The risk for increased COVID-19 severity in people with type 1 diabetes appears similar to that of type 2 diabetes, contrary to some official advice from the Centers for Disease Control and Prevention. The new finding indicates that people with both types should be priority for receiving a vaccine, investigators say.

The study is the first to prospectively evaluate both inpatients and outpatients and to examine COVID-19 severity factors in addition to death in people with type 1 and type 2 diabetes separately, and was published online Dec. 2 in Diabetes Care. 

Among the patients, who were seen at Vanderbilt University Medical Center in Nashville, Tenn., between March and August of 2020, those with both type 1 and type 2 diabetes had between a three- and fourfold greater risk for COVID-19 hospitalization and greater illness severity compared with people without diabetes after adjustments for age, race, and a number of other risk factors.

This finding is important since as of Dec. 1, 2020, the CDC has classified the diabetes types differently in terms of underlying medical conditions that increase the risk for severe COVID-19.

Adults of any age with type 2 diabetes are considered “at increased risk of severe illness” from the virus that causes COVID-19 whereas the CDC says those with type 1 “might be at an increased risk.”

Lead author of the new paper Justin M. Gregory, MD, said in an interview: “I think this needs revision based on the current evidence. I think the data presented in our study and that of Barron et al. in Lancet Endocrinology 2020 indicate the need to place type 1 diabetes at parity with type 2 diabetes.

“These studies indicate both conditions carry an adjusted odds ratio of three to four when compared with people without diabetes for hospitalization, illness severity, and mortality,” he stressed.
 

Vaccines look promising for patients with diabetes

There were no phase 3 vaccine data available for the vaccine at the time that Dr. Gregory, of the Ian M. Burr Division of Pediatric Endocrinology and Diabetes, Vanderbilt University, Nashville, Tenn., and colleagues were writing their manuscript in late summer, so the article does not mention this.

But now, Dr. Gregory said, “Based on the initial press releases from Pfizer and Moderna, I am now optimistic that these vaccines might mitigate the excess morbidity and mortality from COVID-19 experienced by patients with diabetes.

“I am eager to see what we learn on December 10 and 17 [the scheduled dates for the meetings of the Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee to review the Pfizer and Moderna vaccines, respectively].”

But with the winter pandemic surge in the meantime, “Our investigation suggests that as COVID-19 hospitalizations rise, patients with both type 1 and 2 diabetes will comprise a disproportionately higher number of those admissions and, once hospitalized, demonstrate a greater degree of illness severity,” he and his colleagues said.

“In light of these data, we call on our colleagues to emphasize the importance of social distancing measures and hand hygiene, with particular emphasis on patients with diabetes, including those in the most vulnerable communities whom our study affirms will face the most severe impact.”
 

After adjustments, excess severity risk similar for both diabetes types

The new study data came from electronic health records at Vanderbilt University Medical Center, comprising 137 primary care, urgent care, and hospital facilities where patients were tested for SARS-CoV-2 regardless of the reason for their visit.

Between March 17 and August 7, 2020, 6,451 patients tested positive for COVID-19. Of those, 273 had type 2 diabetes and 40 had type 1 diabetes.

Children younger than 18 years accounted for 20% of those with type 1 diabetes and 9.4% of those without diabetes, but none of the type 2 group. The group with type 2 diabetes was considerably older than the type 1 diabetes and no-diabetes groups, 58 years versus 37 and 33 years, respectively. 

Before adjustment for baseline characteristics that differed between groups, patients with type 1 diabetes appeared to have a risk for hospitalization and greater illness severity that was intermediate between the group with no diabetes and the group with type 2 diabetes, the researchers said.

But after adjustment for age, race, sex, hypertension, smoking, and body mass index, people with type 1 diabetes had odds ratios of 3.90 for hospitalization and 3.35 for greater illness severity, which was similar to risk in type 2 diabetes (3.36 and 3.42, respectively), compared to those without diabetes.
 

Deep dive explores COVID-19 severity risk factors in type 1 diabetes

The investigators then conducted a detailed chart review for 37 of the 40 patients with type 1 diabetes and phone surveys with 15 of them.

The majority (28) had not been hospitalized, and only one was hospitalized for diabetic ketoacidosis (DKA) within 14 days of positive SARS-CoV-2 testing.

This contrasts with a report from the T1D Exchange, in which nearly half of 33 patients with type 1 diabetes and COVID-19 had been hospitalized with DKA. The reason for the discrepancy may be that more severe patients would more likely be referred to the T1D Exchange Registry, Dr. Gregory and colleagues hypothesized.

Clinical factors associated with COVID-19 severity (P < .05) in their study included a prior hypertension diagnosis, higher hemoglobin A1c, at least one prior DKA admission in the past year, and not using a continuous glucose monitor (CGM). 

Hospitalizations were twice as likely and illness severity nearly twice as great among those with type 1 diabetes who were Black versus White. Just 8% of those with private insurance were hospitalized, compared with 60% of those with public insurance and 67% with no insurance (P = .001).

“Whereas previous reports have indicated proportionally higher rates of hospitalizations from COVID-19 among Black patients and those with public insurance, this study is the first to show a similar finding in the population with type 1 diabetes,” Dr. Gregory and colleagues wrote.

Only 9% of patients using a CGM were hospitalized versus 47% who used blood glucose meters (P < .016). Similarly, hospitalizations occurred in 6% using an insulin pump versus 33% using multiple daily injections (P < .085).

“Our analysis cannot exclude the possibility that greater amounts of diabetes technology use are a surrogate for higher socioeconomic status,” they noted.

This research was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, JDRF, and the Appleby Foundation. The authors have reported no relevant financial relationships.

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

The risk for increased COVID-19 severity in people with type 1 diabetes appears similar to that of type 2 diabetes, contrary to some official advice from the Centers for Disease Control and Prevention. The new finding indicates that people with both types should be priority for receiving a vaccine, investigators say.

The study is the first to prospectively evaluate both inpatients and outpatients and to examine COVID-19 severity factors in addition to death in people with type 1 and type 2 diabetes separately, and was published online Dec. 2 in Diabetes Care. 

Among the patients, who were seen at Vanderbilt University Medical Center in Nashville, Tenn., between March and August of 2020, those with both type 1 and type 2 diabetes had between a three- and fourfold greater risk for COVID-19 hospitalization and greater illness severity compared with people without diabetes after adjustments for age, race, and a number of other risk factors.

This finding is important since as of Dec. 1, 2020, the CDC has classified the diabetes types differently in terms of underlying medical conditions that increase the risk for severe COVID-19.

Adults of any age with type 2 diabetes are considered “at increased risk of severe illness” from the virus that causes COVID-19 whereas the CDC says those with type 1 “might be at an increased risk.”

Lead author of the new paper Justin M. Gregory, MD, said in an interview: “I think this needs revision based on the current evidence. I think the data presented in our study and that of Barron et al. in Lancet Endocrinology 2020 indicate the need to place type 1 diabetes at parity with type 2 diabetes.

“These studies indicate both conditions carry an adjusted odds ratio of three to four when compared with people without diabetes for hospitalization, illness severity, and mortality,” he stressed.
 

Vaccines look promising for patients with diabetes

There were no phase 3 vaccine data available for the vaccine at the time that Dr. Gregory, of the Ian M. Burr Division of Pediatric Endocrinology and Diabetes, Vanderbilt University, Nashville, Tenn., and colleagues were writing their manuscript in late summer, so the article does not mention this.

But now, Dr. Gregory said, “Based on the initial press releases from Pfizer and Moderna, I am now optimistic that these vaccines might mitigate the excess morbidity and mortality from COVID-19 experienced by patients with diabetes.

“I am eager to see what we learn on December 10 and 17 [the scheduled dates for the meetings of the Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee to review the Pfizer and Moderna vaccines, respectively].”

But with the winter pandemic surge in the meantime, “Our investigation suggests that as COVID-19 hospitalizations rise, patients with both type 1 and 2 diabetes will comprise a disproportionately higher number of those admissions and, once hospitalized, demonstrate a greater degree of illness severity,” he and his colleagues said.

“In light of these data, we call on our colleagues to emphasize the importance of social distancing measures and hand hygiene, with particular emphasis on patients with diabetes, including those in the most vulnerable communities whom our study affirms will face the most severe impact.”
 

After adjustments, excess severity risk similar for both diabetes types

The new study data came from electronic health records at Vanderbilt University Medical Center, comprising 137 primary care, urgent care, and hospital facilities where patients were tested for SARS-CoV-2 regardless of the reason for their visit.

Between March 17 and August 7, 2020, 6,451 patients tested positive for COVID-19. Of those, 273 had type 2 diabetes and 40 had type 1 diabetes.

Children younger than 18 years accounted for 20% of those with type 1 diabetes and 9.4% of those without diabetes, but none of the type 2 group. The group with type 2 diabetes was considerably older than the type 1 diabetes and no-diabetes groups, 58 years versus 37 and 33 years, respectively. 

Before adjustment for baseline characteristics that differed between groups, patients with type 1 diabetes appeared to have a risk for hospitalization and greater illness severity that was intermediate between the group with no diabetes and the group with type 2 diabetes, the researchers said.

But after adjustment for age, race, sex, hypertension, smoking, and body mass index, people with type 1 diabetes had odds ratios of 3.90 for hospitalization and 3.35 for greater illness severity, which was similar to risk in type 2 diabetes (3.36 and 3.42, respectively), compared to those without diabetes.
 

Deep dive explores COVID-19 severity risk factors in type 1 diabetes

The investigators then conducted a detailed chart review for 37 of the 40 patients with type 1 diabetes and phone surveys with 15 of them.

The majority (28) had not been hospitalized, and only one was hospitalized for diabetic ketoacidosis (DKA) within 14 days of positive SARS-CoV-2 testing.

This contrasts with a report from the T1D Exchange, in which nearly half of 33 patients with type 1 diabetes and COVID-19 had been hospitalized with DKA. The reason for the discrepancy may be that more severe patients would more likely be referred to the T1D Exchange Registry, Dr. Gregory and colleagues hypothesized.

Clinical factors associated with COVID-19 severity (P < .05) in their study included a prior hypertension diagnosis, higher hemoglobin A1c, at least one prior DKA admission in the past year, and not using a continuous glucose monitor (CGM). 

Hospitalizations were twice as likely and illness severity nearly twice as great among those with type 1 diabetes who were Black versus White. Just 8% of those with private insurance were hospitalized, compared with 60% of those with public insurance and 67% with no insurance (P = .001).

“Whereas previous reports have indicated proportionally higher rates of hospitalizations from COVID-19 among Black patients and those with public insurance, this study is the first to show a similar finding in the population with type 1 diabetes,” Dr. Gregory and colleagues wrote.

Only 9% of patients using a CGM were hospitalized versus 47% who used blood glucose meters (P < .016). Similarly, hospitalizations occurred in 6% using an insulin pump versus 33% using multiple daily injections (P < .085).

“Our analysis cannot exclude the possibility that greater amounts of diabetes technology use are a surrogate for higher socioeconomic status,” they noted.

This research was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, JDRF, and the Appleby Foundation. The authors have reported no relevant financial relationships.

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

The risk for increased COVID-19 severity in people with type 1 diabetes appears similar to that of type 2 diabetes, contrary to some official advice from the Centers for Disease Control and Prevention. The new finding indicates that people with both types should be priority for receiving a vaccine, investigators say.

The study is the first to prospectively evaluate both inpatients and outpatients and to examine COVID-19 severity factors in addition to death in people with type 1 and type 2 diabetes separately, and was published online Dec. 2 in Diabetes Care. 

Among the patients, who were seen at Vanderbilt University Medical Center in Nashville, Tenn., between March and August of 2020, those with both type 1 and type 2 diabetes had between a three- and fourfold greater risk for COVID-19 hospitalization and greater illness severity compared with people without diabetes after adjustments for age, race, and a number of other risk factors.

This finding is important since as of Dec. 1, 2020, the CDC has classified the diabetes types differently in terms of underlying medical conditions that increase the risk for severe COVID-19.

Adults of any age with type 2 diabetes are considered “at increased risk of severe illness” from the virus that causes COVID-19 whereas the CDC says those with type 1 “might be at an increased risk.”

Lead author of the new paper Justin M. Gregory, MD, said in an interview: “I think this needs revision based on the current evidence. I think the data presented in our study and that of Barron et al. in Lancet Endocrinology 2020 indicate the need to place type 1 diabetes at parity with type 2 diabetes.

“These studies indicate both conditions carry an adjusted odds ratio of three to four when compared with people without diabetes for hospitalization, illness severity, and mortality,” he stressed.
 

Vaccines look promising for patients with diabetes

There were no phase 3 vaccine data available for the vaccine at the time that Dr. Gregory, of the Ian M. Burr Division of Pediatric Endocrinology and Diabetes, Vanderbilt University, Nashville, Tenn., and colleagues were writing their manuscript in late summer, so the article does not mention this.

But now, Dr. Gregory said, “Based on the initial press releases from Pfizer and Moderna, I am now optimistic that these vaccines might mitigate the excess morbidity and mortality from COVID-19 experienced by patients with diabetes.

“I am eager to see what we learn on December 10 and 17 [the scheduled dates for the meetings of the Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee to review the Pfizer and Moderna vaccines, respectively].”

But with the winter pandemic surge in the meantime, “Our investigation suggests that as COVID-19 hospitalizations rise, patients with both type 1 and 2 diabetes will comprise a disproportionately higher number of those admissions and, once hospitalized, demonstrate a greater degree of illness severity,” he and his colleagues said.

“In light of these data, we call on our colleagues to emphasize the importance of social distancing measures and hand hygiene, with particular emphasis on patients with diabetes, including those in the most vulnerable communities whom our study affirms will face the most severe impact.”
 

After adjustments, excess severity risk similar for both diabetes types

The new study data came from electronic health records at Vanderbilt University Medical Center, comprising 137 primary care, urgent care, and hospital facilities where patients were tested for SARS-CoV-2 regardless of the reason for their visit.

Between March 17 and August 7, 2020, 6,451 patients tested positive for COVID-19. Of those, 273 had type 2 diabetes and 40 had type 1 diabetes.

Children younger than 18 years accounted for 20% of those with type 1 diabetes and 9.4% of those without diabetes, but none of the type 2 group. The group with type 2 diabetes was considerably older than the type 1 diabetes and no-diabetes groups, 58 years versus 37 and 33 years, respectively. 

Before adjustment for baseline characteristics that differed between groups, patients with type 1 diabetes appeared to have a risk for hospitalization and greater illness severity that was intermediate between the group with no diabetes and the group with type 2 diabetes, the researchers said.

But after adjustment for age, race, sex, hypertension, smoking, and body mass index, people with type 1 diabetes had odds ratios of 3.90 for hospitalization and 3.35 for greater illness severity, which was similar to risk in type 2 diabetes (3.36 and 3.42, respectively), compared to those without diabetes.
 

Deep dive explores COVID-19 severity risk factors in type 1 diabetes

The investigators then conducted a detailed chart review for 37 of the 40 patients with type 1 diabetes and phone surveys with 15 of them.

