ORLANDO – The Eversense continuous glucose monitoring (CGM) system, recently approved for use in adults with diabetes, also provides safe, durable, and accurate monitoring in the pediatric population, according to findings from a prospective single-arm study of 30 children and 6 adults.

Study subjects, who were all over age 11 years, with an average of 14 years, had the fully implantable sensor inserted at day 0 and removed at day 180, and the mean absolute relative difference (MARD) between sensor and true laboratory glucose values showed high device accuracy, Ronnie Aronson, MD, reported at the annual scientific sessions of the American Diabetes Association.

“Anything under 10% is considered good, and ours was 9.4% – and it didn’t deteriorate throughout the duration, so at 180 days it was still at 9.4%; every accuracy measure we looked at showed similar high levels of accuracy,” Dr. Aronson, founder and chief medical officer of LMC Diabetes & Endocrinology in Ontario, Canada said in a video interview.

The sensor, which is roughly 1.5 cm long, is coated with a material that fluoresces when exposed to glucose; the sensor uses the amount of light emitted to calculate blood glucose levels. Patients use an adhesive patch, changed daily, to attach a “smart” transmitter that overlies the area where the sensor is implanted. This rechargeable transmitter sends blood glucose levels to the mobile app every 5 minutes, and also powers the sensor. The Food and Drug Administration approved it for use in adults on June 21.

The system was highly rated by study participants, he said. “What makes it stand out is that it’s implanted, it’s there for at least 180 days, it’s accurate for 180 days,” the transmitter can be taken on and off, and the results can be seen very easily on a smart phone or Apple Watch.

Dr. Aronson said he also hopes to study the device in younger patients and for longer durations.

Dr. Aronson is an advisor for Novo Nordisk and Sanofi. He also receives research support from AstraZeneca, Eli Lilly, Valeant, Janssen, and Senseonics.

[email protected]

SOURCE: Aronson R et al. ADA 2018 Abstract 13-OR.

ORLANDO – The Eversense continuous glucose monitoring (CGM) system, recently approved for use in adults with diabetes, also provides safe, durable, and accurate monitoring in the pediatric population, according to findings from a prospective single-arm study of 30 children and 6 adults.

Study subjects, who were all over age 11 years, with an average of 14 years, had the fully implantable sensor inserted at day 0 and removed at day 180, and the mean absolute relative difference (MARD) between sensor and true laboratory glucose values showed high device accuracy, Ronnie Aronson, MD, reported at the annual scientific sessions of the American Diabetes Association.

“Anything under 10% is considered good, and ours was 9.4% – and it didn’t deteriorate throughout the duration, so at 180 days it was still at 9.4%; every accuracy measure we looked at showed similar high levels of accuracy,” Dr. Aronson, founder and chief medical officer of LMC Diabetes & Endocrinology in Ontario, Canada said in a video interview.

The sensor, which is roughly 1.5 cm long, is coated with a material that fluoresces when exposed to glucose; the sensor uses the amount of light emitted to calculate blood glucose levels. Patients use an adhesive patch, changed daily, to attach a “smart” transmitter that overlies the area where the sensor is implanted. This rechargeable transmitter sends blood glucose levels to the mobile app every 5 minutes, and also powers the sensor. The Food and Drug Administration approved it for use in adults on June 21.

The system was highly rated by study participants, he said. “What makes it stand out is that it’s implanted, it’s there for at least 180 days, it’s accurate for 180 days,” the transmitter can be taken on and off, and the results can be seen very easily on a smart phone or Apple Watch.

Dr. Aronson said he also hopes to study the device in younger patients and for longer durations.

Dr. Aronson is an advisor for Novo Nordisk and Sanofi. He also receives research support from AstraZeneca, Eli Lilly, Valeant, Janssen, and Senseonics.

[email protected]

SOURCE: Aronson R et al. ADA 2018 Abstract 13-OR.

ORLANDO – The Eversense continuous glucose monitoring (CGM) system, recently approved for use in adults with diabetes, also provides safe, durable, and accurate monitoring in the pediatric population, according to findings from a prospective single-arm study of 30 children and 6 adults.

Study subjects, who were all over age 11 years, with an average of 14 years, had the fully implantable sensor inserted at day 0 and removed at day 180, and the mean absolute relative difference (MARD) between sensor and true laboratory glucose values showed high device accuracy, Ronnie Aronson, MD, reported at the annual scientific sessions of the American Diabetes Association.

“Anything under 10% is considered good, and ours was 9.4% – and it didn’t deteriorate throughout the duration, so at 180 days it was still at 9.4%; every accuracy measure we looked at showed similar high levels of accuracy,” Dr. Aronson, founder and chief medical officer of LMC Diabetes & Endocrinology in Ontario, Canada said in a video interview.

The sensor, which is roughly 1.5 cm long, is coated with a material that fluoresces when exposed to glucose; the sensor uses the amount of light emitted to calculate blood glucose levels. Patients use an adhesive patch, changed daily, to attach a “smart” transmitter that overlies the area where the sensor is implanted. This rechargeable transmitter sends blood glucose levels to the mobile app every 5 minutes, and also powers the sensor. The Food and Drug Administration approved it for use in adults on June 21.

The system was highly rated by study participants, he said. “What makes it stand out is that it’s implanted, it’s there for at least 180 days, it’s accurate for 180 days,” the transmitter can be taken on and off, and the results can be seen very easily on a smart phone or Apple Watch.

Dr. Aronson said he also hopes to study the device in younger patients and for longer durations.

Dr. Aronson is an advisor for Novo Nordisk and Sanofi. He also receives research support from AstraZeneca, Eli Lilly, Valeant, Janssen, and Senseonics.

[email protected]

SOURCE: Aronson R et al. ADA 2018 Abstract 13-OR.

ORLANDO – It’s safe to switch many Medicare beneficiaries with type 2 diabetes to human insulins to save money on analogues, according to a review of 14,635 members of CareMore, a Medicare Advantage company based in Cerritos, Calif.

The company noticed that it’s spending on analogue insulins had ballooned to over $3 million a month by the end of 2014, in the wake of a more than 300% price increase in analogue insulins in recent years, while copays on analogues rose from nothing to $37.50. In 2015, it launched a program to switch type 2 patients to less costly human insulins. Physicians were counseled to stop secretagogues and move patients to premixed insulins at 80% of their former total daily analogue dose, two-thirds at breakfast, and one-third a dinner, with appropriate follow-up.

M. Alexander Otto/MDEdge News

[email protected]

SOURCE: Luo J et al. 2018 American Diabetes Association scientific session abstract 4-OR

ORLANDO – It’s safe to switch many Medicare beneficiaries with type 2 diabetes to human insulins to save money on analogues, according to a review of 14,635 members of CareMore, a Medicare Advantage company based in Cerritos, Calif.

The company noticed that it’s spending on analogue insulins had ballooned to over $3 million a month by the end of 2014, in the wake of a more than 300% price increase in analogue insulins in recent years, while copays on analogues rose from nothing to $37.50. In 2015, it launched a program to switch type 2 patients to less costly human insulins. Physicians were counseled to stop secretagogues and move patients to premixed insulins at 80% of their former total daily analogue dose, two-thirds at breakfast, and one-third a dinner, with appropriate follow-up.

