Clinician Reviews

National guidelines failed to classify many younger African American lung cancer patients as being eligible for lung cancer screening in a recent retrospective study, the lead author reported at the annual meeting of the American College of Chest Physicians.

The finding highlights a health disparity issue that may be addressed through an update of those guidelines that is in the works, said Carol Velez Martinez, MD, a third-year internal medicine resident at Louisiana State University Health Sciences Center in Shreveport, La.

About one-third of the lung cancer patients in the retrospective cohort study were diagnosed before the age of 55 years, which means they would not have been recommended for screening with low-dose computed tomography (LDCT) based on the 2013 lung cancer guidelines from the United States Preventive Services Task Force (USPSTF), said Dr. Velez Martinez.

By contrast, 12.5% of screening-ineligible patients would have been counted as LDCT eligible based on guidelines from the National Comprehensive Cancer Network (NCCN), Dr. Velez Martinez and coauthors found in their analysis.

In a draft recommendation statement posted July 7, the USPSTF said they would now recommend that screening at age 50 years, rather than 55, and that the pack-years of smoking history that would make an individual eligible for screening would be dropped from 30 pack-years to 20, changes that task force members said would be more inclusive of African Americans and women.

Dr. Velez Martinez said she is looking forward to a formal recommendation from USPSTF soon: “I’m hoping that’s where they’re heading,” she said in an interview. “When I’m in practice as a resident, I actually bring it up to my patients, and if I have to call the insurance I don’t have a problem – but I still have to call them because they’re still going by the prior guidelines.”

“I think there are going to be a lot of other health disparities,” Dr. Revelo said in an interview. “[Dr. Velez Martinez’s] study was limited by the fact that she cared mostly for Caucasians and also African Americans, but maybe no Latinos or Hispanics that I’m sure would also be affected if we were looking to that in a bigger or national study.”

The 2013 USPSTF guidelines were based on benefits observed in the National Lung Screening Trial (NLST), which indicated a 20% relative risk reduction in death from lung cancer; however, the generalizability of the study beyond White males has been questioned, said Dr. Velez Martinez in a presentation at the CHEST annual meeting.

About 90% of NSLT participants were White and 59% were male, according to results published in 2011.

Other studies have shown that African Americans are more likely to get lung cancer than Whites, despite comparable smoking rates between the races, and that African American men are more likely to die from lung cancer than White men, Dr. Velez Martinez said. Many African Americans live below the poverty line, which means they have limited resources for insurance and health providers, and they also participate less often in clinical trials, she added.

In their retrospective observational cohort study, Dr. Velez Martinez and coinvestigators reviewed 1,500 medical records of patients with newly diagnosed stage 1-4 lung cancers from the LSU Health Science Center Shreveport between 2011 and 2015.

They found that 33% of those lung cancer patients were diagnosed before the age of 55 years, meaning they did not meet the 2013 USPSTF screening guidelines, which recommend annual LDCT in adults aged 55-80 years with a 30 pack-year smoking history who currently smoke or have quit within the past 15 years.

Next, they sought to classify those screening-ineligible patients based on NCCN guidelines, which recommend LDCT in patients 50 years of age or older with at least a 20 pack-year smoking history and a 6-year risk of lung cancer of at least 1.3% based on the Tammemagi lung cancer risk calculator. The Tammemagi calculator considers factors such as age, education, body mass index, prior lung disease, familial cancer history, race and ethnicity, and smoking history.

After applying the risk stratification, the investigators found that 12.5% of these patients would have been categorized as high risk and therefore recommended for LDCT, and of that group, more than 65% were African American, Dr. Velez Martinez reported.

Dr. Revelo, who chaired the CHEST session where the findings were reported, said that shared decision-making will still be as important regardless of any changes to lung screening guidelines given the recognized potential harms of LDCT screening, such as false positives, radiation exposure, and psychological distress.

“I think we will continue to have a very personal conversation and make important decisions focused on what the patient wants,” he said.

Authors reported no disclosures.

National guidelines failed to classify many younger African American lung cancer patients as being eligible for lung cancer screening in a recent retrospective study, the lead author reported at the annual meeting of the American College of Chest Physicians.

The finding highlights a health disparity issue that may be addressed through an update of those guidelines that is in the works, said Carol Velez Martinez, MD, a third-year internal medicine resident at Louisiana State University Health Sciences Center in Shreveport, La.

About one-third of the lung cancer patients in the retrospective cohort study were diagnosed before the age of 55 years, which means they would not have been recommended for screening with low-dose computed tomography (LDCT) based on the 2013 lung cancer guidelines from the United States Preventive Services Task Force (USPSTF), said Dr. Velez Martinez.

By contrast, 12.5% of screening-ineligible patients would have been counted as LDCT eligible based on guidelines from the National Comprehensive Cancer Network (NCCN), Dr. Velez Martinez and coauthors found in their analysis.

In a draft recommendation statement posted July 7, the USPSTF said they would now recommend that screening at age 50 years, rather than 55, and that the pack-years of smoking history that would make an individual eligible for screening would be dropped from 30 pack-years to 20, changes that task force members said would be more inclusive of African Americans and women.

Dr. Velez Martinez said she is looking forward to a formal recommendation from USPSTF soon: “I’m hoping that’s where they’re heading,” she said in an interview. “When I’m in practice as a resident, I actually bring it up to my patients, and if I have to call the insurance I don’t have a problem – but I still have to call them because they’re still going by the prior guidelines.”

“I think there are going to be a lot of other health disparities,” Dr. Revelo said in an interview. “[Dr. Velez Martinez’s] study was limited by the fact that she cared mostly for Caucasians and also African Americans, but maybe no Latinos or Hispanics that I’m sure would also be affected if we were looking to that in a bigger or national study.”

The 2013 USPSTF guidelines were based on benefits observed in the National Lung Screening Trial (NLST), which indicated a 20% relative risk reduction in death from lung cancer; however, the generalizability of the study beyond White males has been questioned, said Dr. Velez Martinez in a presentation at the CHEST annual meeting.

About 90% of NSLT participants were White and 59% were male, according to results published in 2011.

Other studies have shown that African Americans are more likely to get lung cancer than Whites, despite comparable smoking rates between the races, and that African American men are more likely to die from lung cancer than White men, Dr. Velez Martinez said. Many African Americans live below the poverty line, which means they have limited resources for insurance and health providers, and they also participate less often in clinical trials, she added.

In their retrospective observational cohort study, Dr. Velez Martinez and coinvestigators reviewed 1,500 medical records of patients with newly diagnosed stage 1-4 lung cancers from the LSU Health Science Center Shreveport between 2011 and 2015.

They found that 33% of those lung cancer patients were diagnosed before the age of 55 years, meaning they did not meet the 2013 USPSTF screening guidelines, which recommend annual LDCT in adults aged 55-80 years with a 30 pack-year smoking history who currently smoke or have quit within the past 15 years.

Next, they sought to classify those screening-ineligible patients based on NCCN guidelines, which recommend LDCT in patients 50 years of age or older with at least a 20 pack-year smoking history and a 6-year risk of lung cancer of at least 1.3% based on the Tammemagi lung cancer risk calculator. The Tammemagi calculator considers factors such as age, education, body mass index, prior lung disease, familial cancer history, race and ethnicity, and smoking history.

After applying the risk stratification, the investigators found that 12.5% of these patients would have been categorized as high risk and therefore recommended for LDCT, and of that group, more than 65% were African American, Dr. Velez Martinez reported.

Dr. Revelo, who chaired the CHEST session where the findings were reported, said that shared decision-making will still be as important regardless of any changes to lung screening guidelines given the recognized potential harms of LDCT screening, such as false positives, radiation exposure, and psychological distress.

“I think we will continue to have a very personal conversation and make important decisions focused on what the patient wants,” he said.

Authors reported no disclosures.

National guidelines failed to classify many younger African American lung cancer patients as being eligible for lung cancer screening in a recent retrospective study, the lead author reported at the annual meeting of the American College of Chest Physicians.

The finding highlights a health disparity issue that may be addressed through an update of those guidelines that is in the works, said Carol Velez Martinez, MD, a third-year internal medicine resident at Louisiana State University Health Sciences Center in Shreveport, La.

About one-third of the lung cancer patients in the retrospective cohort study were diagnosed before the age of 55 years, which means they would not have been recommended for screening with low-dose computed tomography (LDCT) based on the 2013 lung cancer guidelines from the United States Preventive Services Task Force (USPSTF), said Dr. Velez Martinez.

By contrast, 12.5% of screening-ineligible patients would have been counted as LDCT eligible based on guidelines from the National Comprehensive Cancer Network (NCCN), Dr. Velez Martinez and coauthors found in their analysis.

In a draft recommendation statement posted July 7, the USPSTF said they would now recommend that screening at age 50 years, rather than 55, and that the pack-years of smoking history that would make an individual eligible for screening would be dropped from 30 pack-years to 20, changes that task force members said would be more inclusive of African Americans and women.

Dr. Velez Martinez said she is looking forward to a formal recommendation from USPSTF soon: “I’m hoping that’s where they’re heading,” she said in an interview. “When I’m in practice as a resident, I actually bring it up to my patients, and if I have to call the insurance I don’t have a problem – but I still have to call them because they’re still going by the prior guidelines.”

“I think there are going to be a lot of other health disparities,” Dr. Revelo said in an interview. “[Dr. Velez Martinez’s] study was limited by the fact that she cared mostly for Caucasians and also African Americans, but maybe no Latinos or Hispanics that I’m sure would also be affected if we were looking to that in a bigger or national study.”

The 2013 USPSTF guidelines were based on benefits observed in the National Lung Screening Trial (NLST), which indicated a 20% relative risk reduction in death from lung cancer; however, the generalizability of the study beyond White males has been questioned, said Dr. Velez Martinez in a presentation at the CHEST annual meeting.

About 90% of NSLT participants were White and 59% were male, according to results published in 2011.

Other studies have shown that African Americans are more likely to get lung cancer than Whites, despite comparable smoking rates between the races, and that African American men are more likely to die from lung cancer than White men, Dr. Velez Martinez said. Many African Americans live below the poverty line, which means they have limited resources for insurance and health providers, and they also participate less often in clinical trials, she added.

In their retrospective observational cohort study, Dr. Velez Martinez and coinvestigators reviewed 1,500 medical records of patients with newly diagnosed stage 1-4 lung cancers from the LSU Health Science Center Shreveport between 2011 and 2015.

They found that 33% of those lung cancer patients were diagnosed before the age of 55 years, meaning they did not meet the 2013 USPSTF screening guidelines, which recommend annual LDCT in adults aged 55-80 years with a 30 pack-year smoking history who currently smoke or have quit within the past 15 years.

Next, they sought to classify those screening-ineligible patients based on NCCN guidelines, which recommend LDCT in patients 50 years of age or older with at least a 20 pack-year smoking history and a 6-year risk of lung cancer of at least 1.3% based on the Tammemagi lung cancer risk calculator. The Tammemagi calculator considers factors such as age, education, body mass index, prior lung disease, familial cancer history, race and ethnicity, and smoking history.

After applying the risk stratification, the investigators found that 12.5% of these patients would have been categorized as high risk and therefore recommended for LDCT, and of that group, more than 65% were African American, Dr. Velez Martinez reported.

Dr. Revelo, who chaired the CHEST session where the findings were reported, said that shared decision-making will still be as important regardless of any changes to lung screening guidelines given the recognized potential harms of LDCT screening, such as false positives, radiation exposure, and psychological distress.

“I think we will continue to have a very personal conversation and make important decisions focused on what the patient wants,” he said.

Authors reported no disclosures.

Adjunctive pimavanserin brought clinically meaningful improvement in patients with anxious major depressive disorder inadequately responsive to standard antidepressants alone in a post hoc analysis of the CLARITY trial, Bryan Dirks, MD, reported at the virtual congress of the European College of Neuropsychopharmacology.