The majority (28) had not been hospitalized, and only one was hospitalized for diabetic ketoacidosis (DKA) within 14 days of positive SARS-CoV-2 testing.

This contrasts with a report from the T1D Exchange, in which nearly half of 33 patients with type 1 diabetes and COVID-19 had been hospitalized with DKA. The reason for the discrepancy may be that more severe patients would more likely be referred to the T1D Exchange Registry, Dr. Gregory and colleagues hypothesized.

Clinical factors associated with COVID-19 severity (P < .05) in their study included a prior hypertension diagnosis, higher hemoglobin A1c, at least one prior DKA admission in the past year, and not using a continuous glucose monitor (CGM). 

Hospitalizations were twice as likely and illness severity nearly twice as great among those with type 1 diabetes who were Black versus White. Just 8% of those with private insurance were hospitalized, compared with 60% of those with public insurance and 67% with no insurance (P = .001).

“Whereas previous reports have indicated proportionally higher rates of hospitalizations from COVID-19 among Black patients and those with public insurance, this study is the first to show a similar finding in the population with type 1 diabetes,” Dr. Gregory and colleagues wrote.

Only 9% of patients using a CGM were hospitalized versus 47% who used blood glucose meters (P < .016). Similarly, hospitalizations occurred in 6% using an insulin pump versus 33% using multiple daily injections (P < .085).

“Our analysis cannot exclude the possibility that greater amounts of diabetes technology use are a surrogate for higher socioeconomic status,” they noted.

This research was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, JDRF, and the Appleby Foundation. The authors have reported no relevant financial relationships.

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

Background: Venous thromboembolism and pulmonary embolism are common after major trauma. Anticoagulant prophylaxis usually is not considered because of the increased risk of bleeding. Despite the limited data, many trauma centers use inferior vena cava (IVC) filters as a primary means to prevent pulmonary embolism.

Study design: Randomized, controlled, and multicenter trial.

Setting: Four tertiary hospitals in Australia.

Synopsis: 240 major trauma patients were randomly assigned to receive either IVC filter or no IVC filter within 72 hours after admission. The primary endpoint was a composite of 90-day mortality or symptomatic pulmonary embolism confirmed on imaging. There was no difference in the rate of composite outcome in those with IVC filter, compared with those with no IVC filter.

Bottom line: After major trauma, early prophylactic placement of IVC filter did not reduce the 90-day mortality or incidence of symptomatic pulmonary embolism.

Citation: Ho KM et al. A multicenter trial of vena cava filters in severely injured patients. N Engl J Med. 2019 Jul 25;381:328-37.

Dr. Hoque Sharmy is a hospitalist and assistant professor of medicine in the division of hospital medicine at St. Louis University School of Medicine.

Background: Venous thromboembolism and pulmonary embolism are common after major trauma. Anticoagulant prophylaxis usually is not considered because of the increased risk of bleeding. Despite the limited data, many trauma centers use inferior vena cava (IVC) filters as a primary means to prevent pulmonary embolism.

Study design: Randomized, controlled, and multicenter trial.

Setting: Four tertiary hospitals in Australia.

Synopsis: 240 major trauma patients were randomly assigned to receive either IVC filter or no IVC filter within 72 hours after admission. The primary endpoint was a composite of 90-day mortality or symptomatic pulmonary embolism confirmed on imaging. There was no difference in the rate of composite outcome in those with IVC filter, compared with those with no IVC filter.

Bottom line: After major trauma, early prophylactic placement of IVC filter did not reduce the 90-day mortality or incidence of symptomatic pulmonary embolism.

Citation: Ho KM et al. A multicenter trial of vena cava filters in severely injured patients. N Engl J Med. 2019 Jul 25;381:328-37.

Dr. Hoque Sharmy is a hospitalist and assistant professor of medicine in the division of hospital medicine at St. Louis University School of Medicine.

Background: Venous thromboembolism and pulmonary embolism are common after major trauma. Anticoagulant prophylaxis usually is not considered because of the increased risk of bleeding. Despite the limited data, many trauma centers use inferior vena cava (IVC) filters as a primary means to prevent pulmonary embolism.

Study design: Randomized, controlled, and multicenter trial.

Setting: Four tertiary hospitals in Australia.

Synopsis: 240 major trauma patients were randomly assigned to receive either IVC filter or no IVC filter within 72 hours after admission. The primary endpoint was a composite of 90-day mortality or symptomatic pulmonary embolism confirmed on imaging. There was no difference in the rate of composite outcome in those with IVC filter, compared with those with no IVC filter.

Bottom line: After major trauma, early prophylactic placement of IVC filter did not reduce the 90-day mortality or incidence of symptomatic pulmonary embolism.

Citation: Ho KM et al. A multicenter trial of vena cava filters in severely injured patients. N Engl J Med. 2019 Jul 25;381:328-37.

Dr. Hoque Sharmy is a hospitalist and assistant professor of medicine in the division of hospital medicine at St. Louis University School of Medicine.

Data from the Apollo study provide proof for the subcutaneous administration (SC) of daratumumab (Darzalex Faspro) in combination with pomalidomide (Pomalyst) and dexamethasone (Pd) for patients with relapsed or refractory multiple myeloma (RRMM).

The SC formulation of daratumumab (with hyaluronidase) was approved in the United States in May, and is administered by injection into the abdomen over 3-5 minutes. Previously the drug was available only as an intravenous infusion.

“The appeal of subcutaneous daratumumab is the 5 minutes it needs for administering, cutting down considerable on ‘chair/clinic’ time. Intravenous daratumumab is given over several hours,” said Joseph Mikhael, MD, MEd, chief medical officer of the International Myeloma Foundation. He also highlighted the low rates of infusion reactions seen with the subcutaneous daratumumab triplet.

“In the COVID era the subcutaneous route may be the way to go,” he said in an interview.

“This is an effective combination with a predictable safety profile that allows for the use of SC daratumumab along with oral pomalidomide and dexamethasone for patients who have received at least one prior line of therapy that included lenalidomide [Revlimid] and a proteasome inhibitor,” commented lead author Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens.

The triplet combination was associated with a 37% reduced risk for progression or death, compared with the two-drug combination of pomalidomide and dexamethasone.

He presented the results from the Apollo trial at the annual meeting of the American Society of Hematology.
 

Treatment landscape of RRMM

Dr. Mikhael, who is also professor in the applied cancer research and drug discovery division at the Translational Genomics Research Institute, Phoenix, provided his insights into Apollo as well as how this triplet fits into the treatment landscape of RRMM.

Daratumumab is approved for use in both RRMM and newly diagnosed MM, either alone or in combination with standard-of-care regimens. The drug already has eight specific indications for the intravenous formulation, and five indications for the SC formulation of daratumumab, Dr. Mikhael noted. The Apollo study “will likely provide the subcutaneous approval for the daratumumab triplet in MM.”

According to Dr. Mikhael, the triplet of daratumumab with pomalidomide and dexamethasone is the most commonly used combination at first relapse, and this phase 3 study provides confirmatory evidence for its initial approval. The initial approval for intravenous daratumumab and Pd was based on a phase 1b study, he noted.

“The Apollo study is the first randomized trial comparing the triplet of D-Pd to Pd,” Noopur Raje, MD, of the Massachusetts General Hospital, Boston, said in an interview. She explained that the majority of patients included in Apollo were refractory to lenalidomide, which is the patient population typically seen at the time of first relapse. “This regimen will be adopted at either first or second relapse in the majority of patients,” Dr. Raje said.

“In keeping with strategy in MM, we use the best triplet first and do not save the best for last,” Dr. Mikhael said. The triplet of the proteasome inhibitor bortezomib (Velcade), lenalidomide, and dexamethasone is used in first-line MM. “Most patients meet the criteria for using D-Pd at first relapse,” he added, noting that all patients in the study have received a proteasome inhibitor and lenalidomide as first-line therapy and had relapsed with or were refractory to these agents.

“The short administration time and significantly low rates of infusion-site reactions are two important considerations for using this triplet with the subcutaneous formulation of daratumumab [at first relapse],” he said.

In the treatment landscape of MM, the triplet of isatuximab (Sarclisa), pomalidomide, and dexamethasone has recently been approved for RRMM based on data from the ICARIA study. Isatuximab and daratumumab are both CD38-directed antibodies. Dr. Mikhael pointed out that the datasets from ICARIA and Apollo with respect to progression-free survival (PFS) and hazard ratios overlapped and were remarkably similar. However, daratumumab now has an advantage in being available as an SC formulation. 

The landscape of MM treatment has been changing rapidly in recent years, and more changes may be afoot. Dr. Mikhael suggested that the quartet of daratumumab, bortezomib, lenalidomide, and dexamethasone is likely to move into the first-line setting for MM based on data from the GRIFFIN study (trial update in Abstract 3243), and then the choice of drugs to use in first relapse would also change.
 

Apollo study details

Apollo was an open-label, phase 3 study that randomly assigned patients with RRMM to receive SC daratumumab in combination with pomalidomide and low-dose dexamethasone (D-Pd; n = 151) or the two-drug combination of Pd (n = 153).

Approximately 80% of the patients were refractory to lenalidomide and half were refractory to a proteasome inhibitor.

Median duration of SC daratumumab administration was 5 minutes. Median duration of study treatment was longer for patients on D-Pd (11.5 months vs. 6.6 months for Pd).

For the primary endpoint, at a median follow up of 16.9 months, median PFS was 12.4 months for patients receiving D-Pd and 6.9 months for those receiving Pd. One-year PFS was 52% for patients receiving the triplet combination and 35% for those receiving Pd. Treatment effect was generally consistent across subgroups examined, Dr. Dimopoulos reported.

Depth of response was significantly higher for patients on D-Pd. Stringent complete remission or CR was seen in 25% of patients on D-Pd versus 4% on Pd. Overall response rate was 69% for patients on D-Pd and 45% for patients on Pd alone (P < .0001). Minimal residual disease negativity was more than four times higher with D-Pd (9% vs. 2% for Pd; P = .0102).

The safety profile of D-Pd was consistent with the known safety profile of SC daratumumab and Pd. Infusion-site reactions were grade 1-2 and occurred in 5% of patients; in addition, only grade 1 injection-site reactions were seen and occurred in 2% of patients. The most serious treatment-emergent adverse events in patients on D-Pd were pneumonia (15% vs. 8% for Pd) and lower respiratory tract infection (12% vs. 9% for Pd). Incidence of secondary primary malignancy was 2% for each group.
 

Apollo results were ‘no surprise’

“These results are of no surprise and further support the current practice of using a three-drug combination in the relapsed setting,” Henry Fung, MD, chair of the department of bone marrow transplant and cellular therapies at Fox Chase Cancer Center, Philadelphia, said in an interview.

Although Dr. Fung agreed that the triplet of a proteasome inhibitor, an immunomodulating drug such as lenalidomide, and the steroid dexamethasone is becoming the standard of care for newly diagnosed MM, D-Pd should be considered an excellent option for patients who have limited choices in the relapsed/refractory setting.

However, he said that the median PFS of 12.4 months for patients receiving D-Pd after a median of two prior regimens is not satisfactory.

“The impact on the natural history of the disease will be limited and the duration of responses decline with each treatment regimen, and the true impact on the disease will be an effective frontline strategy.” Dr. Fung said. “This will not be a practice-changing trial. We need to find out which three-drug regimen works best and what biomarkers can predict the response to individual regimen.”

Dr. Dimopoulos reported receiving honoraria from Beigene, Bristol-Myers Squibb, Amgen, Takeda, Celgene, and Janssen. Dr. Mikhael reported receiving honoraria from Amgen, GlaxoSmithKline, Janssen, Karyopharm, Sanofi, Takeda; consulting with Celgene; and receiving research funding from Celgene and Sanofi. Dr. Fung is on the speakers’ bureau of Apollo and receives honoraria from Jansen Oncology and Celgene/Bristol-Myers Squibb. Dr. Raje is a consultant for Bristol-Myers Squibb and Janssen.  

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

Data from the Apollo study provide proof for the subcutaneous administration (SC) of daratumumab (Darzalex Faspro) in combination with pomalidomide (Pomalyst) and dexamethasone (Pd) for patients with relapsed or refractory multiple myeloma (RRMM).

The SC formulation of daratumumab (with hyaluronidase) was approved in the United States in May, and is administered by injection into the abdomen over 3-5 minutes. Previously the drug was available only as an intravenous infusion.

“The appeal of subcutaneous daratumumab is the 5 minutes it needs for administering, cutting down considerable on ‘chair/clinic’ time. Intravenous daratumumab is given over several hours,” said Joseph Mikhael, MD, MEd, chief medical officer of the International Myeloma Foundation. He also highlighted the low rates of infusion reactions seen with the subcutaneous daratumumab triplet.

“In the COVID era the subcutaneous route may be the way to go,” he said in an interview.

“This is an effective combination with a predictable safety profile that allows for the use of SC daratumumab along with oral pomalidomide and dexamethasone for patients who have received at least one prior line of therapy that included lenalidomide [Revlimid] and a proteasome inhibitor,” commented lead author Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens.

The triplet combination was associated with a 37% reduced risk for progression or death, compared with the two-drug combination of pomalidomide and dexamethasone.

He presented the results from the Apollo trial at the annual meeting of the American Society of Hematology.
 

Treatment landscape of RRMM

Dr. Mikhael, who is also professor in the applied cancer research and drug discovery division at the Translational Genomics Research Institute, Phoenix, provided his insights into Apollo as well as how this triplet fits into the treatment landscape of RRMM.

Daratumumab is approved for use in both RRMM and newly diagnosed MM, either alone or in combination with standard-of-care regimens. The drug already has eight specific indications for the intravenous formulation, and five indications for the SC formulation of daratumumab, Dr. Mikhael noted. The Apollo study “will likely provide the subcutaneous approval for the daratumumab triplet in MM.”

According to Dr. Mikhael, the triplet of daratumumab with pomalidomide and dexamethasone is the most commonly used combination at first relapse, and this phase 3 study provides confirmatory evidence for its initial approval. The initial approval for intravenous daratumumab and Pd was based on a phase 1b study, he noted.

“The Apollo study is the first randomized trial comparing the triplet of D-Pd to Pd,” Noopur Raje, MD, of the Massachusetts General Hospital, Boston, said in an interview. She explained that the majority of patients included in Apollo were refractory to lenalidomide, which is the patient population typically seen at the time of first relapse. “This regimen will be adopted at either first or second relapse in the majority of patients,” Dr. Raje said.

“In keeping with strategy in MM, we use the best triplet first and do not save the best for last,” Dr. Mikhael said. The triplet of the proteasome inhibitor bortezomib (Velcade), lenalidomide, and dexamethasone is used in first-line MM. “Most patients meet the criteria for using D-Pd at first relapse,” he added, noting that all patients in the study have received a proteasome inhibitor and lenalidomide as first-line therapy and had relapsed with or were refractory to these agents.

“The short administration time and significantly low rates of infusion-site reactions are two important considerations for using this triplet with the subcutaneous formulation of daratumumab [at first relapse],” he said.

