starting at age 40, and continuing “as long as they are in good health.”

In the UK, where the study was conducted, a national breast cancer screening program offers mammography to women aged 50-70 years every 3 years.

Given the uncertainty that continues to exist over the optimal age for average-risk women to begin screening, the UK Age Trial set out to assess if screening should begin at a younger age and if that might lead to overdiagnosis of breast cancer.

Results from the study’s 17-year follow-up, published in 2015, showed a reduction in breast cancer mortality with annual screening, beginning at age 40 years, which was significant in the first 10 years after participants were randomized (Lancet Oncol. 2015;16:1123-32).

In the current study, Dr. Duffy and colleagues report on breast cancer incidence and mortality results in the UK Age trial after 23 years of follow-up.

The cohort included 160,921 women enrolled between Oct. 14, 1990, and Sept. 24, 1997, who were randomized to screening (n = 53,883) or the control group (n = 106,953).

Of those screened during the study period, 7,893 (18.1%) had at least one false-positive result. There were 10,439 deaths, of which 683 (7%) were attributed to breast cancer diagnosed during the study period.

At 10 years of follow-up, death from breast cancer was significantly lower among women in the screening versus control group (83 vs 219 deaths; relative risk, 0.75; P = .029).

However, no significant reduction was observed thereafter, with 126 versus 255 deaths occurring after more than 10 years of follow-up (RR, 0.98; 95% confidence interval, 0.79-1.22; P = .86), the authors note.

“This follow-up indicates that the gain in survival was concentrated in the first 10 years after the women began to be screened,” commented Kevin McConway, PhD, emeritus professor of applied statistics at the Open University, Milton Keynes, England.

“In those first 10 years, out of every 10,000 women invited for screening, on average, about 16 died of breast cancer, while in every 10,000 women in the control group who did not get the screening, on average, 21 died. These numbers indicate that lives were saved,” he said.

“But they also indicate that death from breast cancer was pretty rare in women of that age,” he pointed out.

“Because breast cancer deaths in younger women are not common, the estimates of breast cancer death rates are not very precise, despite the fact that the trial involved 160,000 women,” he said.

“Over the whole follow-up period so far, the difference in numbers of deaths between those who were screened in their 40s and those who were not is 6 deaths for every 10,000 women, but because of the statistical uncertainty, this figure could plausibly be larger, at 13 per 10,000. Or, in fact, the data are also consistent with a very slightly higher death rate [1 death per 10,000 women] in those who had the screening,” Dr. McConway explained.

“But none of those numbers is very large, out of 10,000 women. Allowing for the fact that not every woman invited for screening will actually attend the screening, the researchers estimate that 1,150 women would have to be screened in their 40s to prevent one breast cancer death,” he noted.
 

U.S. experts support starting screening at 40

“The American Society of Breast Surgeons has continued to recommend screening women at the age of 40,” said Stephanie Bernik, MD, FACS, chief of breast surgery, Mount Sinai West, and associate professor of surgery at the Icahn School of Medicine at Mount Sinai, New York. “There is no question that screening earlier saves more lives, and this study adds to the body of evidence already available.”

She pointed out that the argument against early screening was that there were many false positives, which, in turn, increased cost and anxiety. “Because women in their 40s are in the prime of their lives, often with young children, it seems as though screening would be paramount. Furthermore, it is well known that the sooner you find a cancer, the better, as the treatment needed to cure the cancer is less toxic and less dramatic.”

Catherine Tuite, MD, section chief, breast radiology, Fox Chase Cancer Center, Philadelphia, echoed a similar viewpoint. “There is no real debate on this issue. The USPSTF recommends beginning screening mammography at age 50, and it is no secret that this is a recommendation based on cost, not on saving women’s lives.”

She emphasized that these recommendations were made without the input of expert physicians. “The data, reaffirmed by this publication, have always been clear that the most years of life saved from deaths due to breast cancer are achieved in women who begin screening mammography at age 40. We know that one-sixth of all breast cancers are diagnosed before age 50, and many of these cancers are the most aggressive types of breast cancer.

“The guidelines from every organization representing health care professionals who actually diagnose and care for women with breast cancer recommend that all women of average risk begin annual screening mammography at age 40 and continue as long as the woman is in good health, with life expectancy of 10 years,” she continued.

As for screening intervals, annual mammogram is also recommended for all age groups in the United States. At her institutions, she explained that they are currently enrolling women into the TMIST screening mammogram trial, which is, among other endpoints, evaluating a biannual screening interval for postmenopausal women of lower than average risk, but again, outside of a trial setting, yearly screening for all women is recommended.

Dr. Duffy commented that, in the United Kingdom, the current screening protocol for mammograms is every 3 years, which he said “works well in women over the age of 50 years.” But for younger women, more frequent screening would be need – in this study, screening was done annually.

“The results not only from our study but from others around the world suggest that this [3-year screening interval] would not be very effective in women under 50, due partly to the denser breast tissue of younger women and partly to the faster progression on average of cancers diagnosed in younger women,” he said. “Some counties in Sweden, for example, offer screening to women under 50 at 18-month intervals, which seems more realistic.”

The study was funded by the Health Technology Assessment program of the National Institute for Health Research. Dr. Duffy reported also receiving grants from the NIHR outside this trial. Dr. Bernik, Dr. Tuite, and Dr. Hodgson reported no relevant financial relationships.

This article first appeared on Medscape.com.

As most of you know, Medicare publishes its proposed rule, which determines the physician fee schedule, around July 1 each year, accepts comments for 60 days, and then publishes a final rule on or around Nov. 1, which becomes final on Jan. 1 of the following year. The proposed rule is watched closely and has great impact, because not only are Medicare fees based on the rule, but most private insurances are based on Medicare.

This year’s proposed rule, announced in early August, is extraordinary by any past standard. It can be found here.

It cuts the conversion factor (which is what the work, practice expense, and malpractice values are multiplied by to get a payment) by 10.6%, from $36.09 to $32.26. This is necessary to maintain “budget neutrality” since there is a fixed pool of money, and payments for cognitive services are increasing. The overall effect on dermatology is a 2% cut, which is mild, compared with other specialties, such as nurse anesthetists and radiologists, both with an 11% decrease; chiropractors, with a 10% decrease; and interventional radiology, pathology, physical and occupational therapy, and cardiac surgery, all with a 9% decrease. General surgery will see a 7% decrease. Those with major increases are endocrinology, with a 17% increase; rheumatology, with a 16% increase; and hematology/oncology, with a 14% increase.

The overall push by CMS (and the relative value update committee) is to improve the pay for cognitive services, that is evaluation and management (E/M) services. Since dermatology also provides such services, the effect of the proposed rule will vary dramatically depending on your case mix. I must also point out that, since existing overhead is relatively fixed, say at 50%, a 10% decrease in revenue may translate into a 20% loss in physician income.


 

The good

Simplified coding and billing requirements for E/M visits will go into effect Jan. 1, 2021. For dermatology, any visit where a decision to do a minor procedure or prescribe a medication takes place will become a level 4 visit. Most of the useless documentation requirements and need to examine multiple organ systems will be eliminated. The most common E/M code currently used by dermatologists is a level 3, and this will on average move up to a level 4. Thus, general dermatology will benefit from the new rule. For example, if a dermatologist sees a patient and does a tangential biopsy of the skin, the payment will be $214.52, compared with $178.65 in 2020.

The bad

As mentioned above, the impact will vary by case mix. Those doing a lot of surgery will see a much larger cut. Mohs surgeons, for example will see about a 6.5% decrease.¹

Aggravating the cuts to surgery is the fact that, while CMS has bolstered the pay for E/M stand-alone codes, they did not increase the reimbursement level of the built-in follow-up visits inside the 10- and 90-day global periods.

The ugly

Procedure codes with a lot of practice expense built into them, such as Mohs and reconstruction, are not hit as hard by the conversion factor cut because the practice expense is generally spared. There is much less practice expense in a pathology code so dermatopathology faces the most severe cuts. Pathology and other specialties that do not generally bill office/outpatient E/M codes are estimated to see the greatest decrease in payment in 2021.

Code 88305, the most common dermatopathology code, will decrease overall from $71.46 to $66.78 (–6.5%). Digging a little deeper, we find that the technical charge (the payment to process and make the slide) actually increases from $32.12 to $32.26, but the professional component (the interpretation of the slide and report generation) decreases from $39.34 to $34.52 (–12.3%).

I must also point out that this proposed rule allows for nurse practitioners (NPs), clinical nurse specialists (CNSs), physician assistants (PAs), and certified nurse-midwives (CNMs) to supervise the performance of diagnostic tests in addition to physicians. I wonder if we will see an increase in billing of dermatopathology by the untrained.

Adding more confusion – and an additional hit to hospital-based practices – is the federal appeals court decision affirming the ability of the Centers for Medicare & Medicaid Services to mandate site-neutral payments for E/M codes. This means that hospital-affiliated practices, which used to enjoy payment of up to 114% more than offices, will be paid the same as offices. This will save CMS $300 million, but these savings will not be flowing back into the physician fee schedule.

Fixing this will require congressional action since CMS is bound by law to maintain budget neutrality. The specialty societies saw this coming and have already been lobbying furiously to waive budget neutrality requirements, especially in this time of a pandemic that has had an adverse impact on physicians. This is noted in detail on the AADA website, accessible to AAD members.

Since this will take a legislative fix, you should contact your congressional representative or senator and ask them to enact legislation to waive Medicare’s budget neutrality requirements to apply the increased E/M adjustment to all 10- and 90-day global code values. You might also inquire where the $300 million saved by site neutral payment reform will go, and suggest applying it towards restoring the conversion factor to a more normal number.

 

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at [email protected].

Reference

1. Calculations and tables courtesy of Brent Moody, M.D., AAD AMA relative value update committee practice expense representative and specialist.

As most of you know, Medicare publishes its proposed rule, which determines the physician fee schedule, around July 1 each year, accepts comments for 60 days, and then publishes a final rule on or around Nov. 1, which becomes final on Jan. 1 of the following year. The proposed rule is watched closely and has great impact, because not only are Medicare fees based on the rule, but most private insurances are based on Medicare.

This year’s proposed rule, announced in early August, is extraordinary by any past standard. It can be found here.

It cuts the conversion factor (which is what the work, practice expense, and malpractice values are multiplied by to get a payment) by 10.6%, from $36.09 to $32.26. This is necessary to maintain “budget neutrality” since there is a fixed pool of money, and payments for cognitive services are increasing. The overall effect on dermatology is a 2% cut, which is mild, compared with other specialties, such as nurse anesthetists and radiologists, both with an 11% decrease; chiropractors, with a 10% decrease; and interventional radiology, pathology, physical and occupational therapy, and cardiac surgery, all with a 9% decrease. General surgery will see a 7% decrease. Those with major increases are endocrinology, with a 17% increase; rheumatology, with a 16% increase; and hematology/oncology, with a 14% increase.

The overall push by CMS (and the relative value update committee) is to improve the pay for cognitive services, that is evaluation and management (E/M) services. Since dermatology also provides such services, the effect of the proposed rule will vary dramatically depending on your case mix. I must also point out that, since existing overhead is relatively fixed, say at 50%, a 10% decrease in revenue may translate into a 20% loss in physician income.


 

The good

Simplified coding and billing requirements for E/M visits will go into effect Jan. 1, 2021. For dermatology, any visit where a decision to do a minor procedure or prescribe a medication takes place will become a level 4 visit. Most of the useless documentation requirements and need to examine multiple organ systems will be eliminated. The most common E/M code currently used by dermatologists is a level 3, and this will on average move up to a level 4. Thus, general dermatology will benefit from the new rule. For example, if a dermatologist sees a patient and does a tangential biopsy of the skin, the payment will be $214.52, compared with $178.65 in 2020.