M. Alexander Otto/MDEdge News

[email protected]

SOURCE: Luo J et al. 2018 American Diabetes Association scientific session abstract 4-OR

ORLANDO – It’s safe to switch many Medicare beneficiaries with type 2 diabetes to human insulins to save money on analogues, according to a review of 14,635 members of CareMore, a Medicare Advantage company based in Cerritos, Calif.

The company noticed that it’s spending on analogue insulins had ballooned to over $3 million a month by the end of 2014, in the wake of a more than 300% price increase in analogue insulins in recent years, while copays on analogues rose from nothing to $37.50. In 2015, it launched a program to switch type 2 patients to less costly human insulins. Physicians were counseled to stop secretagogues and move patients to premixed insulins at 80% of their former total daily analogue dose, two-thirds at breakfast, and one-third a dinner, with appropriate follow-up.

M. Alexander Otto/MDEdge News

[email protected]

SOURCE: Luo J et al. 2018 American Diabetes Association scientific session abstract 4-OR

©ASCO/Scott Morgan 2018

CHICAGO—A novel CD19-targeted T-cell therapy induced complete metabolic responses (CMRs) and no cytokine release syndrome (CRS) in patients with B-cell lymphomas in a first-in-human clinical study.

All subjects achieving CMR at the 1-month safety and efficacy assessment continued to show CMR at 3 months, investigators reported at the 2018 ASCO Annual Meeting (abstract 3049*).

The therapy is built on a novel platform, ARTEMIS, designed to match the potency of chimeric antigen receptor (CAR) T-cell therapy but trigger less cytokine release when the target is engaged, investigators explained.

That platform is “potentially a major improvement” over existing CAR-T cell therapy, said Zhi Tao Ying, MD, of Peking University Cancer Hospital & Institute in Beijing, China, and coauthors in a poster presented at ASCO.

The treatment, called ET190L1-ARTEMIS, utilizes the T-cell receptor platform and a proprietary human anti-CD19 antibody to target CD19-positive malignancies.

The investigators reported on 21 adults with CD-19 positive relapsed and refractory B-cell lymphomas who had received a median of 4 lines of previous therapy.

Patients received autologous ET190L1-ARTEMIS T cells in 1 of 3 dosing cohorts: 3 patients at 1 x 10⁶/kg, 13 at 3 x 10⁶/kg, and 5 at 6 x 10⁶/kg.

Of 17 patients completing a first-month efficacy assessment, 11 (65%) responded, including 7 CMRs and 3 partial responses. One patient had stable disease.

Seven of the 11 responders completed a third-month efficacy assessment, as of this analysis. Of 5 patients with CMR at month 1, all 5 maintained CMR at month 3. Likewise, 1 patient in partial response and 1 with stable disease at month 1 had the same response status at month 3.

There were no cases of CRS or neurotoxicity in 17 patients who completed the 1-month safety and efficacy assessment reported at ASCO. Grade 3 or greater adverse events in those subjects included lymphopenia in 17 (100%) and neutropenia in 5 (29%).

Eureka Therapeutics Inc., of Emeryville, California, is developing ET190L1-ARTEMIS. Co-investigators in this trial were from Eureka, Xi-An Jiaotong University in China, and Duke University School of Medicine in Durham, North Carolina.

A phase 1 trial of ET190L1-ARTEMIS in patients with relapsed and refractory non-Hodgkin lymphoma has been initiated at Duke University, and  investigators say another US phase 1 trial including relapsed and refractory pediatric acute lymphoblastic leukemia patients will begin later this year. 

Data in the abstract differ from that presented in the poster.

©ASCO/Scott Morgan 2018

CHICAGO—A novel CD19-targeted T-cell therapy induced complete metabolic responses (CMRs) and no cytokine release syndrome (CRS) in patients with B-cell lymphomas in a first-in-human clinical study.

All subjects achieving CMR at the 1-month safety and efficacy assessment continued to show CMR at 3 months, investigators reported at the 2018 ASCO Annual Meeting (abstract 3049*).

The therapy is built on a novel platform, ARTEMIS, designed to match the potency of chimeric antigen receptor (CAR) T-cell therapy but trigger less cytokine release when the target is engaged, investigators explained.

That platform is “potentially a major improvement” over existing CAR-T cell therapy, said Zhi Tao Ying, MD, of Peking University Cancer Hospital & Institute in Beijing, China, and coauthors in a poster presented at ASCO.

The treatment, called ET190L1-ARTEMIS, utilizes the T-cell receptor platform and a proprietary human anti-CD19 antibody to target CD19-positive malignancies.

The investigators reported on 21 adults with CD-19 positive relapsed and refractory B-cell lymphomas who had received a median of 4 lines of previous therapy.

Patients received autologous ET190L1-ARTEMIS T cells in 1 of 3 dosing cohorts: 3 patients at 1 x 10⁶/kg, 13 at 3 x 10⁶/kg, and 5 at 6 x 10⁶/kg.

Of 17 patients completing a first-month efficacy assessment, 11 (65%) responded, including 7 CMRs and 3 partial responses. One patient had stable disease.

Seven of the 11 responders completed a third-month efficacy assessment, as of this analysis. Of 5 patients with CMR at month 1, all 5 maintained CMR at month 3. Likewise, 1 patient in partial response and 1 with stable disease at month 1 had the same response status at month 3.

There were no cases of CRS or neurotoxicity in 17 patients who completed the 1-month safety and efficacy assessment reported at ASCO. Grade 3 or greater adverse events in those subjects included lymphopenia in 17 (100%) and neutropenia in 5 (29%).

Eureka Therapeutics Inc., of Emeryville, California, is developing ET190L1-ARTEMIS. Co-investigators in this trial were from Eureka, Xi-An Jiaotong University in China, and Duke University School of Medicine in Durham, North Carolina.

A phase 1 trial of ET190L1-ARTEMIS in patients with relapsed and refractory non-Hodgkin lymphoma has been initiated at Duke University, and  investigators say another US phase 1 trial including relapsed and refractory pediatric acute lymphoblastic leukemia patients will begin later this year. 

Data in the abstract differ from that presented in the poster.

©ASCO/Scott Morgan 2018

CHICAGO—A novel CD19-targeted T-cell therapy induced complete metabolic responses (CMRs) and no cytokine release syndrome (CRS) in patients with B-cell lymphomas in a first-in-human clinical study.

All subjects achieving CMR at the 1-month safety and efficacy assessment continued to show CMR at 3 months, investigators reported at the 2018 ASCO Annual Meeting (abstract 3049*).

The therapy is built on a novel platform, ARTEMIS, designed to match the potency of chimeric antigen receptor (CAR) T-cell therapy but trigger less cytokine release when the target is engaged, investigators explained.

That platform is “potentially a major improvement” over existing CAR-T cell therapy, said Zhi Tao Ying, MD, of Peking University Cancer Hospital & Institute in Beijing, China, and coauthors in a poster presented at ASCO.

The treatment, called ET190L1-ARTEMIS, utilizes the T-cell receptor platform and a proprietary human anti-CD19 antibody to target CD19-positive malignancies.

The investigators reported on 21 adults with CD-19 positive relapsed and refractory B-cell lymphomas who had received a median of 4 lines of previous therapy.

Patients received autologous ET190L1-ARTEMIS T cells in 1 of 3 dosing cohorts: 3 patients at 1 x 10⁶/kg, 13 at 3 x 10⁶/kg, and 5 at 6 x 10⁶/kg.

