Hyperglycemia at hospital admission – regardless of diabetes status – is a key predictor of COVID-19-related death and severity among noncritical patients, new research from Spain finds.

The observational study, the largest to date to investigate this association, was published online Nov. 23 in Annals of Medicine by Francisco Javier Carrasco-Sánchez, MD, PhD, and colleagues.

Among more than 11,000 patients with confirmed COVID-19 from March to May 2020 in a nationwide Spanish registry involving 109 hospitals, admission hyperglycemia independently predicted progression from noncritical to critical condition and death, regardless of prior diabetes history. 

Those with abnormally high glucose levels were more than twice as likely to die from the virus than those with normal readings (41.4% vs 15.7%). They also had an increased need for a ventilator and intensive care unit (ICU) admission.

“These results provided a simple and practical way to stratify risk of death in hospitalized patients with COVID-19. Hence, admission hyperglycemia should not be overlooked, but rather detected and appropriately treated to improve the outcomes of COVID-19 patients with and without diabetes,” Dr. Carrasco-Sánchez and colleagues wrote.

The findings confirm those of previous retrospective observational studies, but the current study “has, by far, the biggest number of patients involved in this kind of study [to date]. All conclusions are consistent to other studies,” Dr. Carrasco-Sánchez, of University Hospital Juan Ramón Jiménez, Huelva, Spain, said in an interview.

However, a surprising finding, he said, “was how hyperglycemia works in the nondiabetic population and [that] glucose levels over 140 [mg/dL] ... increase the risk of death.”
 

Pay attention to even mild hyperglycemia from admission

The study also differs from some of the prior observational ones in that it examines outcome by admission glycemia rather than during the hospital stay, therefore eliminating the effect of any inpatient treatment, such as dexamethasone, he noted.

Although blood glucose measurement at admission is routine for all patients in Spain, as it is in the United States and elsewhere, a mildly elevated level in a person without a diagnosis of diabetes may not be recognized as important.

“In patients with diabetes we start the protocol to control and treat hyperglycemia during hospitalization. However, in nondiabetic patients blood glucose levels under 180 [mg/dL], and even greater, are usually overlooked. This means there is not a correct follow-up of the patients during hospitalization.

“After this study we learned that we need to pay attention to this population ... who develop hyperglycemia from the beginning,” he said.  

The study was limited in that patients who had previously undiagnosed diabetes couldn’t always be distinguished from those with acute “stress hyperglycemia.”

However, both need to be managed during hospitalization, he said. “Unfortunately, there is high variability in inpatient glucose management. The working group of diabetes of the Spanish Society of Internal Medicine is working on specific protocols,” said Dr. Carrasco-Sánchez.
 

All-cause death, progress to critical care higher with hyperglycemia

The retrospective, multicenter study was based on data from 11,312 adult patients with confirmed COVID-19 in 109 hospitals participating in Spain’s SEMI-COVID-19 registry as of May 29, 2020. They had a mean age of 67 years, 57% were male, and 19% had a diagnosis of diabetes. A total of 20% (n = 2,289) died during hospitalization.

Overall all-cause mortality was 41.1% among those with admission blood glucose levels above 180 mg/dL, 33.0% for those with glucose levels 140-180 mg/dL, and 15.7% for levels below 140 mg/dL. All differences were significant (P < .0001), but there were no differences in mortality rates within each blood glucose category between patients with or without a previous diagnosis of diabetes.

After adjustment for confounding factors, elevated admission blood glucose level remained a significant predictor of death. Compared to < 140 mg/dL, the hazard ratios for 140-180 mg/dL and > 180 mg/dL were 1.48 and 1.50, respectively (both P < .001). (Adjustments included age, gender, hypertension, diabetes, chronic obstructive pulmonary disease, lymphopenia, anemia (hemoglobin < 10 g/dL), serum creatinine, C-reactive protein > 60 mg/L, lactate dehydrogenase > 400 U/L and D-dimer >1000 ng/mL.)

Length of stay was 12, 11.5, and 11.1 days for those with admission blood glucose levels > 180, 140-180, and < 140 mg/dL, respectively (P = .011).

Use of mechanical ventilation and admission to intensive care also rose with higher admission blood glucose levels. For the composite of death, mechanical ventilation, and/or ICU admission, odds ratios for 140-180 mg/dL and > 180 mg/dL compared with < 140 mg/dL were 1.70 and 2.02, respectively (both P < .001). 

The study was supported by the Spanish Federation of Internal Medicine. The authors have reported no relevant financial relationships.

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

Hyperglycemia at hospital admission – regardless of diabetes status – is a key predictor of COVID-19-related death and severity among noncritical patients, new research from Spain finds.

The observational study, the largest to date to investigate this association, was published online Nov. 23 in Annals of Medicine by Francisco Javier Carrasco-Sánchez, MD, PhD, and colleagues.

Among more than 11,000 patients with confirmed COVID-19 from March to May 2020 in a nationwide Spanish registry involving 109 hospitals, admission hyperglycemia independently predicted progression from noncritical to critical condition and death, regardless of prior diabetes history. 

Those with abnormally high glucose levels were more than twice as likely to die from the virus than those with normal readings (41.4% vs 15.7%). They also had an increased need for a ventilator and intensive care unit (ICU) admission.

“These results provided a simple and practical way to stratify risk of death in hospitalized patients with COVID-19. Hence, admission hyperglycemia should not be overlooked, but rather detected and appropriately treated to improve the outcomes of COVID-19 patients with and without diabetes,” Dr. Carrasco-Sánchez and colleagues wrote.

The findings confirm those of previous retrospective observational studies, but the current study “has, by far, the biggest number of patients involved in this kind of study [to date]. All conclusions are consistent to other studies,” Dr. Carrasco-Sánchez, of University Hospital Juan Ramón Jiménez, Huelva, Spain, said in an interview.

However, a surprising finding, he said, “was how hyperglycemia works in the nondiabetic population and [that] glucose levels over 140 [mg/dL] ... increase the risk of death.”
 

Pay attention to even mild hyperglycemia from admission

The study also differs from some of the prior observational ones in that it examines outcome by admission glycemia rather than during the hospital stay, therefore eliminating the effect of any inpatient treatment, such as dexamethasone, he noted.

Although blood glucose measurement at admission is routine for all patients in Spain, as it is in the United States and elsewhere, a mildly elevated level in a person without a diagnosis of diabetes may not be recognized as important.

“In patients with diabetes we start the protocol to control and treat hyperglycemia during hospitalization. However, in nondiabetic patients blood glucose levels under 180 [mg/dL], and even greater, are usually overlooked. This means there is not a correct follow-up of the patients during hospitalization.

“After this study we learned that we need to pay attention to this population ... who develop hyperglycemia from the beginning,” he said.  

The study was limited in that patients who had previously undiagnosed diabetes couldn’t always be distinguished from those with acute “stress hyperglycemia.”

However, both need to be managed during hospitalization, he said. “Unfortunately, there is high variability in inpatient glucose management. The working group of diabetes of the Spanish Society of Internal Medicine is working on specific protocols,” said Dr. Carrasco-Sánchez.
 

All-cause death, progress to critical care higher with hyperglycemia

The retrospective, multicenter study was based on data from 11,312 adult patients with confirmed COVID-19 in 109 hospitals participating in Spain’s SEMI-COVID-19 registry as of May 29, 2020. They had a mean age of 67 years, 57% were male, and 19% had a diagnosis of diabetes. A total of 20% (n = 2,289) died during hospitalization.

Overall all-cause mortality was 41.1% among those with admission blood glucose levels above 180 mg/dL, 33.0% for those with glucose levels 140-180 mg/dL, and 15.7% for levels below 140 mg/dL. All differences were significant (P < .0001), but there were no differences in mortality rates within each blood glucose category between patients with or without a previous diagnosis of diabetes.

After adjustment for confounding factors, elevated admission blood glucose level remained a significant predictor of death. Compared to < 140 mg/dL, the hazard ratios for 140-180 mg/dL and > 180 mg/dL were 1.48 and 1.50, respectively (both P < .001). (Adjustments included age, gender, hypertension, diabetes, chronic obstructive pulmonary disease, lymphopenia, anemia (hemoglobin < 10 g/dL), serum creatinine, C-reactive protein > 60 mg/L, lactate dehydrogenase > 400 U/L and D-dimer >1000 ng/mL.)

Length of stay was 12, 11.5, and 11.1 days for those with admission blood glucose levels > 180, 140-180, and < 140 mg/dL, respectively (P = .011).

Use of mechanical ventilation and admission to intensive care also rose with higher admission blood glucose levels. For the composite of death, mechanical ventilation, and/or ICU admission, odds ratios for 140-180 mg/dL and > 180 mg/dL compared with < 140 mg/dL were 1.70 and 2.02, respectively (both P < .001). 

The study was supported by the Spanish Federation of Internal Medicine. The authors have reported no relevant financial relationships.

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

Hyperglycemia at hospital admission – regardless of diabetes status – is a key predictor of COVID-19-related death and severity among noncritical patients, new research from Spain finds.

The observational study, the largest to date to investigate this association, was published online Nov. 23 in Annals of Medicine by Francisco Javier Carrasco-Sánchez, MD, PhD, and colleagues.

Among more than 11,000 patients with confirmed COVID-19 from March to May 2020 in a nationwide Spanish registry involving 109 hospitals, admission hyperglycemia independently predicted progression from noncritical to critical condition and death, regardless of prior diabetes history. 

Those with abnormally high glucose levels were more than twice as likely to die from the virus than those with normal readings (41.4% vs 15.7%). They also had an increased need for a ventilator and intensive care unit (ICU) admission.

“These results provided a simple and practical way to stratify risk of death in hospitalized patients with COVID-19. Hence, admission hyperglycemia should not be overlooked, but rather detected and appropriately treated to improve the outcomes of COVID-19 patients with and without diabetes,” Dr. Carrasco-Sánchez and colleagues wrote.

The findings confirm those of previous retrospective observational studies, but the current study “has, by far, the biggest number of patients involved in this kind of study [to date]. All conclusions are consistent to other studies,” Dr. Carrasco-Sánchez, of University Hospital Juan Ramón Jiménez, Huelva, Spain, said in an interview.

However, a surprising finding, he said, “was how hyperglycemia works in the nondiabetic population and [that] glucose levels over 140 [mg/dL] ... increase the risk of death.”
 

Pay attention to even mild hyperglycemia from admission

The study also differs from some of the prior observational ones in that it examines outcome by admission glycemia rather than during the hospital stay, therefore eliminating the effect of any inpatient treatment, such as dexamethasone, he noted.

Although blood glucose measurement at admission is routine for all patients in Spain, as it is in the United States and elsewhere, a mildly elevated level in a person without a diagnosis of diabetes may not be recognized as important.

“In patients with diabetes we start the protocol to control and treat hyperglycemia during hospitalization. However, in nondiabetic patients blood glucose levels under 180 [mg/dL], and even greater, are usually overlooked. This means there is not a correct follow-up of the patients during hospitalization.

“After this study we learned that we need to pay attention to this population ... who develop hyperglycemia from the beginning,” he said.  

The study was limited in that patients who had previously undiagnosed diabetes couldn’t always be distinguished from those with acute “stress hyperglycemia.”