This is an intriguing observation, because it’s estimated that roughly 50% of individuals with major depressive disorder (MDD) have comorbid anxiety disorders or a high level of anxiety symptoms. Moreover, anxious depression has been associated with increased risk of suicidality, high unemployment, and impaired functioning.

CLARITY was a phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial whose positive results for the primary outcome have been published (J Clin Psychiatry. 2019 Sep 24;80[6]:19m12928. doi: 10.4088/JCP.19m12928). Because the encouraging findings regarding pimavanserin’s impact on anxious depression came from a post hoc analysis, the results need replication. That’s ongoing in a phase 3 trial of adjunctive pimavanserin versus placebo in patients with MDD, according to Dr. Dirks, director of clinical research at Acadia Pharmaceuticals, San Diego.

The CLARITY post hoc analysis included 104 patients with baseline MDD inadequately responsive to an SSRI or a serotonin norepinephrine reuptake inhibitor and anxious depression as defined by a Hamilton Depression Rating Scale (HAMD-17) anxiety/somatization factor subscale score of 7 or more. Twenty-nine of the patients were randomized to 34 mg of adjunctive oral pimavanserin once daily, and 75 to placebo. At 5 weeks, the HAMD-17 anxiety/somatization factor score in the pimavanserin group had dropped by a mean of 5 points from a baseline of 8.8, a significantly greater effect than the 2.8-point drop in placebo-treated controls.

By week 5, the treatment response rate as defined by at least a 50% reduction in HAMD-17 total score from baseline was 55% with pimavanserin and 22% with placebo. The remission rate as indicated by a HAMD-17 total score below 7 was 24% in the pimavanserin group, compared with 5% with placebo. These results translated into an effect size of 0.78, considered by statisticians to be on the border between medium and large. Those response and remission rates in patients with anxious depression were higher with pimavanserin and lower with placebo than in the overall CLARITY trial.

The impact of adjunctive pimavanserin on top of a background SSRI or SNRI was even more pronounced in the subgroup of patients with baseline severe MDD as defined by a HAMD-17 total score of 24 or more plus an anxiety/somatization factor score of 7 or greater. Seventeen such patients were randomized to adjunctive pimavanserin, 36 to placebo. At 5 weeks, the mean HAMD total score had dropped by 17.4 points from a baseline of 27.6 in the pimavanserin group, compared with a 9.3-point reduction in controls.

“Of note, significant differences from placebo were observed as early as week 2 with pimavanserin,” Dr. Dirks said.

Pimavanserin is a novel selective serotonin inverse agonist with a high affinity for 5-HT2A receptors and low affinity for 5-HT2C receptors. At present pimavanserin is Food Drug Administration–approved as Nuplazid only for treatment of hallucinations and delusions associated with Parkinson’s disease psychosis, but because of the drug’s unique mechanism of action it is under study for a variety of other mental disorders. Indeed, pimavanserin is now under FDA review for a possible expanded indication for treatment of dementia-related psychosis. The drug is also under study for schizophrenia as well as for MDD.

The CLARITY trial and this post hoc analysis were sponsored by Acadia Pharmaceuticals.

[email protected]

SOURCE: Dirks B. ECNP 2020. Abstract P 094.

Adjunctive pimavanserin brought clinically meaningful improvement in patients with anxious major depressive disorder inadequately responsive to standard antidepressants alone in a post hoc analysis of the CLARITY trial, Bryan Dirks, MD, reported at the virtual congress of the European College of Neuropsychopharmacology.

This is an intriguing observation, because it’s estimated that roughly 50% of individuals with major depressive disorder (MDD) have comorbid anxiety disorders or a high level of anxiety symptoms. Moreover, anxious depression has been associated with increased risk of suicidality, high unemployment, and impaired functioning.

CLARITY was a phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial whose positive results for the primary outcome have been published (J Clin Psychiatry. 2019 Sep 24;80[6]:19m12928. doi: 10.4088/JCP.19m12928). Because the encouraging findings regarding pimavanserin’s impact on anxious depression came from a post hoc analysis, the results need replication. That’s ongoing in a phase 3 trial of adjunctive pimavanserin versus placebo in patients with MDD, according to Dr. Dirks, director of clinical research at Acadia Pharmaceuticals, San Diego.

The CLARITY post hoc analysis included 104 patients with baseline MDD inadequately responsive to an SSRI or a serotonin norepinephrine reuptake inhibitor and anxious depression as defined by a Hamilton Depression Rating Scale (HAMD-17) anxiety/somatization factor subscale score of 7 or more. Twenty-nine of the patients were randomized to 34 mg of adjunctive oral pimavanserin once daily, and 75 to placebo. At 5 weeks, the HAMD-17 anxiety/somatization factor score in the pimavanserin group had dropped by a mean of 5 points from a baseline of 8.8, a significantly greater effect than the 2.8-point drop in placebo-treated controls.

By week 5, the treatment response rate as defined by at least a 50% reduction in HAMD-17 total score from baseline was 55% with pimavanserin and 22% with placebo. The remission rate as indicated by a HAMD-17 total score below 7 was 24% in the pimavanserin group, compared with 5% with placebo. These results translated into an effect size of 0.78, considered by statisticians to be on the border between medium and large. Those response and remission rates in patients with anxious depression were higher with pimavanserin and lower with placebo than in the overall CLARITY trial.

The impact of adjunctive pimavanserin on top of a background SSRI or SNRI was even more pronounced in the subgroup of patients with baseline severe MDD as defined by a HAMD-17 total score of 24 or more plus an anxiety/somatization factor score of 7 or greater. Seventeen such patients were randomized to adjunctive pimavanserin, 36 to placebo. At 5 weeks, the mean HAMD total score had dropped by 17.4 points from a baseline of 27.6 in the pimavanserin group, compared with a 9.3-point reduction in controls.

“Of note, significant differences from placebo were observed as early as week 2 with pimavanserin,” Dr. Dirks said.

Pimavanserin is a novel selective serotonin inverse agonist with a high affinity for 5-HT2A receptors and low affinity for 5-HT2C receptors. At present pimavanserin is Food Drug Administration–approved as Nuplazid only for treatment of hallucinations and delusions associated with Parkinson’s disease psychosis, but because of the drug’s unique mechanism of action it is under study for a variety of other mental disorders. Indeed, pimavanserin is now under FDA review for a possible expanded indication for treatment of dementia-related psychosis. The drug is also under study for schizophrenia as well as for MDD.

The CLARITY trial and this post hoc analysis were sponsored by Acadia Pharmaceuticals.

[email protected]

SOURCE: Dirks B. ECNP 2020. Abstract P 094.

Adjunctive pimavanserin brought clinically meaningful improvement in patients with anxious major depressive disorder inadequately responsive to standard antidepressants alone in a post hoc analysis of the CLARITY trial, Bryan Dirks, MD, reported at the virtual congress of the European College of Neuropsychopharmacology.

This is an intriguing observation, because it’s estimated that roughly 50% of individuals with major depressive disorder (MDD) have comorbid anxiety disorders or a high level of anxiety symptoms. Moreover, anxious depression has been associated with increased risk of suicidality, high unemployment, and impaired functioning.

CLARITY was a phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial whose positive results for the primary outcome have been published (J Clin Psychiatry. 2019 Sep 24;80[6]:19m12928. doi: 10.4088/JCP.19m12928). Because the encouraging findings regarding pimavanserin’s impact on anxious depression came from a post hoc analysis, the results need replication. That’s ongoing in a phase 3 trial of adjunctive pimavanserin versus placebo in patients with MDD, according to Dr. Dirks, director of clinical research at Acadia Pharmaceuticals, San Diego.

The CLARITY post hoc analysis included 104 patients with baseline MDD inadequately responsive to an SSRI or a serotonin norepinephrine reuptake inhibitor and anxious depression as defined by a Hamilton Depression Rating Scale (HAMD-17) anxiety/somatization factor subscale score of 7 or more. Twenty-nine of the patients were randomized to 34 mg of adjunctive oral pimavanserin once daily, and 75 to placebo. At 5 weeks, the HAMD-17 anxiety/somatization factor score in the pimavanserin group had dropped by a mean of 5 points from a baseline of 8.8, a significantly greater effect than the 2.8-point drop in placebo-treated controls.

By week 5, the treatment response rate as defined by at least a 50% reduction in HAMD-17 total score from baseline was 55% with pimavanserin and 22% with placebo. The remission rate as indicated by a HAMD-17 total score below 7 was 24% in the pimavanserin group, compared with 5% with placebo. These results translated into an effect size of 0.78, considered by statisticians to be on the border between medium and large. Those response and remission rates in patients with anxious depression were higher with pimavanserin and lower with placebo than in the overall CLARITY trial.

The impact of adjunctive pimavanserin on top of a background SSRI or SNRI was even more pronounced in the subgroup of patients with baseline severe MDD as defined by a HAMD-17 total score of 24 or more plus an anxiety/somatization factor score of 7 or greater. Seventeen such patients were randomized to adjunctive pimavanserin, 36 to placebo. At 5 weeks, the mean HAMD total score had dropped by 17.4 points from a baseline of 27.6 in the pimavanserin group, compared with a 9.3-point reduction in controls.

“Of note, significant differences from placebo were observed as early as week 2 with pimavanserin,” Dr. Dirks said.

Pimavanserin is a novel selective serotonin inverse agonist with a high affinity for 5-HT2A receptors and low affinity for 5-HT2C receptors. At present pimavanserin is Food Drug Administration–approved as Nuplazid only for treatment of hallucinations and delusions associated with Parkinson’s disease psychosis, but because of the drug’s unique mechanism of action it is under study for a variety of other mental disorders. Indeed, pimavanserin is now under FDA review for a possible expanded indication for treatment of dementia-related psychosis. The drug is also under study for schizophrenia as well as for MDD.

The CLARITY trial and this post hoc analysis were sponsored by Acadia Pharmaceuticals.

[email protected]

SOURCE: Dirks B. ECNP 2020. Abstract P 094.

ANSWER

The correct answer is koebnerization of pre-existing psoriasis (choice “c”).

DISCUSSION

Tattoos have been known to cause bacterial infection (choice “a”), but this was unlikely given the diffuse nature of the rash and the lack of pain or adenopathy. Allergic reactions to tattoo dyes (choice “b”) are certainly common, but usually red or yellow dyes—which were not used for this tattoo—provoke the worst reactions. Furthermore, itching would have been a more prominent feature of the patient's complaint. Had it been fungal infection (choice “d”), the steroid cream would have made it worse.

One possibility remained: the so-called isomorphic phenomenon (otherwise known as koebnerization). First described by Heinrich Koebner in the mid-19th century, koebnerization is characterized by the appearance of psoriasis in traumatized skin such as surgical wounds, abrasions, burns, or even tattoos. Several other conditions also exhibit this same linear response to trauma, including warts, molluscum, and lichen planus.

To test for this diagnosis, corroborative findings of psoriasis were sought and found in the patient’s nails. His history of rashes on the knees and elbows also contributed to establishing the diagnosis. Moreover, his complaint of arthritis was quite suggestive of psoriatic arthropathy, which afflicts about 25% of patients with psoriasis and has little to do with the severity of the skin disease itself. Once the diagnosis became more apparent, the patient recalled a family history of psoriasis. Had any question remained, a biopsy could remove doubt.

TREATMENT

For the patient, twice-daily application of a stronger steroid cream (augmented betamethasone) was prescribed. Though this quickly cleared the koebnerizing psoriasis, it is likely we haven’t seen the last of this disease.

ANSWER

The correct answer is koebnerization of pre-existing psoriasis (choice “c”).