The bad

As mentioned above, the impact will vary by case mix. Those doing a lot of surgery will see a much larger cut. Mohs surgeons, for example will see about a 6.5% decrease.¹

Aggravating the cuts to surgery is the fact that, while CMS has bolstered the pay for E/M stand-alone codes, they did not increase the reimbursement level of the built-in follow-up visits inside the 10- and 90-day global periods.

The ugly

Procedure codes with a lot of practice expense built into them, such as Mohs and reconstruction, are not hit as hard by the conversion factor cut because the practice expense is generally spared. There is much less practice expense in a pathology code so dermatopathology faces the most severe cuts. Pathology and other specialties that do not generally bill office/outpatient E/M codes are estimated to see the greatest decrease in payment in 2021.

Code 88305, the most common dermatopathology code, will decrease overall from $71.46 to $66.78 (–6.5%). Digging a little deeper, we find that the technical charge (the payment to process and make the slide) actually increases from $32.12 to $32.26, but the professional component (the interpretation of the slide and report generation) decreases from $39.34 to $34.52 (–12.3%).

I must also point out that this proposed rule allows for nurse practitioners (NPs), clinical nurse specialists (CNSs), physician assistants (PAs), and certified nurse-midwives (CNMs) to supervise the performance of diagnostic tests in addition to physicians. I wonder if we will see an increase in billing of dermatopathology by the untrained.

Adding more confusion – and an additional hit to hospital-based practices – is the federal appeals court decision affirming the ability of the Centers for Medicare & Medicaid Services to mandate site-neutral payments for E/M codes. This means that hospital-affiliated practices, which used to enjoy payment of up to 114% more than offices, will be paid the same as offices. This will save CMS $300 million, but these savings will not be flowing back into the physician fee schedule.

Fixing this will require congressional action since CMS is bound by law to maintain budget neutrality. The specialty societies saw this coming and have already been lobbying furiously to waive budget neutrality requirements, especially in this time of a pandemic that has had an adverse impact on physicians. This is noted in detail on the AADA website, accessible to AAD members.

Since this will take a legislative fix, you should contact your congressional representative or senator and ask them to enact legislation to waive Medicare’s budget neutrality requirements to apply the increased E/M adjustment to all 10- and 90-day global code values. You might also inquire where the $300 million saved by site neutral payment reform will go, and suggest applying it towards restoring the conversion factor to a more normal number.

 

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at [email protected].

Reference

1. Calculations and tables courtesy of Brent Moody, M.D., AAD AMA relative value update committee practice expense representative and specialist.

As most of you know, Medicare publishes its proposed rule, which determines the physician fee schedule, around July 1 each year, accepts comments for 60 days, and then publishes a final rule on or around Nov. 1, which becomes final on Jan. 1 of the following year. The proposed rule is watched closely and has great impact, because not only are Medicare fees based on the rule, but most private insurances are based on Medicare.

This year’s proposed rule, announced in early August, is extraordinary by any past standard. It can be found here.

It cuts the conversion factor (which is what the work, practice expense, and malpractice values are multiplied by to get a payment) by 10.6%, from $36.09 to $32.26. This is necessary to maintain “budget neutrality” since there is a fixed pool of money, and payments for cognitive services are increasing. The overall effect on dermatology is a 2% cut, which is mild, compared with other specialties, such as nurse anesthetists and radiologists, both with an 11% decrease; chiropractors, with a 10% decrease; and interventional radiology, pathology, physical and occupational therapy, and cardiac surgery, all with a 9% decrease. General surgery will see a 7% decrease. Those with major increases are endocrinology, with a 17% increase; rheumatology, with a 16% increase; and hematology/oncology, with a 14% increase.

The overall push by CMS (and the relative value update committee) is to improve the pay for cognitive services, that is evaluation and management (E/M) services. Since dermatology also provides such services, the effect of the proposed rule will vary dramatically depending on your case mix. I must also point out that, since existing overhead is relatively fixed, say at 50%, a 10% decrease in revenue may translate into a 20% loss in physician income.


 

The good

Simplified coding and billing requirements for E/M visits will go into effect Jan. 1, 2021. For dermatology, any visit where a decision to do a minor procedure or prescribe a medication takes place will become a level 4 visit. Most of the useless documentation requirements and need to examine multiple organ systems will be eliminated. The most common E/M code currently used by dermatologists is a level 3, and this will on average move up to a level 4. Thus, general dermatology will benefit from the new rule. For example, if a dermatologist sees a patient and does a tangential biopsy of the skin, the payment will be $214.52, compared with $178.65 in 2020.

The bad

As mentioned above, the impact will vary by case mix. Those doing a lot of surgery will see a much larger cut. Mohs surgeons, for example will see about a 6.5% decrease.¹

Aggravating the cuts to surgery is the fact that, while CMS has bolstered the pay for E/M stand-alone codes, they did not increase the reimbursement level of the built-in follow-up visits inside the 10- and 90-day global periods.

The ugly

Procedure codes with a lot of practice expense built into them, such as Mohs and reconstruction, are not hit as hard by the conversion factor cut because the practice expense is generally spared. There is much less practice expense in a pathology code so dermatopathology faces the most severe cuts. Pathology and other specialties that do not generally bill office/outpatient E/M codes are estimated to see the greatest decrease in payment in 2021.

Code 88305, the most common dermatopathology code, will decrease overall from $71.46 to $66.78 (–6.5%). Digging a little deeper, we find that the technical charge (the payment to process and make the slide) actually increases from $32.12 to $32.26, but the professional component (the interpretation of the slide and report generation) decreases from $39.34 to $34.52 (–12.3%).

I must also point out that this proposed rule allows for nurse practitioners (NPs), clinical nurse specialists (CNSs), physician assistants (PAs), and certified nurse-midwives (CNMs) to supervise the performance of diagnostic tests in addition to physicians. I wonder if we will see an increase in billing of dermatopathology by the untrained.

Adding more confusion – and an additional hit to hospital-based practices – is the federal appeals court decision affirming the ability of the Centers for Medicare & Medicaid Services to mandate site-neutral payments for E/M codes. This means that hospital-affiliated practices, which used to enjoy payment of up to 114% more than offices, will be paid the same as offices. This will save CMS $300 million, but these savings will not be flowing back into the physician fee schedule.

Fixing this will require congressional action since CMS is bound by law to maintain budget neutrality. The specialty societies saw this coming and have already been lobbying furiously to waive budget neutrality requirements, especially in this time of a pandemic that has had an adverse impact on physicians. This is noted in detail on the AADA website, accessible to AAD members.

Since this will take a legislative fix, you should contact your congressional representative or senator and ask them to enact legislation to waive Medicare’s budget neutrality requirements to apply the increased E/M adjustment to all 10- and 90-day global code values. You might also inquire where the $300 million saved by site neutral payment reform will go, and suggest applying it towards restoring the conversion factor to a more normal number.

 

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at [email protected].

Reference

1. Calculations and tables courtesy of Brent Moody, M.D., AAD AMA relative value update committee practice expense representative and specialist.

The Diagnosis: Erythropoietic Protoporphyria 

Erythropoietic protoporphyria (EPP) is an autosomal-recessive photodermatosis that results from loss of activity of ferrochelatase, the last enzyme in the heme biosynthetic pathway.¹ Erythropoietic protoporphyria normally involves sun-exposed areas of the body. Skin that is exposed to sunlight develops intense burning and stinging pain followed by erythema, edema, crusting, and petechiae that develops into waxy scarring over time. In contrast to other porphyrias, blistering generally is not seen.² Accurate diagnosis often can be delayed by a decade or more following symptom onset due to the prominence of subjective pain as the presenting sign.  

The histologic appearance of EPP differs depending on the chronicity of lesions. Biopsies of acute lesions show vacuolization of epidermal cells with intercellular edema, vacuolization and cytolysis of endothelial cells in superficial blood vessels, and focal red blood cell extravasation.^3,4 A largely neutrophilic inflammatory infiltrate can be present.⁵ Hyaline cuffing develops over time in and around vessels in the papillary and superficial reticular dermis with notable sparing of adnexal structures. The perivascular deposits are strongly periodic acid-Schiff (PAS) positive and diastase resistant (Figure 1). Direct immunofluorescence shows mainly IgG and some IgM, fibrinogen, and C3 outlining characteristic donut-shaped blood vessels in the papillary dermis.⁶ The prominent thickness of the perivascular hyaline material depositions and the absence of subepidermal blistering can help differentiate EPP from porphyria cutanea tarda (PCT) and pseudoporphyria.^6,7 When the deposition is extensive and involves the surrounding dermis, EPP can mimic colloid milium. Additional histologic differential diagnoses of EPP include other dermal depositional diseases such as lipoid proteinosis and amyloidosis.  

Lipoid proteinosis is an autosomal-recessive multisystem genodermatosis caused by mutations in extracellular matrix gene 1, ECM1. The first clinical sign can be a hoarse cry in infancy due to infiltration of vocal cords.³ Development of papulonodular lesions along the eyelids can result in a string-of-beads appearance called moniliform blepharosis, which is pathognomonic for lipoid proteinosis.⁶ With chronicity, the involved skin can become yellow, waxy, and thickened, particularly in the flexures or areas of trauma. Histologically, the dermis in lipoid proteinosis becomes diffusely thickened due to deposition of PAS-positive eosinophilic hyaline material that stains weakly with Congo red and thioflavin T.⁶ Early lesions demonstrate pale pink, hyalinelike thickening of the papillary dermal capillaries. Chronic lesions reveal an acanthotic epidermis, occasional papillomatosis with overlying hyperkeratosis, and a thickened dermis where diffuse thick bundles of pink hyaline deposits are oriented perpendicularly to the dermoepidermal junction.^1,6 Lipoid proteinosis can be differentiated from EPP by the involvement of adnexal structures such as hair follicles, sebaceous glands, and arrector pili muscles (Figure 2), as opposed to EPP where adnexal structures are spared.¹ Additionally, depositions in lipoid proteinosis are centered around both superficial and deep vessels with an onion skin-like pattern, while EPP involves mainly superficial vessels with more mild and focal hyalinization.