Of 17 patients completing a first-month efficacy assessment, 11 (65%) responded, including 7 CMRs and 3 partial responses. One patient had stable disease.

Seven of the 11 responders completed a third-month efficacy assessment, as of this analysis. Of 5 patients with CMR at month 1, all 5 maintained CMR at month 3. Likewise, 1 patient in partial response and 1 with stable disease at month 1 had the same response status at month 3.

There were no cases of CRS or neurotoxicity in 17 patients who completed the 1-month safety and efficacy assessment reported at ASCO. Grade 3 or greater adverse events in those subjects included lymphopenia in 17 (100%) and neutropenia in 5 (29%).

Eureka Therapeutics Inc., of Emeryville, California, is developing ET190L1-ARTEMIS. Co-investigators in this trial were from Eureka, Xi-An Jiaotong University in China, and Duke University School of Medicine in Durham, North Carolina.

A phase 1 trial of ET190L1-ARTEMIS in patients with relapsed and refractory non-Hodgkin lymphoma has been initiated at Duke University, and  investigators say another US phase 1 trial including relapsed and refractory pediatric acute lymphoblastic leukemia patients will begin later this year. 

Data in the abstract differ from that presented in the poster.

ORLANDO – Rates of diabetic peripheral neuropathy (DPN) in U.S. patients with type 1 diabetes (T1D) may have dipped, possibly because of improving clinical care, a new study suggests. Researchers also found evidence that nonglycemic factors may play important roles in the development of the condition.

There are differences between DPN in T1D and type 2 diabetes: Lifetime incidence in T1D is believed to be 45%, lower than in T2D. However, a 2016 report noted that, “whereas treating hyperglycemia in type 1 DM can significantly reduce the incidence of neuropathy by up to 60 to 70%, glucose control in type 2 DM has only a marginal 5 to 7% reduction in the development of neuropathy.” (F1000Research 2016, 5(F1000 Faculty Rev):738)

Still, DPN is believed to be very common in T1D. According to the new study, previous research has suggested that the DPN rate in this population could be as high as 35%.

For the new study, researchers examined self-reports of DPN from 5,058 patients across 62 sites via the T1D Exchange Registry. All patients were at least 18 years of age and had at least 5 years of T1D. Their mean age was 39 years, the duration of diabetes was 22 years, and their average hemoglobin A1c was 8.1. Over half (56%) were women, and most (88%) were white were white.

A preliminary analysis found that just 10% of the patients had signs of DPN, according to their self-reports. In part, the difference between this number and previous estimates of DPN prevalence may be because previous studies relied on symptoms, exams, and electrophysiologic testing, said study researcher Kara Mizokami-Stout, MD, of the University of Michigan, in an interview.

However, study researcher Rodica Pop-Busui, MD, PhD, noted in an interview that one strength of the new study is that it’s “a broad sample of patients with type 1 diabetes as they are currently treated in clinical care across the United States.”

Versus those without DPN, those with the condition were more likely to be older (mean 52 vs. 37 years), female (61% vs. 55%), and had T1D for a longer period (mean 32 vs. 21 years). They were also poorer and had less education. (All P less than .001)

The DPN group also had slightly higher systolic blood pressure (mean 126 vs. 123), higher triglycerides (117 vs. 95) and more than double the rate of tobacco use (9% vs. 4%), all P less than .001.

Also, cardiovascular disease was more common (26% vs. 6%) even though this group used statins (64% vs. 31%) and ACE inhibitors/ARBs (45% vs. 23%) at much higher levels, all P less than .001.

Researchers also found that this with DPN had higher HbA1c even after controlling for various confounders (8.4% vs. 8.1%, P less than .01).

SOURCE: Mizokami-Stout K, et al. ADA 2018, Abstract 62-OR.
 

ORLANDO – Rates of diabetic peripheral neuropathy (DPN) in U.S. patients with type 1 diabetes (T1D) may have dipped, possibly because of improving clinical care, a new study suggests. Researchers also found evidence that nonglycemic factors may play important roles in the development of the condition.

There are differences between DPN in T1D and type 2 diabetes: Lifetime incidence in T1D is believed to be 45%, lower than in T2D. However, a 2016 report noted that, “whereas treating hyperglycemia in type 1 DM can significantly reduce the incidence of neuropathy by up to 60 to 70%, glucose control in type 2 DM has only a marginal 5 to 7% reduction in the development of neuropathy.” (F1000Research 2016, 5(F1000 Faculty Rev):738)

Still, DPN is believed to be very common in T1D. According to the new study, previous research has suggested that the DPN rate in this population could be as high as 35%.

For the new study, researchers examined self-reports of DPN from 5,058 patients across 62 sites via the T1D Exchange Registry. All patients were at least 18 years of age and had at least 5 years of T1D. Their mean age was 39 years, the duration of diabetes was 22 years, and their average hemoglobin A1c was 8.1. Over half (56%) were women, and most (88%) were white were white.

A preliminary analysis found that just 10% of the patients had signs of DPN, according to their self-reports. In part, the difference between this number and previous estimates of DPN prevalence may be because previous studies relied on symptoms, exams, and electrophysiologic testing, said study researcher Kara Mizokami-Stout, MD, of the University of Michigan, in an interview.

However, study researcher Rodica Pop-Busui, MD, PhD, noted in an interview that one strength of the new study is that it’s “a broad sample of patients with type 1 diabetes as they are currently treated in clinical care across the United States.”

Versus those without DPN, those with the condition were more likely to be older (mean 52 vs. 37 years), female (61% vs. 55%), and had T1D for a longer period (mean 32 vs. 21 years). They were also poorer and had less education. (All P less than .001)

The DPN group also had slightly higher systolic blood pressure (mean 126 vs. 123), higher triglycerides (117 vs. 95) and more than double the rate of tobacco use (9% vs. 4%), all P less than .001.

Also, cardiovascular disease was more common (26% vs. 6%) even though this group used statins (64% vs. 31%) and ACE inhibitors/ARBs (45% vs. 23%) at much higher levels, all P less than .001.

Researchers also found that this with DPN had higher HbA1c even after controlling for various confounders (8.4% vs. 8.1%, P less than .01).

SOURCE: Mizokami-Stout K, et al. ADA 2018, Abstract 62-OR.
 

ORLANDO – Rates of diabetic peripheral neuropathy (DPN) in U.S. patients with type 1 diabetes (T1D) may have dipped, possibly because of improving clinical care, a new study suggests. Researchers also found evidence that nonglycemic factors may play important roles in the development of the condition.

There are differences between DPN in T1D and type 2 diabetes: Lifetime incidence in T1D is believed to be 45%, lower than in T2D. However, a 2016 report noted that, “whereas treating hyperglycemia in type 1 DM can significantly reduce the incidence of neuropathy by up to 60 to 70%, glucose control in type 2 DM has only a marginal 5 to 7% reduction in the development of neuropathy.” (F1000Research 2016, 5(F1000 Faculty Rev):738)

Still, DPN is believed to be very common in T1D. According to the new study, previous research has suggested that the DPN rate in this population could be as high as 35%.

For the new study, researchers examined self-reports of DPN from 5,058 patients across 62 sites via the T1D Exchange Registry. All patients were at least 18 years of age and had at least 5 years of T1D. Their mean age was 39 years, the duration of diabetes was 22 years, and their average hemoglobin A1c was 8.1. Over half (56%) were women, and most (88%) were white were white.