DISCUSSION

Tattoos have been known to cause bacterial infection (choice “a”), but this was unlikely given the diffuse nature of the rash and the lack of pain or adenopathy. Allergic reactions to tattoo dyes (choice “b”) are certainly common, but usually red or yellow dyes—which were not used for this tattoo—provoke the worst reactions. Furthermore, itching would have been a more prominent feature of the patient's complaint. Had it been fungal infection (choice “d”), the steroid cream would have made it worse.

One possibility remained: the so-called isomorphic phenomenon (otherwise known as koebnerization). First described by Heinrich Koebner in the mid-19th century, koebnerization is characterized by the appearance of psoriasis in traumatized skin such as surgical wounds, abrasions, burns, or even tattoos. Several other conditions also exhibit this same linear response to trauma, including warts, molluscum, and lichen planus.

To test for this diagnosis, corroborative findings of psoriasis were sought and found in the patient’s nails. His history of rashes on the knees and elbows also contributed to establishing the diagnosis. Moreover, his complaint of arthritis was quite suggestive of psoriatic arthropathy, which afflicts about 25% of patients with psoriasis and has little to do with the severity of the skin disease itself. Once the diagnosis became more apparent, the patient recalled a family history of psoriasis. Had any question remained, a biopsy could remove doubt.

TREATMENT

For the patient, twice-daily application of a stronger steroid cream (augmented betamethasone) was prescribed. Though this quickly cleared the koebnerizing psoriasis, it is likely we haven’t seen the last of this disease.

ANSWER

The correct answer is koebnerization of pre-existing psoriasis (choice “c”).

DISCUSSION

Tattoos have been known to cause bacterial infection (choice “a”), but this was unlikely given the diffuse nature of the rash and the lack of pain or adenopathy. Allergic reactions to tattoo dyes (choice “b”) are certainly common, but usually red or yellow dyes—which were not used for this tattoo—provoke the worst reactions. Furthermore, itching would have been a more prominent feature of the patient's complaint. Had it been fungal infection (choice “d”), the steroid cream would have made it worse.

One possibility remained: the so-called isomorphic phenomenon (otherwise known as koebnerization). First described by Heinrich Koebner in the mid-19th century, koebnerization is characterized by the appearance of psoriasis in traumatized skin such as surgical wounds, abrasions, burns, or even tattoos. Several other conditions also exhibit this same linear response to trauma, including warts, molluscum, and lichen planus.

To test for this diagnosis, corroborative findings of psoriasis were sought and found in the patient’s nails. His history of rashes on the knees and elbows also contributed to establishing the diagnosis. Moreover, his complaint of arthritis was quite suggestive of psoriatic arthropathy, which afflicts about 25% of patients with psoriasis and has little to do with the severity of the skin disease itself. Once the diagnosis became more apparent, the patient recalled a family history of psoriasis. Had any question remained, a biopsy could remove doubt.

TREATMENT

For the patient, twice-daily application of a stronger steroid cream (augmented betamethasone) was prescribed. Though this quickly cleared the koebnerizing psoriasis, it is likely we haven’t seen the last of this disease.

The combined features of benign breast disease may help better personalize breast cancer screening strategies, according to a retrospective cohort study reported at the 12th European Breast Cancer Conference.

“Benign breast disease is a key risk factor for breast cancer risk prediction,” commented presenting investigator Marta Román, PhD, of the Hospital del Mar Medical Research Institute in Barcelona. “Those women who have had a benign breast disease diagnosis have an increased risk that lasts for at least 20 years.”

To assess the combined influence of various attributes of benign breast disease, the investigators studied 629,087 women, aged 50-69 years, in Spain who underwent population-based mammographic breast cancer screening during 1994-2015 and did not have breast cancer at their prevalent (first) screen. The mean follow-up was 7.8 years.

Results showed that breast cancer risk was about three times higher for women with benign breast disease that was proliferative or that was detected on an incident screen, relative to peers with no benign breast disease. When combinations of factors were considered, breast cancer risk was most elevated – more than four times higher – for women with proliferative benign breast disease with atypia detected on an incident screen.

“We believe that these findings should be considered when discussing risk-based personalized screening strategies because these differences between prevalent and incident screens might be important if we want to personalize the screening, whether it’s the first time a woman comes to the screening program or a subsequent screen,” Dr. Román said.
 

Practice changing?

The study’s large size and population-based design, likely permitting capture of most biopsy results, are strengths, Mark David Pearlman, MD, of the University of Michigan, Ann Arbor, commented in an interview.

But its observational, retrospective nature opens the study up to biases, such as uncertainty as to how many women were symptomatic at the time of their mammogram and the likelihood of heightened monitoring after a biopsy showing hyperplasia, Dr. Pearlman cautioned.

“Moreover, the relative risk in this study for proliferative benign breast disease without atypia is substantially higher than prior observations of this group. This discrepancy was not discussed by the authors,” Dr. Pearlman said.

At present, women’s risk of breast cancer is predicted using well-validated models that include the question of prior breast biopsies, such as the Gail Model, the Tyrer-Cuzick model (IBIS tool), and the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm, Dr. Pearlman noted.

“This study, without further validation within a model, would not change risk assessment,” he said, disagreeing with the investigators’ conclusions. “What I would say is that further study to determine how to use this observation to decide if any change in screening or management should occur would be more appropriate.”
 

Study details

The 629,087 women studied underwent 2,327,384 screens, Dr. Román reported. In total, screening detected 9,184 cases of benign breast disease and 9,431 breast cancers.

Breast cancer was diagnosed in 2.4% and 3.0% of women with benign breast disease detected on prevalent and incident screens, respectively, compared with 1.5% of women without any benign breast disease detected.

Elevation of breast cancer risk varied across benign breast disease subtype. Relative to peers without any benign disease, risk was significantly elevated for women with nonproliferative disease (adjusted hazard ratio, 1.95), proliferative disease without atypia (aHR, 3.19), and proliferative disease with atypia (aHR, 3.82).

Similarly, elevation of risk varied depending on the screening at which the benign disease was detected. Risk was significantly elevated when the disease was found at prevalent screens (aHR, 1.87) and more so when it was found at incident screens (aHR, 2.67).

There was no significant interaction of these two factors (P = .83). However, when combinations were considered, risk was highest for women with proliferative benign breast disease with atypia detected on incident screens (aHR, 4.35) or prevalent screens (aHR, 3.35), and women with proliferative benign breast disease without atypia detected on incident screens (aHR, 3.83).

This study was supported by grants from Instituto de Salud Carlos III FEDER and by the Research Network on Health Services in Chronic Diseases. Dr. Román and Dr. Pearlman disclosed no conflicts of interest.

SOURCE: Román M et al. EBCC-12 Virtual Conference, Abstract 15.

The combined features of benign breast disease may help better personalize breast cancer screening strategies, according to a retrospective cohort study reported at the 12th European Breast Cancer Conference.

“Benign breast disease is a key risk factor for breast cancer risk prediction,” commented presenting investigator Marta Román, PhD, of the Hospital del Mar Medical Research Institute in Barcelona. “Those women who have had a benign breast disease diagnosis have an increased risk that lasts for at least 20 years.”

To assess the combined influence of various attributes of benign breast disease, the investigators studied 629,087 women, aged 50-69 years, in Spain who underwent population-based mammographic breast cancer screening during 1994-2015 and did not have breast cancer at their prevalent (first) screen. The mean follow-up was 7.8 years.

Results showed that breast cancer risk was about three times higher for women with benign breast disease that was proliferative or that was detected on an incident screen, relative to peers with no benign breast disease. When combinations of factors were considered, breast cancer risk was most elevated – more than four times higher – for women with proliferative benign breast disease with atypia detected on an incident screen.

“We believe that these findings should be considered when discussing risk-based personalized screening strategies because these differences between prevalent and incident screens might be important if we want to personalize the screening, whether it’s the first time a woman comes to the screening program or a subsequent screen,” Dr. Román said.
 

Practice changing?

The study’s large size and population-based design, likely permitting capture of most biopsy results, are strengths, Mark David Pearlman, MD, of the University of Michigan, Ann Arbor, commented in an interview.

But its observational, retrospective nature opens the study up to biases, such as uncertainty as to how many women were symptomatic at the time of their mammogram and the likelihood of heightened monitoring after a biopsy showing hyperplasia, Dr. Pearlman cautioned.

“Moreover, the relative risk in this study for proliferative benign breast disease without atypia is substantially higher than prior observations of this group. This discrepancy was not discussed by the authors,” Dr. Pearlman said.

At present, women’s risk of breast cancer is predicted using well-validated models that include the question of prior breast biopsies, such as the Gail Model, the Tyrer-Cuzick model (IBIS tool), and the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm, Dr. Pearlman noted.

“This study, without further validation within a model, would not change risk assessment,” he said, disagreeing with the investigators’ conclusions. “What I would say is that further study to determine how to use this observation to decide if any change in screening or management should occur would be more appropriate.”
 

Study details

The 629,087 women studied underwent 2,327,384 screens, Dr. Román reported. In total, screening detected 9,184 cases of benign breast disease and 9,431 breast cancers.

Breast cancer was diagnosed in 2.4% and 3.0% of women with benign breast disease detected on prevalent and incident screens, respectively, compared with 1.5% of women without any benign breast disease detected.

Elevation of breast cancer risk varied across benign breast disease subtype. Relative to peers without any benign disease, risk was significantly elevated for women with nonproliferative disease (adjusted hazard ratio, 1.95), proliferative disease without atypia (aHR, 3.19), and proliferative disease with atypia (aHR, 3.82).

Similarly, elevation of risk varied depending on the screening at which the benign disease was detected. Risk was significantly elevated when the disease was found at prevalent screens (aHR, 1.87) and more so when it was found at incident screens (aHR, 2.67).

There was no significant interaction of these two factors (P = .83). However, when combinations were considered, risk was highest for women with proliferative benign breast disease with atypia detected on incident screens (aHR, 4.35) or prevalent screens (aHR, 3.35), and women with proliferative benign breast disease without atypia detected on incident screens (aHR, 3.83).

This study was supported by grants from Instituto de Salud Carlos III FEDER and by the Research Network on Health Services in Chronic Diseases. Dr. Román and Dr. Pearlman disclosed no conflicts of interest.

SOURCE: Román M et al. EBCC-12 Virtual Conference, Abstract 15.

The combined features of benign breast disease may help better personalize breast cancer screening strategies, according to a retrospective cohort study reported at the 12th European Breast Cancer Conference.

“Benign breast disease is a key risk factor for breast cancer risk prediction,” commented presenting investigator Marta Román, PhD, of the Hospital del Mar Medical Research Institute in Barcelona. “Those women who have had a benign breast disease diagnosis have an increased risk that lasts for at least 20 years.”

To assess the combined influence of various attributes of benign breast disease, the investigators studied 629,087 women, aged 50-69 years, in Spain who underwent population-based mammographic breast cancer screening during 1994-2015 and did not have breast cancer at their prevalent (first) screen. The mean follow-up was 7.8 years.

Results showed that breast cancer risk was about three times higher for women with benign breast disease that was proliferative or that was detected on an incident screen, relative to peers with no benign breast disease. When combinations of factors were considered, breast cancer risk was most elevated – more than four times higher – for women with proliferative benign breast disease with atypia detected on an incident screen.

“We believe that these findings should be considered when discussing risk-based personalized screening strategies because these differences between prevalent and incident screens might be important if we want to personalize the screening, whether it’s the first time a woman comes to the screening program or a subsequent screen,” Dr. Román said.
 

Practice changing?

The study’s large size and population-based design, likely permitting capture of most biopsy results, are strengths, Mark David Pearlman, MD, of the University of Michigan, Ann Arbor, commented in an interview.