However, both need to be managed during hospitalization, he said. “Unfortunately, there is high variability in inpatient glucose management. The working group of diabetes of the Spanish Society of Internal Medicine is working on specific protocols,” said Dr. Carrasco-Sánchez.
 

All-cause death, progress to critical care higher with hyperglycemia

The retrospective, multicenter study was based on data from 11,312 adult patients with confirmed COVID-19 in 109 hospitals participating in Spain’s SEMI-COVID-19 registry as of May 29, 2020. They had a mean age of 67 years, 57% were male, and 19% had a diagnosis of diabetes. A total of 20% (n = 2,289) died during hospitalization.

Overall all-cause mortality was 41.1% among those with admission blood glucose levels above 180 mg/dL, 33.0% for those with glucose levels 140-180 mg/dL, and 15.7% for levels below 140 mg/dL. All differences were significant (P < .0001), but there were no differences in mortality rates within each blood glucose category between patients with or without a previous diagnosis of diabetes.

After adjustment for confounding factors, elevated admission blood glucose level remained a significant predictor of death. Compared to < 140 mg/dL, the hazard ratios for 140-180 mg/dL and > 180 mg/dL were 1.48 and 1.50, respectively (both P < .001). (Adjustments included age, gender, hypertension, diabetes, chronic obstructive pulmonary disease, lymphopenia, anemia (hemoglobin < 10 g/dL), serum creatinine, C-reactive protein > 60 mg/L, lactate dehydrogenase > 400 U/L and D-dimer >1000 ng/mL.)

Length of stay was 12, 11.5, and 11.1 days for those with admission blood glucose levels > 180, 140-180, and < 140 mg/dL, respectively (P = .011).

Use of mechanical ventilation and admission to intensive care also rose with higher admission blood glucose levels. For the composite of death, mechanical ventilation, and/or ICU admission, odds ratios for 140-180 mg/dL and > 180 mg/dL compared with < 140 mg/dL were 1.70 and 2.02, respectively (both P < .001). 

The study was supported by the Spanish Federation of Internal Medicine. The authors have reported no relevant financial relationships.

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

The interventional cardiology community is mourning the loss of Anthony “Tony” Gershlick, MBBS, who died Nov. 20 of COVID-19. He was 69 years old.

Dr. Gershlick was a “talented, dedicated and much loved colleague,” reads a statement issued by the University of Leicester (England), where he was affiliated for more than 3 decades.

Dr. Gershlick, a consultant cardiologist at Glenfield Hospital and professor of interventional cardiology, University of Leicester, passed away in the intensive care unit of the hospital where he worked.

Nishan Canagarajah, PhD, president and vice-chancellor, University of Leicester, said Dr. Gershlick “left an indelible mark on the life of the University. He will be remembered with great affection by all and will be sorely missed.”

In 2017, Dr. Gershlick was honored with the inaugural British Cardiovascular Intervention Society (BCIS) Lifetime Achievement Career Award for his “outstanding contribution to the specialty of coronary intervention.”

Gershlick was a pioneer in the field of percutaneous coronary intervention. He was the first UK cardiologist to implant a drug-eluting stent and a bioabsorbable stent, according to an article in the European Heart Journal.

Throughout his career, Dr. Gershlick had been involved in “practice-changing” research that changed the way patients are treated and led to national and international guidelines. He was the UK lead for more than 10 international trials, the university said.

“Tony was determined to push the boundaries of clinical care, to make a difference for his patients, and indeed, patients around the world,” said Philip Baker, DM, FMedSci, head of the College of Life Science, University of Leicester.

Andrew Furlong, medical director at the University Hospitals of Leicester, noted that Dr. Gershlick was “deeply committed to the training and development of junior doctors and registrars and known for his dedication to his field and his patients. He made a difference to many, many lives.”

According to the university, Dr. Gershlick had been working in non-COVID environments since April and was doing much of his work via virtual consultations. He took on cases from other consultants to help during the pandemic and had been working “tirelessly” to provide continuing care to cardiology patients.

The news of Dr. Gershlick’s passing prompted an outpouring of sadness and remembrances of him on Twitter.

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

The interventional cardiology community is mourning the loss of Anthony “Tony” Gershlick, MBBS, who died Nov. 20 of COVID-19. He was 69 years old.

Dr. Gershlick was a “talented, dedicated and much loved colleague,” reads a statement issued by the University of Leicester (England), where he was affiliated for more than 3 decades.

Dr. Gershlick, a consultant cardiologist at Glenfield Hospital and professor of interventional cardiology, University of Leicester, passed away in the intensive care unit of the hospital where he worked.

Nishan Canagarajah, PhD, president and vice-chancellor, University of Leicester, said Dr. Gershlick “left an indelible mark on the life of the University. He will be remembered with great affection by all and will be sorely missed.”

In 2017, Dr. Gershlick was honored with the inaugural British Cardiovascular Intervention Society (BCIS) Lifetime Achievement Career Award for his “outstanding contribution to the specialty of coronary intervention.”

Gershlick was a pioneer in the field of percutaneous coronary intervention. He was the first UK cardiologist to implant a drug-eluting stent and a bioabsorbable stent, according to an article in the European Heart Journal.

Throughout his career, Dr. Gershlick had been involved in “practice-changing” research that changed the way patients are treated and led to national and international guidelines. He was the UK lead for more than 10 international trials, the university said.

“Tony was determined to push the boundaries of clinical care, to make a difference for his patients, and indeed, patients around the world,” said Philip Baker, DM, FMedSci, head of the College of Life Science, University of Leicester.

Andrew Furlong, medical director at the University Hospitals of Leicester, noted that Dr. Gershlick was “deeply committed to the training and development of junior doctors and registrars and known for his dedication to his field and his patients. He made a difference to many, many lives.”

According to the university, Dr. Gershlick had been working in non-COVID environments since April and was doing much of his work via virtual consultations. He took on cases from other consultants to help during the pandemic and had been working “tirelessly” to provide continuing care to cardiology patients.

The news of Dr. Gershlick’s passing prompted an outpouring of sadness and remembrances of him on Twitter.

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

The interventional cardiology community is mourning the loss of Anthony “Tony” Gershlick, MBBS, who died Nov. 20 of COVID-19. He was 69 years old.

Dr. Gershlick was a “talented, dedicated and much loved colleague,” reads a statement issued by the University of Leicester (England), where he was affiliated for more than 3 decades.

Dr. Gershlick, a consultant cardiologist at Glenfield Hospital and professor of interventional cardiology, University of Leicester, passed away in the intensive care unit of the hospital where he worked.

Nishan Canagarajah, PhD, president and vice-chancellor, University of Leicester, said Dr. Gershlick “left an indelible mark on the life of the University. He will be remembered with great affection by all and will be sorely missed.”

In 2017, Dr. Gershlick was honored with the inaugural British Cardiovascular Intervention Society (BCIS) Lifetime Achievement Career Award for his “outstanding contribution to the specialty of coronary intervention.”

Gershlick was a pioneer in the field of percutaneous coronary intervention. He was the first UK cardiologist to implant a drug-eluting stent and a bioabsorbable stent, according to an article in the European Heart Journal.

Throughout his career, Dr. Gershlick had been involved in “practice-changing” research that changed the way patients are treated and led to national and international guidelines. He was the UK lead for more than 10 international trials, the university said.

“Tony was determined to push the boundaries of clinical care, to make a difference for his patients, and indeed, patients around the world,” said Philip Baker, DM, FMedSci, head of the College of Life Science, University of Leicester.

Andrew Furlong, medical director at the University Hospitals of Leicester, noted that Dr. Gershlick was “deeply committed to the training and development of junior doctors and registrars and known for his dedication to his field and his patients. He made a difference to many, many lives.”

According to the university, Dr. Gershlick had been working in non-COVID environments since April and was doing much of his work via virtual consultations. He took on cases from other consultants to help during the pandemic and had been working “tirelessly” to provide continuing care to cardiology patients.

The news of Dr. Gershlick’s passing prompted an outpouring of sadness and remembrances of him on Twitter.

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

The known reduction in the risk of type 2 diabetes associated with adoption of the Mediterranean diet appears specifically attributed to its beneficial effects on some key factors, a new study published online in JAMA Network Open reveals.

While a reduction in body mass index may be somewhat obvious, other mechanisms include beneficial effects on insulin resistance, lipoprotein metabolism, and inflammation.

However, the diet’s antidiabetes effect does not appear to extend to people whose weight is considered healthy (BMI under 25 kg/m²), according to the findings.

“It is striking to see in these U.S. women how strong the long-term antidiabetic properties of a Mediterranean-type dietary pattern are,” senior author Samia Mora, MD, of the Center for Lipid Metabolomics, Brigham and Women’s Hospital, Harvard Medical School, Boston, said in an interview.

“While it was known that the Mediterranean diet has many health benefits in particular on metabolism and inflammation, it was not previously known which of these biological pathways may be contributing to the lower risk of diabetes and to what magnitude.

“Our findings support the idea that by improving their diet, people can improve their future risk of type 2 diabetes, particularly if they are overweight or have obesity,” she added.

“And it’s important to note that many of these changes don’t happen right away. While metabolism can change over a short period of time, our study indicates that there are longer term changes happening that may provide protection over decades.”
 

Mediterranean diet reduced diabetes risk in those with BMI ≥ 25 kg/m²

The Mediterranean diet, with an emphasis on healthy olive oil as the predominant source of oil, favors fruits, vegetables, legumes, nuts, seeds, fish, and dairy products, while limiting intake of red and processed meats as well as sweets.

The diet has been linked to as much as a 25%-30% reduction in the risk of diabetes in previous observational studies.

To investigate the precise mechanisms that underlie the prevention of diabetes, lead author Shafqat Ahmad, PhD, also of Harvard, and colleagues examined data from 25,317 healthy women participating in the Women’s Health Study who had baseline assessments between September 1992 and May 1995. They were a mean age of 52.9 years at baseline.

Over the course of the study, 2,307 participants developed type 2 diabetes.

With a mean follow-up of 19.8 years, those who had the highest self-reported adherence to the Mediterranean diet (a score ≥ 6 on a scale of 0-6) at baseline, had as much as a 30% lower risk of developing type 2 diabetes after multivariate adjustments, compared to those with a lower Mediterranean diet score (a score ≤ 3; hazard ratio, 0.70).

The diabetes-related biomarkers that contributed the most to the reduced risk were insulin resistance, accounting for 65% of the reduction, followed by BMI (55.5%), high-density lipoprotein measures (53%), and inflammation (52.5%).

Other factors, though to a lesser degree, included branched-chain amino acids (34.5%), very low-density lipoprotein measures (32.0%), low-density lipoprotein measures (31.0%), blood pressure (29.0%), and apolipoproteins (23.5%).

Differences in hemoglobin A1c levels had a limited effect on the risk (2%).

Notably, a subgroup analysis looking at effects of the diet according to baseline BMI showed the reductions in type 2 diabetes associated with higher intake of the Mediterranean diet extended only to those with an above normal weight (BMI ≥ 25 kg/m²).

Dr. Mora noted that, as this was not a prespecified analysis, these findings should be viewed as hypothesis-generating, but are consistent with the well-known increase in diabetes risk seen with a higher BMI.

“[The finding] fits with the biology and pathogenesis of type 2 diabetes that is driven in large part by excess weight, in particular for visceral adiposity and its resulting metabolic dysregulation and inflammation,” she said.