Juvenile colloid milium (JCM) is a rare condition that presents before puberty with discrete, yellow-brown, translucent papules predominantly located on the cheeks and nose and around the mouth. A gelatinous material can be expressed after puncturing a lesion.⁶ Gingival deposits and ligneous conjunctivitis also can be present. On histopathology, JCM shows degeneration of epidermal keratinocytes that form colloid bodies within the superficial dermis following apoptosis.⁶ Hematoxylin and eosin staining shows amorphous, fissured, pale pink deposits completely filling and expanding the superficial to mid dermis with clefting and no inflammation (Figure 3). Spindle-shaped fibroblasts may be seen within the lines of colloid fissuring and dispersed throughout the deposits.¹ Histologically, JCM can be differentiated from EPP because deposits in EPP are distributed around and within superficial blood vessel walls, causing prominent vascular thickening not seen in JCM.⁶ The adult variant of colloid milium also can be distinguished from EPP by the presence of solar elastosis, which is absent in EPP due to a history of sun avoidance.^3,7  

Lichen amyloidosis presents with highly pruritic, red-brown, hyperkeratotic papules that commonly are found on the anterior lower legs and extensor forearms.¹ The calves, ankles, dorsal aspects of the feet, thighs, and trunk also may be affected. Excoriations, lichenification, and nodular prurigo-like lesions due to chronic scratching can be present.⁶ Lichen amyloidosis is characterized by large, pink, amorphous deposits in the papillary dermis with epidermal acanthosis, hypergranulosis, and hyperkeratosis (Figure 4).⁶ Perivascular deposits are not a feature of primary cutaneous localized amyloid lesions.⁶ The diagnosis can be confirmed with Congo red staining under polarized light, which classically demonstrates apple green birefringence.¹ For cases of amyloid that are not detected by Congo red or are not clear-cut, direct immunofluorescence and immunohistochemistry can be used as adjuncts for diagnosis. Amyloid deposits fluoresce positively for immunoglobulins or complements, particularly IgM and C3,⁸ and immunohistochemistry confirms the presence of keratin epitopes in deposits.⁹  

Porphyria cutanea tarda can appear histologically similar to EPP. Caterpillar bodies, or linearly arranged eosinophilic PAS-positive globules in the epidermis overlying subepidermal bullae, are a diagnostic histopathologic finding in both PCT and EPP but are seen in less than half of both cases.^7,10 Compared to EPP, the perivascular deposits in PCT typically are less pronounced and limited to the vessel wall with smaller hyaline cuffs (Figure 5).⁷ Additionally, solar elastosis can be seen in PCT lesions but not in EPP, as patients with PCT tend to be older and have increased cumulative sun damage.  

The Diagnosis: Erythropoietic Protoporphyria 

Erythropoietic protoporphyria (EPP) is an autosomal-recessive photodermatosis that results from loss of activity of ferrochelatase, the last enzyme in the heme biosynthetic pathway.¹ Erythropoietic protoporphyria normally involves sun-exposed areas of the body. Skin that is exposed to sunlight develops intense burning and stinging pain followed by erythema, edema, crusting, and petechiae that develops into waxy scarring over time. In contrast to other porphyrias, blistering generally is not seen.² Accurate diagnosis often can be delayed by a decade or more following symptom onset due to the prominence of subjective pain as the presenting sign.  

The histologic appearance of EPP differs depending on the chronicity of lesions. Biopsies of acute lesions show vacuolization of epidermal cells with intercellular edema, vacuolization and cytolysis of endothelial cells in superficial blood vessels, and focal red blood cell extravasation.^3,4 A largely neutrophilic inflammatory infiltrate can be present.⁵ Hyaline cuffing develops over time in and around vessels in the papillary and superficial reticular dermis with notable sparing of adnexal structures. The perivascular deposits are strongly periodic acid-Schiff (PAS) positive and diastase resistant (Figure 1). Direct immunofluorescence shows mainly IgG and some IgM, fibrinogen, and C3 outlining characteristic donut-shaped blood vessels in the papillary dermis.⁶ The prominent thickness of the perivascular hyaline material depositions and the absence of subepidermal blistering can help differentiate EPP from porphyria cutanea tarda (PCT) and pseudoporphyria.^6,7 When the deposition is extensive and involves the surrounding dermis, EPP can mimic colloid milium. Additional histologic differential diagnoses of EPP include other dermal depositional diseases such as lipoid proteinosis and amyloidosis.  

Lipoid proteinosis is an autosomal-recessive multisystem genodermatosis caused by mutations in extracellular matrix gene 1, ECM1. The first clinical sign can be a hoarse cry in infancy due to infiltration of vocal cords.³ Development of papulonodular lesions along the eyelids can result in a string-of-beads appearance called moniliform blepharosis, which is pathognomonic for lipoid proteinosis.⁶ With chronicity, the involved skin can become yellow, waxy, and thickened, particularly in the flexures or areas of trauma. Histologically, the dermis in lipoid proteinosis becomes diffusely thickened due to deposition of PAS-positive eosinophilic hyaline material that stains weakly with Congo red and thioflavin T.⁶ Early lesions demonstrate pale pink, hyalinelike thickening of the papillary dermal capillaries. Chronic lesions reveal an acanthotic epidermis, occasional papillomatosis with overlying hyperkeratosis, and a thickened dermis where diffuse thick bundles of pink hyaline deposits are oriented perpendicularly to the dermoepidermal junction.^1,6 Lipoid proteinosis can be differentiated from EPP by the involvement of adnexal structures such as hair follicles, sebaceous glands, and arrector pili muscles (Figure 2), as opposed to EPP where adnexal structures are spared.¹ Additionally, depositions in lipoid proteinosis are centered around both superficial and deep vessels with an onion skin-like pattern, while EPP involves mainly superficial vessels with more mild and focal hyalinization.

Juvenile colloid milium (JCM) is a rare condition that presents before puberty with discrete, yellow-brown, translucent papules predominantly located on the cheeks and nose and around the mouth. A gelatinous material can be expressed after puncturing a lesion.⁶ Gingival deposits and ligneous conjunctivitis also can be present. On histopathology, JCM shows degeneration of epidermal keratinocytes that form colloid bodies within the superficial dermis following apoptosis.⁶ Hematoxylin and eosin staining shows amorphous, fissured, pale pink deposits completely filling and expanding the superficial to mid dermis with clefting and no inflammation (Figure 3). Spindle-shaped fibroblasts may be seen within the lines of colloid fissuring and dispersed throughout the deposits.¹ Histologically, JCM can be differentiated from EPP because deposits in EPP are distributed around and within superficial blood vessel walls, causing prominent vascular thickening not seen in JCM.⁶ The adult variant of colloid milium also can be distinguished from EPP by the presence of solar elastosis, which is absent in EPP due to a history of sun avoidance.^3,7  

Lichen amyloidosis presents with highly pruritic, red-brown, hyperkeratotic papules that commonly are found on the anterior lower legs and extensor forearms.¹ The calves, ankles, dorsal aspects of the feet, thighs, and trunk also may be affected. Excoriations, lichenification, and nodular prurigo-like lesions due to chronic scratching can be present.⁶ Lichen amyloidosis is characterized by large, pink, amorphous deposits in the papillary dermis with epidermal acanthosis, hypergranulosis, and hyperkeratosis (Figure 4).⁶ Perivascular deposits are not a feature of primary cutaneous localized amyloid lesions.⁶ The diagnosis can be confirmed with Congo red staining under polarized light, which classically demonstrates apple green birefringence.¹ For cases of amyloid that are not detected by Congo red or are not clear-cut, direct immunofluorescence and immunohistochemistry can be used as adjuncts for diagnosis. Amyloid deposits fluoresce positively for immunoglobulins or complements, particularly IgM and C3,⁸ and immunohistochemistry confirms the presence of keratin epitopes in deposits.⁹  

Porphyria cutanea tarda can appear histologically similar to EPP. Caterpillar bodies, or linearly arranged eosinophilic PAS-positive globules in the epidermis overlying subepidermal bullae, are a diagnostic histopathologic finding in both PCT and EPP but are seen in less than half of both cases.^7,10 Compared to EPP, the perivascular deposits in PCT typically are less pronounced and limited to the vessel wall with smaller hyaline cuffs (Figure 5).⁷ Additionally, solar elastosis can be seen in PCT lesions but not in EPP, as patients with PCT tend to be older and have increased cumulative sun damage.  

The Diagnosis: Erythropoietic Protoporphyria 

Erythropoietic protoporphyria (EPP) is an autosomal-recessive photodermatosis that results from loss of activity of ferrochelatase, the last enzyme in the heme biosynthetic pathway.¹ Erythropoietic protoporphyria normally involves sun-exposed areas of the body. Skin that is exposed to sunlight develops intense burning and stinging pain followed by erythema, edema, crusting, and petechiae that develops into waxy scarring over time. In contrast to other porphyrias, blistering generally is not seen.² Accurate diagnosis often can be delayed by a decade or more following symptom onset due to the prominence of subjective pain as the presenting sign.  

The histologic appearance of EPP differs depending on the chronicity of lesions. Biopsies of acute lesions show vacuolization of epidermal cells with intercellular edema, vacuolization and cytolysis of endothelial cells in superficial blood vessels, and focal red blood cell extravasation.^3,4 A largely neutrophilic inflammatory infiltrate can be present.⁵ Hyaline cuffing develops over time in and around vessels in the papillary and superficial reticular dermis with notable sparing of adnexal structures. The perivascular deposits are strongly periodic acid-Schiff (PAS) positive and diastase resistant (Figure 1). Direct immunofluorescence shows mainly IgG and some IgM, fibrinogen, and C3 outlining characteristic donut-shaped blood vessels in the papillary dermis.⁶ The prominent thickness of the perivascular hyaline material depositions and the absence of subepidermal blistering can help differentiate EPP from porphyria cutanea tarda (PCT) and pseudoporphyria.^6,7 When the deposition is extensive and involves the surrounding dermis, EPP can mimic colloid milium. Additional histologic differential diagnoses of EPP include other dermal depositional diseases such as lipoid proteinosis and amyloidosis.  

Lipoid proteinosis is an autosomal-recessive multisystem genodermatosis caused by mutations in extracellular matrix gene 1, ECM1. The first clinical sign can be a hoarse cry in infancy due to infiltration of vocal cords.³ Development of papulonodular lesions along the eyelids can result in a string-of-beads appearance called moniliform blepharosis, which is pathognomonic for lipoid proteinosis.⁶ With chronicity, the involved skin can become yellow, waxy, and thickened, particularly in the flexures or areas of trauma. Histologically, the dermis in lipoid proteinosis becomes diffusely thickened due to deposition of PAS-positive eosinophilic hyaline material that stains weakly with Congo red and thioflavin T.⁶ Early lesions demonstrate pale pink, hyalinelike thickening of the papillary dermal capillaries. Chronic lesions reveal an acanthotic epidermis, occasional papillomatosis with overlying hyperkeratosis, and a thickened dermis where diffuse thick bundles of pink hyaline deposits are oriented perpendicularly to the dermoepidermal junction.^1,6 Lipoid proteinosis can be differentiated from EPP by the involvement of adnexal structures such as hair follicles, sebaceous glands, and arrector pili muscles (Figure 2), as opposed to EPP where adnexal structures are spared.¹ Additionally, depositions in lipoid proteinosis are centered around both superficial and deep vessels with an onion skin-like pattern, while EPP involves mainly superficial vessels with more mild and focal hyalinization.