But its observational, retrospective nature opens the study up to biases, such as uncertainty as to how many women were symptomatic at the time of their mammogram and the likelihood of heightened monitoring after a biopsy showing hyperplasia, Dr. Pearlman cautioned.

“Moreover, the relative risk in this study for proliferative benign breast disease without atypia is substantially higher than prior observations of this group. This discrepancy was not discussed by the authors,” Dr. Pearlman said.

At present, women’s risk of breast cancer is predicted using well-validated models that include the question of prior breast biopsies, such as the Gail Model, the Tyrer-Cuzick model (IBIS tool), and the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm, Dr. Pearlman noted.

“This study, without further validation within a model, would not change risk assessment,” he said, disagreeing with the investigators’ conclusions. “What I would say is that further study to determine how to use this observation to decide if any change in screening or management should occur would be more appropriate.”
 

Study details

The 629,087 women studied underwent 2,327,384 screens, Dr. Román reported. In total, screening detected 9,184 cases of benign breast disease and 9,431 breast cancers.

Breast cancer was diagnosed in 2.4% and 3.0% of women with benign breast disease detected on prevalent and incident screens, respectively, compared with 1.5% of women without any benign breast disease detected.

Elevation of breast cancer risk varied across benign breast disease subtype. Relative to peers without any benign disease, risk was significantly elevated for women with nonproliferative disease (adjusted hazard ratio, 1.95), proliferative disease without atypia (aHR, 3.19), and proliferative disease with atypia (aHR, 3.82).

Similarly, elevation of risk varied depending on the screening at which the benign disease was detected. Risk was significantly elevated when the disease was found at prevalent screens (aHR, 1.87) and more so when it was found at incident screens (aHR, 2.67).

There was no significant interaction of these two factors (P = .83). However, when combinations were considered, risk was highest for women with proliferative benign breast disease with atypia detected on incident screens (aHR, 4.35) or prevalent screens (aHR, 3.35), and women with proliferative benign breast disease without atypia detected on incident screens (aHR, 3.83).

This study was supported by grants from Instituto de Salud Carlos III FEDER and by the Research Network on Health Services in Chronic Diseases. Dr. Román and Dr. Pearlman disclosed no conflicts of interest.

SOURCE: Román M et al. EBCC-12 Virtual Conference, Abstract 15.

The recall of extended-release metformin continues this month as 76 more lots have been flagged for a possible cancer-causing ingredient.

The Food and Drug Administration announced the latest recall, involving Marksans Pharma Limited and Sun Pharmaceutical Industries products, on Oct. 5. It involves the 500-mg and 700-mg tablets. More than 175 different drug combinations have been recalled since late May.

Consumers can see all the recalled metformin products at this FDA website. The agency says that immediate-release metformin does not appear to have the same contamination problem.

The FDA has been investigating the presence of nitrosamines, known to be possible carcinogens, in the popular diabetes medications since December, when they were first discovered in drugs in other countries. The agency said this month they still do not know the source of nitrosamines in the medications.

The investigation and subsequent recalls follow similar ones for contamination of popular heartburn and blood pressure drugs also for nitrosamines, such as N-Nitrosodimethylamine (NDMA).

The FDA says patients taking metformin products that have been recalled should continue taking the medication until a doctor or pharmacist gives them a replacement or a different treatment option. It could be dangerous for patients with type 2 diabetes to stop taking the medication without first talking to their doctor.

The agency has asked drug manufacturers to test products before batches are released into the market. The companies must tell the FDA if any product shows levels of nitrosamines above the acceptable limit.

The risk from nitrosamines is not clear. The FDA says they may increase the risk of cancer in people who are exposed to high levels over a long period of time, “but we do not anticipate that shorter-term exposure at levels above the acceptable intake limit would lead to an increase in the risk of cancer.”
 

This article first appeared on WebMD.com.

The recall of extended-release metformin continues this month as 76 more lots have been flagged for a possible cancer-causing ingredient.

The Food and Drug Administration announced the latest recall, involving Marksans Pharma Limited and Sun Pharmaceutical Industries products, on Oct. 5. It involves the 500-mg and 700-mg tablets. More than 175 different drug combinations have been recalled since late May.

Consumers can see all the recalled metformin products at this FDA website. The agency says that immediate-release metformin does not appear to have the same contamination problem.

The FDA has been investigating the presence of nitrosamines, known to be possible carcinogens, in the popular diabetes medications since December, when they were first discovered in drugs in other countries. The agency said this month they still do not know the source of nitrosamines in the medications.

The investigation and subsequent recalls follow similar ones for contamination of popular heartburn and blood pressure drugs also for nitrosamines, such as N-Nitrosodimethylamine (NDMA).

The FDA says patients taking metformin products that have been recalled should continue taking the medication until a doctor or pharmacist gives them a replacement or a different treatment option. It could be dangerous for patients with type 2 diabetes to stop taking the medication without first talking to their doctor.

The agency has asked drug manufacturers to test products before batches are released into the market. The companies must tell the FDA if any product shows levels of nitrosamines above the acceptable limit.

The risk from nitrosamines is not clear. The FDA says they may increase the risk of cancer in people who are exposed to high levels over a long period of time, “but we do not anticipate that shorter-term exposure at levels above the acceptable intake limit would lead to an increase in the risk of cancer.”
 

This article first appeared on WebMD.com.

The recall of extended-release metformin continues this month as 76 more lots have been flagged for a possible cancer-causing ingredient.

The Food and Drug Administration announced the latest recall, involving Marksans Pharma Limited and Sun Pharmaceutical Industries products, on Oct. 5. It involves the 500-mg and 700-mg tablets. More than 175 different drug combinations have been recalled since late May.

Consumers can see all the recalled metformin products at this FDA website. The agency says that immediate-release metformin does not appear to have the same contamination problem.

The FDA has been investigating the presence of nitrosamines, known to be possible carcinogens, in the popular diabetes medications since December, when they were first discovered in drugs in other countries. The agency said this month they still do not know the source of nitrosamines in the medications.

The investigation and subsequent recalls follow similar ones for contamination of popular heartburn and blood pressure drugs also for nitrosamines, such as N-Nitrosodimethylamine (NDMA).

The FDA says patients taking metformin products that have been recalled should continue taking the medication until a doctor or pharmacist gives them a replacement or a different treatment option. It could be dangerous for patients with type 2 diabetes to stop taking the medication without first talking to their doctor.

The agency has asked drug manufacturers to test products before batches are released into the market. The companies must tell the FDA if any product shows levels of nitrosamines above the acceptable limit.

The risk from nitrosamines is not clear. The FDA says they may increase the risk of cancer in people who are exposed to high levels over a long period of time, “but we do not anticipate that shorter-term exposure at levels above the acceptable intake limit would lead to an increase in the risk of cancer.”
 

This article first appeared on WebMD.com.

Patients with COVID-19 who present with ST-segment elevation MI (STEMI) represent a unique, high-risk population with greater risks for in-hospital death and stroke, according to initial results from the North American COVID-19 ST-Segment Elevation Myocardial Infarction Registry (NACMI).

Although COVID-19–confirmed patients were less likely to undergo angiography than patients under investigation (PUI) for COVID-19 or historical STEMI activation controls, 71% underwent primary percutaneous coronary intervention (PCI).

“Primary PCI is preferable and feasible in COVID-19–positive patients, with door-to-balloon times similar to PUI or COVID-negative patients, and that supports the updated COVID-specific STEMI guidelines,” study cochair Timothy D. Henry, MD, said in a late-breaking clinical science session at TCT 2020, the Transcatheter Cardiovascular Therapeutics virtual annual meeting.

The multisociety COVID-specific guidelines were initially issued in April, endorsing PCI as the standard of care and allowing for consideration of fibrinolysis-based therapy at non-PCI capable hospitals.

Five previous publications on a total of 174 COVID-19 patients with ST-elevation have shown there are more frequent in-hospital STEMI presentations, more cases without a clear culprit lesion, more thrombotic lesions and microthrombi, and higher mortality, ranging from 12% to 72%. Still, there has been considerable controversy over exactly what to do when COVID-19 patients with ST elevation reach the cath lab, he said at the meeting sponsored by the Cardiovascular Research Foundation.

NACMI represents the largest experience with ST-elevation patients and is a unique collaboration between the Society for Cardiovascular Angiography and Interventions, Canadian Association of Interventional Cardiology, American College of Cardiology, and Midwest STEMI Consortium, noted Dr. Henry, who is medical director of the Lindner Center for Research and Education at the Christ Hospital, Cincinnati.

The registry enrolled any COVID-19–positive patient or person under investigation older than 18 years with ST-segment elevation or new-onset left bundle branch block on electrocardiogram with a clinical correlate of myocardial ischemia such as chest pain, dyspnea, cardiac arrest, shock, or mechanical ventilation. There were no exclusion criteria.

Data from 171 patients with confirmed COVID-19 and 423 PUI from 64 sites were then propensity-matched to a control population from the Midwest STEMI Consortium, a prospective, multicenter registry of consecutive STEMI patients.

The three groups were similar in sex and age but there was a striking difference in race, with 27% of African American and 24% of Hispanic patients COVID-confirmed, compared with 11% and 6% in the PUI group and 4% and 1% in the control group. Likewise, there was a significant increase in diabetes (44% vs. 33% vs. 20%), which has been reported previously with influenza.

COVID-19–positive patients, as compared with PUI and controls, were significantly more likely to present with cardiogenic shock before PCI (20% vs. 14% vs. 5%), but not cardiac arrest (12% vs. 17% vs. 11%), and to have lower left ventricular ejection fractions (45% vs. 45% vs. 50%).

They also presented with more atypical symptoms than PUI patients, particularly infiltrates on chest x-ray (49% vs. 17%) and dyspnea (58% vs. 38%). Data were not available for these outcomes among historic controls.

Importantly, 21% of the COVID-19 patients did not undergo angiography, compared with 5% of PUI patients and 0% of controls (P < .001), “which is much higher than we would expect or have suspected,” Dr. Henry said. Thrombolytic use was very uncommon in those undergoing angiography, likely as a result of the guidelines.

Very surprisingly, there were no differences in door-to-balloon times between the COVID-positive, PUI, and control groups despite the ongoing pandemic (80 min vs. 78 min vs. 86 min).

But there was clear worsening in in-hospital mortality in COVID-19–positive patients (32% vs. 12% and 6%; P < .001), as well as in-hospital stroke (3.4% vs. 2% vs. 0.6%) that reached statistical significance only when compared with historical controls (P = .039). Total length of stay was twice as long in COVID-confirmed patients as in both PUI and controls (6 days vs. 3 days; P < .001).

Following the formal presentation, invited discussant Philippe Gabriel Steg, MD, Imperial College London, said the researchers have provided a great service in reporting the data so quickly but noted that an ongoing French registry of events before, during, and after the first COVID-19 wave has not seen an increased death rate.

“Can you tease out whether the increased death rate is related to cardiovascular deaths or to COVID-related pneumonias, shocks, ARDSs [acute respiratory distress syndromes], and so on and so forth? Because our impression – and that’s what we’ve published in Lancet Public Health – is that the cardiovascular morality rate doesn’t seem that affected by COVID.”

Dr. Henry replied that these are early data but “I will tell you that patients who did get PCI had a mortality rate that was only around 12% or 13%, and the patients who did not undergo angiography or were treated with medical therapy had higher mortality. Now, of course, that’s selected and we need to do a much better matching and look at that, but that’s our goal and we will have that information,” he said.

During a press briefing on the study, discussant Renu Virmani, MD, president and founder of CVPath Institute, noted that, in their analysis of 40 autopsy cases from Bergamot, Italy, small intramyocardial microthrombi were seen in nine patients, whereas epicardial microthrombi were seen in only three or four.