“We know from other studies, such as the Nurses’ Health Study, that the risk for type 2 diabetes in women increases even at BMI levels below 25 kg/m², but the risk goes up exponentially at around a BMI of 25 and higher.”

Strong role of insulin resistance a surprise

The strong role of insulin resistance was a surprise, Dr. Mora added.

“We were surprised that insulin resistance, measured by a simple blood biomarker, would have the strongest mediating effect – even stronger than BMI – for the Mediterranean diet on risk of diabetes,” she noted.

“This could represent an opportunity to intervene earlier and more intensively on improving insulin resistance through dietary approaches such as the Mediterranean diet, especially [because] insulin resistance can precede by years and decades the overt hyperglycemia and clinical diagnosis of diabetes.”

Yet another surprise was that A1c had no substantial mediating effect on the reduction of diabetes risk with the Mediterranean diet.

“This could suggest that the cat is out of the bag by the time the A1c rises,” Dr. Mora observed.

A study limitation is that the Women’s Health Study consisted of well-educated U.S. women who were health professionals and predominantly White, so the results may not be generalizable to men or individuals of other races or ethnicities.

In addition, BMI was self-reported and participants were not uniformly screened for diabetes, therefore surveillance bias could be possible.

However, the findings suggest that “even a small increase in adherence to the Mediterranean diet has substantial benefits over many years in preventing diabetes, among many other health benefits such as lowering insulin resistance and inflammation, improving lipid metabolism, and lowering blood pressure,” Mora said.

“And of course, the more the adherence, the more the benefit.” 

The study received support through grants from the National Institutes of Health, the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the American Heart Association, and the Molino Family Trust. A coauthor is listed as a coinventor on patents held by Brigham and Women’s Hospital related to the use of inflammatory biomarkers in cardiovascular disease (licensed to AstraZeneca and Siemens).

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

The known reduction in the risk of type 2 diabetes associated with adoption of the Mediterranean diet appears specifically attributed to its beneficial effects on some key factors, a new study published online in JAMA Network Open reveals.

While a reduction in body mass index may be somewhat obvious, other mechanisms include beneficial effects on insulin resistance, lipoprotein metabolism, and inflammation.

However, the diet’s antidiabetes effect does not appear to extend to people whose weight is considered healthy (BMI under 25 kg/m²), according to the findings.

“It is striking to see in these U.S. women how strong the long-term antidiabetic properties of a Mediterranean-type dietary pattern are,” senior author Samia Mora, MD, of the Center for Lipid Metabolomics, Brigham and Women’s Hospital, Harvard Medical School, Boston, said in an interview.

“While it was known that the Mediterranean diet has many health benefits in particular on metabolism and inflammation, it was not previously known which of these biological pathways may be contributing to the lower risk of diabetes and to what magnitude.

“Our findings support the idea that by improving their diet, people can improve their future risk of type 2 diabetes, particularly if they are overweight or have obesity,” she added.

“And it’s important to note that many of these changes don’t happen right away. While metabolism can change over a short period of time, our study indicates that there are longer term changes happening that may provide protection over decades.”
 

Mediterranean diet reduced diabetes risk in those with BMI ≥ 25 kg/m²

The Mediterranean diet, with an emphasis on healthy olive oil as the predominant source of oil, favors fruits, vegetables, legumes, nuts, seeds, fish, and dairy products, while limiting intake of red and processed meats as well as sweets.

The diet has been linked to as much as a 25%-30% reduction in the risk of diabetes in previous observational studies.

To investigate the precise mechanisms that underlie the prevention of diabetes, lead author Shafqat Ahmad, PhD, also of Harvard, and colleagues examined data from 25,317 healthy women participating in the Women’s Health Study who had baseline assessments between September 1992 and May 1995. They were a mean age of 52.9 years at baseline.

Over the course of the study, 2,307 participants developed type 2 diabetes.

With a mean follow-up of 19.8 years, those who had the highest self-reported adherence to the Mediterranean diet (a score ≥ 6 on a scale of 0-6) at baseline, had as much as a 30% lower risk of developing type 2 diabetes after multivariate adjustments, compared to those with a lower Mediterranean diet score (a score ≤ 3; hazard ratio, 0.70).

The diabetes-related biomarkers that contributed the most to the reduced risk were insulin resistance, accounting for 65% of the reduction, followed by BMI (55.5%), high-density lipoprotein measures (53%), and inflammation (52.5%).

Other factors, though to a lesser degree, included branched-chain amino acids (34.5%), very low-density lipoprotein measures (32.0%), low-density lipoprotein measures (31.0%), blood pressure (29.0%), and apolipoproteins (23.5%).

Differences in hemoglobin A1c levels had a limited effect on the risk (2%).

Notably, a subgroup analysis looking at effects of the diet according to baseline BMI showed the reductions in type 2 diabetes associated with higher intake of the Mediterranean diet extended only to those with an above normal weight (BMI ≥ 25 kg/m²).

Dr. Mora noted that, as this was not a prespecified analysis, these findings should be viewed as hypothesis-generating, but are consistent with the well-known increase in diabetes risk seen with a higher BMI.

“[The finding] fits with the biology and pathogenesis of type 2 diabetes that is driven in large part by excess weight, in particular for visceral adiposity and its resulting metabolic dysregulation and inflammation,” she said.

“We know from other studies, such as the Nurses’ Health Study, that the risk for type 2 diabetes in women increases even at BMI levels below 25 kg/m², but the risk goes up exponentially at around a BMI of 25 and higher.”

Strong role of insulin resistance a surprise

The strong role of insulin resistance was a surprise, Dr. Mora added.

“We were surprised that insulin resistance, measured by a simple blood biomarker, would have the strongest mediating effect – even stronger than BMI – for the Mediterranean diet on risk of diabetes,” she noted.

“This could represent an opportunity to intervene earlier and more intensively on improving insulin resistance through dietary approaches such as the Mediterranean diet, especially [because] insulin resistance can precede by years and decades the overt hyperglycemia and clinical diagnosis of diabetes.”

Yet another surprise was that A1c had no substantial mediating effect on the reduction of diabetes risk with the Mediterranean diet.

“This could suggest that the cat is out of the bag by the time the A1c rises,” Dr. Mora observed.

A study limitation is that the Women’s Health Study consisted of well-educated U.S. women who were health professionals and predominantly White, so the results may not be generalizable to men or individuals of other races or ethnicities.

In addition, BMI was self-reported and participants were not uniformly screened for diabetes, therefore surveillance bias could be possible.

However, the findings suggest that “even a small increase in adherence to the Mediterranean diet has substantial benefits over many years in preventing diabetes, among many other health benefits such as lowering insulin resistance and inflammation, improving lipid metabolism, and lowering blood pressure,” Mora said.

“And of course, the more the adherence, the more the benefit.” 

The study received support through grants from the National Institutes of Health, the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the American Heart Association, and the Molino Family Trust. A coauthor is listed as a coinventor on patents held by Brigham and Women’s Hospital related to the use of inflammatory biomarkers in cardiovascular disease (licensed to AstraZeneca and Siemens).

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

The known reduction in the risk of type 2 diabetes associated with adoption of the Mediterranean diet appears specifically attributed to its beneficial effects on some key factors, a new study published online in JAMA Network Open reveals.

While a reduction in body mass index may be somewhat obvious, other mechanisms include beneficial effects on insulin resistance, lipoprotein metabolism, and inflammation.

However, the diet’s antidiabetes effect does not appear to extend to people whose weight is considered healthy (BMI under 25 kg/m²), according to the findings.

“It is striking to see in these U.S. women how strong the long-term antidiabetic properties of a Mediterranean-type dietary pattern are,” senior author Samia Mora, MD, of the Center for Lipid Metabolomics, Brigham and Women’s Hospital, Harvard Medical School, Boston, said in an interview.

“While it was known that the Mediterranean diet has many health benefits in particular on metabolism and inflammation, it was not previously known which of these biological pathways may be contributing to the lower risk of diabetes and to what magnitude.

“Our findings support the idea that by improving their diet, people can improve their future risk of type 2 diabetes, particularly if they are overweight or have obesity,” she added.

“And it’s important to note that many of these changes don’t happen right away. While metabolism can change over a short period of time, our study indicates that there are longer term changes happening that may provide protection over decades.”
 

Mediterranean diet reduced diabetes risk in those with BMI ≥ 25 kg/m²

The Mediterranean diet, with an emphasis on healthy olive oil as the predominant source of oil, favors fruits, vegetables, legumes, nuts, seeds, fish, and dairy products, while limiting intake of red and processed meats as well as sweets.

The diet has been linked to as much as a 25%-30% reduction in the risk of diabetes in previous observational studies.

To investigate the precise mechanisms that underlie the prevention of diabetes, lead author Shafqat Ahmad, PhD, also of Harvard, and colleagues examined data from 25,317 healthy women participating in the Women’s Health Study who had baseline assessments between September 1992 and May 1995. They were a mean age of 52.9 years at baseline.

Over the course of the study, 2,307 participants developed type 2 diabetes.

With a mean follow-up of 19.8 years, those who had the highest self-reported adherence to the Mediterranean diet (a score ≥ 6 on a scale of 0-6) at baseline, had as much as a 30% lower risk of developing type 2 diabetes after multivariate adjustments, compared to those with a lower Mediterranean diet score (a score ≤ 3; hazard ratio, 0.70).

The diabetes-related biomarkers that contributed the most to the reduced risk were insulin resistance, accounting for 65% of the reduction, followed by BMI (55.5%), high-density lipoprotein measures (53%), and inflammation (52.5%).

Other factors, though to a lesser degree, included branched-chain amino acids (34.5%), very low-density lipoprotein measures (32.0%), low-density lipoprotein measures (31.0%), blood pressure (29.0%), and apolipoproteins (23.5%).

Differences in hemoglobin A1c levels had a limited effect on the risk (2%).

Notably, a subgroup analysis looking at effects of the diet according to baseline BMI showed the reductions in type 2 diabetes associated with higher intake of the Mediterranean diet extended only to those with an above normal weight (BMI ≥ 25 kg/m²).

Dr. Mora noted that, as this was not a prespecified analysis, these findings should be viewed as hypothesis-generating, but are consistent with the well-known increase in diabetes risk seen with a higher BMI.

“[The finding] fits with the biology and pathogenesis of type 2 diabetes that is driven in large part by excess weight, in particular for visceral adiposity and its resulting metabolic dysregulation and inflammation,” she said.

“We know from other studies, such as the Nurses’ Health Study, that the risk for type 2 diabetes in women increases even at BMI levels below 25 kg/m², but the risk goes up exponentially at around a BMI of 25 and higher.”

Strong role of insulin resistance a surprise

The strong role of insulin resistance was a surprise, Dr. Mora added.

“We were surprised that insulin resistance, measured by a simple blood biomarker, would have the strongest mediating effect – even stronger than BMI – for the Mediterranean diet on risk of diabetes,” she noted.

“This could represent an opportunity to intervene earlier and more intensively on improving insulin resistance through dietary approaches such as the Mediterranean diet, especially [because] insulin resistance can precede by years and decades the overt hyperglycemia and clinical diagnosis of diabetes.”

Yet another surprise was that A1c had no substantial mediating effect on the reduction of diabetes risk with the Mediterranean diet.