In the treatment landscape of MM, the triplet of isatuximab (Sarclisa), pomalidomide, and dexamethasone has recently been approved for RRMM based on data from the ICARIA study. Isatuximab and daratumumab are both CD38-directed antibodies. Dr. Mikhael pointed out that the datasets from ICARIA and Apollo with respect to progression-free survival (PFS) and hazard ratios overlapped and were remarkably similar. However, daratumumab now has an advantage in being available as an SC formulation. 

The landscape of MM treatment has been changing rapidly in recent years, and more changes may be afoot. Dr. Mikhael suggested that the quartet of daratumumab, bortezomib, lenalidomide, and dexamethasone is likely to move into the first-line setting for MM based on data from the GRIFFIN study (trial update in Abstract 3243), and then the choice of drugs to use in first relapse would also change.
 

Apollo study details

Apollo was an open-label, phase 3 study that randomly assigned patients with RRMM to receive SC daratumumab in combination with pomalidomide and low-dose dexamethasone (D-Pd; n = 151) or the two-drug combination of Pd (n = 153).

Approximately 80% of the patients were refractory to lenalidomide and half were refractory to a proteasome inhibitor.

Median duration of SC daratumumab administration was 5 minutes. Median duration of study treatment was longer for patients on D-Pd (11.5 months vs. 6.6 months for Pd).

For the primary endpoint, at a median follow up of 16.9 months, median PFS was 12.4 months for patients receiving D-Pd and 6.9 months for those receiving Pd. One-year PFS was 52% for patients receiving the triplet combination and 35% for those receiving Pd. Treatment effect was generally consistent across subgroups examined, Dr. Dimopoulos reported.

Depth of response was significantly higher for patients on D-Pd. Stringent complete remission or CR was seen in 25% of patients on D-Pd versus 4% on Pd. Overall response rate was 69% for patients on D-Pd and 45% for patients on Pd alone (P < .0001). Minimal residual disease negativity was more than four times higher with D-Pd (9% vs. 2% for Pd; P = .0102).

The safety profile of D-Pd was consistent with the known safety profile of SC daratumumab and Pd. Infusion-site reactions were grade 1-2 and occurred in 5% of patients; in addition, only grade 1 injection-site reactions were seen and occurred in 2% of patients. The most serious treatment-emergent adverse events in patients on D-Pd were pneumonia (15% vs. 8% for Pd) and lower respiratory tract infection (12% vs. 9% for Pd). Incidence of secondary primary malignancy was 2% for each group.
 

Apollo results were ‘no surprise’

“These results are of no surprise and further support the current practice of using a three-drug combination in the relapsed setting,” Henry Fung, MD, chair of the department of bone marrow transplant and cellular therapies at Fox Chase Cancer Center, Philadelphia, said in an interview.

Although Dr. Fung agreed that the triplet of a proteasome inhibitor, an immunomodulating drug such as lenalidomide, and the steroid dexamethasone is becoming the standard of care for newly diagnosed MM, D-Pd should be considered an excellent option for patients who have limited choices in the relapsed/refractory setting.

However, he said that the median PFS of 12.4 months for patients receiving D-Pd after a median of two prior regimens is not satisfactory.

“The impact on the natural history of the disease will be limited and the duration of responses decline with each treatment regimen, and the true impact on the disease will be an effective frontline strategy.” Dr. Fung said. “This will not be a practice-changing trial. We need to find out which three-drug regimen works best and what biomarkers can predict the response to individual regimen.”

Dr. Dimopoulos reported receiving honoraria from Beigene, Bristol-Myers Squibb, Amgen, Takeda, Celgene, and Janssen. Dr. Mikhael reported receiving honoraria from Amgen, GlaxoSmithKline, Janssen, Karyopharm, Sanofi, Takeda; consulting with Celgene; and receiving research funding from Celgene and Sanofi. Dr. Fung is on the speakers’ bureau of Apollo and receives honoraria from Jansen Oncology and Celgene/Bristol-Myers Squibb. Dr. Raje is a consultant for Bristol-Myers Squibb and Janssen.  

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

Data from the Apollo study provide proof for the subcutaneous administration (SC) of daratumumab (Darzalex Faspro) in combination with pomalidomide (Pomalyst) and dexamethasone (Pd) for patients with relapsed or refractory multiple myeloma (RRMM).

The SC formulation of daratumumab (with hyaluronidase) was approved in the United States in May, and is administered by injection into the abdomen over 3-5 minutes. Previously the drug was available only as an intravenous infusion.

“The appeal of subcutaneous daratumumab is the 5 minutes it needs for administering, cutting down considerable on ‘chair/clinic’ time. Intravenous daratumumab is given over several hours,” said Joseph Mikhael, MD, MEd, chief medical officer of the International Myeloma Foundation. He also highlighted the low rates of infusion reactions seen with the subcutaneous daratumumab triplet.

“In the COVID era the subcutaneous route may be the way to go,” he said in an interview.

“This is an effective combination with a predictable safety profile that allows for the use of SC daratumumab along with oral pomalidomide and dexamethasone for patients who have received at least one prior line of therapy that included lenalidomide [Revlimid] and a proteasome inhibitor,” commented lead author Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens.

The triplet combination was associated with a 37% reduced risk for progression or death, compared with the two-drug combination of pomalidomide and dexamethasone.

He presented the results from the Apollo trial at the annual meeting of the American Society of Hematology.
 

Treatment landscape of RRMM

Dr. Mikhael, who is also professor in the applied cancer research and drug discovery division at the Translational Genomics Research Institute, Phoenix, provided his insights into Apollo as well as how this triplet fits into the treatment landscape of RRMM.

Daratumumab is approved for use in both RRMM and newly diagnosed MM, either alone or in combination with standard-of-care regimens. The drug already has eight specific indications for the intravenous formulation, and five indications for the SC formulation of daratumumab, Dr. Mikhael noted. The Apollo study “will likely provide the subcutaneous approval for the daratumumab triplet in MM.”

According to Dr. Mikhael, the triplet of daratumumab with pomalidomide and dexamethasone is the most commonly used combination at first relapse, and this phase 3 study provides confirmatory evidence for its initial approval. The initial approval for intravenous daratumumab and Pd was based on a phase 1b study, he noted.

“The Apollo study is the first randomized trial comparing the triplet of D-Pd to Pd,” Noopur Raje, MD, of the Massachusetts General Hospital, Boston, said in an interview. She explained that the majority of patients included in Apollo were refractory to lenalidomide, which is the patient population typically seen at the time of first relapse. “This regimen will be adopted at either first or second relapse in the majority of patients,” Dr. Raje said.

“In keeping with strategy in MM, we use the best triplet first and do not save the best for last,” Dr. Mikhael said. The triplet of the proteasome inhibitor bortezomib (Velcade), lenalidomide, and dexamethasone is used in first-line MM. “Most patients meet the criteria for using D-Pd at first relapse,” he added, noting that all patients in the study have received a proteasome inhibitor and lenalidomide as first-line therapy and had relapsed with or were refractory to these agents.

“The short administration time and significantly low rates of infusion-site reactions are two important considerations for using this triplet with the subcutaneous formulation of daratumumab [at first relapse],” he said.

In the treatment landscape of MM, the triplet of isatuximab (Sarclisa), pomalidomide, and dexamethasone has recently been approved for RRMM based on data from the ICARIA study. Isatuximab and daratumumab are both CD38-directed antibodies. Dr. Mikhael pointed out that the datasets from ICARIA and Apollo with respect to progression-free survival (PFS) and hazard ratios overlapped and were remarkably similar. However, daratumumab now has an advantage in being available as an SC formulation. 

The landscape of MM treatment has been changing rapidly in recent years, and more changes may be afoot. Dr. Mikhael suggested that the quartet of daratumumab, bortezomib, lenalidomide, and dexamethasone is likely to move into the first-line setting for MM based on data from the GRIFFIN study (trial update in Abstract 3243), and then the choice of drugs to use in first relapse would also change.
 

Apollo study details

Apollo was an open-label, phase 3 study that randomly assigned patients with RRMM to receive SC daratumumab in combination with pomalidomide and low-dose dexamethasone (D-Pd; n = 151) or the two-drug combination of Pd (n = 153).

Approximately 80% of the patients were refractory to lenalidomide and half were refractory to a proteasome inhibitor.

Median duration of SC daratumumab administration was 5 minutes. Median duration of study treatment was longer for patients on D-Pd (11.5 months vs. 6.6 months for Pd).

For the primary endpoint, at a median follow up of 16.9 months, median PFS was 12.4 months for patients receiving D-Pd and 6.9 months for those receiving Pd. One-year PFS was 52% for patients receiving the triplet combination and 35% for those receiving Pd. Treatment effect was generally consistent across subgroups examined, Dr. Dimopoulos reported.

Depth of response was significantly higher for patients on D-Pd. Stringent complete remission or CR was seen in 25% of patients on D-Pd versus 4% on Pd. Overall response rate was 69% for patients on D-Pd and 45% for patients on Pd alone (P < .0001). Minimal residual disease negativity was more than four times higher with D-Pd (9% vs. 2% for Pd; P = .0102).

The safety profile of D-Pd was consistent with the known safety profile of SC daratumumab and Pd. Infusion-site reactions were grade 1-2 and occurred in 5% of patients; in addition, only grade 1 injection-site reactions were seen and occurred in 2% of patients. The most serious treatment-emergent adverse events in patients on D-Pd were pneumonia (15% vs. 8% for Pd) and lower respiratory tract infection (12% vs. 9% for Pd). Incidence of secondary primary malignancy was 2% for each group.
 

Apollo results were ‘no surprise’

“These results are of no surprise and further support the current practice of using a three-drug combination in the relapsed setting,” Henry Fung, MD, chair of the department of bone marrow transplant and cellular therapies at Fox Chase Cancer Center, Philadelphia, said in an interview.

Although Dr. Fung agreed that the triplet of a proteasome inhibitor, an immunomodulating drug such as lenalidomide, and the steroid dexamethasone is becoming the standard of care for newly diagnosed MM, D-Pd should be considered an excellent option for patients who have limited choices in the relapsed/refractory setting.

However, he said that the median PFS of 12.4 months for patients receiving D-Pd after a median of two prior regimens is not satisfactory.

“The impact on the natural history of the disease will be limited and the duration of responses decline with each treatment regimen, and the true impact on the disease will be an effective frontline strategy.” Dr. Fung said. “This will not be a practice-changing trial. We need to find out which three-drug regimen works best and what biomarkers can predict the response to individual regimen.”

Dr. Dimopoulos reported receiving honoraria from Beigene, Bristol-Myers Squibb, Amgen, Takeda, Celgene, and Janssen. Dr. Mikhael reported receiving honoraria from Amgen, GlaxoSmithKline, Janssen, Karyopharm, Sanofi, Takeda; consulting with Celgene; and receiving research funding from Celgene and Sanofi. Dr. Fung is on the speakers’ bureau of Apollo and receives honoraria from Jansen Oncology and Celgene/Bristol-Myers Squibb. Dr. Raje is a consultant for Bristol-Myers Squibb and Janssen.  

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

After a patient’s face was burned in the outline of a mask worn during a 3-Tesla MRI neck scan, the US Food and Drug Administration (FDA) cautioned that face masks containing metal can heat to unsafe temperatures during scanning.

Clinicians have known for years to ask patients to remove all metal jewelry and other objects prior to an MRI. The widespread wearing of face masks during the COVID-19 pandemic, however, adds one more consideration to the list.

The FDA’s December 7 safety communication applies to surgical and nonsurgical face masks and respirators.

The injury risk relates to rapid heating of metal components. Many face masks contain a nose wire or metal clip that helps the product conform to the face. Some masks contain metal nanoparticles, while others feature antimicrobial coatings with silver or copper. Each of these products should be avoided during MRI scanning. Also watch out for staples on headbands, the FDA warned.

If the metal content of a face mask is unknown, the FDA suggests providing the patient with a facial covering that is known not to contain any metal.

Robert E. Watson Jr, MD, PhD, chair of the American College of Radiology (ACR) Committee on MR Safety, agreed. He recommended that facilities “provide patients with masks known to be MRI-safe and not permit patient-owned masks in the MRI.”

Watson suggested this strategy at a time when face masks are required.

“COVID-19 safety protocols require that patients wear masks when being scanned, to decrease infection risk to MRI staff, decrease risk of contaminating the MRI scanner, and to protect themselves from infection,” he told Medscape Medical News. “Any conducting metal that enters the MRI machine is at risk of heating due to the radiofrequency fields inherent to image generation.”

Adverse events related to the metal components of a face mask should be reported to the FDA using the MedWatch voluntary reporting form. In addition, healthcare providers subject to the FDA user facility reporting requirements should follow procedures at their facilities to report such events.

This article first appeared on Medscape.com.

After a patient’s face was burned in the outline of a mask worn during a 3-Tesla MRI neck scan, the US Food and Drug Administration (FDA) cautioned that face masks containing metal can heat to unsafe temperatures during scanning.

Clinicians have known for years to ask patients to remove all metal jewelry and other objects prior to an MRI. The widespread wearing of face masks during the COVID-19 pandemic, however, adds one more consideration to the list.

The FDA’s December 7 safety communication applies to surgical and nonsurgical face masks and respirators.

The injury risk relates to rapid heating of metal components. Many face masks contain a nose wire or metal clip that helps the product conform to the face. Some masks contain metal nanoparticles, while others feature antimicrobial coatings with silver or copper. Each of these products should be avoided during MRI scanning. Also watch out for staples on headbands, the FDA warned.

If the metal content of a face mask is unknown, the FDA suggests providing the patient with a facial covering that is known not to contain any metal.

Robert E. Watson Jr, MD, PhD, chair of the American College of Radiology (ACR) Committee on MR Safety, agreed. He recommended that facilities “provide patients with masks known to be MRI-safe and not permit patient-owned masks in the MRI.”

Watson suggested this strategy at a time when face masks are required.

“COVID-19 safety protocols require that patients wear masks when being scanned, to decrease infection risk to MRI staff, decrease risk of contaminating the MRI scanner, and to protect themselves from infection,” he told Medscape Medical News. “Any conducting metal that enters the MRI machine is at risk of heating due to the radiofrequency fields inherent to image generation.”

Adverse events related to the metal components of a face mask should be reported to the FDA using the MedWatch voluntary reporting form. In addition, healthcare providers subject to the FDA user facility reporting requirements should follow procedures at their facilities to report such events.

This article first appeared on Medscape.com.

After a patient’s face was burned in the outline of a mask worn during a 3-Tesla MRI neck scan, the US Food and Drug Administration (FDA) cautioned that face masks containing metal can heat to unsafe temperatures during scanning.

Clinicians have known for years to ask patients to remove all metal jewelry and other objects prior to an MRI. The widespread wearing of face masks during the COVID-19 pandemic, however, adds one more consideration to the list.

The FDA’s December 7 safety communication applies to surgical and nonsurgical face masks and respirators.

The injury risk relates to rapid heating of metal components. Many face masks contain a nose wire or metal clip that helps the product conform to the face. Some masks contain metal nanoparticles, while others feature antimicrobial coatings with silver or copper. Each of these products should be avoided during MRI scanning. Also watch out for staples on headbands, the FDA warned.