“Some of the cases are being taken as being related to coronary disease but may be more thrombotic than anything else,” she said. “I think there’s a combination, and that’s why the outcomes are so poor. You didn’t show us TIMI flow but that’s something to think about: Was TIMI flow different in the patients who died because you have very high mortality? I think we need to get to the bottom of what is the underlying cause of that thrombosis.”

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

Patients with COVID-19 who present with ST-segment elevation MI (STEMI) represent a unique, high-risk population with greater risks for in-hospital death and stroke, according to initial results from the North American COVID-19 ST-Segment Elevation Myocardial Infarction Registry (NACMI).

Although COVID-19–confirmed patients were less likely to undergo angiography than patients under investigation (PUI) for COVID-19 or historical STEMI activation controls, 71% underwent primary percutaneous coronary intervention (PCI).

“Primary PCI is preferable and feasible in COVID-19–positive patients, with door-to-balloon times similar to PUI or COVID-negative patients, and that supports the updated COVID-specific STEMI guidelines,” study cochair Timothy D. Henry, MD, said in a late-breaking clinical science session at TCT 2020, the Transcatheter Cardiovascular Therapeutics virtual annual meeting.

The multisociety COVID-specific guidelines were initially issued in April, endorsing PCI as the standard of care and allowing for consideration of fibrinolysis-based therapy at non-PCI capable hospitals.

Five previous publications on a total of 174 COVID-19 patients with ST-elevation have shown there are more frequent in-hospital STEMI presentations, more cases without a clear culprit lesion, more thrombotic lesions and microthrombi, and higher mortality, ranging from 12% to 72%. Still, there has been considerable controversy over exactly what to do when COVID-19 patients with ST elevation reach the cath lab, he said at the meeting sponsored by the Cardiovascular Research Foundation.

NACMI represents the largest experience with ST-elevation patients and is a unique collaboration between the Society for Cardiovascular Angiography and Interventions, Canadian Association of Interventional Cardiology, American College of Cardiology, and Midwest STEMI Consortium, noted Dr. Henry, who is medical director of the Lindner Center for Research and Education at the Christ Hospital, Cincinnati.

The registry enrolled any COVID-19–positive patient or person under investigation older than 18 years with ST-segment elevation or new-onset left bundle branch block on electrocardiogram with a clinical correlate of myocardial ischemia such as chest pain, dyspnea, cardiac arrest, shock, or mechanical ventilation. There were no exclusion criteria.

Data from 171 patients with confirmed COVID-19 and 423 PUI from 64 sites were then propensity-matched to a control population from the Midwest STEMI Consortium, a prospective, multicenter registry of consecutive STEMI patients.

The three groups were similar in sex and age but there was a striking difference in race, with 27% of African American and 24% of Hispanic patients COVID-confirmed, compared with 11% and 6% in the PUI group and 4% and 1% in the control group. Likewise, there was a significant increase in diabetes (44% vs. 33% vs. 20%), which has been reported previously with influenza.

COVID-19–positive patients, as compared with PUI and controls, were significantly more likely to present with cardiogenic shock before PCI (20% vs. 14% vs. 5%), but not cardiac arrest (12% vs. 17% vs. 11%), and to have lower left ventricular ejection fractions (45% vs. 45% vs. 50%).

They also presented with more atypical symptoms than PUI patients, particularly infiltrates on chest x-ray (49% vs. 17%) and dyspnea (58% vs. 38%). Data were not available for these outcomes among historic controls.

Importantly, 21% of the COVID-19 patients did not undergo angiography, compared with 5% of PUI patients and 0% of controls (P < .001), “which is much higher than we would expect or have suspected,” Dr. Henry said. Thrombolytic use was very uncommon in those undergoing angiography, likely as a result of the guidelines.

Very surprisingly, there were no differences in door-to-balloon times between the COVID-positive, PUI, and control groups despite the ongoing pandemic (80 min vs. 78 min vs. 86 min).

But there was clear worsening in in-hospital mortality in COVID-19–positive patients (32% vs. 12% and 6%; P < .001), as well as in-hospital stroke (3.4% vs. 2% vs. 0.6%) that reached statistical significance only when compared with historical controls (P = .039). Total length of stay was twice as long in COVID-confirmed patients as in both PUI and controls (6 days vs. 3 days; P < .001).

Following the formal presentation, invited discussant Philippe Gabriel Steg, MD, Imperial College London, said the researchers have provided a great service in reporting the data so quickly but noted that an ongoing French registry of events before, during, and after the first COVID-19 wave has not seen an increased death rate.

“Can you tease out whether the increased death rate is related to cardiovascular deaths or to COVID-related pneumonias, shocks, ARDSs [acute respiratory distress syndromes], and so on and so forth? Because our impression – and that’s what we’ve published in Lancet Public Health – is that the cardiovascular morality rate doesn’t seem that affected by COVID.”

Dr. Henry replied that these are early data but “I will tell you that patients who did get PCI had a mortality rate that was only around 12% or 13%, and the patients who did not undergo angiography or were treated with medical therapy had higher mortality. Now, of course, that’s selected and we need to do a much better matching and look at that, but that’s our goal and we will have that information,” he said.

During a press briefing on the study, discussant Renu Virmani, MD, president and founder of CVPath Institute, noted that, in their analysis of 40 autopsy cases from Bergamot, Italy, small intramyocardial microthrombi were seen in nine patients, whereas epicardial microthrombi were seen in only three or four.

“Some of the cases are being taken as being related to coronary disease but may be more thrombotic than anything else,” she said. “I think there’s a combination, and that’s why the outcomes are so poor. You didn’t show us TIMI flow but that’s something to think about: Was TIMI flow different in the patients who died because you have very high mortality? I think we need to get to the bottom of what is the underlying cause of that thrombosis.”

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

Patients with COVID-19 who present with ST-segment elevation MI (STEMI) represent a unique, high-risk population with greater risks for in-hospital death and stroke, according to initial results from the North American COVID-19 ST-Segment Elevation Myocardial Infarction Registry (NACMI).

Although COVID-19–confirmed patients were less likely to undergo angiography than patients under investigation (PUI) for COVID-19 or historical STEMI activation controls, 71% underwent primary percutaneous coronary intervention (PCI).

“Primary PCI is preferable and feasible in COVID-19–positive patients, with door-to-balloon times similar to PUI or COVID-negative patients, and that supports the updated COVID-specific STEMI guidelines,” study cochair Timothy D. Henry, MD, said in a late-breaking clinical science session at TCT 2020, the Transcatheter Cardiovascular Therapeutics virtual annual meeting.

The multisociety COVID-specific guidelines were initially issued in April, endorsing PCI as the standard of care and allowing for consideration of fibrinolysis-based therapy at non-PCI capable hospitals.

Five previous publications on a total of 174 COVID-19 patients with ST-elevation have shown there are more frequent in-hospital STEMI presentations, more cases without a clear culprit lesion, more thrombotic lesions and microthrombi, and higher mortality, ranging from 12% to 72%. Still, there has been considerable controversy over exactly what to do when COVID-19 patients with ST elevation reach the cath lab, he said at the meeting sponsored by the Cardiovascular Research Foundation.

NACMI represents the largest experience with ST-elevation patients and is a unique collaboration between the Society for Cardiovascular Angiography and Interventions, Canadian Association of Interventional Cardiology, American College of Cardiology, and Midwest STEMI Consortium, noted Dr. Henry, who is medical director of the Lindner Center for Research and Education at the Christ Hospital, Cincinnati.

The registry enrolled any COVID-19–positive patient or person under investigation older than 18 years with ST-segment elevation or new-onset left bundle branch block on electrocardiogram with a clinical correlate of myocardial ischemia such as chest pain, dyspnea, cardiac arrest, shock, or mechanical ventilation. There were no exclusion criteria.

Data from 171 patients with confirmed COVID-19 and 423 PUI from 64 sites were then propensity-matched to a control population from the Midwest STEMI Consortium, a prospective, multicenter registry of consecutive STEMI patients.

The three groups were similar in sex and age but there was a striking difference in race, with 27% of African American and 24% of Hispanic patients COVID-confirmed, compared with 11% and 6% in the PUI group and 4% and 1% in the control group. Likewise, there was a significant increase in diabetes (44% vs. 33% vs. 20%), which has been reported previously with influenza.

COVID-19–positive patients, as compared with PUI and controls, were significantly more likely to present with cardiogenic shock before PCI (20% vs. 14% vs. 5%), but not cardiac arrest (12% vs. 17% vs. 11%), and to have lower left ventricular ejection fractions (45% vs. 45% vs. 50%).

They also presented with more atypical symptoms than PUI patients, particularly infiltrates on chest x-ray (49% vs. 17%) and dyspnea (58% vs. 38%). Data were not available for these outcomes among historic controls.

Importantly, 21% of the COVID-19 patients did not undergo angiography, compared with 5% of PUI patients and 0% of controls (P < .001), “which is much higher than we would expect or have suspected,” Dr. Henry said. Thrombolytic use was very uncommon in those undergoing angiography, likely as a result of the guidelines.

Very surprisingly, there were no differences in door-to-balloon times between the COVID-positive, PUI, and control groups despite the ongoing pandemic (80 min vs. 78 min vs. 86 min).

But there was clear worsening in in-hospital mortality in COVID-19–positive patients (32% vs. 12% and 6%; P < .001), as well as in-hospital stroke (3.4% vs. 2% vs. 0.6%) that reached statistical significance only when compared with historical controls (P = .039). Total length of stay was twice as long in COVID-confirmed patients as in both PUI and controls (6 days vs. 3 days; P < .001).

Following the formal presentation, invited discussant Philippe Gabriel Steg, MD, Imperial College London, said the researchers have provided a great service in reporting the data so quickly but noted that an ongoing French registry of events before, during, and after the first COVID-19 wave has not seen an increased death rate.

“Can you tease out whether the increased death rate is related to cardiovascular deaths or to COVID-related pneumonias, shocks, ARDSs [acute respiratory distress syndromes], and so on and so forth? Because our impression – and that’s what we’ve published in Lancet Public Health – is that the cardiovascular morality rate doesn’t seem that affected by COVID.”

Dr. Henry replied that these are early data but “I will tell you that patients who did get PCI had a mortality rate that was only around 12% or 13%, and the patients who did not undergo angiography or were treated with medical therapy had higher mortality. Now, of course, that’s selected and we need to do a much better matching and look at that, but that’s our goal and we will have that information,” he said.

During a press briefing on the study, discussant Renu Virmani, MD, president and founder of CVPath Institute, noted that, in their analysis of 40 autopsy cases from Bergamot, Italy, small intramyocardial microthrombi were seen in nine patients, whereas epicardial microthrombi were seen in only three or four.

“Some of the cases are being taken as being related to coronary disease but may be more thrombotic than anything else,” she said. “I think there’s a combination, and that’s why the outcomes are so poor. You didn’t show us TIMI flow but that’s something to think about: Was TIMI flow different in the patients who died because you have very high mortality? I think we need to get to the bottom of what is the underlying cause of that thrombosis.”

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

Long-acting cabotegravir and rilpivirine (CAB/RPV) administered intramuscularly monthly or every 2 months yielded high rates of efficacy and a favorable safety profile in women with HIV, according to results from the ATLAS-2M study, presented at the HIV Glasgow 2020 Virtual Conference, held October 5-8. The women also reported high satisfaction with the regimen, compared with daily oral antiretroviral therapy.

Previously reported results had shown that the two-drug combination administered every 8 weeks (600 mg cabotegravir and 900 mg rilpivirine) was noninferior to injections every 4 weeks (400 mg cabotegravir and 600 mg rilpivirine) in adults with HIV during the open-label phase 3b ATLAS-2M trial. Further, the ATLAS and FLAIR phase 3 trials had shown the 4-week administration of the therapy to be noninferior to a daily oral three-drug antiretroviral therapy.