“This could suggest that the cat is out of the bag by the time the A1c rises,” Dr. Mora observed.

A study limitation is that the Women’s Health Study consisted of well-educated U.S. women who were health professionals and predominantly White, so the results may not be generalizable to men or individuals of other races or ethnicities.

In addition, BMI was self-reported and participants were not uniformly screened for diabetes, therefore surveillance bias could be possible.

However, the findings suggest that “even a small increase in adherence to the Mediterranean diet has substantial benefits over many years in preventing diabetes, among many other health benefits such as lowering insulin resistance and inflammation, improving lipid metabolism, and lowering blood pressure,” Mora said.

“And of course, the more the adherence, the more the benefit.” 

The study received support through grants from the National Institutes of Health, the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the American Heart Association, and the Molino Family Trust. A coauthor is listed as a coinventor on patents held by Brigham and Women’s Hospital related to the use of inflammatory biomarkers in cardiovascular disease (licensed to AstraZeneca and Siemens).

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

LAS VEGAS – Current major guidelines for treatment of psoriatic arthritis (PsA) shortchange the value of the anti–interleukin-17 biologics for this disease, Kenneth B. Gordon, MD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

The 2018 joint American College of Rheumatology/National Psoriasis Association guidelines recommend the anti–tumor necrosis factor agents as first-line biologic therapy for PsA, with the anti–IL-17 biologics held in reserve as second-tier therapy for when the anti-TNFs don’t work. That’s largely because the guidance was developed before the compelling evidence for the anti–IL-17 agents as the biologics of choice was appreciated, according to Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.

“Many people go by these guidelines,” the dermatologist noted. “I think it’s really critical to look at the data and not just the guidelines because the guidelines don’t give full credit to the anti–IL-17 agents,” he added.

“Emerging psoriatic arthritis data may likely put this class of medications into the forefront of treatment for patients who have both psoriasis and psoriatic arthritis because you generally get higher responses for the skin disease than with anti-TNF therapy, and with similar responses in psoriatic arthritis.”

Two IL-17 inhibitors are approved for both PsA and psoriasis: secukinumab (Cosentyx) and ixekizumab (Taltz). In addition, brodalumab (Siliq), approved for psoriasis, is expected to receive an expanded indication for PsA based upon its strong showing in the AMVISION-1 and -2 trials. Data from those trials, as well as the FUTURE 2 trial for secukinumab and SPIRIT-P1 for ixekizumab, consistently document at least 20% improvement in the ACR criteria for PsA severity – that is, an ACR 20 response – in 50%-60% of patients on one of the three IL-17 inhibitors, as well as ACR 50 response rates of around 30%. Those outcomes are quite consistent with the impact of the anti-TNF biologics on joint disease. But the TNF inhibitors can’t touch the anti–IL-17 biologics when it comes to improvement in Psoriasis Area and Severity Index (PASI) scores: The anti–IL-17 agents have week-52 PASI 75 response rates in the range of 80%, PASI 90 response rates of 70%-75%, and PASI 100 response rates of 40%-55%, with the highest-end results being seen with brodalumab, he continued.

A point worth remembering when prescribing secukinumab is that the approved dose for PsA is 150 mg every 4 weeks, which is just half of the typical dose in psoriasis.

“I spend a lot of time convincing my rheumatology colleagues that if you’re treating both psoriasis and psoriatic arthritis, use the psoriasis dose. There’s some evidence that the higher dose provides some benefit in terms of prevention of permanent joint damage by x-ray,” Dr. Gordon said.

Evidence that TNF inhibitors inhibit permanent joint damage in patients with PsA has been considered a major advantage, establishing this medication class as first-line biologic therapy. But anti–IL-17 therapies appear to have a similar beneficial effect. That was demonstrated in the SPIRIT-P1 trial, where Sharp scores – a radiographic measure of progression of joint damage – were similar at 24 weeks in PsA patients randomized to ixekizumab as compared to adalimumab, with both biologics being superior to placebo. An Assessment of SpondyloArthritis International Society 20% improvement (ASAS 20) response or an ACR 50 response doesn’t capture what’s going on with regard to axial disease. That’s assessed through ASAS 20 and ASAS 40 responses – that is, at least 20% or 40% improvement, compared with baseline, in Assessment in Ankylosing Spondylitis scores. And in the MEASURE 1 and 2 trials, secukinumab achieved robust improvement in axial disease as reflected in favorable ASAS 20 and ASAS 40 responses through 52 weeks in patients with active ankylosing spondylitis.

“The anti–IL-17 agents do actually work in ankylosing spondylitis, which might be a surrogate for the treatment effect in axial psoriatic arthritis,” Dr. Gordon commented.

The phase 3b MAXIMISE trial presented at the 2019 EULAR meeting looked specifically at the impact of secukinumab in patients with psoriatic arthritis with axial involvement. An ASAS 20 response at week 12 was seen in 67% and 65% of patients randomized to secukinumab at 150 or 300 mg, respectively, if they were on concomitant methotrexate, and 64% and 61% if they were not, compared with ASAS 20 rates of 34% and 31% in placebo-treated controls.

“This is the only study of an anti–IL-17 agent that’s been done for axial disease to date in psoriatic arthritis. It’s very, very encouraging,” the dermatologist commented.

 

Durability of response and safety

“In terms of safety, the anti–IL-17s have been a truly remarkable success story. There are very low rates of things to be concerned about,” Dr. Gordon said.

Oral candidiasis occurs in 2%-4% of treated patients, but he noted, “It’s almost always very mild disease” that’s easily treatable with nystatin or, in the worst case, with some fluconazole.

Inflammatory bowel disease (IBD) as a side effect of anti–IL-17 therapy has been a controversial issue. Dr. Gordon’s interpretation of the evidence is that there probably is a very slight increase in the risk of developing ulcerative colitis, but not Crohn’s disease.

“This rate is extraordinarily low, so while it’s something that I consider, and if a patient has a personal history of IBD I will sometimes hesitate to use an anti–IL-17 agent, in patients who don’t have a personal history I’ll go ahead,” he explained.

There is a signal of a slight increase in risk of depression in patients on brodalumab, which isn’t the case for secukinumab or ixekizumab.

Importantly, large long-term extension studies with years of follow-up show that the initially low adverse event rates associated with the IL-17 inhibitors don’t increase over time; rather, they remain steady over years of use.

Long-term maintenance of response with these biologics is impressive. “It’s not perfect, but it’s still a tremendous advantage for patients, especially if you can get them through that initial period,” Dr. Gordon said.

For example, in the long-term extension of the UNCOVER-1 trial, psoriasis patients who had clear or almost clear skin at week 12 on ixekizumab and continued to take the medication open label for 5 years had PASI 75, 90, and 100 response rates of 94%, 82%, and 47%, respectively, at week 264.
 

What about IL-12/23 and IL-23 inhibitors in PsA?

In a separate presentation at the MedscapeLive seminar, Bruce E. Strober, MD, PhD, said that, although ustekinumab (Stelara) is approved for both psoriasis and PsA, the IL-12/-23 inhibitor’s efficacy in PsA is inconsistent and lower than other approved biologics. In contrast, the IL-23 inhibitor guselkumab (Tremfya), which also has the dual indications, is a strong performer in both. In the DISCOVER-2 trial, conducted in treatment-naive patients with PsA, guselkumab at the approved dose of 100 mg every 8 weeks achieved ACR 20, 50, and 70 rates of 64%, 31%, and 19%, respectively. It was also significantly better than placebo for resolution of enthesitis.

An important caveat: While radiographic inhibition of progression of joint disease occurred with guselkumab dosed at 100 mg every 4 weeks in DISCOVER-2, that’s not the approved dose. At 100 mg every 8 weeks – the FDA-approved dosing for both psoriatic arthritis and psoriasis – radiographic inhibition wasn’t better than with placebo, noted Dr. Strober, a dermatologist at Yale University, New Haven, Conn.

Dr. Gordon and Dr. Strober are clinical trialists who reported receiving research support and/or honoraria from more than a dozen pharmaceutical companies, including virtually all of those with biologics for dermatology.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

LAS VEGAS – Current major guidelines for treatment of psoriatic arthritis (PsA) shortchange the value of the anti–interleukin-17 biologics for this disease, Kenneth B. Gordon, MD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

The 2018 joint American College of Rheumatology/National Psoriasis Association guidelines recommend the anti–tumor necrosis factor agents as first-line biologic therapy for PsA, with the anti–IL-17 biologics held in reserve as second-tier therapy for when the anti-TNFs don’t work. That’s largely because the guidance was developed before the compelling evidence for the anti–IL-17 agents as the biologics of choice was appreciated, according to Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.

“Many people go by these guidelines,” the dermatologist noted. “I think it’s really critical to look at the data and not just the guidelines because the guidelines don’t give full credit to the anti–IL-17 agents,” he added.

“Emerging psoriatic arthritis data may likely put this class of medications into the forefront of treatment for patients who have both psoriasis and psoriatic arthritis because you generally get higher responses for the skin disease than with anti-TNF therapy, and with similar responses in psoriatic arthritis.”

Two IL-17 inhibitors are approved for both PsA and psoriasis: secukinumab (Cosentyx) and ixekizumab (Taltz). In addition, brodalumab (Siliq), approved for psoriasis, is expected to receive an expanded indication for PsA based upon its strong showing in the AMVISION-1 and -2 trials. Data from those trials, as well as the FUTURE 2 trial for secukinumab and SPIRIT-P1 for ixekizumab, consistently document at least 20% improvement in the ACR criteria for PsA severity – that is, an ACR 20 response – in 50%-60% of patients on one of the three IL-17 inhibitors, as well as ACR 50 response rates of around 30%. Those outcomes are quite consistent with the impact of the anti-TNF biologics on joint disease. But the TNF inhibitors can’t touch the anti–IL-17 biologics when it comes to improvement in Psoriasis Area and Severity Index (PASI) scores: The anti–IL-17 agents have week-52 PASI 75 response rates in the range of 80%, PASI 90 response rates of 70%-75%, and PASI 100 response rates of 40%-55%, with the highest-end results being seen with brodalumab, he continued.

A point worth remembering when prescribing secukinumab is that the approved dose for PsA is 150 mg every 4 weeks, which is just half of the typical dose in psoriasis.

“I spend a lot of time convincing my rheumatology colleagues that if you’re treating both psoriasis and psoriatic arthritis, use the psoriasis dose. There’s some evidence that the higher dose provides some benefit in terms of prevention of permanent joint damage by x-ray,” Dr. Gordon said.

Evidence that TNF inhibitors inhibit permanent joint damage in patients with PsA has been considered a major advantage, establishing this medication class as first-line biologic therapy. But anti–IL-17 therapies appear to have a similar beneficial effect. That was demonstrated in the SPIRIT-P1 trial, where Sharp scores – a radiographic measure of progression of joint damage – were similar at 24 weeks in PsA patients randomized to ixekizumab as compared to adalimumab, with both biologics being superior to placebo. An Assessment of SpondyloArthritis International Society 20% improvement (ASAS 20) response or an ACR 50 response doesn’t capture what’s going on with regard to axial disease. That’s assessed through ASAS 20 and ASAS 40 responses – that is, at least 20% or 40% improvement, compared with baseline, in Assessment in Ankylosing Spondylitis scores. And in the MEASURE 1 and 2 trials, secukinumab achieved robust improvement in axial disease as reflected in favorable ASAS 20 and ASAS 40 responses through 52 weeks in patients with active ankylosing spondylitis.