A preliminary analysis found that just 10% of the patients had signs of DPN, according to their self-reports. In part, the difference between this number and previous estimates of DPN prevalence may be because previous studies relied on symptoms, exams, and electrophysiologic testing, said study researcher Kara Mizokami-Stout, MD, of the University of Michigan, in an interview.

However, study researcher Rodica Pop-Busui, MD, PhD, noted in an interview that one strength of the new study is that it’s “a broad sample of patients with type 1 diabetes as they are currently treated in clinical care across the United States.”

Versus those without DPN, those with the condition were more likely to be older (mean 52 vs. 37 years), female (61% vs. 55%), and had T1D for a longer period (mean 32 vs. 21 years). They were also poorer and had less education. (All P less than .001)

The DPN group also had slightly higher systolic blood pressure (mean 126 vs. 123), higher triglycerides (117 vs. 95) and more than double the rate of tobacco use (9% vs. 4%), all P less than .001.

Also, cardiovascular disease was more common (26% vs. 6%) even though this group used statins (64% vs. 31%) and ACE inhibitors/ARBs (45% vs. 23%) at much higher levels, all P less than .001.

Researchers also found that this with DPN had higher HbA1c even after controlling for various confounders (8.4% vs. 8.1%, P less than .01).

SOURCE: Mizokami-Stout K, et al. ADA 2018, Abstract 62-OR.
 

Chronic use of prescription opioid drugs correlated with support for the Republican candidate in the 2016 U.S. presidential election, according to a cross-sectional analysis published in JAMA Network Open.

The mean Republican presidential vote was 60% in U.S. counties with significantly higher-than-average rates of prescriptions for prolonged opioid use, versus 39% for counties with significantly lower rates, according to the study, which was based on prescription data for Medicare Part D enrollees (JAMA Network Open. 2018;1(2):e180450).

Those findings suggest the importance of economic, cultural, and environmental factors in the opioid epidemic, according to study author James S. Goodwin, MD, of the University of Texas Medical Branch, Galveston, and co-authors.

“Public health policy directed at stemming the opioid epidemic must go beyond the medical model and incorporate socioenvironmental disadvantage factors and health behaviors into policy planning and implementation,” Dr. Goodwin and co-authors wrote.

The cross-sectional analysis included data for 3.76 million Medicare Part D enrollees. They looked specifically at the proportion of enrollees with chronic opioid use, which they defined as receipt of at least a 90-day supply in 1 year.

After adjusting for age, disability, and other factors, they found 693 out of 3,100 counties (22.4%) had rates of chronic opioid use higher than the mean, and 638 (20.6%) had rates lower than the mean. The correlation between opioid use rates and the presidential vote was 0.42 (P < .001), according to investigators.

They also published two county maps that they said shared some similar patterns. The first shows the proportion of older chronic opioid users by quintile, and the second shows Republican vote percentages, also by quintile. The correlation coefficient between those two rates was 0.32 (P < .001).

This study adds to the emerging literature on the relationships between health status and support of Donald Trump in the 2016 election, according to authors.

However, there were limitations to the study, they added. Of note, the presidential vote data was from 2016, but the information on prolonged opioid prescriptions was from 2015. Moreover, the voting data included all voters, while the opioid data came only from Medicare Part D enrollees, which represent about 72% of the full Medicare population.

One study author reported grants from the National Institute on Drug Abuse and Agency for Healthcare Research and Quality. Another reported membership in Physicians for Responsible Opioid Prescribing

SOURCE: Goodwin JS, et al. JAMA Network Open. 2018;1(2):e180450.

This article was updated 6/26/18.

Chronic use of prescription opioid drugs correlated with support for the Republican candidate in the 2016 U.S. presidential election, according to a cross-sectional analysis published in JAMA Network Open.

The mean Republican presidential vote was 60% in U.S. counties with significantly higher-than-average rates of prescriptions for prolonged opioid use, versus 39% for counties with significantly lower rates, according to the study, which was based on prescription data for Medicare Part D enrollees (JAMA Network Open. 2018;1(2):e180450).

Those findings suggest the importance of economic, cultural, and environmental factors in the opioid epidemic, according to study author James S. Goodwin, MD, of the University of Texas Medical Branch, Galveston, and co-authors.

“Public health policy directed at stemming the opioid epidemic must go beyond the medical model and incorporate socioenvironmental disadvantage factors and health behaviors into policy planning and implementation,” Dr. Goodwin and co-authors wrote.

The cross-sectional analysis included data for 3.76 million Medicare Part D enrollees. They looked specifically at the proportion of enrollees with chronic opioid use, which they defined as receipt of at least a 90-day supply in 1 year.

After adjusting for age, disability, and other factors, they found 693 out of 3,100 counties (22.4%) had rates of chronic opioid use higher than the mean, and 638 (20.6%) had rates lower than the mean. The correlation between opioid use rates and the presidential vote was 0.42 (P < .001), according to investigators.

They also published two county maps that they said shared some similar patterns. The first shows the proportion of older chronic opioid users by quintile, and the second shows Republican vote percentages, also by quintile. The correlation coefficient between those two rates was 0.32 (P < .001).

This study adds to the emerging literature on the relationships between health status and support of Donald Trump in the 2016 election, according to authors.

However, there were limitations to the study, they added. Of note, the presidential vote data was from 2016, but the information on prolonged opioid prescriptions was from 2015. Moreover, the voting data included all voters, while the opioid data came only from Medicare Part D enrollees, which represent about 72% of the full Medicare population.

One study author reported grants from the National Institute on Drug Abuse and Agency for Healthcare Research and Quality. Another reported membership in Physicians for Responsible Opioid Prescribing

SOURCE: Goodwin JS, et al. JAMA Network Open. 2018;1(2):e180450.

This article was updated 6/26/18.

Chronic use of prescription opioid drugs correlated with support for the Republican candidate in the 2016 U.S. presidential election, according to a cross-sectional analysis published in JAMA Network Open.

The mean Republican presidential vote was 60% in U.S. counties with significantly higher-than-average rates of prescriptions for prolonged opioid use, versus 39% for counties with significantly lower rates, according to the study, which was based on prescription data for Medicare Part D enrollees (JAMA Network Open. 2018;1(2):e180450).

Those findings suggest the importance of economic, cultural, and environmental factors in the opioid epidemic, according to study author James S. Goodwin, MD, of the University of Texas Medical Branch, Galveston, and co-authors.

“Public health policy directed at stemming the opioid epidemic must go beyond the medical model and incorporate socioenvironmental disadvantage factors and health behaviors into policy planning and implementation,” Dr. Goodwin and co-authors wrote.

The cross-sectional analysis included data for 3.76 million Medicare Part D enrollees. They looked specifically at the proportion of enrollees with chronic opioid use, which they defined as receipt of at least a 90-day supply in 1 year.

After adjusting for age, disability, and other factors, they found 693 out of 3,100 counties (22.4%) had rates of chronic opioid use higher than the mean, and 638 (20.6%) had rates lower than the mean. The correlation between opioid use rates and the presidential vote was 0.42 (P < .001), according to investigators.

They also published two county maps that they said shared some similar patterns. The first shows the proportion of older chronic opioid users by quintile, and the second shows Republican vote percentages, also by quintile. The correlation coefficient between those two rates was 0.32 (P < .001).