Juvenile colloid milium (JCM) is a rare condition that presents before puberty with discrete, yellow-brown, translucent papules predominantly located on the cheeks and nose and around the mouth. A gelatinous material can be expressed after puncturing a lesion.⁶ Gingival deposits and ligneous conjunctivitis also can be present. On histopathology, JCM shows degeneration of epidermal keratinocytes that form colloid bodies within the superficial dermis following apoptosis.⁶ Hematoxylin and eosin staining shows amorphous, fissured, pale pink deposits completely filling and expanding the superficial to mid dermis with clefting and no inflammation (Figure 3). Spindle-shaped fibroblasts may be seen within the lines of colloid fissuring and dispersed throughout the deposits.¹ Histologically, JCM can be differentiated from EPP because deposits in EPP are distributed around and within superficial blood vessel walls, causing prominent vascular thickening not seen in JCM.⁶ The adult variant of colloid milium also can be distinguished from EPP by the presence of solar elastosis, which is absent in EPP due to a history of sun avoidance.^3,7  

Lichen amyloidosis presents with highly pruritic, red-brown, hyperkeratotic papules that commonly are found on the anterior lower legs and extensor forearms.¹ The calves, ankles, dorsal aspects of the feet, thighs, and trunk also may be affected. Excoriations, lichenification, and nodular prurigo-like lesions due to chronic scratching can be present.⁶ Lichen amyloidosis is characterized by large, pink, amorphous deposits in the papillary dermis with epidermal acanthosis, hypergranulosis, and hyperkeratosis (Figure 4).⁶ Perivascular deposits are not a feature of primary cutaneous localized amyloid lesions.⁶ The diagnosis can be confirmed with Congo red staining under polarized light, which classically demonstrates apple green birefringence.¹ For cases of amyloid that are not detected by Congo red or are not clear-cut, direct immunofluorescence and immunohistochemistry can be used as adjuncts for diagnosis. Amyloid deposits fluoresce positively for immunoglobulins or complements, particularly IgM and C3,⁸ and immunohistochemistry confirms the presence of keratin epitopes in deposits.⁹  

Porphyria cutanea tarda can appear histologically similar to EPP. Caterpillar bodies, or linearly arranged eosinophilic PAS-positive globules in the epidermis overlying subepidermal bullae, are a diagnostic histopathologic finding in both PCT and EPP but are seen in less than half of both cases.^7,10 Compared to EPP, the perivascular deposits in PCT typically are less pronounced and limited to the vessel wall with smaller hyaline cuffs (Figure 5).⁷ Additionally, solar elastosis can be seen in PCT lesions but not in EPP, as patients with PCT tend to be older and have increased cumulative sun damage.  

Combining specimens from several low-risk inpatients in a single test for SARS-CoV-2 infection allowed hospital staff to stretch testing supplies and provide test results quickly for many more patients than they might have otherwise, researchers found.

“We believe this strategy conserved [personal protective equipment (PPE)], led to a marked reduction in staff and patient anxiety, and improved patient care,” wrote David Mastrianni, MD, and colleagues from Saratoga Hospital in Saratoga Springs, N.Y. “Our impression is that testing all admitted patients has also been reassuring to our community.”

The researchers published their findings July 20 in the Journal of Hospital Medicine.

“What was really important about this study was they were actually able to implement pooled testing after communication with the [Food and Drug Administration],” Samir S. Shah, MD, MSCE, SFHM, the journal’s editor-in-chief, said in an interview.

“Pooled testing combines samples from multiple people within a single test. The benefit is, if the test is negative [you know that] everyone whose sample was combined … is negative. So you’ve effectively tested anywhere from three to five people with the resources required for only one test,” Dr. Shah continued.

The challenge is that, if the test is positive, everyone in that testing group must be retested individually because one or more of them has the infection, said Dr. Shah, director of hospital medicine at Cincinnati Children’s Hospital Medical Center.

Dr. Mastrianni said early in the pandemic they started getting the “New York surge” at their hospital, located approximately 3 hours from New York City. They wanted to test all of the inpatients at their hospital for COVID-19 and they had a rapid in-house test that worked well, “but we just didn’t have enough cartridges, and we couldn’t get deliveries, and we started pooling.” In fact, they ran out of testing supplies at one point during the study but were able to replenish their supply in about a day, he noted.

For the current study, all patients admitted to the hospital, including those admitted for observation, underwent testing for SARS-CoV-2. Staff in the emergency department designated patients as low risk if they had no symptoms or other clinical evidence of COVID-19; those patients underwent pooled testing.

Patients with clinical evidence of COVID-19, such as respiratory symptoms or laboratory or radiographic findings consistent with infection, were considered high risk and were tested on an individual basis and thus excluded from the current analysis.

The pooled testing strategy required some patients to be held in the emergency department until there were three available for pooled testing. On several occasions when this was not practical, specimens from two patients were pooled.

Between April 17 and May 11, clinicians tested 530 patients via pooled testing using 179 cartridges (172 with swabs from three patients and 7 with swabs from two patients). There were four positive pooled tests, which necessitated the use of an additional 11 cartridges. Overall, the testing used 190 cartridges, which is 340 fewer than would have been used if all patients had been tested individually. 

Among the low-risk patients, the positive rate was 0.8% (4/530). No patients from pools that were negative tested positive later during their hospitalization or developed evidence of the infection.
 

Team effort, flexibility needed

Dr. Mastrianni said he expected their study to find that pooled testing saved testing resources, but he “was surprised by the complexity of the logistics in the hospital, and how it really required getting everybody to work together. …There were a lot of details, and it really took a lot of teamwork.”

The nursing supervisor in the emergency department was in charge of the batch and coordinated with the laboratory, he explained. There were many moving parts to manage, including monitoring how many patients were being admitted, what their conditions were, whether they were high or low risk, and where they would house those patients as the emergency department became increasingly busy. “It’s a lot for them, but they’ve adapted really well,” Dr. Mastrianni said.

Pooling tests seems to work best for three to five patients at a time; larger batches increase the chance of having a positive test, and thus identifying the sick individual(s) becomes more challenging and expensive, Dr. Shah said.

“It’s a fine line between having a pool large enough that you save on testing supplies and testing costs but not having the pool so large that you dramatically increase your likelihood of having a positive test,” Dr. Shah said.

Hospitals will likely need to be flexible and adapt as the local positivity rate changes and supply levels vary, according to the authors.

“Pooled testing is mainly dependent on the COVID-19 positive rate in the population of interest in addition to the sensitivity of the [reverse transcriptase-polymerase chain reaction (RT-PCR)] method used for COVID-19 testing,” said Baha Abdalhamid, MD, PhD, of the department of pathology and microbiology at the University of Nebraska Medical Center in Omaha.

“Each laboratory and hospital needs to do their own validation testing because it is dependent on the positive rate of COVID-19,” added Dr. Abdalhamid, who was not involved in the current study.

It’s important for clinicians to “do a good history to find who’s high risk and who’s low risk,” Dr. Mastrianni said. Clinicians also need to remember that, although a patient may test negative initially, they may still have COVID-19, he warned. That test reflects a single point in time, and a patient could be infected and not yet be ill, so clinicians need to be alert to a change in the patient’s status.
 

Best for settings with low-risk individuals

“Pooled COVID-19 testing is a straightforward, cost-effective, and efficient approach,” Dr. Abdalhamid said. He and his colleagues found pooled testing could increase testing capability by 69% or more when the incidence rate of SARS-CoV-2 infection is 10% or lower.

He said the approach would be helpful in other settings “as long as the positive rate is equal to or less than 10%. Asymptomatic population or surveillance groups such as students, athletes, and military service members are [an] interesting population to test using pooling testing because we expect these populations to have low positive rates, which makes pooled testing ideal.” 
 

Benefit outweighs risk

“There is risk of missing specimens with low concentration of the virus,” Dr. Abdalhamid cautioned. “These specimens might be missed due to the dilution factor of pooling [false-negative specimens]. We did not have a single false-negative specimen in our proof-of-concept study. In addition, there are practical approaches to deal with false-negative pooled specimens.

“The benefit definitely outweighs the risk of false-negative specimens because false-negative results rarely occur, if any. In addition, there is significant saving of time, reagents, and supplies in [a] pooled specimens approach as well as expansion of the test for higher number of patients,” Dr. Abdalhamid continued. 

Dr. Mastrianni’s hospital currently has enough testing cartridges, but they are continuing to conduct pooled testing to conserve resources for the benefit of their own hospital and for the nation as a whole, he said.

The authors have disclosed no relevant financial relationships. Dr. Abdalhamid and Dr. Shah have disclosed no relevant financial relationships.

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

Combining specimens from several low-risk inpatients in a single test for SARS-CoV-2 infection allowed hospital staff to stretch testing supplies and provide test results quickly for many more patients than they might have otherwise, researchers found.

“We believe this strategy conserved [personal protective equipment (PPE)], led to a marked reduction in staff and patient anxiety, and improved patient care,” wrote David Mastrianni, MD, and colleagues from Saratoga Hospital in Saratoga Springs, N.Y. “Our impression is that testing all admitted patients has also been reassuring to our community.”

The researchers published their findings July 20 in the Journal of Hospital Medicine.

“What was really important about this study was they were actually able to implement pooled testing after communication with the [Food and Drug Administration],” Samir S. Shah, MD, MSCE, SFHM, the journal’s editor-in-chief, said in an interview.

“Pooled testing combines samples from multiple people within a single test. The benefit is, if the test is negative [you know that] everyone whose sample was combined … is negative. So you’ve effectively tested anywhere from three to five people with the resources required for only one test,” Dr. Shah continued.

The challenge is that, if the test is positive, everyone in that testing group must be retested individually because one or more of them has the infection, said Dr. Shah, director of hospital medicine at Cincinnati Children’s Hospital Medical Center.

Dr. Mastrianni said early in the pandemic they started getting the “New York surge” at their hospital, located approximately 3 hours from New York City. They wanted to test all of the inpatients at their hospital for COVID-19 and they had a rapid in-house test that worked well, “but we just didn’t have enough cartridges, and we couldn’t get deliveries, and we started pooling.” In fact, they ran out of testing supplies at one point during the study but were able to replenish their supply in about a day, he noted.

For the current study, all patients admitted to the hospital, including those admitted for observation, underwent testing for SARS-CoV-2. Staff in the emergency department designated patients as low risk if they had no symptoms or other clinical evidence of COVID-19; those patients underwent pooled testing.

Patients with clinical evidence of COVID-19, such as respiratory symptoms or laboratory or radiographic findings consistent with infection, were considered high risk and were tested on an individual basis and thus excluded from the current analysis.

The pooled testing strategy required some patients to be held in the emergency department until there were three available for pooled testing. On several occasions when this was not practical, specimens from two patients were pooled.

Between April 17 and May 11, clinicians tested 530 patients via pooled testing using 179 cartridges (172 with swabs from three patients and 7 with swabs from two patients). There were four positive pooled tests, which necessitated the use of an additional 11 cartridges. Overall, the testing used 190 cartridges, which is 340 fewer than would have been used if all patients had been tested individually. 

Among the low-risk patients, the positive rate was 0.8% (4/530). No patients from pools that were negative tested positive later during their hospitalization or developed evidence of the infection.
 

Team effort, flexibility needed

Dr. Mastrianni said he expected their study to find that pooled testing saved testing resources, but he “was surprised by the complexity of the logistics in the hospital, and how it really required getting everybody to work together. …There were a lot of details, and it really took a lot of teamwork.”

The nursing supervisor in the emergency department was in charge of the batch and coordinated with the laboratory, he explained. There were many moving parts to manage, including monitoring how many patients were being admitted, what their conditions were, whether they were high or low risk, and where they would house those patients as the emergency department became increasingly busy. “It’s a lot for them, but they’ve adapted really well,” Dr. Mastrianni said.

Pooling tests seems to work best for three to five patients at a time; larger batches increase the chance of having a positive test, and thus identifying the sick individual(s) becomes more challenging and expensive, Dr. Shah said.

“It’s a fine line between having a pool large enough that you save on testing supplies and testing costs but not having the pool so large that you dramatically increase your likelihood of having a positive test,” Dr. Shah said.

Hospitals will likely need to be flexible and adapt as the local positivity rate changes and supply levels vary, according to the authors.

“Pooled testing is mainly dependent on the COVID-19 positive rate in the population of interest in addition to the sensitivity of the [reverse transcriptase-polymerase chain reaction (RT-PCR)] method used for COVID-19 testing,” said Baha Abdalhamid, MD, PhD, of the department of pathology and microbiology at the University of Nebraska Medical Center in Omaha.

“Each laboratory and hospital needs to do their own validation testing because it is dependent on the positive rate of COVID-19,” added Dr. Abdalhamid, who was not involved in the current study.