“The anti–IL-17 agents do actually work in ankylosing spondylitis, which might be a surrogate for the treatment effect in axial psoriatic arthritis,” Dr. Gordon commented.

The phase 3b MAXIMISE trial presented at the 2019 EULAR meeting looked specifically at the impact of secukinumab in patients with psoriatic arthritis with axial involvement. An ASAS 20 response at week 12 was seen in 67% and 65% of patients randomized to secukinumab at 150 or 300 mg, respectively, if they were on concomitant methotrexate, and 64% and 61% if they were not, compared with ASAS 20 rates of 34% and 31% in placebo-treated controls.

“This is the only study of an anti–IL-17 agent that’s been done for axial disease to date in psoriatic arthritis. It’s very, very encouraging,” the dermatologist commented.

 

Durability of response and safety

“In terms of safety, the anti–IL-17s have been a truly remarkable success story. There are very low rates of things to be concerned about,” Dr. Gordon said.

Oral candidiasis occurs in 2%-4% of treated patients, but he noted, “It’s almost always very mild disease” that’s easily treatable with nystatin or, in the worst case, with some fluconazole.

Inflammatory bowel disease (IBD) as a side effect of anti–IL-17 therapy has been a controversial issue. Dr. Gordon’s interpretation of the evidence is that there probably is a very slight increase in the risk of developing ulcerative colitis, but not Crohn’s disease.

“This rate is extraordinarily low, so while it’s something that I consider, and if a patient has a personal history of IBD I will sometimes hesitate to use an anti–IL-17 agent, in patients who don’t have a personal history I’ll go ahead,” he explained.

There is a signal of a slight increase in risk of depression in patients on brodalumab, which isn’t the case for secukinumab or ixekizumab.

Importantly, large long-term extension studies with years of follow-up show that the initially low adverse event rates associated with the IL-17 inhibitors don’t increase over time; rather, they remain steady over years of use.

Long-term maintenance of response with these biologics is impressive. “It’s not perfect, but it’s still a tremendous advantage for patients, especially if you can get them through that initial period,” Dr. Gordon said.

For example, in the long-term extension of the UNCOVER-1 trial, psoriasis patients who had clear or almost clear skin at week 12 on ixekizumab and continued to take the medication open label for 5 years had PASI 75, 90, and 100 response rates of 94%, 82%, and 47%, respectively, at week 264.
 

What about IL-12/23 and IL-23 inhibitors in PsA?

In a separate presentation at the MedscapeLive seminar, Bruce E. Strober, MD, PhD, said that, although ustekinumab (Stelara) is approved for both psoriasis and PsA, the IL-12/-23 inhibitor’s efficacy in PsA is inconsistent and lower than other approved biologics. In contrast, the IL-23 inhibitor guselkumab (Tremfya), which also has the dual indications, is a strong performer in both. In the DISCOVER-2 trial, conducted in treatment-naive patients with PsA, guselkumab at the approved dose of 100 mg every 8 weeks achieved ACR 20, 50, and 70 rates of 64%, 31%, and 19%, respectively. It was also significantly better than placebo for resolution of enthesitis.

An important caveat: While radiographic inhibition of progression of joint disease occurred with guselkumab dosed at 100 mg every 4 weeks in DISCOVER-2, that’s not the approved dose. At 100 mg every 8 weeks – the FDA-approved dosing for both psoriatic arthritis and psoriasis – radiographic inhibition wasn’t better than with placebo, noted Dr. Strober, a dermatologist at Yale University, New Haven, Conn.

Dr. Gordon and Dr. Strober are clinical trialists who reported receiving research support and/or honoraria from more than a dozen pharmaceutical companies, including virtually all of those with biologics for dermatology.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

LAS VEGAS – Current major guidelines for treatment of psoriatic arthritis (PsA) shortchange the value of the anti–interleukin-17 biologics for this disease, Kenneth B. Gordon, MD, said at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

The 2018 joint American College of Rheumatology/National Psoriasis Association guidelines recommend the anti–tumor necrosis factor agents as first-line biologic therapy for PsA, with the anti–IL-17 biologics held in reserve as second-tier therapy for when the anti-TNFs don’t work. That’s largely because the guidance was developed before the compelling evidence for the anti–IL-17 agents as the biologics of choice was appreciated, according to Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.

“Many people go by these guidelines,” the dermatologist noted. “I think it’s really critical to look at the data and not just the guidelines because the guidelines don’t give full credit to the anti–IL-17 agents,” he added.

“Emerging psoriatic arthritis data may likely put this class of medications into the forefront of treatment for patients who have both psoriasis and psoriatic arthritis because you generally get higher responses for the skin disease than with anti-TNF therapy, and with similar responses in psoriatic arthritis.”

Two IL-17 inhibitors are approved for both PsA and psoriasis: secukinumab (Cosentyx) and ixekizumab (Taltz). In addition, brodalumab (Siliq), approved for psoriasis, is expected to receive an expanded indication for PsA based upon its strong showing in the AMVISION-1 and -2 trials. Data from those trials, as well as the FUTURE 2 trial for secukinumab and SPIRIT-P1 for ixekizumab, consistently document at least 20% improvement in the ACR criteria for PsA severity – that is, an ACR 20 response – in 50%-60% of patients on one of the three IL-17 inhibitors, as well as ACR 50 response rates of around 30%. Those outcomes are quite consistent with the impact of the anti-TNF biologics on joint disease. But the TNF inhibitors can’t touch the anti–IL-17 biologics when it comes to improvement in Psoriasis Area and Severity Index (PASI) scores: The anti–IL-17 agents have week-52 PASI 75 response rates in the range of 80%, PASI 90 response rates of 70%-75%, and PASI 100 response rates of 40%-55%, with the highest-end results being seen with brodalumab, he continued.

A point worth remembering when prescribing secukinumab is that the approved dose for PsA is 150 mg every 4 weeks, which is just half of the typical dose in psoriasis.

“I spend a lot of time convincing my rheumatology colleagues that if you’re treating both psoriasis and psoriatic arthritis, use the psoriasis dose. There’s some evidence that the higher dose provides some benefit in terms of prevention of permanent joint damage by x-ray,” Dr. Gordon said.

Evidence that TNF inhibitors inhibit permanent joint damage in patients with PsA has been considered a major advantage, establishing this medication class as first-line biologic therapy. But anti–IL-17 therapies appear to have a similar beneficial effect. That was demonstrated in the SPIRIT-P1 trial, where Sharp scores – a radiographic measure of progression of joint damage – were similar at 24 weeks in PsA patients randomized to ixekizumab as compared to adalimumab, with both biologics being superior to placebo. An Assessment of SpondyloArthritis International Society 20% improvement (ASAS 20) response or an ACR 50 response doesn’t capture what’s going on with regard to axial disease. That’s assessed through ASAS 20 and ASAS 40 responses – that is, at least 20% or 40% improvement, compared with baseline, in Assessment in Ankylosing Spondylitis scores. And in the MEASURE 1 and 2 trials, secukinumab achieved robust improvement in axial disease as reflected in favorable ASAS 20 and ASAS 40 responses through 52 weeks in patients with active ankylosing spondylitis.

“The anti–IL-17 agents do actually work in ankylosing spondylitis, which might be a surrogate for the treatment effect in axial psoriatic arthritis,” Dr. Gordon commented.

The phase 3b MAXIMISE trial presented at the 2019 EULAR meeting looked specifically at the impact of secukinumab in patients with psoriatic arthritis with axial involvement. An ASAS 20 response at week 12 was seen in 67% and 65% of patients randomized to secukinumab at 150 or 300 mg, respectively, if they were on concomitant methotrexate, and 64% and 61% if they were not, compared with ASAS 20 rates of 34% and 31% in placebo-treated controls.

“This is the only study of an anti–IL-17 agent that’s been done for axial disease to date in psoriatic arthritis. It’s very, very encouraging,” the dermatologist commented.

 

Durability of response and safety

“In terms of safety, the anti–IL-17s have been a truly remarkable success story. There are very low rates of things to be concerned about,” Dr. Gordon said.

Oral candidiasis occurs in 2%-4% of treated patients, but he noted, “It’s almost always very mild disease” that’s easily treatable with nystatin or, in the worst case, with some fluconazole.

Inflammatory bowel disease (IBD) as a side effect of anti–IL-17 therapy has been a controversial issue. Dr. Gordon’s interpretation of the evidence is that there probably is a very slight increase in the risk of developing ulcerative colitis, but not Crohn’s disease.

“This rate is extraordinarily low, so while it’s something that I consider, and if a patient has a personal history of IBD I will sometimes hesitate to use an anti–IL-17 agent, in patients who don’t have a personal history I’ll go ahead,” he explained.

There is a signal of a slight increase in risk of depression in patients on brodalumab, which isn’t the case for secukinumab or ixekizumab.

Importantly, large long-term extension studies with years of follow-up show that the initially low adverse event rates associated with the IL-17 inhibitors don’t increase over time; rather, they remain steady over years of use.

Long-term maintenance of response with these biologics is impressive. “It’s not perfect, but it’s still a tremendous advantage for patients, especially if you can get them through that initial period,” Dr. Gordon said.

For example, in the long-term extension of the UNCOVER-1 trial, psoriasis patients who had clear or almost clear skin at week 12 on ixekizumab and continued to take the medication open label for 5 years had PASI 75, 90, and 100 response rates of 94%, 82%, and 47%, respectively, at week 264.
 

What about IL-12/23 and IL-23 inhibitors in PsA?

In a separate presentation at the MedscapeLive seminar, Bruce E. Strober, MD, PhD, said that, although ustekinumab (Stelara) is approved for both psoriasis and PsA, the IL-12/-23 inhibitor’s efficacy in PsA is inconsistent and lower than other approved biologics. In contrast, the IL-23 inhibitor guselkumab (Tremfya), which also has the dual indications, is a strong performer in both. In the DISCOVER-2 trial, conducted in treatment-naive patients with PsA, guselkumab at the approved dose of 100 mg every 8 weeks achieved ACR 20, 50, and 70 rates of 64%, 31%, and 19%, respectively. It was also significantly better than placebo for resolution of enthesitis.

An important caveat: While radiographic inhibition of progression of joint disease occurred with guselkumab dosed at 100 mg every 4 weeks in DISCOVER-2, that’s not the approved dose. At 100 mg every 8 weeks – the FDA-approved dosing for both psoriatic arthritis and psoriasis – radiographic inhibition wasn’t better than with placebo, noted Dr. Strober, a dermatologist at Yale University, New Haven, Conn.

Dr. Gordon and Dr. Strober are clinical trialists who reported receiving research support and/or honoraria from more than a dozen pharmaceutical companies, including virtually all of those with biologics for dermatology.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

Most potential complications associated with filler and neuromodulator injections can be managed or prevented, and the right protocols can help in the rare cases of serious complications, Katie Beleznay, MD, of the University of British Columbia, Vancouver, said in a virtual presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

The number of reported cases of vascular complications in patients receiving fillers has increased in recent years, said Dr. Beleznay, who also treats patients in private practice in Vancouver. However, knowing the facial anatomy and recognizing that there is no “one-size-fits-all” approach goes a long way in preventing and managing complications.