This study adds to the emerging literature on the relationships between health status and support of Donald Trump in the 2016 election, according to authors.

However, there were limitations to the study, they added. Of note, the presidential vote data was from 2016, but the information on prolonged opioid prescriptions was from 2015. Moreover, the voting data included all voters, while the opioid data came only from Medicare Part D enrollees, which represent about 72% of the full Medicare population.

One study author reported grants from the National Institute on Drug Abuse and Agency for Healthcare Research and Quality. Another reported membership in Physicians for Responsible Opioid Prescribing

SOURCE: Goodwin JS, et al. JAMA Network Open. 2018;1(2):e180450.

This article was updated 6/26/18.

ORLANDO – Significant discordance exists between average glucose and hemoglobin A_1c (HbA_1c) measures in patients with certain comorbidities, according to findings from a retrospective chart review.

For example, there was a complete lack of correlation between average glucose (AG) and A_1c measures in patients with advanced renal dysfunction and non-alcoholic fatty liver disease, (NAFLD) Jordan E. Perlman, MD, reported at the annual scientific sessions of the American Diabetes Association.

KatarzynaBialasiewicz/Thinkstock

Also, fingersticks inflate discordance.

“A better assessment of ADAG would be to measure only CGM averages in comorbities, though this may need to be a prospective trial as only 17% of our patients who have identified comorbidities use CGM,” she said.

Dr. Perlman concluded that fingersticks and CGM can provide important confirmation of A1c, but said this applies only at the population level and not to individual patients.

“For individual patients, any level of A1c can translate to a large range of average glucoses. We see this even in our concordant patients,” she said.

Further, while discordance is increased by some comorbidities, it also occurs absent of comorbidities at a rate of 28.7%.

“So here’s the bottom line: We need a professional consensus to help define acceptable discordance before clinical use of the ADAG equation can be safely broadened,” she said.

Dr. Perlman reported having no disclosures. Senior author Irl B. Hirsch, MD, professor of medicine at the University of Washington, Seattle, disclosed financial relationships diabetes drug and device manufacturers Abbot, ADOCIA, Bigfoot Biomedical, Roche, and Medtronic MiniMed.

[email protected]

SOURCE: Perlman J et al., ADA 2018 Abstract 12-OR.

ORLANDO – Significant discordance exists between average glucose and hemoglobin A_1c (HbA_1c) measures in patients with certain comorbidities, according to findings from a retrospective chart review.

For example, there was a complete lack of correlation between average glucose (AG) and A_1c measures in patients with advanced renal dysfunction and non-alcoholic fatty liver disease, (NAFLD) Jordan E. Perlman, MD, reported at the annual scientific sessions of the American Diabetes Association.

KatarzynaBialasiewicz/Thinkstock

Also, fingersticks inflate discordance.

“A better assessment of ADAG would be to measure only CGM averages in comorbities, though this may need to be a prospective trial as only 17% of our patients who have identified comorbidities use CGM,” she said.

Dr. Perlman concluded that fingersticks and CGM can provide important confirmation of A1c, but said this applies only at the population level and not to individual patients.

“For individual patients, any level of A1c can translate to a large range of average glucoses. We see this even in our concordant patients,” she said.

Further, while discordance is increased by some comorbidities, it also occurs absent of comorbidities at a rate of 28.7%.

“So here’s the bottom line: We need a professional consensus to help define acceptable discordance before clinical use of the ADAG equation can be safely broadened,” she said.

Dr. Perlman reported having no disclosures. Senior author Irl B. Hirsch, MD, professor of medicine at the University of Washington, Seattle, disclosed financial relationships diabetes drug and device manufacturers Abbot, ADOCIA, Bigfoot Biomedical, Roche, and Medtronic MiniMed.

[email protected]

SOURCE: Perlman J et al., ADA 2018 Abstract 12-OR.

ORLANDO – Significant discordance exists between average glucose and hemoglobin A_1c (HbA_1c) measures in patients with certain comorbidities, according to findings from a retrospective chart review.

For example, there was a complete lack of correlation between average glucose (AG) and A_1c measures in patients with advanced renal dysfunction and non-alcoholic fatty liver disease, (NAFLD) Jordan E. Perlman, MD, reported at the annual scientific sessions of the American Diabetes Association.

KatarzynaBialasiewicz/Thinkstock

Also, fingersticks inflate discordance.

“A better assessment of ADAG would be to measure only CGM averages in comorbities, though this may need to be a prospective trial as only 17% of our patients who have identified comorbidities use CGM,” she said.

Dr. Perlman concluded that fingersticks and CGM can provide important confirmation of A1c, but said this applies only at the population level and not to individual patients.

“For individual patients, any level of A1c can translate to a large range of average glucoses. We see this even in our concordant patients,” she said.

Further, while discordance is increased by some comorbidities, it also occurs absent of comorbidities at a rate of 28.7%.

“So here’s the bottom line: We need a professional consensus to help define acceptable discordance before clinical use of the ADAG equation can be safely broadened,” she said.

Dr. Perlman reported having no disclosures. Senior author Irl B. Hirsch, MD, professor of medicine at the University of Washington, Seattle, disclosed financial relationships diabetes drug and device manufacturers Abbot, ADOCIA, Bigfoot Biomedical, Roche, and Medtronic MiniMed.

[email protected]

SOURCE: Perlman J et al., ADA 2018 Abstract 12-OR.

ORLANDO – About a quarter of diabetes patients use less insulin than prescribed because they can’t afford it, and they have worse glycemic control because of it, according to a survey of patients at the Yale Diabetes Center in New Haven, Conn.

The soaring cost of insulin – especially analogues – has been in the news following a more than 300% increase from 2004-2018. The cash price for a 10 mL vial of insulin lispro (Humalog), for example, has climbed from $59 to $320. The American Diabetes Association recently released a white paper on the issue, citing a “lack of transparency throughout the insulin supply chain” that obscures the reasons for the surge. It’s working with other groups to ensure affordable access.

[email protected]

SOURCE: Herkert D et al. ADA 2018 abstract 2-OR

ORLANDO – About a quarter of diabetes patients use less insulin than prescribed because they can’t afford it, and they have worse glycemic control because of it, according to a survey of patients at the Yale Diabetes Center in New Haven, Conn.

The soaring cost of insulin – especially analogues – has been in the news following a more than 300% increase from 2004-2018. The cash price for a 10 mL vial of insulin lispro (Humalog), for example, has climbed from $59 to $320. The American Diabetes Association recently released a white paper on the issue, citing a “lack of transparency throughout the insulin supply chain” that obscures the reasons for the surge. It’s working with other groups to ensure affordable access.

[email protected]

SOURCE: Herkert D et al. ADA 2018 abstract 2-OR

ORLANDO – About a quarter of diabetes patients use less insulin than prescribed because they can’t afford it, and they have worse glycemic control because of it, according to a survey of patients at the Yale Diabetes Center in New Haven, Conn.

The soaring cost of insulin – especially analogues – has been in the news following a more than 300% increase from 2004-2018. The cash price for a 10 mL vial of insulin lispro (Humalog), for example, has climbed from $59 to $320. The American Diabetes Association recently released a white paper on the issue, citing a “lack of transparency throughout the insulin supply chain” that obscures the reasons for the surge. It’s working with other groups to ensure affordable access.