It’s important for clinicians to “do a good history to find who’s high risk and who’s low risk,” Dr. Mastrianni said. Clinicians also need to remember that, although a patient may test negative initially, they may still have COVID-19, he warned. That test reflects a single point in time, and a patient could be infected and not yet be ill, so clinicians need to be alert to a change in the patient’s status.
 

Best for settings with low-risk individuals

“Pooled COVID-19 testing is a straightforward, cost-effective, and efficient approach,” Dr. Abdalhamid said. He and his colleagues found pooled testing could increase testing capability by 69% or more when the incidence rate of SARS-CoV-2 infection is 10% or lower.

He said the approach would be helpful in other settings “as long as the positive rate is equal to or less than 10%. Asymptomatic population or surveillance groups such as students, athletes, and military service members are [an] interesting population to test using pooling testing because we expect these populations to have low positive rates, which makes pooled testing ideal.” 
 

Benefit outweighs risk

“There is risk of missing specimens with low concentration of the virus,” Dr. Abdalhamid cautioned. “These specimens might be missed due to the dilution factor of pooling [false-negative specimens]. We did not have a single false-negative specimen in our proof-of-concept study. In addition, there are practical approaches to deal with false-negative pooled specimens.

“The benefit definitely outweighs the risk of false-negative specimens because false-negative results rarely occur, if any. In addition, there is significant saving of time, reagents, and supplies in [a] pooled specimens approach as well as expansion of the test for higher number of patients,” Dr. Abdalhamid continued. 

Dr. Mastrianni’s hospital currently has enough testing cartridges, but they are continuing to conduct pooled testing to conserve resources for the benefit of their own hospital and for the nation as a whole, he said.

The authors have disclosed no relevant financial relationships. Dr. Abdalhamid and Dr. Shah have disclosed no relevant financial relationships.

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

Combining specimens from several low-risk inpatients in a single test for SARS-CoV-2 infection allowed hospital staff to stretch testing supplies and provide test results quickly for many more patients than they might have otherwise, researchers found.

“We believe this strategy conserved [personal protective equipment (PPE)], led to a marked reduction in staff and patient anxiety, and improved patient care,” wrote David Mastrianni, MD, and colleagues from Saratoga Hospital in Saratoga Springs, N.Y. “Our impression is that testing all admitted patients has also been reassuring to our community.”

The researchers published their findings July 20 in the Journal of Hospital Medicine.

“What was really important about this study was they were actually able to implement pooled testing after communication with the [Food and Drug Administration],” Samir S. Shah, MD, MSCE, SFHM, the journal’s editor-in-chief, said in an interview.

“Pooled testing combines samples from multiple people within a single test. The benefit is, if the test is negative [you know that] everyone whose sample was combined … is negative. So you’ve effectively tested anywhere from three to five people with the resources required for only one test,” Dr. Shah continued.

The challenge is that, if the test is positive, everyone in that testing group must be retested individually because one or more of them has the infection, said Dr. Shah, director of hospital medicine at Cincinnati Children’s Hospital Medical Center.

Dr. Mastrianni said early in the pandemic they started getting the “New York surge” at their hospital, located approximately 3 hours from New York City. They wanted to test all of the inpatients at their hospital for COVID-19 and they had a rapid in-house test that worked well, “but we just didn’t have enough cartridges, and we couldn’t get deliveries, and we started pooling.” In fact, they ran out of testing supplies at one point during the study but were able to replenish their supply in about a day, he noted.

For the current study, all patients admitted to the hospital, including those admitted for observation, underwent testing for SARS-CoV-2. Staff in the emergency department designated patients as low risk if they had no symptoms or other clinical evidence of COVID-19; those patients underwent pooled testing.

Patients with clinical evidence of COVID-19, such as respiratory symptoms or laboratory or radiographic findings consistent with infection, were considered high risk and were tested on an individual basis and thus excluded from the current analysis.

The pooled testing strategy required some patients to be held in the emergency department until there were three available for pooled testing. On several occasions when this was not practical, specimens from two patients were pooled.

Between April 17 and May 11, clinicians tested 530 patients via pooled testing using 179 cartridges (172 with swabs from three patients and 7 with swabs from two patients). There were four positive pooled tests, which necessitated the use of an additional 11 cartridges. Overall, the testing used 190 cartridges, which is 340 fewer than would have been used if all patients had been tested individually. 

Among the low-risk patients, the positive rate was 0.8% (4/530). No patients from pools that were negative tested positive later during their hospitalization or developed evidence of the infection.
 

Team effort, flexibility needed

Dr. Mastrianni said he expected their study to find that pooled testing saved testing resources, but he “was surprised by the complexity of the logistics in the hospital, and how it really required getting everybody to work together. …There were a lot of details, and it really took a lot of teamwork.”

The nursing supervisor in the emergency department was in charge of the batch and coordinated with the laboratory, he explained. There were many moving parts to manage, including monitoring how many patients were being admitted, what their conditions were, whether they were high or low risk, and where they would house those patients as the emergency department became increasingly busy. “It’s a lot for them, but they’ve adapted really well,” Dr. Mastrianni said.

Pooling tests seems to work best for three to five patients at a time; larger batches increase the chance of having a positive test, and thus identifying the sick individual(s) becomes more challenging and expensive, Dr. Shah said.

“It’s a fine line between having a pool large enough that you save on testing supplies and testing costs but not having the pool so large that you dramatically increase your likelihood of having a positive test,” Dr. Shah said.

Hospitals will likely need to be flexible and adapt as the local positivity rate changes and supply levels vary, according to the authors.

“Pooled testing is mainly dependent on the COVID-19 positive rate in the population of interest in addition to the sensitivity of the [reverse transcriptase-polymerase chain reaction (RT-PCR)] method used for COVID-19 testing,” said Baha Abdalhamid, MD, PhD, of the department of pathology and microbiology at the University of Nebraska Medical Center in Omaha.

“Each laboratory and hospital needs to do their own validation testing because it is dependent on the positive rate of COVID-19,” added Dr. Abdalhamid, who was not involved in the current study.

It’s important for clinicians to “do a good history to find who’s high risk and who’s low risk,” Dr. Mastrianni said. Clinicians also need to remember that, although a patient may test negative initially, they may still have COVID-19, he warned. That test reflects a single point in time, and a patient could be infected and not yet be ill, so clinicians need to be alert to a change in the patient’s status.
 

Best for settings with low-risk individuals

“Pooled COVID-19 testing is a straightforward, cost-effective, and efficient approach,” Dr. Abdalhamid said. He and his colleagues found pooled testing could increase testing capability by 69% or more when the incidence rate of SARS-CoV-2 infection is 10% or lower.

He said the approach would be helpful in other settings “as long as the positive rate is equal to or less than 10%. Asymptomatic population or surveillance groups such as students, athletes, and military service members are [an] interesting population to test using pooling testing because we expect these populations to have low positive rates, which makes pooled testing ideal.” 
 

Benefit outweighs risk

“There is risk of missing specimens with low concentration of the virus,” Dr. Abdalhamid cautioned. “These specimens might be missed due to the dilution factor of pooling [false-negative specimens]. We did not have a single false-negative specimen in our proof-of-concept study. In addition, there are practical approaches to deal with false-negative pooled specimens.

“The benefit definitely outweighs the risk of false-negative specimens because false-negative results rarely occur, if any. In addition, there is significant saving of time, reagents, and supplies in [a] pooled specimens approach as well as expansion of the test for higher number of patients,” Dr. Abdalhamid continued. 

Dr. Mastrianni’s hospital currently has enough testing cartridges, but they are continuing to conduct pooled testing to conserve resources for the benefit of their own hospital and for the nation as a whole, he said.

The authors have disclosed no relevant financial relationships. Dr. Abdalhamid and Dr. Shah have disclosed no relevant financial relationships.

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

Let us begin with a thought exercise. Close your eyes and picture the word, “hero.” What comes to mind? A relative, a teacher, a fictional character wielding a hammer or flying gracefully through the air?

© Maridav / iStockphoto.com

Several months ago, our country was introduced to a foe that brought us to our knees. Before that time, the idea of a hero had fluctuated with circumstance and had been guided by aging and maturity; however, since the moment COVID-19 struck, a new image has emerged. Not all heroes wear capes, but some wield stethoscopes.

Over these past months the phrase, “Health Care Heroes” has spread throughout our collective consciousness, highlighted everywhere from talk shows and news media to billboards and journals. Doctors, nurses, and other health care professionals are lauded for their strength, dedication, resilience, and compassion. Citizens line up to clap, honk horns, and shower praise in recognition of those who have risked their health, sacrificed their personal lives, and committed themselves to the greater good. Yet, what does it mean to be a hero, and what is the cost of hero worship?

The focus of medical training has gradually shifted to include the physical as well as mental well-being of future physicians, but the remnants of traditional doctrine linger. Hours of focused training through study and direct clinical interaction reinforce dedication to patient care. Rewards are given for time spent and compassion lent, and research is lauded, but family time is rarely applauded. We are encouraged to do our greatest, work our hardest, be the best, rise and defeat every test. Failure (or the perception thereof) is not an option.

According to Rikinkumar S. Patel, MD, MPH, and associates, physicians have nearly twice the burnout rate of other professionals (Behav Sci. [Basel]. 2018 Nov;8[11]:98). The dedication to our craft propels excellence as well as sacrifice. When COVID-19 entered our lives, many of my colleagues did not hesitate to heed to the call for action. They immersed themselves in the ICU, led triage units, and extended work hours in the service of the sick and dying. Several were years removed from emergency/intensive care, while others were allocated from their chosen residency programs and voluntarily thrust into an environment they had never before traversed.

These individuals are praised as “brave,” “dedicated,” “selfless.” A few even provided insight into their experiences through various publications highlighting their appreciation and gratitude toward such a treacherous, albeit, tremendous experience. Even though their words are an honest perspective of life through one of the worst health care crises in 100 years, in effect, they perpetuate the noble hero; the myth of the super doctor.

In a profession that has borne witness to multiple suicides over the past few months, why do we not encourage open dialogue of our victories as well as our defeats? Our wins as much as our losses? Why does an esteemed veteran physician feel guilt over declining to provide emergency services to patients whom they have long forgotten how to manage? What drives the guilt and the self-doubt? Are we ashamed of what others will think? Is it that the fear of not living up to our cherished medical oath outweighs our own boundaries and acknowledgment of our limitations?

A hero is an entity, a person encompassing a state of being, yet health care professionals are bestowed this title and this burden on a near-daily basis. Physicians are people. We love, we fear, we hesitate, we fight, we deem to overcome. We are perfectly imperfect. The more in tune we are to vulnerability, the more honest we can become with ourselves and one another.
 

Dr. Thomas is a board-certified adult psychiatrist with an interest in chronic illness, women’s behavioral health, and minority mental health. She currently practices in North Kingstown and East Providence, R.I. She has no conflicts of interest.

Let us begin with a thought exercise. Close your eyes and picture the word, “hero.” What comes to mind? A relative, a teacher, a fictional character wielding a hammer or flying gracefully through the air?

© Maridav / iStockphoto.com

Several months ago, our country was introduced to a foe that brought us to our knees. Before that time, the idea of a hero had fluctuated with circumstance and had been guided by aging and maturity; however, since the moment COVID-19 struck, a new image has emerged. Not all heroes wear capes, but some wield stethoscopes.