In terms of neuromodulators such as Botox, the upper face is the most common area for treatment, and potential complications include eyelid ptosis, brow ptosis, and the “Spock brow,” Dr. Beleznay noted. For example, patients won’t be able to engage elevator muscles, such as the frontalis, if too much neuromodulator is injected. But, a couple of units in the upper forehead can help make the effect look natural, soften the lines, without being too frozen.

To help avoid eyelid ptosis with neuromodulators, inject at least one centimeter above the supraorbital rim at the midpupillary line, Dr. Beleznay advised. “I will feel the muscle,” because some brows are drawn or microbladed on, she noted. Patients who develop eyelid ptosis can be treated with apraclonidine drops.

To avoid brow ptosis with neuromodulators, it is important to assess the anatomy at baseline, Dr. Beleznay said. Some patients like to be able to lift their brows, and too much Botox will prevent their doing so. In order to mitigate this, it is important to treat brow depressors to balance and provide lift, and staying above the first horizontal forehead rhytid when injecting can help reduce brow ptosis risk.

Remember when injecting the upper face there are several glabellar contraction patterns, so “be sure you are targeting the treatment for the muscle pulling pattern that you see,” she said.
 

Complications associated with fillers

When injecting fillers, there are rare complications, including blindness, that are worth acknowledging, said Dr. Beleznay, lead author of a study on global cases of blindness caused by fillers published in 2015, including 98 cases up to 2015, and another 48 cases in a study published in 2019.

The highest-risk areas for causing blindness with fillers are the glabella and the nose, but “anywhere you are injecting is at risk for this complication,” she commented.

Explaining the mechanism of action for blindness resulting from filler injections, she said: “When the tip of the needle gets into the vessel, if you put enough pressure on the plunger, the filler can travel retrograde in the vessel back into the ophthalmic artery system, and then travels distally and blocks blood supply to the retina,” causing vision complications.

Understanding the potential mechanism for these complications informs preventive strategies, Dr. Beleznay emphasized.

If vision complications from fillers occur, they are likely to happen immediately, she said. There could be skin involvement or stroke-like features in addition to vision complications, so it is important to screen for these conditions as well if patients complain of vision loss.

Tips for prevention

Knowing the anatomy is the first step to maximize safe placement of fillers, Dr. Beleznay said. For example, the glabella is a high-risk location and includes the supraorbital and supratrochlear arteries, which start deep and become more superficial as they travel up the forehead.

When Dr. Beleznay injects in the glabella area, “I will do a true intradermal injection using tiny microdroplets, because that feels safest to me.” A video with additional details on surface anatomy and safer planes for injecting is available online to members of the American Society of Dermatologic Surgery.

Other tips to reduce the risk of vascular complications include injecting slowly and with a minimal amount of pressure, Dr. Beleznay emphasized. Injecting in small increments, moving the needle tip between injections, and using a cannula also may help reduce risk.

Always ask and use caution if patients have had other recent surgical procedures, she added.

Vascular complications such as blindness can be devastating, but the overall risks remain low. It’s important that clinicians know their anatomy, educate patients, and have prepared treatment protocols in place in the event of serious complications, Dr. Beleznay noted.

Dr. Beleznay disclosed relationships as an investigator, speaker, and/or consultant with AbbVie, Actelion, Allergan, Almirall, Amgen, Bausch Health, Celgene, Cipher, Evolus, Galderma, Johnson & Johnson, L’Oreal, Leo, Merz, Novartis, Procter & Gamble, Prollenium, Revance, Sandoz, Sanofi, Valeant, Vichy, and Zeltiq.

MedscapeLive and this news organization are owned by the same parent company.

Most potential complications associated with filler and neuromodulator injections can be managed or prevented, and the right protocols can help in the rare cases of serious complications, Katie Beleznay, MD, of the University of British Columbia, Vancouver, said in a virtual presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

The number of reported cases of vascular complications in patients receiving fillers has increased in recent years, said Dr. Beleznay, who also treats patients in private practice in Vancouver. However, knowing the facial anatomy and recognizing that there is no “one-size-fits-all” approach goes a long way in preventing and managing complications.

In terms of neuromodulators such as Botox, the upper face is the most common area for treatment, and potential complications include eyelid ptosis, brow ptosis, and the “Spock brow,” Dr. Beleznay noted. For example, patients won’t be able to engage elevator muscles, such as the frontalis, if too much neuromodulator is injected. But, a couple of units in the upper forehead can help make the effect look natural, soften the lines, without being too frozen.

To help avoid eyelid ptosis with neuromodulators, inject at least one centimeter above the supraorbital rim at the midpupillary line, Dr. Beleznay advised. “I will feel the muscle,” because some brows are drawn or microbladed on, she noted. Patients who develop eyelid ptosis can be treated with apraclonidine drops.

To avoid brow ptosis with neuromodulators, it is important to assess the anatomy at baseline, Dr. Beleznay said. Some patients like to be able to lift their brows, and too much Botox will prevent their doing so. In order to mitigate this, it is important to treat brow depressors to balance and provide lift, and staying above the first horizontal forehead rhytid when injecting can help reduce brow ptosis risk.

Remember when injecting the upper face there are several glabellar contraction patterns, so “be sure you are targeting the treatment for the muscle pulling pattern that you see,” she said.
 

Complications associated with fillers

When injecting fillers, there are rare complications, including blindness, that are worth acknowledging, said Dr. Beleznay, lead author of a study on global cases of blindness caused by fillers published in 2015, including 98 cases up to 2015, and another 48 cases in a study published in 2019.

The highest-risk areas for causing blindness with fillers are the glabella and the nose, but “anywhere you are injecting is at risk for this complication,” she commented.

Explaining the mechanism of action for blindness resulting from filler injections, she said: “When the tip of the needle gets into the vessel, if you put enough pressure on the plunger, the filler can travel retrograde in the vessel back into the ophthalmic artery system, and then travels distally and blocks blood supply to the retina,” causing vision complications.

Understanding the potential mechanism for these complications informs preventive strategies, Dr. Beleznay emphasized.

If vision complications from fillers occur, they are likely to happen immediately, she said. There could be skin involvement or stroke-like features in addition to vision complications, so it is important to screen for these conditions as well if patients complain of vision loss.

Tips for prevention

Knowing the anatomy is the first step to maximize safe placement of fillers, Dr. Beleznay said. For example, the glabella is a high-risk location and includes the supraorbital and supratrochlear arteries, which start deep and become more superficial as they travel up the forehead.

When Dr. Beleznay injects in the glabella area, “I will do a true intradermal injection using tiny microdroplets, because that feels safest to me.” A video with additional details on surface anatomy and safer planes for injecting is available online to members of the American Society of Dermatologic Surgery.

Other tips to reduce the risk of vascular complications include injecting slowly and with a minimal amount of pressure, Dr. Beleznay emphasized. Injecting in small increments, moving the needle tip between injections, and using a cannula also may help reduce risk.

Always ask and use caution if patients have had other recent surgical procedures, she added.

Vascular complications such as blindness can be devastating, but the overall risks remain low. It’s important that clinicians know their anatomy, educate patients, and have prepared treatment protocols in place in the event of serious complications, Dr. Beleznay noted.

Dr. Beleznay disclosed relationships as an investigator, speaker, and/or consultant with AbbVie, Actelion, Allergan, Almirall, Amgen, Bausch Health, Celgene, Cipher, Evolus, Galderma, Johnson & Johnson, L’Oreal, Leo, Merz, Novartis, Procter & Gamble, Prollenium, Revance, Sandoz, Sanofi, Valeant, Vichy, and Zeltiq.

MedscapeLive and this news organization are owned by the same parent company.

Most potential complications associated with filler and neuromodulator injections can be managed or prevented, and the right protocols can help in the rare cases of serious complications, Katie Beleznay, MD, of the University of British Columbia, Vancouver, said in a virtual presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.

The number of reported cases of vascular complications in patients receiving fillers has increased in recent years, said Dr. Beleznay, who also treats patients in private practice in Vancouver. However, knowing the facial anatomy and recognizing that there is no “one-size-fits-all” approach goes a long way in preventing and managing complications.

In terms of neuromodulators such as Botox, the upper face is the most common area for treatment, and potential complications include eyelid ptosis, brow ptosis, and the “Spock brow,” Dr. Beleznay noted. For example, patients won’t be able to engage elevator muscles, such as the frontalis, if too much neuromodulator is injected. But, a couple of units in the upper forehead can help make the effect look natural, soften the lines, without being too frozen.

To help avoid eyelid ptosis with neuromodulators, inject at least one centimeter above the supraorbital rim at the midpupillary line, Dr. Beleznay advised. “I will feel the muscle,” because some brows are drawn or microbladed on, she noted. Patients who develop eyelid ptosis can be treated with apraclonidine drops.

To avoid brow ptosis with neuromodulators, it is important to assess the anatomy at baseline, Dr. Beleznay said. Some patients like to be able to lift their brows, and too much Botox will prevent their doing so. In order to mitigate this, it is important to treat brow depressors to balance and provide lift, and staying above the first horizontal forehead rhytid when injecting can help reduce brow ptosis risk.

Remember when injecting the upper face there are several glabellar contraction patterns, so “be sure you are targeting the treatment for the muscle pulling pattern that you see,” she said.
 

Complications associated with fillers

When injecting fillers, there are rare complications, including blindness, that are worth acknowledging, said Dr. Beleznay, lead author of a study on global cases of blindness caused by fillers published in 2015, including 98 cases up to 2015, and another 48 cases in a study published in 2019.

The highest-risk areas for causing blindness with fillers are the glabella and the nose, but “anywhere you are injecting is at risk for this complication,” she commented.

Explaining the mechanism of action for blindness resulting from filler injections, she said: “When the tip of the needle gets into the vessel, if you put enough pressure on the plunger, the filler can travel retrograde in the vessel back into the ophthalmic artery system, and then travels distally and blocks blood supply to the retina,” causing vision complications.

Understanding the potential mechanism for these complications informs preventive strategies, Dr. Beleznay emphasized.

If vision complications from fillers occur, they are likely to happen immediately, she said. There could be skin involvement or stroke-like features in addition to vision complications, so it is important to screen for these conditions as well if patients complain of vision loss.

Tips for prevention

Knowing the anatomy is the first step to maximize safe placement of fillers, Dr. Beleznay said. For example, the glabella is a high-risk location and includes the supraorbital and supratrochlear arteries, which start deep and become more superficial as they travel up the forehead.

When Dr. Beleznay injects in the glabella area, “I will do a true intradermal injection using tiny microdroplets, because that feels safest to me.” A video with additional details on surface anatomy and safer planes for injecting is available online to members of the American Society of Dermatologic Surgery.

Other tips to reduce the risk of vascular complications include injecting slowly and with a minimal amount of pressure, Dr. Beleznay emphasized. Injecting in small increments, moving the needle tip between injections, and using a cannula also may help reduce risk.

Always ask and use caution if patients have had other recent surgical procedures, she added.

Vascular complications such as blindness can be devastating, but the overall risks remain low. It’s important that clinicians know their anatomy, educate patients, and have prepared treatment protocols in place in the event of serious complications, Dr. Beleznay noted.