Paul Benn, MBBS, of ViiV Healthcare (which is seeking regulatory approval for CAB/RPV treatment), and his colleagues completed a planned subgroup analysis of women in the ATLAS-2M trial. The primary endpoint was the proportion of intention-to-treat participants with plasma HIV-1 RNA of at least 50 copies/mL with a noninferiority margin of 4% at 48 weeks. The secondary endpoint was the proportion of participants with HIV-1 RNA under 50 copies/mL with a noninferiority margin of 10%.

Among the 280 women enrolled, 137 were randomly assigned to receive injections every 8 weeks, and 143 to receive injections every 4 weeks. A majority of the women (56%) were White, the median age was 44 years, and just over half (53%) were treatment naive with cabotegravir and rilpivirine.

At 48 weeks, 3.6% of women in the 8-week group and 0% of women in the 4-week group had at least 50 copies/mL of HIV-1 RNA. In both arms, 91% of participants had HIV-1 RNA under 50 copies/mL. Plasma concentrations of cabotegravir and rilpivirine were similar between the women and the overall study population.

Confirmed virologic failure occurred in five women, all before week 24. Three of the women were subtype A/A1, and four of them had archived nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance–associated mutations.

There were no significant differences in the safety profile between the groups; 99% of injection site reactions that occurred were mild to moderate and lasted a median 3-4 days. Fewer than 4% of participants discontinued because of adverse events – five women in the 8-week group and five women in the 4-week group. Four women cited injection site reactions as the reason for discontinuation.

Women not previously treated with CAB/RPV reported increased treatment satisfaction on the HIV Treatment Satisfaction Questionnaire, a score of 5.4 in the 8-week group and 3.9 in the 4-week group. Among those with prior CAB/RPV treatment, 88% preferred the 8-weekly injections, 8% preferred the 4-weekly injections, and 2% preferred oral dosing.

Long-acting CAB/RPV is an investigational formulation. In December 2019, the Food and Drug Administration denied approval to the formulation on the basis of manufacturing and chemistry concerns, according to a company press release.
 

This article first appeared on Medscape.com.

Long-acting cabotegravir and rilpivirine (CAB/RPV) administered intramuscularly monthly or every 2 months yielded high rates of efficacy and a favorable safety profile in women with HIV, according to results from the ATLAS-2M study, presented at the HIV Glasgow 2020 Virtual Conference, held October 5-8. The women also reported high satisfaction with the regimen, compared with daily oral antiretroviral therapy.

Previously reported results had shown that the two-drug combination administered every 8 weeks (600 mg cabotegravir and 900 mg rilpivirine) was noninferior to injections every 4 weeks (400 mg cabotegravir and 600 mg rilpivirine) in adults with HIV during the open-label phase 3b ATLAS-2M trial. Further, the ATLAS and FLAIR phase 3 trials had shown the 4-week administration of the therapy to be noninferior to a daily oral three-drug antiretroviral therapy.

Paul Benn, MBBS, of ViiV Healthcare (which is seeking regulatory approval for CAB/RPV treatment), and his colleagues completed a planned subgroup analysis of women in the ATLAS-2M trial. The primary endpoint was the proportion of intention-to-treat participants with plasma HIV-1 RNA of at least 50 copies/mL with a noninferiority margin of 4% at 48 weeks. The secondary endpoint was the proportion of participants with HIV-1 RNA under 50 copies/mL with a noninferiority margin of 10%.

Among the 280 women enrolled, 137 were randomly assigned to receive injections every 8 weeks, and 143 to receive injections every 4 weeks. A majority of the women (56%) were White, the median age was 44 years, and just over half (53%) were treatment naive with cabotegravir and rilpivirine.

At 48 weeks, 3.6% of women in the 8-week group and 0% of women in the 4-week group had at least 50 copies/mL of HIV-1 RNA. In both arms, 91% of participants had HIV-1 RNA under 50 copies/mL. Plasma concentrations of cabotegravir and rilpivirine were similar between the women and the overall study population.

Confirmed virologic failure occurred in five women, all before week 24. Three of the women were subtype A/A1, and four of them had archived nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance–associated mutations.

There were no significant differences in the safety profile between the groups; 99% of injection site reactions that occurred were mild to moderate and lasted a median 3-4 days. Fewer than 4% of participants discontinued because of adverse events – five women in the 8-week group and five women in the 4-week group. Four women cited injection site reactions as the reason for discontinuation.

Women not previously treated with CAB/RPV reported increased treatment satisfaction on the HIV Treatment Satisfaction Questionnaire, a score of 5.4 in the 8-week group and 3.9 in the 4-week group. Among those with prior CAB/RPV treatment, 88% preferred the 8-weekly injections, 8% preferred the 4-weekly injections, and 2% preferred oral dosing.

Long-acting CAB/RPV is an investigational formulation. In December 2019, the Food and Drug Administration denied approval to the formulation on the basis of manufacturing and chemistry concerns, according to a company press release.
 

This article first appeared on Medscape.com.

Long-acting cabotegravir and rilpivirine (CAB/RPV) administered intramuscularly monthly or every 2 months yielded high rates of efficacy and a favorable safety profile in women with HIV, according to results from the ATLAS-2M study, presented at the HIV Glasgow 2020 Virtual Conference, held October 5-8. The women also reported high satisfaction with the regimen, compared with daily oral antiretroviral therapy.

Previously reported results had shown that the two-drug combination administered every 8 weeks (600 mg cabotegravir and 900 mg rilpivirine) was noninferior to injections every 4 weeks (400 mg cabotegravir and 600 mg rilpivirine) in adults with HIV during the open-label phase 3b ATLAS-2M trial. Further, the ATLAS and FLAIR phase 3 trials had shown the 4-week administration of the therapy to be noninferior to a daily oral three-drug antiretroviral therapy.

Paul Benn, MBBS, of ViiV Healthcare (which is seeking regulatory approval for CAB/RPV treatment), and his colleagues completed a planned subgroup analysis of women in the ATLAS-2M trial. The primary endpoint was the proportion of intention-to-treat participants with plasma HIV-1 RNA of at least 50 copies/mL with a noninferiority margin of 4% at 48 weeks. The secondary endpoint was the proportion of participants with HIV-1 RNA under 50 copies/mL with a noninferiority margin of 10%.

Among the 280 women enrolled, 137 were randomly assigned to receive injections every 8 weeks, and 143 to receive injections every 4 weeks. A majority of the women (56%) were White, the median age was 44 years, and just over half (53%) were treatment naive with cabotegravir and rilpivirine.

At 48 weeks, 3.6% of women in the 8-week group and 0% of women in the 4-week group had at least 50 copies/mL of HIV-1 RNA. In both arms, 91% of participants had HIV-1 RNA under 50 copies/mL. Plasma concentrations of cabotegravir and rilpivirine were similar between the women and the overall study population.

Confirmed virologic failure occurred in five women, all before week 24. Three of the women were subtype A/A1, and four of them had archived nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance–associated mutations.

There were no significant differences in the safety profile between the groups; 99% of injection site reactions that occurred were mild to moderate and lasted a median 3-4 days. Fewer than 4% of participants discontinued because of adverse events – five women in the 8-week group and five women in the 4-week group. Four women cited injection site reactions as the reason for discontinuation.

Women not previously treated with CAB/RPV reported increased treatment satisfaction on the HIV Treatment Satisfaction Questionnaire, a score of 5.4 in the 8-week group and 3.9 in the 4-week group. Among those with prior CAB/RPV treatment, 88% preferred the 8-weekly injections, 8% preferred the 4-weekly injections, and 2% preferred oral dosing.

Long-acting CAB/RPV is an investigational formulation. In December 2019, the Food and Drug Administration denied approval to the formulation on the basis of manufacturing and chemistry concerns, according to a company press release.
 

This article first appeared on Medscape.com.

Measuring glycated albumin (glycoalbumin, GA) in tears could be a future way for those with diabetes to monitor their blood sugar levels noninvasively.

In a 100-patient trial, levels of GA in tears were found to be strongly correlated (r = .722; P < .001) with those in the blood.

“GA levels in blood are widely measured in clinical practice in Japan,” said study investigator Masakazu Aihara, MD, PhD, in an interview.

“It’s a biomarker that reflects the 2-week average blood glucose level like fructosamine,” explained the researcher from the department of diabetes and metabolic diseases in the Graduate School of Medicine at the University of Tokyo.

This could make it a better biomarker for detecting earlier changes in blood glucose than glycated hemoglobin (HbA_1c), which reflects changes in blood glucose over the preceding 2-3 months.

Prior studies had shown that glucose levels can be measured in tear samples and that tear glucose levels correlated with blood glucose levels, Dr. Aihara and fellow researchers observed in a poster presentation at the virtual annual meeting of the European Association for the Study of Diabetes.

“While looking for noninvasive diabetes-related markers, we found that tears contained albumin. Based on this fact, we thought that GA could be measured in tears,” Dr. Aihara explained.

Using tears to test for biomarkers is not a new idea – tears not only protect the eye, they contain a variety of large proteins, and their composition can change with disease. Indeed, researchers have been looking at their usefulness in helping find biomarkers for Parkinson’s disease and diabetic peripheral neuropathy.

During their study, Dr. Aihara and associates collected tear and blood samples at the same time. Tear samples were assessed using liquid chromatography (LC) and mass spectrometry (MS). An enzymic method was used to measure GA levels in blood. Several diagnosis assay kits for GA are sold in Japan, Dr. Aihara said, and at least one of these has U.S. Food and Drug Administration approval.

Multiple regression analysis revealed that the correlation between GA levels in tears and in blood was maintained even after adjustment for age, gender, nephropathy stage, and obesity (P < .001). The results obtained from the tests were thought unlikely to be affected by any changes in the concentration or dilution of tear samples.

“Since GA levels in blood are clinically used in all types of diabetes, GA levels in tears is also expected to be useful in all types of diabetes,” Dr. Aihara said, noting that the effects of receiving treatment on GA levels in tears is something that he would like to look at.

The team would also like to optimize how tear samples are collected and reduce the volume of tears that are required for analysis. At the moment tears are collected via a dropper and about 100 mcL of tear fluid is required for measurement.

“At present, it is difficult to measure for dry eye patients because sufficient tears cannot be collected, but if the required amount of tears decreases in the future, it may be indicated for dry eye patients,” Dr. Aihara noted.

Discussing further research plans, he added: “We would like to examine the conditions of LC-MS/MS so that the correlation coefficient with GA in blood can be improved.

“Since LC-MS/MS is a large equipment in the laboratory, I would like to develop a device that can measure at the clinic or at home in the future.”

The study was funded by a grant from the Japan Agency for Medical Research and Development. Dr. Aihara had no conflicts of interest.

SOURCE: Aihara M et al. EASD 2020, poster presentation 624.

Measuring glycated albumin (glycoalbumin, GA) in tears could be a future way for those with diabetes to monitor their blood sugar levels noninvasively.

In a 100-patient trial, levels of GA in tears were found to be strongly correlated (r = .722; P < .001) with those in the blood.

“GA levels in blood are widely measured in clinical practice in Japan,” said study investigator Masakazu Aihara, MD, PhD, in an interview.

“It’s a biomarker that reflects the 2-week average blood glucose level like fructosamine,” explained the researcher from the department of diabetes and metabolic diseases in the Graduate School of Medicine at the University of Tokyo.

This could make it a better biomarker for detecting earlier changes in blood glucose than glycated hemoglobin (HbA_1c), which reflects changes in blood glucose over the preceding 2-3 months.

Prior studies had shown that glucose levels can be measured in tear samples and that tear glucose levels correlated with blood glucose levels, Dr. Aihara and fellow researchers observed in a poster presentation at the virtual annual meeting of the European Association for the Study of Diabetes.