Over these past months the phrase, “Health Care Heroes” has spread throughout our collective consciousness, highlighted everywhere from talk shows and news media to billboards and journals. Doctors, nurses, and other health care professionals are lauded for their strength, dedication, resilience, and compassion. Citizens line up to clap, honk horns, and shower praise in recognition of those who have risked their health, sacrificed their personal lives, and committed themselves to the greater good. Yet, what does it mean to be a hero, and what is the cost of hero worship?

The focus of medical training has gradually shifted to include the physical as well as mental well-being of future physicians, but the remnants of traditional doctrine linger. Hours of focused training through study and direct clinical interaction reinforce dedication to patient care. Rewards are given for time spent and compassion lent, and research is lauded, but family time is rarely applauded. We are encouraged to do our greatest, work our hardest, be the best, rise and defeat every test. Failure (or the perception thereof) is not an option.

According to Rikinkumar S. Patel, MD, MPH, and associates, physicians have nearly twice the burnout rate of other professionals (Behav Sci. [Basel]. 2018 Nov;8[11]:98). The dedication to our craft propels excellence as well as sacrifice. When COVID-19 entered our lives, many of my colleagues did not hesitate to heed to the call for action. They immersed themselves in the ICU, led triage units, and extended work hours in the service of the sick and dying. Several were years removed from emergency/intensive care, while others were allocated from their chosen residency programs and voluntarily thrust into an environment they had never before traversed.

These individuals are praised as “brave,” “dedicated,” “selfless.” A few even provided insight into their experiences through various publications highlighting their appreciation and gratitude toward such a treacherous, albeit, tremendous experience. Even though their words are an honest perspective of life through one of the worst health care crises in 100 years, in effect, they perpetuate the noble hero; the myth of the super doctor.

In a profession that has borne witness to multiple suicides over the past few months, why do we not encourage open dialogue of our victories as well as our defeats? Our wins as much as our losses? Why does an esteemed veteran physician feel guilt over declining to provide emergency services to patients whom they have long forgotten how to manage? What drives the guilt and the self-doubt? Are we ashamed of what others will think? Is it that the fear of not living up to our cherished medical oath outweighs our own boundaries and acknowledgment of our limitations?

A hero is an entity, a person encompassing a state of being, yet health care professionals are bestowed this title and this burden on a near-daily basis. Physicians are people. We love, we fear, we hesitate, we fight, we deem to overcome. We are perfectly imperfect. The more in tune we are to vulnerability, the more honest we can become with ourselves and one another.
 

Dr. Thomas is a board-certified adult psychiatrist with an interest in chronic illness, women’s behavioral health, and minority mental health. She currently practices in North Kingstown and East Providence, R.I. She has no conflicts of interest.

Let us begin with a thought exercise. Close your eyes and picture the word, “hero.” What comes to mind? A relative, a teacher, a fictional character wielding a hammer or flying gracefully through the air?

© Maridav / iStockphoto.com

Several months ago, our country was introduced to a foe that brought us to our knees. Before that time, the idea of a hero had fluctuated with circumstance and had been guided by aging and maturity; however, since the moment COVID-19 struck, a new image has emerged. Not all heroes wear capes, but some wield stethoscopes.

Over these past months the phrase, “Health Care Heroes” has spread throughout our collective consciousness, highlighted everywhere from talk shows and news media to billboards and journals. Doctors, nurses, and other health care professionals are lauded for their strength, dedication, resilience, and compassion. Citizens line up to clap, honk horns, and shower praise in recognition of those who have risked their health, sacrificed their personal lives, and committed themselves to the greater good. Yet, what does it mean to be a hero, and what is the cost of hero worship?

The focus of medical training has gradually shifted to include the physical as well as mental well-being of future physicians, but the remnants of traditional doctrine linger. Hours of focused training through study and direct clinical interaction reinforce dedication to patient care. Rewards are given for time spent and compassion lent, and research is lauded, but family time is rarely applauded. We are encouraged to do our greatest, work our hardest, be the best, rise and defeat every test. Failure (or the perception thereof) is not an option.

According to Rikinkumar S. Patel, MD, MPH, and associates, physicians have nearly twice the burnout rate of other professionals (Behav Sci. [Basel]. 2018 Nov;8[11]:98). The dedication to our craft propels excellence as well as sacrifice. When COVID-19 entered our lives, many of my colleagues did not hesitate to heed to the call for action. They immersed themselves in the ICU, led triage units, and extended work hours in the service of the sick and dying. Several were years removed from emergency/intensive care, while others were allocated from their chosen residency programs and voluntarily thrust into an environment they had never before traversed.

These individuals are praised as “brave,” “dedicated,” “selfless.” A few even provided insight into their experiences through various publications highlighting their appreciation and gratitude toward such a treacherous, albeit, tremendous experience. Even though their words are an honest perspective of life through one of the worst health care crises in 100 years, in effect, they perpetuate the noble hero; the myth of the super doctor.

In a profession that has borne witness to multiple suicides over the past few months, why do we not encourage open dialogue of our victories as well as our defeats? Our wins as much as our losses? Why does an esteemed veteran physician feel guilt over declining to provide emergency services to patients whom they have long forgotten how to manage? What drives the guilt and the self-doubt? Are we ashamed of what others will think? Is it that the fear of not living up to our cherished medical oath outweighs our own boundaries and acknowledgment of our limitations?

A hero is an entity, a person encompassing a state of being, yet health care professionals are bestowed this title and this burden on a near-daily basis. Physicians are people. We love, we fear, we hesitate, we fight, we deem to overcome. We are perfectly imperfect. The more in tune we are to vulnerability, the more honest we can become with ourselves and one another.
 

Dr. Thomas is a board-certified adult psychiatrist with an interest in chronic illness, women’s behavioral health, and minority mental health. She currently practices in North Kingstown and East Providence, R.I. She has no conflicts of interest.

The American Gastroenterological Association (AGA) has released a clinical practice guideline for gastrointestinal evaluation of iron-deficiency anemia.

The seven recommendations aim to improve quality of care and reduce practice variability, according to lead author Cynthia W. Ko, MD, of the University of Washington , Seattle, and four copanelists.

First, the panel recommended that iron deficiency be defined by a serum ferritin level less than 45 ng/mL, instead of 15 ng/mL. Data from 55 studies showed that the higher cutoff value had a sensitivity of 85% and a specificity of 92%, compared with respective values of 59% and 99% for the lower threshold.

“Optimizing the threshold ferritin level with high sensitivity will detect the great majority of patients who are truly iron deficient, minimize delays in diagnostic workup, and minimize the number of patients in whom serious underlying etiologies such as gastrointestinal malignancy might be missed,” the panelists wrote. The guideline was published in Gastroenterology.

For asymptomatic postmenopausal women and men with iron-deficiency anemia, the panel recommended bidirectional endoscopy instead of no endoscopy. A similar recommendation was given for premenopausal women, calling for bidirectional endoscopy instead of iron-replacement therapy alone.

Dr. Ko and colleagues noted that these recommendations differ from those issued by the British Society of Gastroenterology (BSG).

For postmenopausal women and men, the BSG suggests that symptoms and local availability of endoscopy should inform diagnostic workup, with either colonoscopy or CT colonography used for assessment. The BSG recommends against bidirectional endoscopy in premenopausal women, unless they are older than 50 years, have a family history of colorectal cancer, or show symptoms of gastrointestinal disease.

“In contrast, the AGA recommends bidirectional endoscopy as the mainstay for gastrointestinal evaluation, particularly in men and in postmenopausal women where no other unequivocal source of iron deficiency has been identified,” the panelists wrote.

When bidirectional endoscopy does not reveal an etiology, the panelists recommended noninvasive testing for Helicobacter pylori.

“An association between H. pylori infection and iron deficiency has been demonstrated in observational studies,” noted Dr. Ko and colleagues.

They also cited three randomized controlled trials in which treating patients with iron-deficiency anemia for H. pylori infection in combination with iron replacement therapy led to a 23.2-ng/mL mean improvement in serum ferritin, compared with patients who received iron-replacement therapy alone.

According to the guideline, if asymptomatic patients with negative bidirectional endoscopy are also negative for H. pylori, then they should receive trial iron supplementation, instead of undergoing video capsule endoscopy.

“[T]he evidence required to evaluate the benefits of video capsule endoscopy in iron-deficiency anemia is not currently available,” the panelists noted.

Dr. Ko and colleagues also recommended against routine gastric biopsies to diagnose autoimmune atrophic gastritis, as earlier diagnosis does not appear to affect outcomes or management of iron-deficiency anemia.

Finally, the panelists recommended that asymptomatic patients with iron-deficiency anemia and suspected celiac disease undergo serologic testing first, with small bowel biopsy only performed if testing is positive.

The only two strong recommendations in the guideline are for the ferritin cutoff value and the use of bidirectional endoscopy in men and postmenopausal women. The other five recommendations are conditional, three of which are based on very low quality evidence. As such, the guideline includes a discussion of research needs.

Dr. Ko and colleagues called for more studies investigating the prevalence of gastrointestinal lesions and risks of bidirectional endoscopy in premenopausal women, role of fecal occult blood testing, timing of serologic testing for H. pylori and celiac disease in relation to endoscopy, patient subgroups, comparative efficacy of small bowel visualization techniques, and other topics.

The investigators disclosed no conflicts of interest. The guideline was funded by the AGA Institute.

SOURCE: Ko CW et al. Gastroenterology 2020 Aug 15. doi: 10.1053/j.gastro.2020.06.046.

The American Gastroenterological Association (AGA) has released a clinical practice guideline for gastrointestinal evaluation of iron-deficiency anemia.

The seven recommendations aim to improve quality of care and reduce practice variability, according to lead author Cynthia W. Ko, MD, of the University of Washington , Seattle, and four copanelists.

First, the panel recommended that iron deficiency be defined by a serum ferritin level less than 45 ng/mL, instead of 15 ng/mL. Data from 55 studies showed that the higher cutoff value had a sensitivity of 85% and a specificity of 92%, compared with respective values of 59% and 99% for the lower threshold.

“Optimizing the threshold ferritin level with high sensitivity will detect the great majority of patients who are truly iron deficient, minimize delays in diagnostic workup, and minimize the number of patients in whom serious underlying etiologies such as gastrointestinal malignancy might be missed,” the panelists wrote. The guideline was published in Gastroenterology.

For asymptomatic postmenopausal women and men with iron-deficiency anemia, the panel recommended bidirectional endoscopy instead of no endoscopy. A similar recommendation was given for premenopausal women, calling for bidirectional endoscopy instead of iron-replacement therapy alone.

Dr. Ko and colleagues noted that these recommendations differ from those issued by the British Society of Gastroenterology (BSG).

For postmenopausal women and men, the BSG suggests that symptoms and local availability of endoscopy should inform diagnostic workup, with either colonoscopy or CT colonography used for assessment. The BSG recommends against bidirectional endoscopy in premenopausal women, unless they are older than 50 years, have a family history of colorectal cancer, or show symptoms of gastrointestinal disease.

“In contrast, the AGA recommends bidirectional endoscopy as the mainstay for gastrointestinal evaluation, particularly in men and in postmenopausal women where no other unequivocal source of iron deficiency has been identified,” the panelists wrote.

When bidirectional endoscopy does not reveal an etiology, the panelists recommended noninvasive testing for Helicobacter pylori.

“An association between H. pylori infection and iron deficiency has been demonstrated in observational studies,” noted Dr. Ko and colleagues.

They also cited three randomized controlled trials in which treating patients with iron-deficiency anemia for H. pylori infection in combination with iron replacement therapy led to a 23.2-ng/mL mean improvement in serum ferritin, compared with patients who received iron-replacement therapy alone.