If the metal content of a face mask is unknown, the FDA suggests providing the patient with a facial covering that is known not to contain any metal.

Robert E. Watson Jr, MD, PhD, chair of the American College of Radiology (ACR) Committee on MR Safety, agreed. He recommended that facilities “provide patients with masks known to be MRI-safe and not permit patient-owned masks in the MRI.”

Watson suggested this strategy at a time when face masks are required.

“COVID-19 safety protocols require that patients wear masks when being scanned, to decrease infection risk to MRI staff, decrease risk of contaminating the MRI scanner, and to protect themselves from infection,” he told Medscape Medical News. “Any conducting metal that enters the MRI machine is at risk of heating due to the radiofrequency fields inherent to image generation.”

Adverse events related to the metal components of a face mask should be reported to the FDA using the MedWatch voluntary reporting form. In addition, healthcare providers subject to the FDA user facility reporting requirements should follow procedures at their facilities to report such events.

This article first appeared on Medscape.com.

The widespread use of biologics extended life expectancy but also increased medical costs for adults with RA, based on insurance claims data from nearly 30,000 cases.

“With the advancement of treatment in recent decades, the mortality seems to decrease, while medical expenditures increase,” but previous studies estimating the life-years lost because of RA have shown large variations in results, wrote Ying-Ming Chiu, MD, PhD, of China Medical University, Taichung, Taiwan, and colleagues.

“Estimating long-term or lifetime costs could provide an overall figure of the future impact on the health care system after disease occurrence, and would be useful for cost-effectiveness analysis,” they added.

In a study published in Arthritis & Rheumatology, the researchers identified 29,352 new cases of RA in Taiwan between 2003 and 2016, after the introduction of biologics in Taiwan in 2003. They estimate survival using an algorithm with matched controls and used the survival rates to calculate monthly and lifetime health care expenses.

Overall, the average estimated life expectancy after a diagnosis of RA was 26.3 years, and the average lifetime cost was $72,953 (USD). The average life expectancy was 23.4 years for women and 21.6 years for men. The average lifetime cost was higher for women than for men ($73,112 vs. $63,557), but the annual costs were similar for women and men ($3,123 vs. $2,942). However, “the older the age of diagnosis of RA, the higher the average annual cost for treating RA,” regardless of gender, the researchers noted.

Despite the reduced mortality during the study period, the researchers also identified some loss of life expectancy among RA patients, compared with the general population. The average loss of life expectancy was nearly 5 years during the 14-year study period. The loss of life expectancy ranged from 2 to 13 years (average 9.7 years) for women with RA and from 2 to 8 years (average 4.1 years) for men with RA, compared with those without RA after controlling for age, gender, and year of diagnosis.

The study findings were limited by several factors including the lack of data on quality of life and functional disability, possible underestimation of life expectancy because of delayed RA diagnosis, and limited accuracy on follow-up of younger patients, the researchers noted.

However, the results support evidence from previous studies of an overall increase in life expectancy after the introduction of biologics, with increased expenses that should be monitored for cost-effectiveness, they concluded. More research is needed to determine the effect of biologics on functional disability, quality of life, and cost-effectiveness in a way that also incorporates productivity loss and the need for social services such as long-term care in order to inform decision-making for RA treatment.

The study was supported by the Ministry of Science and Technology, Taiwan, and China Medical University Hospital. The researchers had no financial conflicts to disclose.

SOURCE: Chiu Y-M et al. Arthritis Rheumatol. 2020 Dec 8. doi: 10.1002/ART.41597.

The widespread use of biologics extended life expectancy but also increased medical costs for adults with RA, based on insurance claims data from nearly 30,000 cases.

“With the advancement of treatment in recent decades, the mortality seems to decrease, while medical expenditures increase,” but previous studies estimating the life-years lost because of RA have shown large variations in results, wrote Ying-Ming Chiu, MD, PhD, of China Medical University, Taichung, Taiwan, and colleagues.

“Estimating long-term or lifetime costs could provide an overall figure of the future impact on the health care system after disease occurrence, and would be useful for cost-effectiveness analysis,” they added.

In a study published in Arthritis & Rheumatology, the researchers identified 29,352 new cases of RA in Taiwan between 2003 and 2016, after the introduction of biologics in Taiwan in 2003. They estimate survival using an algorithm with matched controls and used the survival rates to calculate monthly and lifetime health care expenses.

Overall, the average estimated life expectancy after a diagnosis of RA was 26.3 years, and the average lifetime cost was $72,953 (USD). The average life expectancy was 23.4 years for women and 21.6 years for men. The average lifetime cost was higher for women than for men ($73,112 vs. $63,557), but the annual costs were similar for women and men ($3,123 vs. $2,942). However, “the older the age of diagnosis of RA, the higher the average annual cost for treating RA,” regardless of gender, the researchers noted.

Despite the reduced mortality during the study period, the researchers also identified some loss of life expectancy among RA patients, compared with the general population. The average loss of life expectancy was nearly 5 years during the 14-year study period. The loss of life expectancy ranged from 2 to 13 years (average 9.7 years) for women with RA and from 2 to 8 years (average 4.1 years) for men with RA, compared with those without RA after controlling for age, gender, and year of diagnosis.

The study findings were limited by several factors including the lack of data on quality of life and functional disability, possible underestimation of life expectancy because of delayed RA diagnosis, and limited accuracy on follow-up of younger patients, the researchers noted.

However, the results support evidence from previous studies of an overall increase in life expectancy after the introduction of biologics, with increased expenses that should be monitored for cost-effectiveness, they concluded. More research is needed to determine the effect of biologics on functional disability, quality of life, and cost-effectiveness in a way that also incorporates productivity loss and the need for social services such as long-term care in order to inform decision-making for RA treatment.

The study was supported by the Ministry of Science and Technology, Taiwan, and China Medical University Hospital. The researchers had no financial conflicts to disclose.

SOURCE: Chiu Y-M et al. Arthritis Rheumatol. 2020 Dec 8. doi: 10.1002/ART.41597.

The widespread use of biologics extended life expectancy but also increased medical costs for adults with RA, based on insurance claims data from nearly 30,000 cases.

“With the advancement of treatment in recent decades, the mortality seems to decrease, while medical expenditures increase,” but previous studies estimating the life-years lost because of RA have shown large variations in results, wrote Ying-Ming Chiu, MD, PhD, of China Medical University, Taichung, Taiwan, and colleagues.

“Estimating long-term or lifetime costs could provide an overall figure of the future impact on the health care system after disease occurrence, and would be useful for cost-effectiveness analysis,” they added.

In a study published in Arthritis & Rheumatology, the researchers identified 29,352 new cases of RA in Taiwan between 2003 and 2016, after the introduction of biologics in Taiwan in 2003. They estimate survival using an algorithm with matched controls and used the survival rates to calculate monthly and lifetime health care expenses.

Overall, the average estimated life expectancy after a diagnosis of RA was 26.3 years, and the average lifetime cost was $72,953 (USD). The average life expectancy was 23.4 years for women and 21.6 years for men. The average lifetime cost was higher for women than for men ($73,112 vs. $63,557), but the annual costs were similar for women and men ($3,123 vs. $2,942). However, “the older the age of diagnosis of RA, the higher the average annual cost for treating RA,” regardless of gender, the researchers noted.

Despite the reduced mortality during the study period, the researchers also identified some loss of life expectancy among RA patients, compared with the general population. The average loss of life expectancy was nearly 5 years during the 14-year study period. The loss of life expectancy ranged from 2 to 13 years (average 9.7 years) for women with RA and from 2 to 8 years (average 4.1 years) for men with RA, compared with those without RA after controlling for age, gender, and year of diagnosis.

The study findings were limited by several factors including the lack of data on quality of life and functional disability, possible underestimation of life expectancy because of delayed RA diagnosis, and limited accuracy on follow-up of younger patients, the researchers noted.

However, the results support evidence from previous studies of an overall increase in life expectancy after the introduction of biologics, with increased expenses that should be monitored for cost-effectiveness, they concluded. More research is needed to determine the effect of biologics on functional disability, quality of life, and cost-effectiveness in a way that also incorporates productivity loss and the need for social services such as long-term care in order to inform decision-making for RA treatment.

The study was supported by the Ministry of Science and Technology, Taiwan, and China Medical University Hospital. The researchers had no financial conflicts to disclose.

SOURCE: Chiu Y-M et al. Arthritis Rheumatol. 2020 Dec 8. doi: 10.1002/ART.41597.

New technologies being developed at the Wellman Center for Photomedicine, Boston, that dermatologists will likely be using in the next 5 years include injection of ice slurry to remove fat, a cooling device for benign pigmented lesions, and a focused laser beam that delivers energy without injuring the skin’s surface.

During a virtual course on laser and aesthetic skin therapy, Lilit Garibyan, MD, PhD, discussed findings from a swine study published online in January 2020 that used an injectable physiologic ice slurry for the nonsurgical removal of fat, a technology that could give CoolSculpting a run for its money. “It does lead to more efficient and effective cryolipolysis,” said Dr. Garibyan, the lead study author who is an assistant professor of dermatology at Harvard University, and director of The Magic Wand Initiative at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston. “The treatment of fat tissue with ice slurry injection can be done in less than 1 minute, as opposed to an hour of cooling with CoolSculpting. In addition, because cooling is delivered directly into target tissue, it is more effective.”

For the study, she and her colleagues at the Wellman Center injected the slurry – a mix of ice, saline, and glycol – into the flanks of swine and followed them for up to 8 weeks. They used ultrasound imaging to show the location of the fat loss and to quantify it. The researchers observed about 40%-50% loss of fat in the treated area, compared with a 60% fat gain in swine who served as controls. “This is because the pig is growing and gaining weight, so the fat is increasing,” she explained.

Gross histologic images also showed fat loss in the subcutaneous fat tissue of treated swine, but not in controls. “When we quantified this loss, there was about a 60% loss of fat after a single injection of ice slurry in the subcutaneous fat,” Dr. Garibyan said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “On histology there was loss of fat in the subcutaneous area and it was replaced by new collagen. No damage to surrounding skin or muscle tissue was seen.”

She characterized the approach as “a minimally invasive and novel method of adipose tissue removal. It’s very simple, because it’s just a simple injection, and it’s very efficient and effective in fat removal. Most importantly, it can target any anatomic site accessible with a needle.”

Human studies are currently underway.

Another emerging technology Dr. Garibyan discussed is a novel controlled skin cooling device for the treatment of benign pigmented lesions. The approach, known as Cryomodulation, was invented by R. Rox Anderson, MD, Dieter Manstein, MD, PhD, and Henry HL Chan, MD, at Massachusetts General Hospital, Boston, and is being commercialized by R2 Technologies. It delivers precise controlled and titratable freezing of benign pigmented lesions without damage to the epidermal barrier. It has been cleared by the Food and Drug Administration, and R2 Technologies plans to launch its first commercial product in the United States in December 2020.

The handpiece of the device, which is placed on top of the skin, provides localized and controlled freezing to targeted benign pigmented lesions. “The cold, or the freeze, is delivered to where the melanocytes reside,” Dr. Garibyan said. “The ice nucleation essentially pauses melanin production. As cell turnover occurs, cells that are melanin-free migrate upward and renew freshly healthy skin. So, melanocyte function is still preserved but there is no destruction to the epidermal barrier. This technology is totally color blind, and there is no persistent inflammatory response.”

After this treatment, histology reveals a reduction of epidermal melanin without destruction of melanocytes. The treatment impairs melanocyte transfer, but not the melanocytes. “Clinically, that is seen as lightening of the skin,” she said. More than 550 patients have been treated with Cryomodulation to demonstrate its safety and effectiveness, described in a study published in 2019, and an ASLMS e-poster.

The final technology Dr. Garibyan discussed is a novel device for removing dermal pigment with a highly focused laser beam. “The problem with current lasers is that the maximum absorption of energy happens at the dermal/epidermal junction,” she said. “This not only increases the risk of epidermal injury, especially in skin of color, but it also leaves very little energy to reach the pigmented target tissue or cells. In addition, there is scattering in the skin, which also reduces the amount of fluence or energy that can reach the target depth, therefore reducing the efficacy of treatment with currently available laser.”

The investigative focused laser beam with high-speed scanning creates a large differential between the fluence at the surface and the fluence at the target, which improves safety. “It’s able to deliver enhanced energy to the target,” she said. “Therefore it’s more effective than destroying the target pigmented cells. There is no injury outside of the focal point, so it offers improved safety, efficacy, and spatial selectivity. The end result on histology is a selective destruction of the pigmented cells, which are typically melanophages.”

Dr. Garibyan predicted that this device will be an ideal therapy for postinflammatory hyperpigmentation and for melasma, “as no effective therapies are available for those conditions.”

She disclosed that she has received royalties/inventorship assigned to MGH. She holds equity in, is a consultant to, and is a member of the scientific advisory board of Brixton Biosciences. She is a consultant to Vyome Therapeutics, Blossom Innovations, Aegle Therapeutics, and ClearifiRx.

[email protected]

New technologies being developed at the Wellman Center for Photomedicine, Boston, that dermatologists will likely be using in the next 5 years include injection of ice slurry to remove fat, a cooling device for benign pigmented lesions, and a focused laser beam that delivers energy without injuring the skin’s surface.

During a virtual course on laser and aesthetic skin therapy, Lilit Garibyan, MD, PhD, discussed findings from a swine study published online in January 2020 that used an injectable physiologic ice slurry for the nonsurgical removal of fat, a technology that could give CoolSculpting a run for its money. “It does lead to more efficient and effective cryolipolysis,” said Dr. Garibyan, the lead study author who is an assistant professor of dermatology at Harvard University, and director of The Magic Wand Initiative at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston. “The treatment of fat tissue with ice slurry injection can be done in less than 1 minute, as opposed to an hour of cooling with CoolSculpting. In addition, because cooling is delivered directly into target tissue, it is more effective.”

For the study, she and her colleagues at the Wellman Center injected the slurry – a mix of ice, saline, and glycol – into the flanks of swine and followed them for up to 8 weeks. They used ultrasound imaging to show the location of the fat loss and to quantify it. The researchers observed about 40%-50% loss of fat in the treated area, compared with a 60% fat gain in swine who served as controls. “This is because the pig is growing and gaining weight, so the fat is increasing,” she explained.

Gross histologic images also showed fat loss in the subcutaneous fat tissue of treated swine, but not in controls. “When we quantified this loss, there was about a 60% loss of fat after a single injection of ice slurry in the subcutaneous fat,” Dr. Garibyan said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “On histology there was loss of fat in the subcutaneous area and it was replaced by new collagen. No damage to surrounding skin or muscle tissue was seen.”

She characterized the approach as “a minimally invasive and novel method of adipose tissue removal. It’s very simple, because it’s just a simple injection, and it’s very efficient and effective in fat removal. Most importantly, it can target any anatomic site accessible with a needle.”

Human studies are currently underway.