[email protected]

SOURCE: Herkert D et al. ADA 2018 abstract 2-OR

First described in 2000 in a case series of 15 patients, nephrogenic systemic fibrosis (NSF) is a rare scleroderma-like fibrosing skin condition associated with gadolinium exposure in end stage renal disease (ESRD).¹ Patients with advanced chronic kidney disease (CKD) or ESRD are at the highest risk for this condition when exposed to gadolinium-based contrast dyes.

Nephrogenic systemic fibrosis is a devastating and rapidly progressive condition, making its prevention in at-risk populations of utmost importance. In this article, the authors describe a case of a patient who developed NSF in the setting of gadolinium exposure and multiple inflammatory dermatologic conditions. This case illustrates the possible role of a pro-inflammatory state in predisposing to NSF, which may help further elucidate its mechanism of action.

Case Presentation

A 61-year-old Hispanic male with a history of IV heroin use with ESRD secondary to membranous glomerulonephritis on hemodialysis and chronic hepatitis C infection presented to the West Los Angeles VAMC with fevers and night sweats that had persisted for 2 weeks. His physical examination was notable for diffuse tender palpable purpura and petechiae (including his palms and soles), altered mental status, and diffuse myoclonic jerks, which necessitated endotracheal intubation and mechanical ventilation for airway protection. Blood cultures were positive for methicillin-sensitive Staphylococcus aureus (MSSA). Laboratory results were notable for an elevated sedimentation rate of 53 mm/h (0-10 mm/h), C-reactive protein of 19.8 mg/L (< 0.744 mg/dL), and albumin of 1.2 g/dL (3.2-4.8 g/dL). An extensive rheumatologic workup was unrevealing, and a lumbar puncture was unremarkable. A biopsy of his skin lesions was consistent with leukocytoclastic vasculitis.

The patient’s prior hemodialysis access, a tunneled dialysis catheter in the right subclavian vein, was removed given concern for line infection and replaced with an internal jugular temporary hemodialysis line. Given his altered mental status and myoclonic jerks, the decision was made to pursue a magnetic resonance imaging (MRI) scan of the brain and spine with gadolinium contrast to evaluate for cerebral vasculitis and/or septic emboli to the brain.

The patient received 15 mL of gadoversetamide contrast in accordance with hospital imaging protocol. The MRI revealed only chronic ischemic changes. The patient underwent hemodialysis about 18 hours later. The patient was treated with a 6-week course of IV penicillin G. His altered mental status and myoclonic jerks resolved without intervention, and he was then discharged to an acute rehabilitation unit.

Eight weeks after his initial presentation the patient developed a purulent wound on his right forearm (Figure 1) 

The patient was discharged to continue physical and occupational therapy to preserve his functional mobility, as no other treatment options were available. 

Discussion

Nephrogenic systemic fibrosis is a poorly understood inflammatory condition that produces diffuse fibrosis of the skin. Typically, the disease begins with progressive skin induration of the extremities. Systemic involvement may occur, leading to fibrosis of skeletal muscle, fascia, and multiple organs. Flexion contractures may develop that limit physical function. Fibrosis can become apparent within days to months after exposure to gadolinium contrast.

Beyond renal insufficiency, it is unclear what other risk factors predispose patients to developing this condition. Only a minority of patients with CKD stages 1 through 4 will develop NSF on exposure to gadolinium contrast. However, the incidence of NSF among patients with CKD stage 5 who are exposed to gadolinium has been estimated to be about 13.4% in a prospective study involving 18 patients.²

In a 2015 meta-analysis by Zhang and colleagues, the only clear risk factor identified for the development of NSF, aside from gadolinium exposure, was severe renal insufficiency with a glomerular filtration rate of < 30 mL/min/1.75m².³ Due to the limited number of patients identified with this disease, it is difficult to identify other risk factors associated with the development of NSF. Based on in vitro studies, it has been postulated that a pro-inflammatory state predisposes patients to develop NSF.^4,5 The proposed mechanism for NSF involves extravasation of gadolinium in the setting of vascular endothelial permeability.^5,6 Gadolinium then interacts with tissue macrophages, which induce the release of inflammatory cytokines and the secretion of smooth muscle actin by dermal fibroblasts.^6,7

Treatment of NSF has been largely unsuccessful. Multiple modalities of treatment that included topical and oral steroids, immunosuppression, plasmapheresis, and ultraviolent therapy have been attempted, none of which have been proven to consistently limit progression of the disease.⁸ The most effective intervention is early physical therapy to preserve functionality and prevent contracture formation. For patients who are eligible, early renal transplantation may offer the best chance of improved mobility. In a case series review by Cuffy and colleagues, 5 of 6 patients who underwent renal transplantation after the development of NSF experienced softening of the involved skin, and 2 patients had improved mobility of joints.⁹

Conclusion

The case presented here illustrates a possible association between a pro-inflammatory state and the development of NSF. This patient had multiple inflammatory conditions, including MSSA bacteremia, leukocytoclastic vasculitis, and pyoderma gangrenosum (the latter 2 conditions were thought to be associated with his underlying chronic hepatitis C infection), which the authors believe predisposed him to endothelial permeability and risk for developing NSF. The risk of developing NSF in at-risk patients with each episode of gadolinium exposure is estimated around 2.4%, or an incidence of 4.3 cases per 1,000 patient-years, leading the American College of Radiologists to recommend against the administration of gadolinium-based contrast except in cases in which benefits clearly outweigh risks.¹⁰ However, an MRI with gadolinium contrast can offer high diagnostic yield in cases such as the one presented here in which a diagnosis remains elusive. Moreover, the use of linear gadolinium-based contrast agents such as gadoversetamide, as in this case, has been reported to be associated with higher incidence of NSF.⁵ Since this case, the West Los Angeles VAMC has switched to gadobutrol contrast for its MRI protocol, which has been purported to be a lower risk agent compared with that of linear gadolinium-based contrast agents (although several cases of NSF have been reported with gadobutrol in the literature).¹¹

Providers weighing the decision to administer gadolinium contrast to patients with ESRD should discuss the risks and benefits thoroughly, especially in patients with preexisting inflammatory conditions. In addition, although it has not been shown to effectively reduce the risk of NSF after administration of gadolinium, hemodialysis is recommended 2 hours after contrast administration for individuals at risk (the study patient received hemodialysis approximately 18 hours after).¹² Given the lack of effective treatment options for NSF, prevention is key. A deeper understanding of the pathophysiology of NSF and identification of its risk factors is paramount to the prevention of this devastating disease.

First described in 2000 in a case series of 15 patients, nephrogenic systemic fibrosis (NSF) is a rare scleroderma-like fibrosing skin condition associated with gadolinium exposure in end stage renal disease (ESRD).¹ Patients with advanced chronic kidney disease (CKD) or ESRD are at the highest risk for this condition when exposed to gadolinium-based contrast dyes.

Nephrogenic systemic fibrosis is a devastating and rapidly progressive condition, making its prevention in at-risk populations of utmost importance. In this article, the authors describe a case of a patient who developed NSF in the setting of gadolinium exposure and multiple inflammatory dermatologic conditions. This case illustrates the possible role of a pro-inflammatory state in predisposing to NSF, which may help further elucidate its mechanism of action.