Dr. Beleznay disclosed relationships as an investigator, speaker, and/or consultant with AbbVie, Actelion, Allergan, Almirall, Amgen, Bausch Health, Celgene, Cipher, Evolus, Galderma, Johnson & Johnson, L’Oreal, Leo, Merz, Novartis, Procter & Gamble, Prollenium, Revance, Sandoz, Sanofi, Valeant, Vichy, and Zeltiq.

MedscapeLive and this news organization are owned by the same parent company.

Black patients with extensive-stage small cell lung cancer (ES-SCLC) are less likely to receive chemotherapy but have better survival, compared with White patients, according to a study published in JTO Clinical Research and Reports.

This study provides a large-scale analysis of real-world data identifying racial and socioeconomic factors impacting systemic therapy delivery and survival in ES-SCLC.

“The most important finding was the significant disparity in receipt of chemotherapy,” said study author Umit Tapan, MD, of Boston Medical Center.

“Black individuals with ES-SCLC were less likely to receive chemotherapy compared to Whites and other racial groups. Similarly, elderly, uninsured patients, patients with nonprivate health insurance, and those with lower education levels were less likely to be treated with chemotherapy,” Dr. Tapan said.

Using the National Cancer Data Base (NCDB), Dr. Tapan and colleagues identified 148,961 patients who were diagnosed with stage IV ES-SCLC during 2004-2016. In all, 82,592 patients were included in the study.
 

Results: Treatment and survival

Compared with White patients, Black patients (adjusted odds ratio, 0.85; P = .0004) and patients from other racial groups (aOR, 0.87; P = .126) had lower odds of receiving chemotherapy on multivariate analysis.

However, survival was superior in Black patients (adjusted hazard ratio, 0.92; P < .0001) and other non-White patients (aHR 0.86; P < .0001).

“We speculate that additional factors, such as performance status, which is not captured by NCDB, might have accounted for better survival for Black patients,” Dr. Tapan said, noting that the analysis was adjusted for known possible confounding factors, such as age, gender, and comorbidity status.

Black patients had higher odds of receiving chemotherapy between 2010 and 2016 compared with 2004 and 2009. “This suggests a positive impact of the Patient Protection and Affordable Care Act (ACA) in 2010,” Dr. Tapan said.

Another surprising finding pertained to patients with nonprivate insurance. These patients had even lower odds of getting chemotherapy after the implementation of ACA, Dr. Tapan said. Patients who had private insurance had higher survival compared with those who were uninsured.

Higher level of education, measured by percentage of residents with a high school degree, increased the odds of receiving chemotherapy.

Age also had a significant impact on receipt of chemotherapy. About 83% of patients over age 80 years received chemotherapy, compared with 94% of patients aged 40-64 years.
 

Real-world data

Minorities are underrepresented in cancer clinical trials in the United States, with only 2% of National Cancer Institute trials having sufficient minority participants, Dr. Tapan said. A study published in Academic Medicine in 2018 showed that only 13% of 782 National Institute of Health–sponsored clinical trials reported outcomes by race and ethnicity.

As a result, we are missing data on patient care in minority populations, Dr. Tapan said. “Collecting and analyzing real-world data becomes critical to study treatment patterns and outcomes,” he added.

The current real-world study had a somewhat diverse patient population, but 90.6% of patients were White, 7.8% were Black, and 1.7% were other races.

“We would have expected a higher percentage of Black patients considering the most recent U.S. Census Bureau estimates that 76.3% of the U.S. population is White and 13.4% is Black,” Dr. Tapan said. “There are conflicting results in the literature regarding racial disparities in SCLC and survival. Many of these studies were performed via state-based cancer registries instead of on a national level, making prior reports less generalizable.”
 

‘More work to do’

While the new study showed patients with nonprivate insurance or those with no insurance were less likely to receive chemotherapy, studies have shown that chemotherapy administration was not impacted by insurance status in limited-stage SCLC.

This is in contrast to radiotherapy delivery. Studies have revealed a lower likelihood of radiotherapy delivery in limited-stage SCLC for patients with government health insurance such as Medicare/Medicaid, Dr. Tapan said.

“Access to cancer care has been shown to be one of the most important barriers in racial disparity. Studies analyzing outcomes in the equal access health systems, such as the Veteran Administration, have revealed less racial disparities,” Dr. Tapan said.

Even when Black patients have equal access to care, they might receive suboptimal treatment, Dr. Tapan noted.

“Studies have shown that Black patients are not only more likely to refuse surgery, but also are more likely to be given a negative recommendation by a surgeon as compared to Whites, suggesting potential involvement of miscommunication or bias during patient-physician encounters,” Dr. Tapan said. “In the same vein, physicians would need to acknowledge their patients’ beliefs. Not doing so may lead to unsatisfactory physician-patient interactions and suboptimal decision-making.”

“Measures to reduce physician bias are an important step to reduce disparities,” Dr. Tapan continued. “Studies have shown that Black patients are perceived to be less intelligent and educated, less likely to have social support, and more likely to be at risk of noncompliance. For some patients and oncologists, extra effort is needed so that every patient can access the best possible treatments and outcomes. It is the oncologist’s responsibility to advocate for patients, but, ultimately, further legislative actions are needed to mitigate the disparities around cancer care.”

Dr. Tapan noted that, in 1966, Martin Luther King Jr., PhD, stated that “of all the forms of inequality, injustice in health care is the most shocking and inhumane.”

Dr. Tapan said: “We have overcome some barriers since 1966, but we have more work to do.” He and colleagues had no disclosures related to this study.

SOURCE: Tapan U et al. JTO Clin Res Rep. 2020. doi: 10.1016/j.jtocrr.2020.100109.

Black patients with extensive-stage small cell lung cancer (ES-SCLC) are less likely to receive chemotherapy but have better survival, compared with White patients, according to a study published in JTO Clinical Research and Reports.

This study provides a large-scale analysis of real-world data identifying racial and socioeconomic factors impacting systemic therapy delivery and survival in ES-SCLC.

“The most important finding was the significant disparity in receipt of chemotherapy,” said study author Umit Tapan, MD, of Boston Medical Center.

“Black individuals with ES-SCLC were less likely to receive chemotherapy compared to Whites and other racial groups. Similarly, elderly, uninsured patients, patients with nonprivate health insurance, and those with lower education levels were less likely to be treated with chemotherapy,” Dr. Tapan said.

Using the National Cancer Data Base (NCDB), Dr. Tapan and colleagues identified 148,961 patients who were diagnosed with stage IV ES-SCLC during 2004-2016. In all, 82,592 patients were included in the study.
 

Results: Treatment and survival

Compared with White patients, Black patients (adjusted odds ratio, 0.85; P = .0004) and patients from other racial groups (aOR, 0.87; P = .126) had lower odds of receiving chemotherapy on multivariate analysis.

However, survival was superior in Black patients (adjusted hazard ratio, 0.92; P < .0001) and other non-White patients (aHR 0.86; P < .0001).

“We speculate that additional factors, such as performance status, which is not captured by NCDB, might have accounted for better survival for Black patients,” Dr. Tapan said, noting that the analysis was adjusted for known possible confounding factors, such as age, gender, and comorbidity status.

Black patients had higher odds of receiving chemotherapy between 2010 and 2016 compared with 2004 and 2009. “This suggests a positive impact of the Patient Protection and Affordable Care Act (ACA) in 2010,” Dr. Tapan said.

Another surprising finding pertained to patients with nonprivate insurance. These patients had even lower odds of getting chemotherapy after the implementation of ACA, Dr. Tapan said. Patients who had private insurance had higher survival compared with those who were uninsured.

Higher level of education, measured by percentage of residents with a high school degree, increased the odds of receiving chemotherapy.

Age also had a significant impact on receipt of chemotherapy. About 83% of patients over age 80 years received chemotherapy, compared with 94% of patients aged 40-64 years.
 

Real-world data

Minorities are underrepresented in cancer clinical trials in the United States, with only 2% of National Cancer Institute trials having sufficient minority participants, Dr. Tapan said. A study published in Academic Medicine in 2018 showed that only 13% of 782 National Institute of Health–sponsored clinical trials reported outcomes by race and ethnicity.

As a result, we are missing data on patient care in minority populations, Dr. Tapan said. “Collecting and analyzing real-world data becomes critical to study treatment patterns and outcomes,” he added.

The current real-world study had a somewhat diverse patient population, but 90.6% of patients were White, 7.8% were Black, and 1.7% were other races.

“We would have expected a higher percentage of Black patients considering the most recent U.S. Census Bureau estimates that 76.3% of the U.S. population is White and 13.4% is Black,” Dr. Tapan said. “There are conflicting results in the literature regarding racial disparities in SCLC and survival. Many of these studies were performed via state-based cancer registries instead of on a national level, making prior reports less generalizable.”
 

‘More work to do’

While the new study showed patients with nonprivate insurance or those with no insurance were less likely to receive chemotherapy, studies have shown that chemotherapy administration was not impacted by insurance status in limited-stage SCLC.

This is in contrast to radiotherapy delivery. Studies have revealed a lower likelihood of radiotherapy delivery in limited-stage SCLC for patients with government health insurance such as Medicare/Medicaid, Dr. Tapan said.

“Access to cancer care has been shown to be one of the most important barriers in racial disparity. Studies analyzing outcomes in the equal access health systems, such as the Veteran Administration, have revealed less racial disparities,” Dr. Tapan said.

Even when Black patients have equal access to care, they might receive suboptimal treatment, Dr. Tapan noted.

“Studies have shown that Black patients are not only more likely to refuse surgery, but also are more likely to be given a negative recommendation by a surgeon as compared to Whites, suggesting potential involvement of miscommunication or bias during patient-physician encounters,” Dr. Tapan said. “In the same vein, physicians would need to acknowledge their patients’ beliefs. Not doing so may lead to unsatisfactory physician-patient interactions and suboptimal decision-making.”

“Measures to reduce physician bias are an important step to reduce disparities,” Dr. Tapan continued. “Studies have shown that Black patients are perceived to be less intelligent and educated, less likely to have social support, and more likely to be at risk of noncompliance. For some patients and oncologists, extra effort is needed so that every patient can access the best possible treatments and outcomes. It is the oncologist’s responsibility to advocate for patients, but, ultimately, further legislative actions are needed to mitigate the disparities around cancer care.”

Dr. Tapan noted that, in 1966, Martin Luther King Jr., PhD, stated that “of all the forms of inequality, injustice in health care is the most shocking and inhumane.”

Dr. Tapan said: “We have overcome some barriers since 1966, but we have more work to do.” He and colleagues had no disclosures related to this study.

SOURCE: Tapan U et al. JTO Clin Res Rep. 2020. doi: 10.1016/j.jtocrr.2020.100109.

Black patients with extensive-stage small cell lung cancer (ES-SCLC) are less likely to receive chemotherapy but have better survival, compared with White patients, according to a study published in JTO Clinical Research and Reports.

This study provides a large-scale analysis of real-world data identifying racial and socioeconomic factors impacting systemic therapy delivery and survival in ES-SCLC.

“The most important finding was the significant disparity in receipt of chemotherapy,” said study author Umit Tapan, MD, of Boston Medical Center.

“Black individuals with ES-SCLC were less likely to receive chemotherapy compared to Whites and other racial groups. Similarly, elderly, uninsured patients, patients with nonprivate health insurance, and those with lower education levels were less likely to be treated with chemotherapy,” Dr. Tapan said.