Another emerging technology Dr. Garibyan discussed is a novel controlled skin cooling device for the treatment of benign pigmented lesions. The approach, known as Cryomodulation, was invented by R. Rox Anderson, MD, Dieter Manstein, MD, PhD, and Henry HL Chan, MD, at Massachusetts General Hospital, Boston, and is being commercialized by R2 Technologies. It delivers precise controlled and titratable freezing of benign pigmented lesions without damage to the epidermal barrier. It has been cleared by the Food and Drug Administration, and R2 Technologies plans to launch its first commercial product in the United States in December 2020.

The handpiece of the device, which is placed on top of the skin, provides localized and controlled freezing to targeted benign pigmented lesions. “The cold, or the freeze, is delivered to where the melanocytes reside,” Dr. Garibyan said. “The ice nucleation essentially pauses melanin production. As cell turnover occurs, cells that are melanin-free migrate upward and renew freshly healthy skin. So, melanocyte function is still preserved but there is no destruction to the epidermal barrier. This technology is totally color blind, and there is no persistent inflammatory response.”

After this treatment, histology reveals a reduction of epidermal melanin without destruction of melanocytes. The treatment impairs melanocyte transfer, but not the melanocytes. “Clinically, that is seen as lightening of the skin,” she said. More than 550 patients have been treated with Cryomodulation to demonstrate its safety and effectiveness, described in a study published in 2019, and an ASLMS e-poster.

The final technology Dr. Garibyan discussed is a novel device for removing dermal pigment with a highly focused laser beam. “The problem with current lasers is that the maximum absorption of energy happens at the dermal/epidermal junction,” she said. “This not only increases the risk of epidermal injury, especially in skin of color, but it also leaves very little energy to reach the pigmented target tissue or cells. In addition, there is scattering in the skin, which also reduces the amount of fluence or energy that can reach the target depth, therefore reducing the efficacy of treatment with currently available laser.”

The investigative focused laser beam with high-speed scanning creates a large differential between the fluence at the surface and the fluence at the target, which improves safety. “It’s able to deliver enhanced energy to the target,” she said. “Therefore it’s more effective than destroying the target pigmented cells. There is no injury outside of the focal point, so it offers improved safety, efficacy, and spatial selectivity. The end result on histology is a selective destruction of the pigmented cells, which are typically melanophages.”

Dr. Garibyan predicted that this device will be an ideal therapy for postinflammatory hyperpigmentation and for melasma, “as no effective therapies are available for those conditions.”

She disclosed that she has received royalties/inventorship assigned to MGH. She holds equity in, is a consultant to, and is a member of the scientific advisory board of Brixton Biosciences. She is a consultant to Vyome Therapeutics, Blossom Innovations, Aegle Therapeutics, and ClearifiRx.

[email protected]

New technologies being developed at the Wellman Center for Photomedicine, Boston, that dermatologists will likely be using in the next 5 years include injection of ice slurry to remove fat, a cooling device for benign pigmented lesions, and a focused laser beam that delivers energy without injuring the skin’s surface.

During a virtual course on laser and aesthetic skin therapy, Lilit Garibyan, MD, PhD, discussed findings from a swine study published online in January 2020 that used an injectable physiologic ice slurry for the nonsurgical removal of fat, a technology that could give CoolSculpting a run for its money. “It does lead to more efficient and effective cryolipolysis,” said Dr. Garibyan, the lead study author who is an assistant professor of dermatology at Harvard University, and director of The Magic Wand Initiative at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston. “The treatment of fat tissue with ice slurry injection can be done in less than 1 minute, as opposed to an hour of cooling with CoolSculpting. In addition, because cooling is delivered directly into target tissue, it is more effective.”

For the study, she and her colleagues at the Wellman Center injected the slurry – a mix of ice, saline, and glycol – into the flanks of swine and followed them for up to 8 weeks. They used ultrasound imaging to show the location of the fat loss and to quantify it. The researchers observed about 40%-50% loss of fat in the treated area, compared with a 60% fat gain in swine who served as controls. “This is because the pig is growing and gaining weight, so the fat is increasing,” she explained.

Gross histologic images also showed fat loss in the subcutaneous fat tissue of treated swine, but not in controls. “When we quantified this loss, there was about a 60% loss of fat after a single injection of ice slurry in the subcutaneous fat,” Dr. Garibyan said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “On histology there was loss of fat in the subcutaneous area and it was replaced by new collagen. No damage to surrounding skin or muscle tissue was seen.”

She characterized the approach as “a minimally invasive and novel method of adipose tissue removal. It’s very simple, because it’s just a simple injection, and it’s very efficient and effective in fat removal. Most importantly, it can target any anatomic site accessible with a needle.”

Human studies are currently underway.

Another emerging technology Dr. Garibyan discussed is a novel controlled skin cooling device for the treatment of benign pigmented lesions. The approach, known as Cryomodulation, was invented by R. Rox Anderson, MD, Dieter Manstein, MD, PhD, and Henry HL Chan, MD, at Massachusetts General Hospital, Boston, and is being commercialized by R2 Technologies. It delivers precise controlled and titratable freezing of benign pigmented lesions without damage to the epidermal barrier. It has been cleared by the Food and Drug Administration, and R2 Technologies plans to launch its first commercial product in the United States in December 2020.

The handpiece of the device, which is placed on top of the skin, provides localized and controlled freezing to targeted benign pigmented lesions. “The cold, or the freeze, is delivered to where the melanocytes reside,” Dr. Garibyan said. “The ice nucleation essentially pauses melanin production. As cell turnover occurs, cells that are melanin-free migrate upward and renew freshly healthy skin. So, melanocyte function is still preserved but there is no destruction to the epidermal barrier. This technology is totally color blind, and there is no persistent inflammatory response.”

After this treatment, histology reveals a reduction of epidermal melanin without destruction of melanocytes. The treatment impairs melanocyte transfer, but not the melanocytes. “Clinically, that is seen as lightening of the skin,” she said. More than 550 patients have been treated with Cryomodulation to demonstrate its safety and effectiveness, described in a study published in 2019, and an ASLMS e-poster.

The final technology Dr. Garibyan discussed is a novel device for removing dermal pigment with a highly focused laser beam. “The problem with current lasers is that the maximum absorption of energy happens at the dermal/epidermal junction,” she said. “This not only increases the risk of epidermal injury, especially in skin of color, but it also leaves very little energy to reach the pigmented target tissue or cells. In addition, there is scattering in the skin, which also reduces the amount of fluence or energy that can reach the target depth, therefore reducing the efficacy of treatment with currently available laser.”

The investigative focused laser beam with high-speed scanning creates a large differential between the fluence at the surface and the fluence at the target, which improves safety. “It’s able to deliver enhanced energy to the target,” she said. “Therefore it’s more effective than destroying the target pigmented cells. There is no injury outside of the focal point, so it offers improved safety, efficacy, and spatial selectivity. The end result on histology is a selective destruction of the pigmented cells, which are typically melanophages.”

Dr. Garibyan predicted that this device will be an ideal therapy for postinflammatory hyperpigmentation and for melasma, “as no effective therapies are available for those conditions.”

She disclosed that she has received royalties/inventorship assigned to MGH. She holds equity in, is a consultant to, and is a member of the scientific advisory board of Brixton Biosciences. She is a consultant to Vyome Therapeutics, Blossom Innovations, Aegle Therapeutics, and ClearifiRx.

[email protected]

The cognitive and emotional status of children with sickle cell disease (SCD) appears to have a significant effect on how they cope with pain and use health care resources, investigators have found.

Results of a retrospective study of 112 children and adolescents with SCD, the majority of whom had sickle cell anemia, showed that ED visits and hospitalizations were significantly lower among children with SCD who performed better on an attention task, as well as those who were better able to cope emotionally with having SCD and pain, reported Zaria Williams, a second-year medical student at Howard University, Washington, and colleagues.

“Since I started learning more about sickle cell disease, I’ve been very concerned about the great disease burden that this condition can place on pediatric patients, particularly those who suffer from pain,” Ms. Williams said in an oral abstract presented at the annual meeting of the American Society of Hematology.

Although many children and adolescents with SCD can have their pain effectively managed at home with opioids and other medications, some require ED visits and potentially hospitalizations for pain management.

“There is great variability in health care utilization among patients with sickle cell disease, with some having to come to the ED and be admit to the hospital more than others. In searching for reasons why this might be the case, we thought about cognitive function and emotional differences between children with sickle cell disease as potentially affecting disease management,” she said.
 

Anxiety and catastrophizing

Children with SCD are known to be susceptible to affective comorbidities such as anxiety and catastrophizing, and to conditions that have the potential for deleterious effects on executive function, attention, and working memory. To determine whether cognitive and emotional factors affect the disease self-management in children and adolescents with SCD, Ms. Williams and coinvestigators looked at a cohort of 112 SCD patients aged 7-16 years treated at Children’s National Hospital in Washington, D.C.

The patients had participated in a previous pilot study of computerized working memory training. The authors reviewed charts for data on health care utilization, focusing on ED visits and hospitalization for pain 1 and 3 years after enrollment in the study.

They collected data on SCD genotype, disease-related variables, psychosocial information, and measures of cognition and emotion from the dataset. The information included socioeconomic status, parent education level, household income, and number of adults in the household.

Cognitive measures included the Weschler Intelligence Scale for Children full scale IQ, and the Cogstate computerized cognitive assessment system, which measures attention, executive function, and working memory.

Emotional measures were captured from the Pediatric Quality of Life Inventory Sickle Cell Disease module, including questions about worrying and emotions such as anger regarding SCD and pain.

The mean age of participants was 10.61 years. Of the 112 children/adolescents in the study, 65 (58%) were female, and 83 (74%) had sickle cell anemia (either HbSS or HbSβ0 thalassemia).

The participants had a median number of ED visits for pain of one within a year of enrollment, and a median of three within 3 years of enrollment,

The median number of hospital admissions for pain was zero and one, respectively.
 

Attention, emotions linked to higher use

Factors significantly associated with ED visits for pain within the first year were higher (worse) scores for attention (P = .001) and self-reported emotion (P = .049). ED visits within 3 years of enrollment were associated with attention (P = .003) and working memory (P = .039).

Similarly, hospitalizations for pain within the first year were significantly associated with worse attention scores (P = .009) and child-reported emotion (P = .013). Hospitalizations for pain within 3 years of enrollment were also significantly associated with attention deficits (P = .006) and with worse emotional function as reported by a parent (P = .020).

There was no significant effect of SCD genotype or socioeconomic status on either pain-related ED visits or hospitalizations, however.

The investigators theorized that poor attention may make it difficult to distract children from focusing on their pain, and could also hamper disease self-management strategies such as medication adherence and avoiding pain triggers.
 

Age-related differences?

In the question-and-answer session following her presentation, comoderator Susanna A Curtis, MD, from Yale New Haven (Conn.) Hospital, commented that “some previous work has shown that adolescents and young adults with sickle cell disease have higher utilization as compared to their younger counterparts,” and asked whether the investigators found differences between cognition and utilization among different age groups within the cohort.

“We didn’t find a significant association with age, but I’m also very interested in that as well, especially considering that maybe there is more or less parent involvement, considering how old the child is,” Ms. Williams said.

Dr. Curtis noted that many of the comorbidities of sickle cell disease such as stroke or degree of anemia can affect cognitive function, but can also have an effect on health care utilization as well, asked whether the investigators were able to look at the potential confounding effects of comorbidities.

Ms. Williams said that, although they have not looked at potential confounders as yet, they hope to do so in future research.

Asked by another audience member whether the authors had considered using the Pain Catastrophizing Scale for children and/or their parents, in addition to other markers, Ms. Williams replied that “I definitely have considered it. Under recommendations from my mentors, we just focused on the quality-of-life scale first, but catastrophizing is something I’m very interested in. Especially, I would love to have the parent factors as well, so along the journey I hope to include that.”

The study was sponsored in part by a grant from the Doris Duke Charitable Foundation. Ms Williams is the recipient of an ASH Minority Medical Student Award. Dr. Curtis and Ms. Williams both reported no relevant conflicts of interest to disclose.

SOURCE: Williams Z et al. ASH 2020, Abstract 366

The cognitive and emotional status of children with sickle cell disease (SCD) appears to have a significant effect on how they cope with pain and use health care resources, investigators have found.

Results of a retrospective study of 112 children and adolescents with SCD, the majority of whom had sickle cell anemia, showed that ED visits and hospitalizations were significantly lower among children with SCD who performed better on an attention task, as well as those who were better able to cope emotionally with having SCD and pain, reported Zaria Williams, a second-year medical student at Howard University, Washington, and colleagues.

“Since I started learning more about sickle cell disease, I’ve been very concerned about the great disease burden that this condition can place on pediatric patients, particularly those who suffer from pain,” Ms. Williams said in an oral abstract presented at the annual meeting of the American Society of Hematology.

Although many children and adolescents with SCD can have their pain effectively managed at home with opioids and other medications, some require ED visits and potentially hospitalizations for pain management.

“There is great variability in health care utilization among patients with sickle cell disease, with some having to come to the ED and be admit to the hospital more than others. In searching for reasons why this might be the case, we thought about cognitive function and emotional differences between children with sickle cell disease as potentially affecting disease management,” she said.
 

Anxiety and catastrophizing

Children with SCD are known to be susceptible to affective comorbidities such as anxiety and catastrophizing, and to conditions that have the potential for deleterious effects on executive function, attention, and working memory. To determine whether cognitive and emotional factors affect the disease self-management in children and adolescents with SCD, Ms. Williams and coinvestigators looked at a cohort of 112 SCD patients aged 7-16 years treated at Children’s National Hospital in Washington, D.C.

The patients had participated in a previous pilot study of computerized working memory training. The authors reviewed charts for data on health care utilization, focusing on ED visits and hospitalization for pain 1 and 3 years after enrollment in the study.

They collected data on SCD genotype, disease-related variables, psychosocial information, and measures of cognition and emotion from the dataset. The information included socioeconomic status, parent education level, household income, and number of adults in the household.

Cognitive measures included the Weschler Intelligence Scale for Children full scale IQ, and the Cogstate computerized cognitive assessment system, which measures attention, executive function, and working memory.

Emotional measures were captured from the Pediatric Quality of Life Inventory Sickle Cell Disease module, including questions about worrying and emotions such as anger regarding SCD and pain.

The mean age of participants was 10.61 years. Of the 112 children/adolescents in the study, 65 (58%) were female, and 83 (74%) had sickle cell anemia (either HbSS or HbSβ0 thalassemia).

The participants had a median number of ED visits for pain of one within a year of enrollment, and a median of three within 3 years of enrollment,

The median number of hospital admissions for pain was zero and one, respectively.
 

Attention, emotions linked to higher use

Factors significantly associated with ED visits for pain within the first year were higher (worse) scores for attention (P = .001) and self-reported emotion (P = .049). ED visits within 3 years of enrollment were associated with attention (P = .003) and working memory (P = .039).

Similarly, hospitalizations for pain within the first year were significantly associated with worse attention scores (P = .009) and child-reported emotion (P = .013). Hospitalizations for pain within 3 years of enrollment were also significantly associated with attention deficits (P = .006) and with worse emotional function as reported by a parent (P = .020).