Case Presentation

A 61-year-old Hispanic male with a history of IV heroin use with ESRD secondary to membranous glomerulonephritis on hemodialysis and chronic hepatitis C infection presented to the West Los Angeles VAMC with fevers and night sweats that had persisted for 2 weeks. His physical examination was notable for diffuse tender palpable purpura and petechiae (including his palms and soles), altered mental status, and diffuse myoclonic jerks, which necessitated endotracheal intubation and mechanical ventilation for airway protection. Blood cultures were positive for methicillin-sensitive Staphylococcus aureus (MSSA). Laboratory results were notable for an elevated sedimentation rate of 53 mm/h (0-10 mm/h), C-reactive protein of 19.8 mg/L (< 0.744 mg/dL), and albumin of 1.2 g/dL (3.2-4.8 g/dL). An extensive rheumatologic workup was unrevealing, and a lumbar puncture was unremarkable. A biopsy of his skin lesions was consistent with leukocytoclastic vasculitis.

The patient’s prior hemodialysis access, a tunneled dialysis catheter in the right subclavian vein, was removed given concern for line infection and replaced with an internal jugular temporary hemodialysis line. Given his altered mental status and myoclonic jerks, the decision was made to pursue a magnetic resonance imaging (MRI) scan of the brain and spine with gadolinium contrast to evaluate for cerebral vasculitis and/or septic emboli to the brain.

The patient received 15 mL of gadoversetamide contrast in accordance with hospital imaging protocol. The MRI revealed only chronic ischemic changes. The patient underwent hemodialysis about 18 hours later. The patient was treated with a 6-week course of IV penicillin G. His altered mental status and myoclonic jerks resolved without intervention, and he was then discharged to an acute rehabilitation unit.

Eight weeks after his initial presentation the patient developed a purulent wound on his right forearm (Figure 1) 

The patient was discharged to continue physical and occupational therapy to preserve his functional mobility, as no other treatment options were available. 

Discussion

Nephrogenic systemic fibrosis is a poorly understood inflammatory condition that produces diffuse fibrosis of the skin. Typically, the disease begins with progressive skin induration of the extremities. Systemic involvement may occur, leading to fibrosis of skeletal muscle, fascia, and multiple organs. Flexion contractures may develop that limit physical function. Fibrosis can become apparent within days to months after exposure to gadolinium contrast.

Beyond renal insufficiency, it is unclear what other risk factors predispose patients to developing this condition. Only a minority of patients with CKD stages 1 through 4 will develop NSF on exposure to gadolinium contrast. However, the incidence of NSF among patients with CKD stage 5 who are exposed to gadolinium has been estimated to be about 13.4% in a prospective study involving 18 patients.²

In a 2015 meta-analysis by Zhang and colleagues, the only clear risk factor identified for the development of NSF, aside from gadolinium exposure, was severe renal insufficiency with a glomerular filtration rate of < 30 mL/min/1.75m².³ Due to the limited number of patients identified with this disease, it is difficult to identify other risk factors associated with the development of NSF. Based on in vitro studies, it has been postulated that a pro-inflammatory state predisposes patients to develop NSF.^4,5 The proposed mechanism for NSF involves extravasation of gadolinium in the setting of vascular endothelial permeability.^5,6 Gadolinium then interacts with tissue macrophages, which induce the release of inflammatory cytokines and the secretion of smooth muscle actin by dermal fibroblasts.^6,7

Treatment of NSF has been largely unsuccessful. Multiple modalities of treatment that included topical and oral steroids, immunosuppression, plasmapheresis, and ultraviolent therapy have been attempted, none of which have been proven to consistently limit progression of the disease.⁸ The most effective intervention is early physical therapy to preserve functionality and prevent contracture formation. For patients who are eligible, early renal transplantation may offer the best chance of improved mobility. In a case series review by Cuffy and colleagues, 5 of 6 patients who underwent renal transplantation after the development of NSF experienced softening of the involved skin, and 2 patients had improved mobility of joints.⁹

Conclusion

The case presented here illustrates a possible association between a pro-inflammatory state and the development of NSF. This patient had multiple inflammatory conditions, including MSSA bacteremia, leukocytoclastic vasculitis, and pyoderma gangrenosum (the latter 2 conditions were thought to be associated with his underlying chronic hepatitis C infection), which the authors believe predisposed him to endothelial permeability and risk for developing NSF. The risk of developing NSF in at-risk patients with each episode of gadolinium exposure is estimated around 2.4%, or an incidence of 4.3 cases per 1,000 patient-years, leading the American College of Radiologists to recommend against the administration of gadolinium-based contrast except in cases in which benefits clearly outweigh risks.¹⁰ However, an MRI with gadolinium contrast can offer high diagnostic yield in cases such as the one presented here in which a diagnosis remains elusive. Moreover, the use of linear gadolinium-based contrast agents such as gadoversetamide, as in this case, has been reported to be associated with higher incidence of NSF.⁵ Since this case, the West Los Angeles VAMC has switched to gadobutrol contrast for its MRI protocol, which has been purported to be a lower risk agent compared with that of linear gadolinium-based contrast agents (although several cases of NSF have been reported with gadobutrol in the literature).¹¹

Providers weighing the decision to administer gadolinium contrast to patients with ESRD should discuss the risks and benefits thoroughly, especially in patients with preexisting inflammatory conditions. In addition, although it has not been shown to effectively reduce the risk of NSF after administration of gadolinium, hemodialysis is recommended 2 hours after contrast administration for individuals at risk (the study patient received hemodialysis approximately 18 hours after).¹² Given the lack of effective treatment options for NSF, prevention is key. A deeper understanding of the pathophysiology of NSF and identification of its risk factors is paramount to the prevention of this devastating disease.

First described in 2000 in a case series of 15 patients, nephrogenic systemic fibrosis (NSF) is a rare scleroderma-like fibrosing skin condition associated with gadolinium exposure in end stage renal disease (ESRD).¹ Patients with advanced chronic kidney disease (CKD) or ESRD are at the highest risk for this condition when exposed to gadolinium-based contrast dyes.

Nephrogenic systemic fibrosis is a devastating and rapidly progressive condition, making its prevention in at-risk populations of utmost importance. In this article, the authors describe a case of a patient who developed NSF in the setting of gadolinium exposure and multiple inflammatory dermatologic conditions. This case illustrates the possible role of a pro-inflammatory state in predisposing to NSF, which may help further elucidate its mechanism of action.

Case Presentation

A 61-year-old Hispanic male with a history of IV heroin use with ESRD secondary to membranous glomerulonephritis on hemodialysis and chronic hepatitis C infection presented to the West Los Angeles VAMC with fevers and night sweats that had persisted for 2 weeks. His physical examination was notable for diffuse tender palpable purpura and petechiae (including his palms and soles), altered mental status, and diffuse myoclonic jerks, which necessitated endotracheal intubation and mechanical ventilation for airway protection. Blood cultures were positive for methicillin-sensitive Staphylococcus aureus (MSSA). Laboratory results were notable for an elevated sedimentation rate of 53 mm/h (0-10 mm/h), C-reactive protein of 19.8 mg/L (< 0.744 mg/dL), and albumin of 1.2 g/dL (3.2-4.8 g/dL). An extensive rheumatologic workup was unrevealing, and a lumbar puncture was unremarkable. A biopsy of his skin lesions was consistent with leukocytoclastic vasculitis.