According to the guideline, if asymptomatic patients with negative bidirectional endoscopy are also negative for H. pylori, then they should receive trial iron supplementation, instead of undergoing video capsule endoscopy.

“[T]he evidence required to evaluate the benefits of video capsule endoscopy in iron-deficiency anemia is not currently available,” the panelists noted.

Dr. Ko and colleagues also recommended against routine gastric biopsies to diagnose autoimmune atrophic gastritis, as earlier diagnosis does not appear to affect outcomes or management of iron-deficiency anemia.

Finally, the panelists recommended that asymptomatic patients with iron-deficiency anemia and suspected celiac disease undergo serologic testing first, with small bowel biopsy only performed if testing is positive.

The only two strong recommendations in the guideline are for the ferritin cutoff value and the use of bidirectional endoscopy in men and postmenopausal women. The other five recommendations are conditional, three of which are based on very low quality evidence. As such, the guideline includes a discussion of research needs.

Dr. Ko and colleagues called for more studies investigating the prevalence of gastrointestinal lesions and risks of bidirectional endoscopy in premenopausal women, role of fecal occult blood testing, timing of serologic testing for H. pylori and celiac disease in relation to endoscopy, patient subgroups, comparative efficacy of small bowel visualization techniques, and other topics.

The investigators disclosed no conflicts of interest. The guideline was funded by the AGA Institute.

SOURCE: Ko CW et al. Gastroenterology 2020 Aug 15. doi: 10.1053/j.gastro.2020.06.046.

The American Gastroenterological Association (AGA) has released a clinical practice guideline for gastrointestinal evaluation of iron-deficiency anemia.

The seven recommendations aim to improve quality of care and reduce practice variability, according to lead author Cynthia W. Ko, MD, of the University of Washington , Seattle, and four copanelists.

First, the panel recommended that iron deficiency be defined by a serum ferritin level less than 45 ng/mL, instead of 15 ng/mL. Data from 55 studies showed that the higher cutoff value had a sensitivity of 85% and a specificity of 92%, compared with respective values of 59% and 99% for the lower threshold.

“Optimizing the threshold ferritin level with high sensitivity will detect the great majority of patients who are truly iron deficient, minimize delays in diagnostic workup, and minimize the number of patients in whom serious underlying etiologies such as gastrointestinal malignancy might be missed,” the panelists wrote. The guideline was published in Gastroenterology.

For asymptomatic postmenopausal women and men with iron-deficiency anemia, the panel recommended bidirectional endoscopy instead of no endoscopy. A similar recommendation was given for premenopausal women, calling for bidirectional endoscopy instead of iron-replacement therapy alone.

Dr. Ko and colleagues noted that these recommendations differ from those issued by the British Society of Gastroenterology (BSG).

For postmenopausal women and men, the BSG suggests that symptoms and local availability of endoscopy should inform diagnostic workup, with either colonoscopy or CT colonography used for assessment. The BSG recommends against bidirectional endoscopy in premenopausal women, unless they are older than 50 years, have a family history of colorectal cancer, or show symptoms of gastrointestinal disease.

“In contrast, the AGA recommends bidirectional endoscopy as the mainstay for gastrointestinal evaluation, particularly in men and in postmenopausal women where no other unequivocal source of iron deficiency has been identified,” the panelists wrote.

When bidirectional endoscopy does not reveal an etiology, the panelists recommended noninvasive testing for Helicobacter pylori.

“An association between H. pylori infection and iron deficiency has been demonstrated in observational studies,” noted Dr. Ko and colleagues.

They also cited three randomized controlled trials in which treating patients with iron-deficiency anemia for H. pylori infection in combination with iron replacement therapy led to a 23.2-ng/mL mean improvement in serum ferritin, compared with patients who received iron-replacement therapy alone.

According to the guideline, if asymptomatic patients with negative bidirectional endoscopy are also negative for H. pylori, then they should receive trial iron supplementation, instead of undergoing video capsule endoscopy.

“[T]he evidence required to evaluate the benefits of video capsule endoscopy in iron-deficiency anemia is not currently available,” the panelists noted.

Dr. Ko and colleagues also recommended against routine gastric biopsies to diagnose autoimmune atrophic gastritis, as earlier diagnosis does not appear to affect outcomes or management of iron-deficiency anemia.

Finally, the panelists recommended that asymptomatic patients with iron-deficiency anemia and suspected celiac disease undergo serologic testing first, with small bowel biopsy only performed if testing is positive.

The only two strong recommendations in the guideline are for the ferritin cutoff value and the use of bidirectional endoscopy in men and postmenopausal women. The other five recommendations are conditional, three of which are based on very low quality evidence. As such, the guideline includes a discussion of research needs.

Dr. Ko and colleagues called for more studies investigating the prevalence of gastrointestinal lesions and risks of bidirectional endoscopy in premenopausal women, role of fecal occult blood testing, timing of serologic testing for H. pylori and celiac disease in relation to endoscopy, patient subgroups, comparative efficacy of small bowel visualization techniques, and other topics.

The investigators disclosed no conflicts of interest. The guideline was funded by the AGA Institute.

SOURCE: Ko CW et al. Gastroenterology 2020 Aug 15. doi: 10.1053/j.gastro.2020.06.046.

In an international survey, most oncologists said they would recommend cytotoxic chemotherapy, immune checkpoint inhibitors, and steroids less often during the COVID-19 pandemic.

While neoadjuvant treatment recommendations were not strongly affected by the pandemic, about half of oncologists reported increased hesitancy over recommending frontline chemotherapy for metastatic disease, and a vast majority said they would recommend second- or third-line chemotherapy less often in the metastatic setting.

Most oncologists said they did not perform routine COVID-19 testing via reverse transcriptase–polymerase chain reaction (RT-PCR) before treating cancer patients. In fact, only 3% said they performed COVID-19 RT-PCR testing routinely.

Yüksel Ürün, MD, of Ankara (Turkey) University, and colleagues reported these findings in JCO Global Oncology.

The goal of the survey was to “understand readiness measures taken by oncologists to protect patients and health care workers from the novel coronavirus (COVID-19) and how their clinical decision-making was influenced by the pandemic,” the authors wrote.

The online survey was conducted among 343 oncologists from 28 countries. Responses were collected anonymously, a majority (71%) from university or academic centers, with 95% received between April 1 and April 29, 2020.

Use of telemedicine was common (80%) among respondents, as was use of surgical masks (90%) and personal protective equipment in general.

Only 33% of respondents described using N95 masks. However, the proportion of oncologists who had access to N95 masks while caring for patients known to have COVID-19, especially while doing invasive procedures such as intubation, bronchoscopy, and any airway-related manipulations, was not captured by the survey.
 

COVID testing and cancer treatment

Most respondents (58%) said they did not perform routine COVID-19 RT-PCR testing prior to administering systemic cancer treatment, with 39% stating they performed RT-PCR tests in selected patients, and 3% saying they performed such testing in all patients.

The survey indicated that hormonal treatments, tyrosine kinase inhibitors, and bone-modifying agents were considered relatively safe, but cytotoxic chemotherapy and immune therapies were not.

Nearly all oncologists said the pandemic would cause them to make no change to their recommendations regarding hormone therapy, and nearly 80% said they would make no changes regarding tyrosine kinase inhibitors or bone-modifying agents.

However, more than 90% of respondents said they would recommend cytotoxic chemotherapy less often, about 70% said they would recommend corticosteroids less often, and around 50% said they would recommend anti–programmed death-1/PD-ligand 1 or anti–cytotoxic T-lymphocyte–associated protein 4 antibodies less often.

The pandemic made most respondents more reluctant to recommend second- or third-line chemotherapy in the metastatic setting. About 80% and 70% of respondents, respectively, would recommend second- or third-line chemotherapy less often.

However, first-line chemotherapy for metastatic disease, as well as adjuvant and neoadjuvant therapy, were less affected. About 30% of respondents said they would recommend neoadjuvant therapy less often, and 50%-55% would recommend adjuvant therapy or frontline chemotherapy for metastatic disease less often.

Most respondents (78%) said they would use granulocyte colony–stimulating factor (G-CSF) more frequently during the pandemic.

The factors most likely to affect oncologists’ treatment decisions were patient age (81%) and concomitant disease (92%). Additionally, 80% of respondents’ treatment decisions were influenced by Eastern Cooperative Oncology Group performance status of 2 or higher, or the presence of chronic obstructive pulmonary disease.

Interpretation and implications

“These results highlight that, even in the early phases of COVID-19 – during which there was considerable uncertainty – basic core principles were guideposts for oncologists,” observed Aly-Khan Lalani, MD, of Juravinski Cancer Centre and McMaster University, Hamilton, Ont., who was not involved in this study.

“For example, [oncologists were] prioritizing strategies for treatments with the largest expected impact and carefully tailoring treatment according to patient comorbidities and performance status,” Dr. Lalani said.

Another oncologist who was not involved in the study expressed concern over reductions in adjuvant therapy supported by half of oncologists surveyed.

“Although benefits may be marginal in some cases, these are curative settings and especially warrant careful individual-level risk/benefit discussions,” said Kartik Sehgal, MD, of Dana-Farber Cancer Institute/Brigham and Women’s Hospital in Boston.

His concern extended as well to the small proportion (3%) of oncologists testing for COVID-19 in all patients. “Systematic testing is the need of the hour,” Dr. Sehgal said.

In their discussion of the findings, Dr. Ürün and colleagues noted a lack of consensus on monoclonal antibody and immunotherapy safety among surveyed oncologists. The steroids needed to manage severe immune-mediated toxicity with immune checkpoint inhibitors has led to some prescribing reluctance during the pandemic.

Immunosuppressive properties of immune checkpoint inhibitors also raise concern that they can increase COVID-19 severity. Studies are few, and findings to date are inconsistent with respect to the effect of immune checkpoint inhibitors on COVID-19 clinical course. However, a recently presented study suggested that immune checkpoint inhibitors do not increase the risk of death among cancer patients with COVID-19 (AACR: COVID-19 and Cancer, Abstract S02-01).

Dr. Ürün and colleagues noted that greater COVID-19 severity has been shown in patients with performance status greater than 1, hematologic malignancies, lung cancer, stage IV metastatic disease, chemotherapy within the prior 3 months, cancer treatment in the last 14 days, and the presence of chronic obstructive pulmonary disease. Nonmetastatic cancer has not been shown to affect COVID-19 severity, however.

Dr. Ürün and colleagues also underscored the need for research evidence to balance potential reductions in neutropenic complications with G-CSF (and therefore, reduced hospitalizations) with a theoretical risk of G-CSF–mediated pulmonary injury through its stimulation of an excessive immune response.

Finally, the authors urged oncologists to evaluate each proposed therapy’s risk/benefit ratio on an individual patient basis, and the team tasked the oncology community with gathering comprehensive, rigorous data.

There was no funding source declared for this study. Dr. Ürün and colleagues disclosed various relationships with many pharmaceutical companies, which included receiving research funding. Dr. Sehgal and Dr. Lalani reported no relevant conflicts.
 

SOURCE: Ürün Y et al. JCO Glob Oncol. 2020 Aug;6:1248-57.

In an international survey, most oncologists said they would recommend cytotoxic chemotherapy, immune checkpoint inhibitors, and steroids less often during the COVID-19 pandemic.

While neoadjuvant treatment recommendations were not strongly affected by the pandemic, about half of oncologists reported increased hesitancy over recommending frontline chemotherapy for metastatic disease, and a vast majority said they would recommend second- or third-line chemotherapy less often in the metastatic setting.