There was no significant effect of SCD genotype or socioeconomic status on either pain-related ED visits or hospitalizations, however.

The investigators theorized that poor attention may make it difficult to distract children from focusing on their pain, and could also hamper disease self-management strategies such as medication adherence and avoiding pain triggers.
 

Age-related differences?

In the question-and-answer session following her presentation, comoderator Susanna A Curtis, MD, from Yale New Haven (Conn.) Hospital, commented that “some previous work has shown that adolescents and young adults with sickle cell disease have higher utilization as compared to their younger counterparts,” and asked whether the investigators found differences between cognition and utilization among different age groups within the cohort.

“We didn’t find a significant association with age, but I’m also very interested in that as well, especially considering that maybe there is more or less parent involvement, considering how old the child is,” Ms. Williams said.

Dr. Curtis noted that many of the comorbidities of sickle cell disease such as stroke or degree of anemia can affect cognitive function, but can also have an effect on health care utilization as well, asked whether the investigators were able to look at the potential confounding effects of comorbidities.

Ms. Williams said that, although they have not looked at potential confounders as yet, they hope to do so in future research.

Asked by another audience member whether the authors had considered using the Pain Catastrophizing Scale for children and/or their parents, in addition to other markers, Ms. Williams replied that “I definitely have considered it. Under recommendations from my mentors, we just focused on the quality-of-life scale first, but catastrophizing is something I’m very interested in. Especially, I would love to have the parent factors as well, so along the journey I hope to include that.”

The study was sponsored in part by a grant from the Doris Duke Charitable Foundation. Ms Williams is the recipient of an ASH Minority Medical Student Award. Dr. Curtis and Ms. Williams both reported no relevant conflicts of interest to disclose.

SOURCE: Williams Z et al. ASH 2020, Abstract 366

The cognitive and emotional status of children with sickle cell disease (SCD) appears to have a significant effect on how they cope with pain and use health care resources, investigators have found.

Results of a retrospective study of 112 children and adolescents with SCD, the majority of whom had sickle cell anemia, showed that ED visits and hospitalizations were significantly lower among children with SCD who performed better on an attention task, as well as those who were better able to cope emotionally with having SCD and pain, reported Zaria Williams, a second-year medical student at Howard University, Washington, and colleagues.

“Since I started learning more about sickle cell disease, I’ve been very concerned about the great disease burden that this condition can place on pediatric patients, particularly those who suffer from pain,” Ms. Williams said in an oral abstract presented at the annual meeting of the American Society of Hematology.

Although many children and adolescents with SCD can have their pain effectively managed at home with opioids and other medications, some require ED visits and potentially hospitalizations for pain management.

“There is great variability in health care utilization among patients with sickle cell disease, with some having to come to the ED and be admit to the hospital more than others. In searching for reasons why this might be the case, we thought about cognitive function and emotional differences between children with sickle cell disease as potentially affecting disease management,” she said.
 

Anxiety and catastrophizing

Children with SCD are known to be susceptible to affective comorbidities such as anxiety and catastrophizing, and to conditions that have the potential for deleterious effects on executive function, attention, and working memory. To determine whether cognitive and emotional factors affect the disease self-management in children and adolescents with SCD, Ms. Williams and coinvestigators looked at a cohort of 112 SCD patients aged 7-16 years treated at Children’s National Hospital in Washington, D.C.

The patients had participated in a previous pilot study of computerized working memory training. The authors reviewed charts for data on health care utilization, focusing on ED visits and hospitalization for pain 1 and 3 years after enrollment in the study.

They collected data on SCD genotype, disease-related variables, psychosocial information, and measures of cognition and emotion from the dataset. The information included socioeconomic status, parent education level, household income, and number of adults in the household.

Cognitive measures included the Weschler Intelligence Scale for Children full scale IQ, and the Cogstate computerized cognitive assessment system, which measures attention, executive function, and working memory.

Emotional measures were captured from the Pediatric Quality of Life Inventory Sickle Cell Disease module, including questions about worrying and emotions such as anger regarding SCD and pain.

The mean age of participants was 10.61 years. Of the 112 children/adolescents in the study, 65 (58%) were female, and 83 (74%) had sickle cell anemia (either HbSS or HbSβ0 thalassemia).

The participants had a median number of ED visits for pain of one within a year of enrollment, and a median of three within 3 years of enrollment,

The median number of hospital admissions for pain was zero and one, respectively.
 

Attention, emotions linked to higher use

Factors significantly associated with ED visits for pain within the first year were higher (worse) scores for attention (P = .001) and self-reported emotion (P = .049). ED visits within 3 years of enrollment were associated with attention (P = .003) and working memory (P = .039).

Similarly, hospitalizations for pain within the first year were significantly associated with worse attention scores (P = .009) and child-reported emotion (P = .013). Hospitalizations for pain within 3 years of enrollment were also significantly associated with attention deficits (P = .006) and with worse emotional function as reported by a parent (P = .020).

There was no significant effect of SCD genotype or socioeconomic status on either pain-related ED visits or hospitalizations, however.

The investigators theorized that poor attention may make it difficult to distract children from focusing on their pain, and could also hamper disease self-management strategies such as medication adherence and avoiding pain triggers.
 

Age-related differences?

In the question-and-answer session following her presentation, comoderator Susanna A Curtis, MD, from Yale New Haven (Conn.) Hospital, commented that “some previous work has shown that adolescents and young adults with sickle cell disease have higher utilization as compared to their younger counterparts,” and asked whether the investigators found differences between cognition and utilization among different age groups within the cohort.

“We didn’t find a significant association with age, but I’m also very interested in that as well, especially considering that maybe there is more or less parent involvement, considering how old the child is,” Ms. Williams said.

Dr. Curtis noted that many of the comorbidities of sickle cell disease such as stroke or degree of anemia can affect cognitive function, but can also have an effect on health care utilization as well, asked whether the investigators were able to look at the potential confounding effects of comorbidities.

Ms. Williams said that, although they have not looked at potential confounders as yet, they hope to do so in future research.

Asked by another audience member whether the authors had considered using the Pain Catastrophizing Scale for children and/or their parents, in addition to other markers, Ms. Williams replied that “I definitely have considered it. Under recommendations from my mentors, we just focused on the quality-of-life scale first, but catastrophizing is something I’m very interested in. Especially, I would love to have the parent factors as well, so along the journey I hope to include that.”

The study was sponsored in part by a grant from the Doris Duke Charitable Foundation. Ms Williams is the recipient of an ASH Minority Medical Student Award. Dr. Curtis and Ms. Williams both reported no relevant conflicts of interest to disclose.

SOURCE: Williams Z et al. ASH 2020, Abstract 366

A high-polyphenol, calorie-restricted Mediterranean diet supplemented with green tea and the Mankai strain of duckweed optimized the microbiome for autologous fecal microbiota transplantation, which maintained both weight loss and insulin sensitivity after the diet ended, according to the findings of a novel clinical trial.

Eight months after the diet ended, 17% of individuals in the autologous fecal microbiota transplantation (aFMT) group had regained weight, compared with 50% of those who received oral placebo (P = .02). Gains in weight circumference were 1.89 cm and 5.05 cm, respectively (P = .01), and changes in fasting insulin levels were 1.46 (standard deviation, 3.6 mIU/mL) and 1.64 mIU/mL (standard deviation, 4.7 mIU/mL; P = .04). Notably, aFMT did not achieve these results after weight loss on a typical Mediterranean diet, with or without calorie restriction. “Diet-induced weight loss can be preserved, along with glycemic control, for months after a diet via aFMT capsules. A high-polyphenols, green plant-based or Mankai diet better optimizes the microbiome for an aFMT procedure,” Ehud Rinott, an MD, PhD student at Ben-Gurion University of the Negev in Beer-Sheva, Israel, and his associates wrote in Gastroenterology.

Significant weight regain after dieting is common and undermines cardiometabolic strides. In animal studies, FMT from lean to obese individuals induces both weight loss and metabolic improvements, and limited data point to similar benefits in humans. However, allogenic FMT in humans raises safety concerns and “practical barriers,” Mr. Rinott and his associates noted. Hypothesizing that aFMT of microbiota obtained at nadir weight might prevent postdiet rebounds, they randomly assigned 294 obese or dyslipidemic adults (average age, 52 years) to receive the calorie-restricted “green” Mediterranean diet or a standard Mediterranean diet with or without calorie restrictions for 6 months. At this time, microbiota obtained from fecal samples were frozen in colorless, odorless oral capsules that were considered indistinguishable from placebo capsules. Ninety participants who had lost at least 3.5% of their body weight (average loss, 8.3 kg) were then rerandomized in a double-blinded manner to receive once-daily aFMT or placebo capsules during months 8 through 14.

In all, 96% of participants consumed at least 80% of the capsules, a high rate of compliance. No adverse events from aFMT were reported. Metagenomic sequencing and 16s ribosomal RNA sequencing showed that only the “green” Mediterranean diet induced significant alterations in the gut microbiome during the weight-loss phase. In a complementary study of obese mice, autologous transplantation of microbiota obtained at nadir weight confirmed that adding Mankai during weight loss helped protect against subsequent regain and loss of insulin sensitivity.

All diets in this study emphasized vegetables while reducing sugars, salt, dietary cholesterol, trans and saturated fats, and poultry, and omitting processed and red meats. The “green” and standard calorie-restricted Mediterranean diets both limited calories to 1,500-1,800 per day for men and 1,200-1,400 per day for women (women comprised only 9% of study participants). In these two diets, fats – mainly monounsaturated and polyunsaturated – made up 40% of calories (including 28 g walnuts per day, containing 440 mg polyphenols), while carbohydrates were limited to less than 40 g per day in the first 2 months and then gradually increased to 80 g per day. The green Mediterranean diet added 3-4 cups of green tea daily and a shake containing 100 g of Mankai, which provided another 800 mg of polyphenols. All participants received free gym memberships and were told to exercise throughout the study (aerobic exercise for 45-60 minutes three to four times weekly, and resistance exercise two to three times weekly).

Funders included the Israeli Science Foundation, Israeli Ministry of Health, Israel Ministry of Science and Technology, German Research Foundation, California Walnuts Commission, and others. Mr. Rinott had no conflicts. Three coinvestigators disclosed ties to CoreBiome, Hinoman, and Mybiotics.

SOURCE: Rinott E et al. Gastroenterology. 2020 Aug 25. doi: 10.1053/j.gastro.2020.08.041.

A high-polyphenol, calorie-restricted Mediterranean diet supplemented with green tea and the Mankai strain of duckweed optimized the microbiome for autologous fecal microbiota transplantation, which maintained both weight loss and insulin sensitivity after the diet ended, according to the findings of a novel clinical trial.

Eight months after the diet ended, 17% of individuals in the autologous fecal microbiota transplantation (aFMT) group had regained weight, compared with 50% of those who received oral placebo (P = .02). Gains in weight circumference were 1.89 cm and 5.05 cm, respectively (P = .01), and changes in fasting insulin levels were 1.46 (standard deviation, 3.6 mIU/mL) and 1.64 mIU/mL (standard deviation, 4.7 mIU/mL; P = .04). Notably, aFMT did not achieve these results after weight loss on a typical Mediterranean diet, with or without calorie restriction. “Diet-induced weight loss can be preserved, along with glycemic control, for months after a diet via aFMT capsules. A high-polyphenols, green plant-based or Mankai diet better optimizes the microbiome for an aFMT procedure,” Ehud Rinott, an MD, PhD student at Ben-Gurion University of the Negev in Beer-Sheva, Israel, and his associates wrote in Gastroenterology.

Significant weight regain after dieting is common and undermines cardiometabolic strides. In animal studies, FMT from lean to obese individuals induces both weight loss and metabolic improvements, and limited data point to similar benefits in humans. However, allogenic FMT in humans raises safety concerns and “practical barriers,” Mr. Rinott and his associates noted. Hypothesizing that aFMT of microbiota obtained at nadir weight might prevent postdiet rebounds, they randomly assigned 294 obese or dyslipidemic adults (average age, 52 years) to receive the calorie-restricted “green” Mediterranean diet or a standard Mediterranean diet with or without calorie restrictions for 6 months. At this time, microbiota obtained from fecal samples were frozen in colorless, odorless oral capsules that were considered indistinguishable from placebo capsules. Ninety participants who had lost at least 3.5% of their body weight (average loss, 8.3 kg) were then rerandomized in a double-blinded manner to receive once-daily aFMT or placebo capsules during months 8 through 14.

In all, 96% of participants consumed at least 80% of the capsules, a high rate of compliance. No adverse events from aFMT were reported. Metagenomic sequencing and 16s ribosomal RNA sequencing showed that only the “green” Mediterranean diet induced significant alterations in the gut microbiome during the weight-loss phase. In a complementary study of obese mice, autologous transplantation of microbiota obtained at nadir weight confirmed that adding Mankai during weight loss helped protect against subsequent regain and loss of insulin sensitivity.

All diets in this study emphasized vegetables while reducing sugars, salt, dietary cholesterol, trans and saturated fats, and poultry, and omitting processed and red meats. The “green” and standard calorie-restricted Mediterranean diets both limited calories to 1,500-1,800 per day for men and 1,200-1,400 per day for women (women comprised only 9% of study participants). In these two diets, fats – mainly monounsaturated and polyunsaturated – made up 40% of calories (including 28 g walnuts per day, containing 440 mg polyphenols), while carbohydrates were limited to less than 40 g per day in the first 2 months and then gradually increased to 80 g per day. The green Mediterranean diet added 3-4 cups of green tea daily and a shake containing 100 g of Mankai, which provided another 800 mg of polyphenols. All participants received free gym memberships and were told to exercise throughout the study (aerobic exercise for 45-60 minutes three to four times weekly, and resistance exercise two to three times weekly).

Funders included the Israeli Science Foundation, Israeli Ministry of Health, Israel Ministry of Science and Technology, German Research Foundation, California Walnuts Commission, and others. Mr. Rinott had no conflicts. Three coinvestigators disclosed ties to CoreBiome, Hinoman, and Mybiotics.

SOURCE: Rinott E et al. Gastroenterology. 2020 Aug 25. doi: 10.1053/j.gastro.2020.08.041.

A high-polyphenol, calorie-restricted Mediterranean diet supplemented with green tea and the Mankai strain of duckweed optimized the microbiome for autologous fecal microbiota transplantation, which maintained both weight loss and insulin sensitivity after the diet ended, according to the findings of a novel clinical trial.

Eight months after the diet ended, 17% of individuals in the autologous fecal microbiota transplantation (aFMT) group had regained weight, compared with 50% of those who received oral placebo (P = .02). Gains in weight circumference were 1.89 cm and 5.05 cm, respectively (P = .01), and changes in fasting insulin levels were 1.46 (standard deviation, 3.6 mIU/mL) and 1.64 mIU/mL (standard deviation, 4.7 mIU/mL; P = .04). Notably, aFMT did not achieve these results after weight loss on a typical Mediterranean diet, with or without calorie restriction. “Diet-induced weight loss can be preserved, along with glycemic control, for months after a diet via aFMT capsules. A high-polyphenols, green plant-based or Mankai diet better optimizes the microbiome for an aFMT procedure,” Ehud Rinott, an MD, PhD student at Ben-Gurion University of the Negev in Beer-Sheva, Israel, and his associates wrote in Gastroenterology.