Using the National Cancer Data Base (NCDB), Dr. Tapan and colleagues identified 148,961 patients who were diagnosed with stage IV ES-SCLC during 2004-2016. In all, 82,592 patients were included in the study.
 

Results: Treatment and survival

Compared with White patients, Black patients (adjusted odds ratio, 0.85; P = .0004) and patients from other racial groups (aOR, 0.87; P = .126) had lower odds of receiving chemotherapy on multivariate analysis.

However, survival was superior in Black patients (adjusted hazard ratio, 0.92; P < .0001) and other non-White patients (aHR 0.86; P < .0001).

“We speculate that additional factors, such as performance status, which is not captured by NCDB, might have accounted for better survival for Black patients,” Dr. Tapan said, noting that the analysis was adjusted for known possible confounding factors, such as age, gender, and comorbidity status.

Black patients had higher odds of receiving chemotherapy between 2010 and 2016 compared with 2004 and 2009. “This suggests a positive impact of the Patient Protection and Affordable Care Act (ACA) in 2010,” Dr. Tapan said.

Another surprising finding pertained to patients with nonprivate insurance. These patients had even lower odds of getting chemotherapy after the implementation of ACA, Dr. Tapan said. Patients who had private insurance had higher survival compared with those who were uninsured.

Higher level of education, measured by percentage of residents with a high school degree, increased the odds of receiving chemotherapy.

Age also had a significant impact on receipt of chemotherapy. About 83% of patients over age 80 years received chemotherapy, compared with 94% of patients aged 40-64 years.
 

Real-world data

Minorities are underrepresented in cancer clinical trials in the United States, with only 2% of National Cancer Institute trials having sufficient minority participants, Dr. Tapan said. A study published in Academic Medicine in 2018 showed that only 13% of 782 National Institute of Health–sponsored clinical trials reported outcomes by race and ethnicity.

As a result, we are missing data on patient care in minority populations, Dr. Tapan said. “Collecting and analyzing real-world data becomes critical to study treatment patterns and outcomes,” he added.

The current real-world study had a somewhat diverse patient population, but 90.6% of patients were White, 7.8% were Black, and 1.7% were other races.

“We would have expected a higher percentage of Black patients considering the most recent U.S. Census Bureau estimates that 76.3% of the U.S. population is White and 13.4% is Black,” Dr. Tapan said. “There are conflicting results in the literature regarding racial disparities in SCLC and survival. Many of these studies were performed via state-based cancer registries instead of on a national level, making prior reports less generalizable.”
 

‘More work to do’

While the new study showed patients with nonprivate insurance or those with no insurance were less likely to receive chemotherapy, studies have shown that chemotherapy administration was not impacted by insurance status in limited-stage SCLC.

This is in contrast to radiotherapy delivery. Studies have revealed a lower likelihood of radiotherapy delivery in limited-stage SCLC for patients with government health insurance such as Medicare/Medicaid, Dr. Tapan said.

“Access to cancer care has been shown to be one of the most important barriers in racial disparity. Studies analyzing outcomes in the equal access health systems, such as the Veteran Administration, have revealed less racial disparities,” Dr. Tapan said.

Even when Black patients have equal access to care, they might receive suboptimal treatment, Dr. Tapan noted.

“Studies have shown that Black patients are not only more likely to refuse surgery, but also are more likely to be given a negative recommendation by a surgeon as compared to Whites, suggesting potential involvement of miscommunication or bias during patient-physician encounters,” Dr. Tapan said. “In the same vein, physicians would need to acknowledge their patients’ beliefs. Not doing so may lead to unsatisfactory physician-patient interactions and suboptimal decision-making.”

“Measures to reduce physician bias are an important step to reduce disparities,” Dr. Tapan continued. “Studies have shown that Black patients are perceived to be less intelligent and educated, less likely to have social support, and more likely to be at risk of noncompliance. For some patients and oncologists, extra effort is needed so that every patient can access the best possible treatments and outcomes. It is the oncologist’s responsibility to advocate for patients, but, ultimately, further legislative actions are needed to mitigate the disparities around cancer care.”

Dr. Tapan noted that, in 1966, Martin Luther King Jr., PhD, stated that “of all the forms of inequality, injustice in health care is the most shocking and inhumane.”

Dr. Tapan said: “We have overcome some barriers since 1966, but we have more work to do.” He and colleagues had no disclosures related to this study.

SOURCE: Tapan U et al. JTO Clin Res Rep. 2020. doi: 10.1016/j.jtocrr.2020.100109.

Amidst the pandemic and election, two anniversaries passed almost unnoticed in early November.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Amidst the pandemic and election, two anniversaries passed almost unnoticed in early November.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Amidst the pandemic and election, two anniversaries passed almost unnoticed in early November.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Background: Adverse events in the immediate posthospitalization period are a serious threat to patients 65 years and older who are residents of long-term care facilities. Changes during hospitalization – such as fasting for procedures, immobility, change in surroundings, disruption of sleep, and medication adjustments – can lead to adverse events such as falls, pressure ulcers, adverse drug reactions, and health care–acquired infections. However, the frequency and preventability of these adverse events has not been measured.

Of the 555 residents, 65.5% were female and the mean age was 82.2. There were 379 adverse events identified; 52% involved pressure ulcers, skin tears, and falls with injury, which were deemed preventable. Healthcare-acquired infections totaled 28.5% and adverse drug events were 16.5%. Close to half of the events were serious, life threatening, or fatal. The study was limited by subjectivity in classifying the adverse events.

Hospitalists should ensure proper coordination and handoff when transitioning patients back to their nursing home.

Bottom line: Adverse events occur in 4 of 10 discharges from the hospital to long-term care facilities, and most events are preventable.

Citation: Kapoor A et al. Adverse events in long-term care residents transitioning from hospital back to nursing home. JAMA Intern Med. 2019 Jul 22;179(9):1254-61.

Dr. Ali is assistant professor of internal medicine and section chief of hospital medicine at St. Louis University School of Medicine.

Background: Adverse events in the immediate posthospitalization period are a serious threat to patients 65 years and older who are residents of long-term care facilities. Changes during hospitalization – such as fasting for procedures, immobility, change in surroundings, disruption of sleep, and medication adjustments – can lead to adverse events such as falls, pressure ulcers, adverse drug reactions, and health care–acquired infections. However, the frequency and preventability of these adverse events has not been measured.

Of the 555 residents, 65.5% were female and the mean age was 82.2. There were 379 adverse events identified; 52% involved pressure ulcers, skin tears, and falls with injury, which were deemed preventable. Healthcare-acquired infections totaled 28.5% and adverse drug events were 16.5%. Close to half of the events were serious, life threatening, or fatal. The study was limited by subjectivity in classifying the adverse events.

Hospitalists should ensure proper coordination and handoff when transitioning patients back to their nursing home.

Bottom line: Adverse events occur in 4 of 10 discharges from the hospital to long-term care facilities, and most events are preventable.

Citation: Kapoor A et al. Adverse events in long-term care residents transitioning from hospital back to nursing home. JAMA Intern Med. 2019 Jul 22;179(9):1254-61.

Dr. Ali is assistant professor of internal medicine and section chief of hospital medicine at St. Louis University School of Medicine.

Background: Adverse events in the immediate posthospitalization period are a serious threat to patients 65 years and older who are residents of long-term care facilities. Changes during hospitalization – such as fasting for procedures, immobility, change in surroundings, disruption of sleep, and medication adjustments – can lead to adverse events such as falls, pressure ulcers, adverse drug reactions, and health care–acquired infections. However, the frequency and preventability of these adverse events has not been measured.

Of the 555 residents, 65.5% were female and the mean age was 82.2. There were 379 adverse events identified; 52% involved pressure ulcers, skin tears, and falls with injury, which were deemed preventable. Healthcare-acquired infections totaled 28.5% and adverse drug events were 16.5%. Close to half of the events were serious, life threatening, or fatal. The study was limited by subjectivity in classifying the adverse events.

Hospitalists should ensure proper coordination and handoff when transitioning patients back to their nursing home.

Bottom line: Adverse events occur in 4 of 10 discharges from the hospital to long-term care facilities, and most events are preventable.

Citation: Kapoor A et al. Adverse events in long-term care residents transitioning from hospital back to nursing home. JAMA Intern Med. 2019 Jul 22;179(9):1254-61.

Dr. Ali is assistant professor of internal medicine and section chief of hospital medicine at St. Louis University School of Medicine.

Q2. Correct answer: D  
 
Rationale  
Deficient intake of fiber and folate may originate in the food choice of the individual, whereas some deficiencies of intake, such as thiamine, appear to be celiac specific. The provider should encourage intake of nutrient-dense foods including wholegrain foods, enriched if possible, legumes, fruits, vegetables, lean meat, fish, chicken, and eggs. It is not necessary to prioritize micronutrient supplements over achieving nutritional adequacy through dietary intake. Iron deficiency is an effect of untreated celiac disease.  
 
Reference  
1. Shepherd SJ, Gibson PR. J Human Nutr Dietet. 2012;26:349-58. 
 

Q2. Correct answer: D  
 
Rationale  
Deficient intake of fiber and folate may originate in the food choice of the individual, whereas some deficiencies of intake, such as thiamine, appear to be celiac specific. The provider should encourage intake of nutrient-dense foods including wholegrain foods, enriched if possible, legumes, fruits, vegetables, lean meat, fish, chicken, and eggs. It is not necessary to prioritize micronutrient supplements over achieving nutritional adequacy through dietary intake. Iron deficiency is an effect of untreated celiac disease.  
 
Reference  
1. Shepherd SJ, Gibson PR. J Human Nutr Dietet. 2012;26:349-58. 
 

Q2. Correct answer: D  
 
Rationale  
Deficient intake of fiber and folate may originate in the food choice of the individual, whereas some deficiencies of intake, such as thiamine, appear to be celiac specific. The provider should encourage intake of nutrient-dense foods including wholegrain foods, enriched if possible, legumes, fruits, vegetables, lean meat, fish, chicken, and eggs. It is not necessary to prioritize micronutrient supplements over achieving nutritional adequacy through dietary intake. Iron deficiency is an effect of untreated celiac disease.  
 
Reference  
1. Shepherd SJ, Gibson PR. J Human Nutr Dietet. 2012;26:349-58. 
 

Correct answer: C  
 
Rationale  
According to the Multi-Society Task Force on Colorectal Cancer, colonoscopy should be performed 1 year after resection, and again 3 years later, in order to decrease the risk of metachronous colorectal cancer.  
 
Reference  
1. Kahi CJ, Boland CR, Dominitz JA. Gastroenterology. 2016. 150(3):758-68.e11.

Correct answer: C  
 
Rationale  
According to the Multi-Society Task Force on Colorectal Cancer, colonoscopy should be performed 1 year after resection, and again 3 years later, in order to decrease the risk of metachronous colorectal cancer.  
 
Reference  
1. Kahi CJ, Boland CR, Dominitz JA. Gastroenterology. 2016. 150(3):758-68.e11.

Correct answer: C  
 
Rationale  
According to the Multi-Society Task Force on Colorectal Cancer, colonoscopy should be performed 1 year after resection, and again 3 years later, in order to decrease the risk of metachronous colorectal cancer.  
 
Reference  
1. Kahi CJ, Boland CR, Dominitz JA. Gastroenterology. 2016. 150(3):758-68.e11.