“While looking for noninvasive diabetes-related markers, we found that tears contained albumin. Based on this fact, we thought that GA could be measured in tears,” Dr. Aihara explained.

Using tears to test for biomarkers is not a new idea – tears not only protect the eye, they contain a variety of large proteins, and their composition can change with disease. Indeed, researchers have been looking at their usefulness in helping find biomarkers for Parkinson’s disease and diabetic peripheral neuropathy.

During their study, Dr. Aihara and associates collected tear and blood samples at the same time. Tear samples were assessed using liquid chromatography (LC) and mass spectrometry (MS). An enzymic method was used to measure GA levels in blood. Several diagnosis assay kits for GA are sold in Japan, Dr. Aihara said, and at least one of these has U.S. Food and Drug Administration approval.

Multiple regression analysis revealed that the correlation between GA levels in tears and in blood was maintained even after adjustment for age, gender, nephropathy stage, and obesity (P < .001). The results obtained from the tests were thought unlikely to be affected by any changes in the concentration or dilution of tear samples.

“Since GA levels in blood are clinically used in all types of diabetes, GA levels in tears is also expected to be useful in all types of diabetes,” Dr. Aihara said, noting that the effects of receiving treatment on GA levels in tears is something that he would like to look at.

The team would also like to optimize how tear samples are collected and reduce the volume of tears that are required for analysis. At the moment tears are collected via a dropper and about 100 mcL of tear fluid is required for measurement.

“At present, it is difficult to measure for dry eye patients because sufficient tears cannot be collected, but if the required amount of tears decreases in the future, it may be indicated for dry eye patients,” Dr. Aihara noted.

Discussing further research plans, he added: “We would like to examine the conditions of LC-MS/MS so that the correlation coefficient with GA in blood can be improved.

“Since LC-MS/MS is a large equipment in the laboratory, I would like to develop a device that can measure at the clinic or at home in the future.”

The study was funded by a grant from the Japan Agency for Medical Research and Development. Dr. Aihara had no conflicts of interest.

SOURCE: Aihara M et al. EASD 2020, poster presentation 624.

Measuring glycated albumin (glycoalbumin, GA) in tears could be a future way for those with diabetes to monitor their blood sugar levels noninvasively.

In a 100-patient trial, levels of GA in tears were found to be strongly correlated (r = .722; P < .001) with those in the blood.

“GA levels in blood are widely measured in clinical practice in Japan,” said study investigator Masakazu Aihara, MD, PhD, in an interview.

“It’s a biomarker that reflects the 2-week average blood glucose level like fructosamine,” explained the researcher from the department of diabetes and metabolic diseases in the Graduate School of Medicine at the University of Tokyo.

This could make it a better biomarker for detecting earlier changes in blood glucose than glycated hemoglobin (HbA_1c), which reflects changes in blood glucose over the preceding 2-3 months.

Prior studies had shown that glucose levels can be measured in tear samples and that tear glucose levels correlated with blood glucose levels, Dr. Aihara and fellow researchers observed in a poster presentation at the virtual annual meeting of the European Association for the Study of Diabetes.

“While looking for noninvasive diabetes-related markers, we found that tears contained albumin. Based on this fact, we thought that GA could be measured in tears,” Dr. Aihara explained.

Using tears to test for biomarkers is not a new idea – tears not only protect the eye, they contain a variety of large proteins, and their composition can change with disease. Indeed, researchers have been looking at their usefulness in helping find biomarkers for Parkinson’s disease and diabetic peripheral neuropathy.

During their study, Dr. Aihara and associates collected tear and blood samples at the same time. Tear samples were assessed using liquid chromatography (LC) and mass spectrometry (MS). An enzymic method was used to measure GA levels in blood. Several diagnosis assay kits for GA are sold in Japan, Dr. Aihara said, and at least one of these has U.S. Food and Drug Administration approval.

Multiple regression analysis revealed that the correlation between GA levels in tears and in blood was maintained even after adjustment for age, gender, nephropathy stage, and obesity (P < .001). The results obtained from the tests were thought unlikely to be affected by any changes in the concentration or dilution of tear samples.

“Since GA levels in blood are clinically used in all types of diabetes, GA levels in tears is also expected to be useful in all types of diabetes,” Dr. Aihara said, noting that the effects of receiving treatment on GA levels in tears is something that he would like to look at.

The team would also like to optimize how tear samples are collected and reduce the volume of tears that are required for analysis. At the moment tears are collected via a dropper and about 100 mcL of tear fluid is required for measurement.

“At present, it is difficult to measure for dry eye patients because sufficient tears cannot be collected, but if the required amount of tears decreases in the future, it may be indicated for dry eye patients,” Dr. Aihara noted.

Discussing further research plans, he added: “We would like to examine the conditions of LC-MS/MS so that the correlation coefficient with GA in blood can be improved.

“Since LC-MS/MS is a large equipment in the laboratory, I would like to develop a device that can measure at the clinic or at home in the future.”

The study was funded by a grant from the Japan Agency for Medical Research and Development. Dr. Aihara had no conflicts of interest.

SOURCE: Aihara M et al. EASD 2020, poster presentation 624.

As the COVID-19 pandemic continues to chug along, some communities feel it slowing to a pace at which they might feel comfortable about a return to, if not quite “business as usual,” at least “business as sort of normal-ish.” They are ready to accept a level of disease that signals they have reached a steady state. However, in other communities, the virus has picked up speed and is threatening to overwhelm the medical infrastructure. If you are in one of those fortunate and skillfully managed states in which folks are beginning to talk seriously, but with little evidence, that it is time to return to normal, it is probably far too early. Are there any metrics that could be applied to make the decision to ease restrictions more rational?

Courtesy Dr. William G. Wilkoff

Eons ago in pandemic terms, the World Health Organization in Thailand published a list of criteria to aid in determining when a community could consider lifting the limits that seemed to have been effective in halting transmission of the virus (“Transitioning to and maintaining a steady state of low-level or no transmission,” WHO, Thailand, 2020 Apr 18). While much more has been learned about the behavior of the virus since the spring of 2020, the criteria from the WHO in Thailand are worth considering.

Here is my summary of their criteria for returning to normalcy. First, virus transmission is controlled to the point that only sporadic cases and small clusters exist, and that all of these are traceable in origin. Second, health care and public health systems are in place with sufficient capacities to manage a shift from detection to treatment should the case load increase dramatically; this capacity should include detection, testing, isolation, and quarantine. Third, outbreaks in high-risk populations such as nursing homes have been minimized. Fourth, workplace prevention strategies are in place and have been demonstrated to be effective. Fifth, risk of imported cases is at manageable levels. Finally, communities are engaged.

It is hard to argue with the rationale behind each of these criteria. However, the United States is not Thailand, and just thinking about how this country would go about meeting those criteria provides a window into some of the reasons why we have done so poorly and will continue to be challenged in dealing with the pandemic.

First, notice that the criteria make no mention of a vaccine. One gets the sense that from the top down our country is banking too heavily on the effectiveness and widespread delivery of a vaccine. Even if and when a vaccine is developed and delivered, all of these criteria still must be met and kept in mind for a future pandemic.

Second, the criteria call for an effective health care system, but it is abundantly clear that the United States does not have a cohesive health care system and probably won’t for the foreseeable future. The best we can hope for is individual states cobbling together their own systems, which may in turn serve as examples for those states who haven’t had the foresight. We have had a public health system of sorts, but its credibility and effectiveness has been neutered to the point that again we must rely on each state’s ability to see through the haze and create it’s own systems for detection, testing, tracking, isolating, and quarantining – often with little help in materiel support from the federal government. The sliver of good news is that, after a bit of a stumbling start, detecting and limiting the importation of cases from abroad is being addressed.

We continue to hear and see evidence that there are segments of the population who are not engaged in the activities that we have learned are necessary to stabilize the pandemic. My sense is that those people represent a very small minority. But, it is probably large enough to make the route to a steady state on a national level long and painful. This unfortunately is to be expected in a country that was built on a framework of personal freedoms. The best you can hope for in achieving a steady state is to live in one of the states that seems to be achieving the fine balance between personal freedoms and the common good.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

As the COVID-19 pandemic continues to chug along, some communities feel it slowing to a pace at which they might feel comfortable about a return to, if not quite “business as usual,” at least “business as sort of normal-ish.” They are ready to accept a level of disease that signals they have reached a steady state. However, in other communities, the virus has picked up speed and is threatening to overwhelm the medical infrastructure. If you are in one of those fortunate and skillfully managed states in which folks are beginning to talk seriously, but with little evidence, that it is time to return to normal, it is probably far too early. Are there any metrics that could be applied to make the decision to ease restrictions more rational?

Courtesy Dr. William G. Wilkoff

Eons ago in pandemic terms, the World Health Organization in Thailand published a list of criteria to aid in determining when a community could consider lifting the limits that seemed to have been effective in halting transmission of the virus (“Transitioning to and maintaining a steady state of low-level or no transmission,” WHO, Thailand, 2020 Apr 18). While much more has been learned about the behavior of the virus since the spring of 2020, the criteria from the WHO in Thailand are worth considering.

Here is my summary of their criteria for returning to normalcy. First, virus transmission is controlled to the point that only sporadic cases and small clusters exist, and that all of these are traceable in origin. Second, health care and public health systems are in place with sufficient capacities to manage a shift from detection to treatment should the case load increase dramatically; this capacity should include detection, testing, isolation, and quarantine. Third, outbreaks in high-risk populations such as nursing homes have been minimized. Fourth, workplace prevention strategies are in place and have been demonstrated to be effective. Fifth, risk of imported cases is at manageable levels. Finally, communities are engaged.

It is hard to argue with the rationale behind each of these criteria. However, the United States is not Thailand, and just thinking about how this country would go about meeting those criteria provides a window into some of the reasons why we have done so poorly and will continue to be challenged in dealing with the pandemic.

First, notice that the criteria make no mention of a vaccine. One gets the sense that from the top down our country is banking too heavily on the effectiveness and widespread delivery of a vaccine. Even if and when a vaccine is developed and delivered, all of these criteria still must be met and kept in mind for a future pandemic.

Second, the criteria call for an effective health care system, but it is abundantly clear that the United States does not have a cohesive health care system and probably won’t for the foreseeable future. The best we can hope for is individual states cobbling together their own systems, which may in turn serve as examples for those states who haven’t had the foresight. We have had a public health system of sorts, but its credibility and effectiveness has been neutered to the point that again we must rely on each state’s ability to see through the haze and create it’s own systems for detection, testing, tracking, isolating, and quarantining – often with little help in materiel support from the federal government. The sliver of good news is that, after a bit of a stumbling start, detecting and limiting the importation of cases from abroad is being addressed.

We continue to hear and see evidence that there are segments of the population who are not engaged in the activities that we have learned are necessary to stabilize the pandemic. My sense is that those people represent a very small minority. But, it is probably large enough to make the route to a steady state on a national level long and painful. This unfortunately is to be expected in a country that was built on a framework of personal freedoms. The best you can hope for in achieving a steady state is to live in one of the states that seems to be achieving the fine balance between personal freedoms and the common good.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

As the COVID-19 pandemic continues to chug along, some communities feel it slowing to a pace at which they might feel comfortable about a return to, if not quite “business as usual,” at least “business as sort of normal-ish.” They are ready to accept a level of disease that signals they have reached a steady state. However, in other communities, the virus has picked up speed and is threatening to overwhelm the medical infrastructure. If you are in one of those fortunate and skillfully managed states in which folks are beginning to talk seriously, but with little evidence, that it is time to return to normal, it is probably far too early. Are there any metrics that could be applied to make the decision to ease restrictions more rational?