Significant weight regain after dieting is common and undermines cardiometabolic strides. In animal studies, FMT from lean to obese individuals induces both weight loss and metabolic improvements, and limited data point to similar benefits in humans. However, allogenic FMT in humans raises safety concerns and “practical barriers,” Mr. Rinott and his associates noted. Hypothesizing that aFMT of microbiota obtained at nadir weight might prevent postdiet rebounds, they randomly assigned 294 obese or dyslipidemic adults (average age, 52 years) to receive the calorie-restricted “green” Mediterranean diet or a standard Mediterranean diet with or without calorie restrictions for 6 months. At this time, microbiota obtained from fecal samples were frozen in colorless, odorless oral capsules that were considered indistinguishable from placebo capsules. Ninety participants who had lost at least 3.5% of their body weight (average loss, 8.3 kg) were then rerandomized in a double-blinded manner to receive once-daily aFMT or placebo capsules during months 8 through 14.

In all, 96% of participants consumed at least 80% of the capsules, a high rate of compliance. No adverse events from aFMT were reported. Metagenomic sequencing and 16s ribosomal RNA sequencing showed that only the “green” Mediterranean diet induced significant alterations in the gut microbiome during the weight-loss phase. In a complementary study of obese mice, autologous transplantation of microbiota obtained at nadir weight confirmed that adding Mankai during weight loss helped protect against subsequent regain and loss of insulin sensitivity.

All diets in this study emphasized vegetables while reducing sugars, salt, dietary cholesterol, trans and saturated fats, and poultry, and omitting processed and red meats. The “green” and standard calorie-restricted Mediterranean diets both limited calories to 1,500-1,800 per day for men and 1,200-1,400 per day for women (women comprised only 9% of study participants). In these two diets, fats – mainly monounsaturated and polyunsaturated – made up 40% of calories (including 28 g walnuts per day, containing 440 mg polyphenols), while carbohydrates were limited to less than 40 g per day in the first 2 months and then gradually increased to 80 g per day. The green Mediterranean diet added 3-4 cups of green tea daily and a shake containing 100 g of Mankai, which provided another 800 mg of polyphenols. All participants received free gym memberships and were told to exercise throughout the study (aerobic exercise for 45-60 minutes three to four times weekly, and resistance exercise two to three times weekly).

Funders included the Israeli Science Foundation, Israeli Ministry of Health, Israel Ministry of Science and Technology, German Research Foundation, California Walnuts Commission, and others. Mr. Rinott had no conflicts. Three coinvestigators disclosed ties to CoreBiome, Hinoman, and Mybiotics.

SOURCE: Rinott E et al. Gastroenterology. 2020 Aug 25. doi: 10.1053/j.gastro.2020.08.041.

When a new phenotype approach to the diagnosis of rosacea was proposed 2 years ago, this simpler and more accurate method was accompanied by several corollary advantages, including a more rational approach to treatment and better methods of measuring treatment efficacy, according to an expert speaking at the annual Coastal Dermatology Symposium, held virtually.

“By looking at rosacea in a more simple way – but a more accurate way – we are able to track what happens [to key features] over time,” explained Jerry Tan, MD, of the University of Western Ontario, London.

The newer method of diagnosing rosacea, which relies on phenotyping rather than subtyping, focuses on symptoms and their clinical impact. With the previous method of subtyping, many rosacea patients failed to fit neatly into any of the four categories, producing confusion and diverting attention from troublesome symptoms.

“Rosacea patients often present with a range of features that span multiple subtypes or progress between them,” Dr. Tan explained. The risk is not just a delay in diagnosis but a failure to focus on symptoms patients find most bothersome.

The previous diagnostic criteria for rosacea, published in 2002, identified primary and secondary symptoms within its four subtypes. The new diagnostic criteria, endorsed by the National Rosacea Society and published in 2018, rely on phenotypes defined by diagnostic, major, and minor symptoms. Rather than the four previous subtypes, which were erythematotelangiectatic, papulopustular, phymatous, and ocular, the phenotypes facilitate diagnosis in patients with mixed features.

By replacing “the old thought process of subtyping” with a newer focus on phenotypes, the updated criteria were “aimed toward accuracy, simplicity and practicality,” Dr. Tan said.

Moreover, without squeezing patients into subgroups where they do not neatly fit, the new criteria draw attention to the specific symptoms that bring patients to the clinician.

The phenotype approach to treatment strategies was reflected in a systematic review of treatments based on phenotypes that was published in 2019, not long after the new classification system became available. In this review, coauthored by Dr. Tan, the GRADE certainty-of-evidence approach was employed to identify effective therapies, matching specific symptoms with specific therapies such as low-dose isotretinoin for papules or omega-3 fatty acids for dry eyes.

Based on a patient-centric approach that emphasizes control of key symptoms, Dr. Tan also described a method of documenting the severity of major and minor symptoms at each visit. With this method, called a rosacea patient tracker, patients and physicians can determine whether therapies are effective against the signs and symptoms of disease that they find most burdensome, according to Dr. Tan, who was the first author of an article he cited as a reference to this phenotype-based methodology.

Overall, the phenotype approach to rosacea “rationalizes treatment,” he said.

Specifically, the heterogeneity of symptoms in rosacea is mirrored in the heterogeneity of underlying pathophysiology. According to Dr. Tan, the upregulation of cytokines for inflammation, of angiogenic pathways for vascular symptoms, and of matrix metalloproteinases for tissue remodeling are all implicated in rosacea but drive different types of symptoms. While appropriate skin care and efforts to identify and minimize symptom triggers is appropriate for all patients, phenotypes provide a guide to the most appropriate therapies.

He said he hopes that the focus on phenotypes will draw attention to differences in these pathophysiological mechanisms. According to Dr. Tan, evaluating rosacea from the perspective of phenotypes has represented an important paradigm shift that extends beyond diagnosis.

“The move to the phenotype approach is hopefully simpler, more accurate, and more relevant,” Dr. Tan said.

This same approach has been advocated by others, including Esther J. van Zurren, MD, professor of dermatology at Leiden University Medical Centre in the Netherlands, the lead author of the 2018 systematic review article discussed by Dr. Tan. In this review article on the phenotype approach, specific strategies were recommended for specific symptoms on the basis of grading by an international group of experts that included Dr. Tan, a coauthor.

“These strategies should be directed toward achieving improvements in general well-being by targeting those aspects most bothersome to the patient,” the article advises. Like Dr. Tan, she considers this phenotype-based approach to diagnosis and treatment to be a meaningful clinical advance over the guidelines published in 2002.

“Management strategies for people with rosacea should include phenotype-based treatments,” she agreed, adding that specific choices should be made on the basis of these phenotypes “instead of the previous subtype classification.”

The meeting was jointly presented by the University of Louisville and Global Academy for Medical Education. This publication and Global Academy for Medical Education are owned by the same parent company.
 

When a new phenotype approach to the diagnosis of rosacea was proposed 2 years ago, this simpler and more accurate method was accompanied by several corollary advantages, including a more rational approach to treatment and better methods of measuring treatment efficacy, according to an expert speaking at the annual Coastal Dermatology Symposium, held virtually.

“By looking at rosacea in a more simple way – but a more accurate way – we are able to track what happens [to key features] over time,” explained Jerry Tan, MD, of the University of Western Ontario, London.

The newer method of diagnosing rosacea, which relies on phenotyping rather than subtyping, focuses on symptoms and their clinical impact. With the previous method of subtyping, many rosacea patients failed to fit neatly into any of the four categories, producing confusion and diverting attention from troublesome symptoms.

“Rosacea patients often present with a range of features that span multiple subtypes or progress between them,” Dr. Tan explained. The risk is not just a delay in diagnosis but a failure to focus on symptoms patients find most bothersome.

The previous diagnostic criteria for rosacea, published in 2002, identified primary and secondary symptoms within its four subtypes. The new diagnostic criteria, endorsed by the National Rosacea Society and published in 2018, rely on phenotypes defined by diagnostic, major, and minor symptoms. Rather than the four previous subtypes, which were erythematotelangiectatic, papulopustular, phymatous, and ocular, the phenotypes facilitate diagnosis in patients with mixed features.

By replacing “the old thought process of subtyping” with a newer focus on phenotypes, the updated criteria were “aimed toward accuracy, simplicity and practicality,” Dr. Tan said.

Moreover, without squeezing patients into subgroups where they do not neatly fit, the new criteria draw attention to the specific symptoms that bring patients to the clinician.

The phenotype approach to treatment strategies was reflected in a systematic review of treatments based on phenotypes that was published in 2019, not long after the new classification system became available. In this review, coauthored by Dr. Tan, the GRADE certainty-of-evidence approach was employed to identify effective therapies, matching specific symptoms with specific therapies such as low-dose isotretinoin for papules or omega-3 fatty acids for dry eyes.

Based on a patient-centric approach that emphasizes control of key symptoms, Dr. Tan also described a method of documenting the severity of major and minor symptoms at each visit. With this method, called a rosacea patient tracker, patients and physicians can determine whether therapies are effective against the signs and symptoms of disease that they find most burdensome, according to Dr. Tan, who was the first author of an article he cited as a reference to this phenotype-based methodology.

Overall, the phenotype approach to rosacea “rationalizes treatment,” he said.

Specifically, the heterogeneity of symptoms in rosacea is mirrored in the heterogeneity of underlying pathophysiology. According to Dr. Tan, the upregulation of cytokines for inflammation, of angiogenic pathways for vascular symptoms, and of matrix metalloproteinases for tissue remodeling are all implicated in rosacea but drive different types of symptoms. While appropriate skin care and efforts to identify and minimize symptom triggers is appropriate for all patients, phenotypes provide a guide to the most appropriate therapies.

He said he hopes that the focus on phenotypes will draw attention to differences in these pathophysiological mechanisms. According to Dr. Tan, evaluating rosacea from the perspective of phenotypes has represented an important paradigm shift that extends beyond diagnosis.

“The move to the phenotype approach is hopefully simpler, more accurate, and more relevant,” Dr. Tan said.

This same approach has been advocated by others, including Esther J. van Zurren, MD, professor of dermatology at Leiden University Medical Centre in the Netherlands, the lead author of the 2018 systematic review article discussed by Dr. Tan. In this review article on the phenotype approach, specific strategies were recommended for specific symptoms on the basis of grading by an international group of experts that included Dr. Tan, a coauthor.

“These strategies should be directed toward achieving improvements in general well-being by targeting those aspects most bothersome to the patient,” the article advises. Like Dr. Tan, she considers this phenotype-based approach to diagnosis and treatment to be a meaningful clinical advance over the guidelines published in 2002.

“Management strategies for people with rosacea should include phenotype-based treatments,” she agreed, adding that specific choices should be made on the basis of these phenotypes “instead of the previous subtype classification.”

The meeting was jointly presented by the University of Louisville and Global Academy for Medical Education. This publication and Global Academy for Medical Education are owned by the same parent company.
 

When a new phenotype approach to the diagnosis of rosacea was proposed 2 years ago, this simpler and more accurate method was accompanied by several corollary advantages, including a more rational approach to treatment and better methods of measuring treatment efficacy, according to an expert speaking at the annual Coastal Dermatology Symposium, held virtually.

“By looking at rosacea in a more simple way – but a more accurate way – we are able to track what happens [to key features] over time,” explained Jerry Tan, MD, of the University of Western Ontario, London.

The newer method of diagnosing rosacea, which relies on phenotyping rather than subtyping, focuses on symptoms and their clinical impact. With the previous method of subtyping, many rosacea patients failed to fit neatly into any of the four categories, producing confusion and diverting attention from troublesome symptoms.

“Rosacea patients often present with a range of features that span multiple subtypes or progress between them,” Dr. Tan explained. The risk is not just a delay in diagnosis but a failure to focus on symptoms patients find most bothersome.

The previous diagnostic criteria for rosacea, published in 2002, identified primary and secondary symptoms within its four subtypes. The new diagnostic criteria, endorsed by the National Rosacea Society and published in 2018, rely on phenotypes defined by diagnostic, major, and minor symptoms. Rather than the four previous subtypes, which were erythematotelangiectatic, papulopustular, phymatous, and ocular, the phenotypes facilitate diagnosis in patients with mixed features.

By replacing “the old thought process of subtyping” with a newer focus on phenotypes, the updated criteria were “aimed toward accuracy, simplicity and practicality,” Dr. Tan said.

Moreover, without squeezing patients into subgroups where they do not neatly fit, the new criteria draw attention to the specific symptoms that bring patients to the clinician.

The phenotype approach to treatment strategies was reflected in a systematic review of treatments based on phenotypes that was published in 2019, not long after the new classification system became available. In this review, coauthored by Dr. Tan, the GRADE certainty-of-evidence approach was employed to identify effective therapies, matching specific symptoms with specific therapies such as low-dose isotretinoin for papules or omega-3 fatty acids for dry eyes.

Based on a patient-centric approach that emphasizes control of key symptoms, Dr. Tan also described a method of documenting the severity of major and minor symptoms at each visit. With this method, called a rosacea patient tracker, patients and physicians can determine whether therapies are effective against the signs and symptoms of disease that they find most burdensome, according to Dr. Tan, who was the first author of an article he cited as a reference to this phenotype-based methodology.

Overall, the phenotype approach to rosacea “rationalizes treatment,” he said.

Specifically, the heterogeneity of symptoms in rosacea is mirrored in the heterogeneity of underlying pathophysiology. According to Dr. Tan, the upregulation of cytokines for inflammation, of angiogenic pathways for vascular symptoms, and of matrix metalloproteinases for tissue remodeling are all implicated in rosacea but drive different types of symptoms. While appropriate skin care and efforts to identify and minimize symptom triggers is appropriate for all patients, phenotypes provide a guide to the most appropriate therapies.

He said he hopes that the focus on phenotypes will draw attention to differences in these pathophysiological mechanisms. According to Dr. Tan, evaluating rosacea from the perspective of phenotypes has represented an important paradigm shift that extends beyond diagnosis.

“The move to the phenotype approach is hopefully simpler, more accurate, and more relevant,” Dr. Tan said.

This same approach has been advocated by others, including Esther J. van Zurren, MD, professor of dermatology at Leiden University Medical Centre in the Netherlands, the lead author of the 2018 systematic review article discussed by Dr. Tan. In this review article on the phenotype approach, specific strategies were recommended for specific symptoms on the basis of grading by an international group of experts that included Dr. Tan, a coauthor.

“These strategies should be directed toward achieving improvements in general well-being by targeting those aspects most bothersome to the patient,” the article advises. Like Dr. Tan, she considers this phenotype-based approach to diagnosis and treatment to be a meaningful clinical advance over the guidelines published in 2002.