Most oncologists said they did not perform routine COVID-19 testing via reverse transcriptase–polymerase chain reaction (RT-PCR) before treating cancer patients. In fact, only 3% said they performed COVID-19 RT-PCR testing routinely.

Yüksel Ürün, MD, of Ankara (Turkey) University, and colleagues reported these findings in JCO Global Oncology.

The goal of the survey was to “understand readiness measures taken by oncologists to protect patients and health care workers from the novel coronavirus (COVID-19) and how their clinical decision-making was influenced by the pandemic,” the authors wrote.

The online survey was conducted among 343 oncologists from 28 countries. Responses were collected anonymously, a majority (71%) from university or academic centers, with 95% received between April 1 and April 29, 2020.

Use of telemedicine was common (80%) among respondents, as was use of surgical masks (90%) and personal protective equipment in general.

Only 33% of respondents described using N95 masks. However, the proportion of oncologists who had access to N95 masks while caring for patients known to have COVID-19, especially while doing invasive procedures such as intubation, bronchoscopy, and any airway-related manipulations, was not captured by the survey.
 

COVID testing and cancer treatment

Most respondents (58%) said they did not perform routine COVID-19 RT-PCR testing prior to administering systemic cancer treatment, with 39% stating they performed RT-PCR tests in selected patients, and 3% saying they performed such testing in all patients.

The survey indicated that hormonal treatments, tyrosine kinase inhibitors, and bone-modifying agents were considered relatively safe, but cytotoxic chemotherapy and immune therapies were not.

Nearly all oncologists said the pandemic would cause them to make no change to their recommendations regarding hormone therapy, and nearly 80% said they would make no changes regarding tyrosine kinase inhibitors or bone-modifying agents.

However, more than 90% of respondents said they would recommend cytotoxic chemotherapy less often, about 70% said they would recommend corticosteroids less often, and around 50% said they would recommend anti–programmed death-1/PD-ligand 1 or anti–cytotoxic T-lymphocyte–associated protein 4 antibodies less often.

The pandemic made most respondents more reluctant to recommend second- or third-line chemotherapy in the metastatic setting. About 80% and 70% of respondents, respectively, would recommend second- or third-line chemotherapy less often.

However, first-line chemotherapy for metastatic disease, as well as adjuvant and neoadjuvant therapy, were less affected. About 30% of respondents said they would recommend neoadjuvant therapy less often, and 50%-55% would recommend adjuvant therapy or frontline chemotherapy for metastatic disease less often.

Most respondents (78%) said they would use granulocyte colony–stimulating factor (G-CSF) more frequently during the pandemic.

The factors most likely to affect oncologists’ treatment decisions were patient age (81%) and concomitant disease (92%). Additionally, 80% of respondents’ treatment decisions were influenced by Eastern Cooperative Oncology Group performance status of 2 or higher, or the presence of chronic obstructive pulmonary disease.

Interpretation and implications

“These results highlight that, even in the early phases of COVID-19 – during which there was considerable uncertainty – basic core principles were guideposts for oncologists,” observed Aly-Khan Lalani, MD, of Juravinski Cancer Centre and McMaster University, Hamilton, Ont., who was not involved in this study.

“For example, [oncologists were] prioritizing strategies for treatments with the largest expected impact and carefully tailoring treatment according to patient comorbidities and performance status,” Dr. Lalani said.

Another oncologist who was not involved in the study expressed concern over reductions in adjuvant therapy supported by half of oncologists surveyed.

“Although benefits may be marginal in some cases, these are curative settings and especially warrant careful individual-level risk/benefit discussions,” said Kartik Sehgal, MD, of Dana-Farber Cancer Institute/Brigham and Women’s Hospital in Boston.

His concern extended as well to the small proportion (3%) of oncologists testing for COVID-19 in all patients. “Systematic testing is the need of the hour,” Dr. Sehgal said.

In their discussion of the findings, Dr. Ürün and colleagues noted a lack of consensus on monoclonal antibody and immunotherapy safety among surveyed oncologists. The steroids needed to manage severe immune-mediated toxicity with immune checkpoint inhibitors has led to some prescribing reluctance during the pandemic.

Immunosuppressive properties of immune checkpoint inhibitors also raise concern that they can increase COVID-19 severity. Studies are few, and findings to date are inconsistent with respect to the effect of immune checkpoint inhibitors on COVID-19 clinical course. However, a recently presented study suggested that immune checkpoint inhibitors do not increase the risk of death among cancer patients with COVID-19 (AACR: COVID-19 and Cancer, Abstract S02-01).

Dr. Ürün and colleagues noted that greater COVID-19 severity has been shown in patients with performance status greater than 1, hematologic malignancies, lung cancer, stage IV metastatic disease, chemotherapy within the prior 3 months, cancer treatment in the last 14 days, and the presence of chronic obstructive pulmonary disease. Nonmetastatic cancer has not been shown to affect COVID-19 severity, however.

Dr. Ürün and colleagues also underscored the need for research evidence to balance potential reductions in neutropenic complications with G-CSF (and therefore, reduced hospitalizations) with a theoretical risk of G-CSF–mediated pulmonary injury through its stimulation of an excessive immune response.

Finally, the authors urged oncologists to evaluate each proposed therapy’s risk/benefit ratio on an individual patient basis, and the team tasked the oncology community with gathering comprehensive, rigorous data.

There was no funding source declared for this study. Dr. Ürün and colleagues disclosed various relationships with many pharmaceutical companies, which included receiving research funding. Dr. Sehgal and Dr. Lalani reported no relevant conflicts.
 

SOURCE: Ürün Y et al. JCO Glob Oncol. 2020 Aug;6:1248-57.

In an international survey, most oncologists said they would recommend cytotoxic chemotherapy, immune checkpoint inhibitors, and steroids less often during the COVID-19 pandemic.

While neoadjuvant treatment recommendations were not strongly affected by the pandemic, about half of oncologists reported increased hesitancy over recommending frontline chemotherapy for metastatic disease, and a vast majority said they would recommend second- or third-line chemotherapy less often in the metastatic setting.

Most oncologists said they did not perform routine COVID-19 testing via reverse transcriptase–polymerase chain reaction (RT-PCR) before treating cancer patients. In fact, only 3% said they performed COVID-19 RT-PCR testing routinely.

Yüksel Ürün, MD, of Ankara (Turkey) University, and colleagues reported these findings in JCO Global Oncology.

The goal of the survey was to “understand readiness measures taken by oncologists to protect patients and health care workers from the novel coronavirus (COVID-19) and how their clinical decision-making was influenced by the pandemic,” the authors wrote.

The online survey was conducted among 343 oncologists from 28 countries. Responses were collected anonymously, a majority (71%) from university or academic centers, with 95% received between April 1 and April 29, 2020.

Use of telemedicine was common (80%) among respondents, as was use of surgical masks (90%) and personal protective equipment in general.

Only 33% of respondents described using N95 masks. However, the proportion of oncologists who had access to N95 masks while caring for patients known to have COVID-19, especially while doing invasive procedures such as intubation, bronchoscopy, and any airway-related manipulations, was not captured by the survey.
 

COVID testing and cancer treatment

Most respondents (58%) said they did not perform routine COVID-19 RT-PCR testing prior to administering systemic cancer treatment, with 39% stating they performed RT-PCR tests in selected patients, and 3% saying they performed such testing in all patients.

The survey indicated that hormonal treatments, tyrosine kinase inhibitors, and bone-modifying agents were considered relatively safe, but cytotoxic chemotherapy and immune therapies were not.

Nearly all oncologists said the pandemic would cause them to make no change to their recommendations regarding hormone therapy, and nearly 80% said they would make no changes regarding tyrosine kinase inhibitors or bone-modifying agents.

However, more than 90% of respondents said they would recommend cytotoxic chemotherapy less often, about 70% said they would recommend corticosteroids less often, and around 50% said they would recommend anti–programmed death-1/PD-ligand 1 or anti–cytotoxic T-lymphocyte–associated protein 4 antibodies less often.

The pandemic made most respondents more reluctant to recommend second- or third-line chemotherapy in the metastatic setting. About 80% and 70% of respondents, respectively, would recommend second- or third-line chemotherapy less often.

However, first-line chemotherapy for metastatic disease, as well as adjuvant and neoadjuvant therapy, were less affected. About 30% of respondents said they would recommend neoadjuvant therapy less often, and 50%-55% would recommend adjuvant therapy or frontline chemotherapy for metastatic disease less often.

Most respondents (78%) said they would use granulocyte colony–stimulating factor (G-CSF) more frequently during the pandemic.

The factors most likely to affect oncologists’ treatment decisions were patient age (81%) and concomitant disease (92%). Additionally, 80% of respondents’ treatment decisions were influenced by Eastern Cooperative Oncology Group performance status of 2 or higher, or the presence of chronic obstructive pulmonary disease.

Interpretation and implications

“These results highlight that, even in the early phases of COVID-19 – during which there was considerable uncertainty – basic core principles were guideposts for oncologists,” observed Aly-Khan Lalani, MD, of Juravinski Cancer Centre and McMaster University, Hamilton, Ont., who was not involved in this study.

“For example, [oncologists were] prioritizing strategies for treatments with the largest expected impact and carefully tailoring treatment according to patient comorbidities and performance status,” Dr. Lalani said.

Another oncologist who was not involved in the study expressed concern over reductions in adjuvant therapy supported by half of oncologists surveyed.

“Although benefits may be marginal in some cases, these are curative settings and especially warrant careful individual-level risk/benefit discussions,” said Kartik Sehgal, MD, of Dana-Farber Cancer Institute/Brigham and Women’s Hospital in Boston.

His concern extended as well to the small proportion (3%) of oncologists testing for COVID-19 in all patients. “Systematic testing is the need of the hour,” Dr. Sehgal said.

In their discussion of the findings, Dr. Ürün and colleagues noted a lack of consensus on monoclonal antibody and immunotherapy safety among surveyed oncologists. The steroids needed to manage severe immune-mediated toxicity with immune checkpoint inhibitors has led to some prescribing reluctance during the pandemic.

Immunosuppressive properties of immune checkpoint inhibitors also raise concern that they can increase COVID-19 severity. Studies are few, and findings to date are inconsistent with respect to the effect of immune checkpoint inhibitors on COVID-19 clinical course. However, a recently presented study suggested that immune checkpoint inhibitors do not increase the risk of death among cancer patients with COVID-19 (AACR: COVID-19 and Cancer, Abstract S02-01).

Dr. Ürün and colleagues noted that greater COVID-19 severity has been shown in patients with performance status greater than 1, hematologic malignancies, lung cancer, stage IV metastatic disease, chemotherapy within the prior 3 months, cancer treatment in the last 14 days, and the presence of chronic obstructive pulmonary disease. Nonmetastatic cancer has not been shown to affect COVID-19 severity, however.

Dr. Ürün and colleagues also underscored the need for research evidence to balance potential reductions in neutropenic complications with G-CSF (and therefore, reduced hospitalizations) with a theoretical risk of G-CSF–mediated pulmonary injury through its stimulation of an excessive immune response.

Finally, the authors urged oncologists to evaluate each proposed therapy’s risk/benefit ratio on an individual patient basis, and the team tasked the oncology community with gathering comprehensive, rigorous data.

There was no funding source declared for this study. Dr. Ürün and colleagues disclosed various relationships with many pharmaceutical companies, which included receiving research funding. Dr. Sehgal and Dr. Lalani reported no relevant conflicts.
 

SOURCE: Ürün Y et al. JCO Glob Oncol. 2020 Aug;6:1248-57.