Courtesy Dr. William G. Wilkoff

Eons ago in pandemic terms, the World Health Organization in Thailand published a list of criteria to aid in determining when a community could consider lifting the limits that seemed to have been effective in halting transmission of the virus (“Transitioning to and maintaining a steady state of low-level or no transmission,” WHO, Thailand, 2020 Apr 18). While much more has been learned about the behavior of the virus since the spring of 2020, the criteria from the WHO in Thailand are worth considering.

Here is my summary of their criteria for returning to normalcy. First, virus transmission is controlled to the point that only sporadic cases and small clusters exist, and that all of these are traceable in origin. Second, health care and public health systems are in place with sufficient capacities to manage a shift from detection to treatment should the case load increase dramatically; this capacity should include detection, testing, isolation, and quarantine. Third, outbreaks in high-risk populations such as nursing homes have been minimized. Fourth, workplace prevention strategies are in place and have been demonstrated to be effective. Fifth, risk of imported cases is at manageable levels. Finally, communities are engaged.

It is hard to argue with the rationale behind each of these criteria. However, the United States is not Thailand, and just thinking about how this country would go about meeting those criteria provides a window into some of the reasons why we have done so poorly and will continue to be challenged in dealing with the pandemic.

First, notice that the criteria make no mention of a vaccine. One gets the sense that from the top down our country is banking too heavily on the effectiveness and widespread delivery of a vaccine. Even if and when a vaccine is developed and delivered, all of these criteria still must be met and kept in mind for a future pandemic.

Second, the criteria call for an effective health care system, but it is abundantly clear that the United States does not have a cohesive health care system and probably won’t for the foreseeable future. The best we can hope for is individual states cobbling together their own systems, which may in turn serve as examples for those states who haven’t had the foresight. We have had a public health system of sorts, but its credibility and effectiveness has been neutered to the point that again we must rely on each state’s ability to see through the haze and create it’s own systems for detection, testing, tracking, isolating, and quarantining – often with little help in materiel support from the federal government. The sliver of good news is that, after a bit of a stumbling start, detecting and limiting the importation of cases from abroad is being addressed.

We continue to hear and see evidence that there are segments of the population who are not engaged in the activities that we have learned are necessary to stabilize the pandemic. My sense is that those people represent a very small minority. But, it is probably large enough to make the route to a steady state on a national level long and painful. This unfortunately is to be expected in a country that was built on a framework of personal freedoms. The best you can hope for in achieving a steady state is to live in one of the states that seems to be achieving the fine balance between personal freedoms and the common good.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

The mental health consequences of COVID-19 deaths are likely to overwhelm an already tattered U.S. mental health system, leading to a lack of access, particularly for the most vulnerable, experts warn.

“A second wave of devastation is imminent, attributable to mental health consequences of COVID-19,” write Naomi Simon, MD, and coauthors with the department of psychiatry, New York University.

In a Viewpoint article published in JAMA on Oct. 12, physicians offer some sobering statistics.

Since February 2020, COVID-19 has taken the lives of more than 214,000 Americans. The number of deaths currently attributed to the virus is nearly four times the number of Americans killed during the Vietnam War. The magnitude of death over a short period is a tragedy on a “historic scale,” wrote Dr. Simon and colleagues.

The surge in mental health problems related to COVID-19 deaths will bring further challenges to individuals, families, and communities, including a spike in deaths from suicide and drug overdoses, they warned.

It’s important to consider, they noted, that each COVID-19 death leaves an estimated nine family members bereaved, which is projected to lead to an estimated 2 million bereaved individuals in the United States.

“This interpersonal loss on a massive scale is compounded by societal disruption,” they wrote. The necessary social distancing and quarantine measures implemented to fight the virus have amplified emotional turmoil and have disrupted the ability of personal support networks and communities to come together and grieve.

“Of central concern is the transformation of normal grief and distress into prolonged grief and major depressive disorder and symptoms of posttraumatic stress disorder,” Simon and colleagues said.

“Once established, these conditions can become chronic with additional comorbidities such as substance use disorders. Prolonged grief affects approximately 10% of bereaved individuals, but this is likely an underestimate for grief related to deaths from COVID-19,” they wrote.

As with the first COVID-19 wave, the mental health wave will disproportionately affect Black persons, Hispanic persons, older adults, persons in lower socioeconomic groups of all races and ethnicities, and healthcare workers, they note.

The psychological risks for health care and other essential workers are of particular concern, they say. “Supporting the mental health of these and other essential workforce is critical to readiness for managing recurrent waves of the pandemic,” they stated.

How will the United States manage this impending wave of mental health problems?

“The solution will require increased funding for mental health; widespread screening to identify individuals at highest risk including suicide risk; availability of primary care clinicians and mental health professionals trained to treat those with prolonged grief, depression, traumatic stress, and substance abuse; and a diligent focus on families and communities to creatively restore the approaches by which they have managed tragedy and loss over generations,” the authors wrote.

“History has shown that societies recover from such devastation when leaders and members are joined by a shared purpose, acting in a unified way to facilitate recovery. In such societies, there is a shared understanding that its members must care for one another because the loss of one is a loss for all. Above all, this shared understanding must be restored,” they concluded.

Dr. Simon has received personal fees from Vanda Pharmaceuticals Inc, MGH Psychiatry Academy, Axovant Sciences, Springworks, Praxis Therapeutics, Aptinyx, Genomind, and Wiley (deputy editor, Depression and Anxiety). Saxe has received royalties from Guilford Press for the book Trauma Systems Therapy for Children and Teens (2016). Marmar serves on the scientific advisory board and owns equity in Receptor Life Sciences and serves on the PTSD advisory board for Otsuka Pharmaceutical.
 

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

The mental health consequences of COVID-19 deaths are likely to overwhelm an already tattered U.S. mental health system, leading to a lack of access, particularly for the most vulnerable, experts warn.

“A second wave of devastation is imminent, attributable to mental health consequences of COVID-19,” write Naomi Simon, MD, and coauthors with the department of psychiatry, New York University.

In a Viewpoint article published in JAMA on Oct. 12, physicians offer some sobering statistics.

Since February 2020, COVID-19 has taken the lives of more than 214,000 Americans. The number of deaths currently attributed to the virus is nearly four times the number of Americans killed during the Vietnam War. The magnitude of death over a short period is a tragedy on a “historic scale,” wrote Dr. Simon and colleagues.

The surge in mental health problems related to COVID-19 deaths will bring further challenges to individuals, families, and communities, including a spike in deaths from suicide and drug overdoses, they warned.

It’s important to consider, they noted, that each COVID-19 death leaves an estimated nine family members bereaved, which is projected to lead to an estimated 2 million bereaved individuals in the United States.

“This interpersonal loss on a massive scale is compounded by societal disruption,” they wrote. The necessary social distancing and quarantine measures implemented to fight the virus have amplified emotional turmoil and have disrupted the ability of personal support networks and communities to come together and grieve.

“Of central concern is the transformation of normal grief and distress into prolonged grief and major depressive disorder and symptoms of posttraumatic stress disorder,” Simon and colleagues said.

“Once established, these conditions can become chronic with additional comorbidities such as substance use disorders. Prolonged grief affects approximately 10% of bereaved individuals, but this is likely an underestimate for grief related to deaths from COVID-19,” they wrote.

As with the first COVID-19 wave, the mental health wave will disproportionately affect Black persons, Hispanic persons, older adults, persons in lower socioeconomic groups of all races and ethnicities, and healthcare workers, they note.

The psychological risks for health care and other essential workers are of particular concern, they say. “Supporting the mental health of these and other essential workforce is critical to readiness for managing recurrent waves of the pandemic,” they stated.

How will the United States manage this impending wave of mental health problems?

“The solution will require increased funding for mental health; widespread screening to identify individuals at highest risk including suicide risk; availability of primary care clinicians and mental health professionals trained to treat those with prolonged grief, depression, traumatic stress, and substance abuse; and a diligent focus on families and communities to creatively restore the approaches by which they have managed tragedy and loss over generations,” the authors wrote.

“History has shown that societies recover from such devastation when leaders and members are joined by a shared purpose, acting in a unified way to facilitate recovery. In such societies, there is a shared understanding that its members must care for one another because the loss of one is a loss for all. Above all, this shared understanding must be restored,” they concluded.

Dr. Simon has received personal fees from Vanda Pharmaceuticals Inc, MGH Psychiatry Academy, Axovant Sciences, Springworks, Praxis Therapeutics, Aptinyx, Genomind, and Wiley (deputy editor, Depression and Anxiety). Saxe has received royalties from Guilford Press for the book Trauma Systems Therapy for Children and Teens (2016). Marmar serves on the scientific advisory board and owns equity in Receptor Life Sciences and serves on the PTSD advisory board for Otsuka Pharmaceutical.
 

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

The mental health consequences of COVID-19 deaths are likely to overwhelm an already tattered U.S. mental health system, leading to a lack of access, particularly for the most vulnerable, experts warn.

“A second wave of devastation is imminent, attributable to mental health consequences of COVID-19,” write Naomi Simon, MD, and coauthors with the department of psychiatry, New York University.

In a Viewpoint article published in JAMA on Oct. 12, physicians offer some sobering statistics.

Since February 2020, COVID-19 has taken the lives of more than 214,000 Americans. The number of deaths currently attributed to the virus is nearly four times the number of Americans killed during the Vietnam War. The magnitude of death over a short period is a tragedy on a “historic scale,” wrote Dr. Simon and colleagues.

The surge in mental health problems related to COVID-19 deaths will bring further challenges to individuals, families, and communities, including a spike in deaths from suicide and drug overdoses, they warned.

It’s important to consider, they noted, that each COVID-19 death leaves an estimated nine family members bereaved, which is projected to lead to an estimated 2 million bereaved individuals in the United States.

“This interpersonal loss on a massive scale is compounded by societal disruption,” they wrote. The necessary social distancing and quarantine measures implemented to fight the virus have amplified emotional turmoil and have disrupted the ability of personal support networks and communities to come together and grieve.

“Of central concern is the transformation of normal grief and distress into prolonged grief and major depressive disorder and symptoms of posttraumatic stress disorder,” Simon and colleagues said.

“Once established, these conditions can become chronic with additional comorbidities such as substance use disorders. Prolonged grief affects approximately 10% of bereaved individuals, but this is likely an underestimate for grief related to deaths from COVID-19,” they wrote.

As with the first COVID-19 wave, the mental health wave will disproportionately affect Black persons, Hispanic persons, older adults, persons in lower socioeconomic groups of all races and ethnicities, and healthcare workers, they note.

The psychological risks for health care and other essential workers are of particular concern, they say. “Supporting the mental health of these and other essential workforce is critical to readiness for managing recurrent waves of the pandemic,” they stated.

How will the United States manage this impending wave of mental health problems?

“The solution will require increased funding for mental health; widespread screening to identify individuals at highest risk including suicide risk; availability of primary care clinicians and mental health professionals trained to treat those with prolonged grief, depression, traumatic stress, and substance abuse; and a diligent focus on families and communities to creatively restore the approaches by which they have managed tragedy and loss over generations,” the authors wrote.

“History has shown that societies recover from such devastation when leaders and members are joined by a shared purpose, acting in a unified way to facilitate recovery. In such societies, there is a shared understanding that its members must care for one another because the loss of one is a loss for all. Above all, this shared understanding must be restored,” they concluded.

Dr. Simon has received personal fees from Vanda Pharmaceuticals Inc, MGH Psychiatry Academy, Axovant Sciences, Springworks, Praxis Therapeutics, Aptinyx, Genomind, and Wiley (deputy editor, Depression and Anxiety). Saxe has received royalties from Guilford Press for the book Trauma Systems Therapy for Children and Teens (2016). Marmar serves on the scientific advisory board and owns equity in Receptor Life Sciences and serves on the PTSD advisory board for Otsuka Pharmaceutical.
 

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