“Management strategies for people with rosacea should include phenotype-based treatments,” she agreed, adding that specific choices should be made on the basis of these phenotypes “instead of the previous subtype classification.”

The meeting was jointly presented by the University of Louisville and Global Academy for Medical Education. This publication and Global Academy for Medical Education are owned by the same parent company.
 

Americans have made no secret of their skepticism of COVID-19 vaccines this year, with fears of political interference and a “warp speed” timeline blunting confidence in the shots. As recently as September, nearly half of U.S. adults said they didn’t intend to be inoculated.

But with two promising vaccines primed for release, likely within weeks, experts in ethics and immunization behavior say they expect attitudes to shift quickly from widespread hesitancy to urgent, even heated demand.

“People talk about the antivaccine people being able to kind of squelch uptake. I don’t see that happening,” Dr. Paul Offit, MD, a vaccinologist with Children’s Hospital of Philadelphia, told viewers of a recent JAMA Network webinar. “This, to me, is more like the Beanie Baby phenomenon. The attractiveness of a limited edition.”

Reports that vaccines produced by drugmakers Pfizer and BioNTech and Moderna appear to be safe and effective, along with the deliberate emphasis on science-based guidance from the incoming Biden administration, are likely to reverse uncertainty in a big way, said Arthur Caplan, PhD, director of the division of medical ethics at New York University.

“I think that’s going to flip the trust issue,” he said.

The shift is already apparent. A new poll by the Pew Research Center found that by the end of November 60% of Americans said they would get a vaccine for the coronavirus. This month, even as a federal advisory group met to hash out guidelines for vaccine distribution, a long list of advocacy groups – from those representing home-based health workers and community health centers to patients with kidney disease – were lobbying state and federal officials in hopes their constituents would be prioritized for the first scarce doses.

“As we get closer to the vaccine being a reality, there’s a lot of jockeying, to be sure,” said Katie Smith Sloan, chief executive of LeadingAge, a nonprofit organization pushing for staff and patients at long-term care centers to be included in the highest-priority category.

Certainly, some consumers remain wary, said Rupali Limaye, PhD, a social and behavioral health scientist at the Johns Hopkins Bloomberg School of Public Health, Baltimore. Fears that drugmakers and regulators might cut corners to speed a vaccine linger, even as details of the trials become public and the review process is made more transparent. Some health care workers, who are at the front of the line for the shots, are not eager to go first.

“There will be people who will say, ‘I will wait a little bit more for safety data,” Dr. Limaye said.

But those doubts likely will recede once the vaccines are approved for use and begin to circulate broadly, said Dr. Offit, who sits on the Food and Drug Administration advisory panel set to review the requests for emergency authorization Pfizer and Moderna have submitted.

He predicted demand for the COVID vaccines could rival the clamor that occurred in 2004, when production problems caused a severe shortage of flu shots just as influenza season began. That led to long lines, rationed doses and ethical debates over distribution.

“That was a highly desired vaccine,” Dr. Offit said. “I think in many ways that might happen here.”

Initially, vaccine supplies will be tight, with federal officials planning to ship 6.4 million doses within 24 hours of FDA authorization and up to 40 million doses by the end of the year. The CDC panel recommended that the first shots go to the 21 million health care workers in the United States and 3 million nursing home staff and residents, before being rolled out to other groups based on a hierarchy of risk factors.

Even before any vaccine is available, some people are trying to boost their chances of access, said Allison Kempe, MD, a professor of pediatrics at the University of Coloradoat Denver, Aurora, and expert in vaccine dissemination. “People have called me and said, ‘How can I get the vaccine?’” she said. “I think that not everyone will be happy to wait, that’s for sure. I don’t think there will be rioting in the streets, but there may be pressure brought to bear.”

That likely will include emotional debates over how, when, and to whom next doses should be distributed, said Dr. Caplan. Under the CDC recommendations, vulnerable groups next in line include 87 million workers whose jobs are deemed “essential” – a broad and ill-defined category – as well as 53 million adults age 65 and older.

“We’re going to have some fights about high-risk groups,” Dr. Caplan said.

The conversations will be complicated. Should prisoners, who have little control over their COVID exposure, get vaccine priority? How about professional sports teams, whose performance could bolster society’s overall morale? And what about residents of facilities providing care for people with intellectual and developmental disabilities, who are three times more likely to die from COVID-19 than the general population?

Control over vaccination allocation rests with the states, so that’s where the biggest conflicts will occur, Dr. Caplan said. “It’s a short fight, I hope, in the sense in which it gets done in a few months, but I think it will be pretty vocal.”

Once vaccine supplies become more plentiful, perhaps by May or June, another consideration is sure to boost demand: requirements for proof of COVID vaccination for work and travel.

“It’s inevitable that you’re going to see immunity passports or that you’re required to show a certificate on the train, airplane, bus, or subway,” Dr. Caplan predicted. “Probably also to enter certain hospitals, probably to enter certain restaurants and government facilities.”

But with a grueling winter surge ahead, and new predictions that COVID-19 will fell as many as 450,000 Americans by February, the tragic reality of the disease will no doubt fuel ample demand for vaccination.

“People now know someone who has gotten COVID, who has been hospitalized or has unfortunately died,” Dr. Limaye said.

“We’re all seeing this now,” said Dr. Kempe. “Even deniers are beginning to see what this illness can do.”

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

Americans have made no secret of their skepticism of COVID-19 vaccines this year, with fears of political interference and a “warp speed” timeline blunting confidence in the shots. As recently as September, nearly half of U.S. adults said they didn’t intend to be inoculated.

But with two promising vaccines primed for release, likely within weeks, experts in ethics and immunization behavior say they expect attitudes to shift quickly from widespread hesitancy to urgent, even heated demand.

“People talk about the antivaccine people being able to kind of squelch uptake. I don’t see that happening,” Dr. Paul Offit, MD, a vaccinologist with Children’s Hospital of Philadelphia, told viewers of a recent JAMA Network webinar. “This, to me, is more like the Beanie Baby phenomenon. The attractiveness of a limited edition.”

Reports that vaccines produced by drugmakers Pfizer and BioNTech and Moderna appear to be safe and effective, along with the deliberate emphasis on science-based guidance from the incoming Biden administration, are likely to reverse uncertainty in a big way, said Arthur Caplan, PhD, director of the division of medical ethics at New York University.

“I think that’s going to flip the trust issue,” he said.

The shift is already apparent. A new poll by the Pew Research Center found that by the end of November 60% of Americans said they would get a vaccine for the coronavirus. This month, even as a federal advisory group met to hash out guidelines for vaccine distribution, a long list of advocacy groups – from those representing home-based health workers and community health centers to patients with kidney disease – were lobbying state and federal officials in hopes their constituents would be prioritized for the first scarce doses.

“As we get closer to the vaccine being a reality, there’s a lot of jockeying, to be sure,” said Katie Smith Sloan, chief executive of LeadingAge, a nonprofit organization pushing for staff and patients at long-term care centers to be included in the highest-priority category.

Certainly, some consumers remain wary, said Rupali Limaye, PhD, a social and behavioral health scientist at the Johns Hopkins Bloomberg School of Public Health, Baltimore. Fears that drugmakers and regulators might cut corners to speed a vaccine linger, even as details of the trials become public and the review process is made more transparent. Some health care workers, who are at the front of the line for the shots, are not eager to go first.

“There will be people who will say, ‘I will wait a little bit more for safety data,” Dr. Limaye said.

But those doubts likely will recede once the vaccines are approved for use and begin to circulate broadly, said Dr. Offit, who sits on the Food and Drug Administration advisory panel set to review the requests for emergency authorization Pfizer and Moderna have submitted.

He predicted demand for the COVID vaccines could rival the clamor that occurred in 2004, when production problems caused a severe shortage of flu shots just as influenza season began. That led to long lines, rationed doses and ethical debates over distribution.

“That was a highly desired vaccine,” Dr. Offit said. “I think in many ways that might happen here.”

Initially, vaccine supplies will be tight, with federal officials planning to ship 6.4 million doses within 24 hours of FDA authorization and up to 40 million doses by the end of the year. The CDC panel recommended that the first shots go to the 21 million health care workers in the United States and 3 million nursing home staff and residents, before being rolled out to other groups based on a hierarchy of risk factors.

Even before any vaccine is available, some people are trying to boost their chances of access, said Allison Kempe, MD, a professor of pediatrics at the University of Coloradoat Denver, Aurora, and expert in vaccine dissemination. “People have called me and said, ‘How can I get the vaccine?’” she said. “I think that not everyone will be happy to wait, that’s for sure. I don’t think there will be rioting in the streets, but there may be pressure brought to bear.”

That likely will include emotional debates over how, when, and to whom next doses should be distributed, said Dr. Caplan. Under the CDC recommendations, vulnerable groups next in line include 87 million workers whose jobs are deemed “essential” – a broad and ill-defined category – as well as 53 million adults age 65 and older.

“We’re going to have some fights about high-risk groups,” Dr. Caplan said.

The conversations will be complicated. Should prisoners, who have little control over their COVID exposure, get vaccine priority? How about professional sports teams, whose performance could bolster society’s overall morale? And what about residents of facilities providing care for people with intellectual and developmental disabilities, who are three times more likely to die from COVID-19 than the general population?

Control over vaccination allocation rests with the states, so that’s where the biggest conflicts will occur, Dr. Caplan said. “It’s a short fight, I hope, in the sense in which it gets done in a few months, but I think it will be pretty vocal.”

Once vaccine supplies become more plentiful, perhaps by May or June, another consideration is sure to boost demand: requirements for proof of COVID vaccination for work and travel.

“It’s inevitable that you’re going to see immunity passports or that you’re required to show a certificate on the train, airplane, bus, or subway,” Dr. Caplan predicted. “Probably also to enter certain hospitals, probably to enter certain restaurants and government facilities.”

But with a grueling winter surge ahead, and new predictions that COVID-19 will fell as many as 450,000 Americans by February, the tragic reality of the disease will no doubt fuel ample demand for vaccination.

“People now know someone who has gotten COVID, who has been hospitalized or has unfortunately died,” Dr. Limaye said.

“We’re all seeing this now,” said Dr. Kempe. “Even deniers are beginning to see what this illness can do.”

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

Americans have made no secret of their skepticism of COVID-19 vaccines this year, with fears of political interference and a “warp speed” timeline blunting confidence in the shots. As recently as September, nearly half of U.S. adults said they didn’t intend to be inoculated.

But with two promising vaccines primed for release, likely within weeks, experts in ethics and immunization behavior say they expect attitudes to shift quickly from widespread hesitancy to urgent, even heated demand.

“People talk about the antivaccine people being able to kind of squelch uptake. I don’t see that happening,” Dr. Paul Offit, MD, a vaccinologist with Children’s Hospital of Philadelphia, told viewers of a recent JAMA Network webinar. “This, to me, is more like the Beanie Baby phenomenon. The attractiveness of a limited edition.”

Reports that vaccines produced by drugmakers Pfizer and BioNTech and Moderna appear to be safe and effective, along with the deliberate emphasis on science-based guidance from the incoming Biden administration, are likely to reverse uncertainty in a big way, said Arthur Caplan, PhD, director of the division of medical ethics at New York University.

“I think that’s going to flip the trust issue,” he said.

The shift is already apparent. A new poll by the Pew Research Center found that by the end of November 60% of Americans said they would get a vaccine for the coronavirus. This month, even as a federal advisory group met to hash out guidelines for vaccine distribution, a long list of advocacy groups – from those representing home-based health workers and community health centers to patients with kidney disease – were lobbying state and federal officials in hopes their constituents would be prioritized for the first scarce doses.

“As we get closer to the vaccine being a reality, there’s a lot of jockeying, to be sure,” said Katie Smith Sloan, chief executive of LeadingAge, a nonprofit organization pushing for staff and patients at long-term care centers to be included in the highest-priority category.

Certainly, some consumers remain wary, said Rupali Limaye, PhD, a social and behavioral health scientist at the Johns Hopkins Bloomberg School of Public Health, Baltimore. Fears that drugmakers and regulators might cut corners to speed a vaccine linger, even as details of the trials become public and the review process is made more transparent. Some health care workers, who are at the front of the line for the shots, are not eager to go first.

“There will be people who will say, ‘I will wait a little bit more for safety data,” Dr. Limaye said.

But those doubts likely will recede once the vaccines are approved for use and begin to circulate broadly, said Dr. Offit, who sits on the Food and Drug Administration advisory panel set to review the requests for emergency authorization Pfizer and Moderna have submitted.

He predicted demand for the COVID vaccines could rival the clamor that occurred in 2004, when production problems caused a severe shortage of flu shots just as influenza season began. That led to long lines, rationed doses and ethical debates over distribution.

“That was a highly desired vaccine,” Dr. Offit said. “I think in many ways that might happen here.”

Initially, vaccine supplies will be tight, with federal officials planning to ship 6.4 million doses within 24 hours of FDA authorization and up to 40 million doses by the end of the year. The CDC panel recommended that the first shots go to the 21 million health care workers in the United States and 3 million nursing home staff and residents, before being rolled out to other groups based on a hierarchy of risk factors.

Even before any vaccine is available, some people are trying to boost their chances of access, said Allison Kempe, MD, a professor of pediatrics at the University of Coloradoat Denver, Aurora, and expert in vaccine dissemination. “People have called me and said, ‘How can I get the vaccine?’” she said. “I think that not everyone will be happy to wait, that’s for sure. I don’t think there will be rioting in the streets, but there may be pressure brought to bear.”

That likely will include emotional debates over how, when, and to whom next doses should be distributed, said Dr. Caplan. Under the CDC recommendations, vulnerable groups next in line include 87 million workers whose jobs are deemed “essential” – a broad and ill-defined category – as well as 53 million adults age 65 and older.

“We’re going to have some fights about high-risk groups,” Dr. Caplan said.

The conversations will be complicated. Should prisoners, who have little control over their COVID exposure, get vaccine priority? How about professional sports teams, whose performance could bolster society’s overall morale? And what about residents of facilities providing care for people with intellectual and developmental disabilities, who are three times more likely to die from COVID-19 than the general population?

Control over vaccination allocation rests with the states, so that’s where the biggest conflicts will occur, Dr. Caplan said. “It’s a short fight, I hope, in the sense in which it gets done in a few months, but I think it will be pretty vocal.”

Once vaccine supplies become more plentiful, perhaps by May or June, another consideration is sure to boost demand: requirements for proof of COVID vaccination for work and travel.

“It’s inevitable that you’re going to see immunity passports or that you’re required to show a certificate on the train, airplane, bus, or subway,” Dr. Caplan predicted. “Probably also to enter certain hospitals, probably to enter certain restaurants and government facilities.”

But with a grueling winter surge ahead, and new predictions that COVID-19 will fell as many as 450,000 Americans by February, the tragic reality of the disease will no doubt fuel ample demand for vaccination.

“People now know someone who has gotten COVID, who has been hospitalized or has unfortunately died,” Dr. Limaye said.

“We’re all seeing this now,” said Dr. Kempe. “Even deniers are beginning to see what this illness can do.”

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.