The patient’s prior hemodialysis access, a tunneled dialysis catheter in the right subclavian vein, was removed given concern for line infection and replaced with an internal jugular temporary hemodialysis line. Given his altered mental status and myoclonic jerks, the decision was made to pursue a magnetic resonance imaging (MRI) scan of the brain and spine with gadolinium contrast to evaluate for cerebral vasculitis and/or septic emboli to the brain.

The patient received 15 mL of gadoversetamide contrast in accordance with hospital imaging protocol. The MRI revealed only chronic ischemic changes. The patient underwent hemodialysis about 18 hours later. The patient was treated with a 6-week course of IV penicillin G. His altered mental status and myoclonic jerks resolved without intervention, and he was then discharged to an acute rehabilitation unit.

Eight weeks after his initial presentation the patient developed a purulent wound on his right forearm (Figure 1) 

The patient was discharged to continue physical and occupational therapy to preserve his functional mobility, as no other treatment options were available. 

Discussion

Nephrogenic systemic fibrosis is a poorly understood inflammatory condition that produces diffuse fibrosis of the skin. Typically, the disease begins with progressive skin induration of the extremities. Systemic involvement may occur, leading to fibrosis of skeletal muscle, fascia, and multiple organs. Flexion contractures may develop that limit physical function. Fibrosis can become apparent within days to months after exposure to gadolinium contrast.

Beyond renal insufficiency, it is unclear what other risk factors predispose patients to developing this condition. Only a minority of patients with CKD stages 1 through 4 will develop NSF on exposure to gadolinium contrast. However, the incidence of NSF among patients with CKD stage 5 who are exposed to gadolinium has been estimated to be about 13.4% in a prospective study involving 18 patients.²

In a 2015 meta-analysis by Zhang and colleagues, the only clear risk factor identified for the development of NSF, aside from gadolinium exposure, was severe renal insufficiency with a glomerular filtration rate of < 30 mL/min/1.75m².³ Due to the limited number of patients identified with this disease, it is difficult to identify other risk factors associated with the development of NSF. Based on in vitro studies, it has been postulated that a pro-inflammatory state predisposes patients to develop NSF.^4,5 The proposed mechanism for NSF involves extravasation of gadolinium in the setting of vascular endothelial permeability.^5,6 Gadolinium then interacts with tissue macrophages, which induce the release of inflammatory cytokines and the secretion of smooth muscle actin by dermal fibroblasts.^6,7

Treatment of NSF has been largely unsuccessful. Multiple modalities of treatment that included topical and oral steroids, immunosuppression, plasmapheresis, and ultraviolent therapy have been attempted, none of which have been proven to consistently limit progression of the disease.⁸ The most effective intervention is early physical therapy to preserve functionality and prevent contracture formation. For patients who are eligible, early renal transplantation may offer the best chance of improved mobility. In a case series review by Cuffy and colleagues, 5 of 6 patients who underwent renal transplantation after the development of NSF experienced softening of the involved skin, and 2 patients had improved mobility of joints.⁹

Conclusion

The case presented here illustrates a possible association between a pro-inflammatory state and the development of NSF. This patient had multiple inflammatory conditions, including MSSA bacteremia, leukocytoclastic vasculitis, and pyoderma gangrenosum (the latter 2 conditions were thought to be associated with his underlying chronic hepatitis C infection), which the authors believe predisposed him to endothelial permeability and risk for developing NSF. The risk of developing NSF in at-risk patients with each episode of gadolinium exposure is estimated around 2.4%, or an incidence of 4.3 cases per 1,000 patient-years, leading the American College of Radiologists to recommend against the administration of gadolinium-based contrast except in cases in which benefits clearly outweigh risks.¹⁰ However, an MRI with gadolinium contrast can offer high diagnostic yield in cases such as the one presented here in which a diagnosis remains elusive. Moreover, the use of linear gadolinium-based contrast agents such as gadoversetamide, as in this case, has been reported to be associated with higher incidence of NSF.⁵ Since this case, the West Los Angeles VAMC has switched to gadobutrol contrast for its MRI protocol, which has been purported to be a lower risk agent compared with that of linear gadolinium-based contrast agents (although several cases of NSF have been reported with gadobutrol in the literature).¹¹

Providers weighing the decision to administer gadolinium contrast to patients with ESRD should discuss the risks and benefits thoroughly, especially in patients with preexisting inflammatory conditions. In addition, although it has not been shown to effectively reduce the risk of NSF after administration of gadolinium, hemodialysis is recommended 2 hours after contrast administration for individuals at risk (the study patient received hemodialysis approximately 18 hours after).¹² Given the lack of effective treatment options for NSF, prevention is key. A deeper understanding of the pathophysiology of NSF and identification of its risk factors is paramount to the prevention of this devastating disease.

Photo from EHA

STOCKHOLM—A new survey has revealed patients’ perceptions of immune thrombocytopenia (ITP) and how the condition impacts their quality of life (QOL).

Patients reported delays in diagnosis, lack of support, severe fatigue, and impacts on both emotional well-being and their ability to work.

Interim results of this survey, the ITP World Impact Survey (I-WISh), were presented in a poster (abstract PF654) at the 23rd Congress of the European Hematology Association (EHA).

I-WISh is a cross-sectional survey of ITP patients developed by global ITP experts, patient groups, and Novartis.

Interim results of the survey included patients from 12 countries (Canada, China, Colombia, France, Germany, Italy, India, Japan, Spain, Turkey, UK, and US) who completed an online questionnaire beginning in January 2018.

As of May 14, 2018, 1400 adults (age 18 and older) had completed the survey. Sixty-five percent were female, and they had a mean age of 47.1 years. The patients’ mean length of time with ITP was 110 months.

Most patients (63%) reported a high score for their current health state (5 to 7 on the Likert scale), but 15% reported a low score (1-3).

Most patients were working full-time (45%) or part-time (16%) at the time of the survey. Nineteen percent were retired, 6% were homemakers, 4% were students, and 10% were not seeking employment, on long-term sick leave or disability, or “other.”

Diagnosis

Twenty-two percent of all patients (307/1400) felt they had a delay in their ITP diagnosis caused by waiting for additional tests (49%, 150/307) or referral to a specialist (37%, 114/307).

Three-quarters of patients with a perceived delay (229/307) were anxious throughout diagnosis.

And 66% of all patients (927/1400) wanted more support during their diagnosis.

Symptoms

Patients reported fatigue as one of the most severe symptoms at diagnosis (75%, 627/839) and at survey completion (66%, 480/722).

The other “most severe” symptoms at diagnosis were heavy menstrual bleeding (85%, 353/416) and anxiety surrounding unstable platelet count (78%, 382/487). The other “most severe” symptoms at survey completion were thrombosis (73%, 24/33) and anxiety surrounding unstable platelet count (66%, 284/431).

“Severe fatigue, in particular, was reported by many patients as the most difficult-to-manage symptom of ITP,” said study investigator Nichola Cooper, MD, of Hammersmith Hospital, Imperial College London, in the UK.

“This is an important message for healthcare providers treating patients with this rare disease. ITP is about more than bruising and risk of bleeding.”

QOL

Forty-four percent of respondents (611/1398) said ITP impacted their energy levels more than half the time, and 36% (501/1398) said ITP had a negative impact on their normal capacity to exercise more than half the time.

Half of all patients (697/1400) said ITP had a high impact on their emotional well-being.

Eighty-three percent (1157/1400) said they felt a stable and safe platelet count was important, 64% (900/1400) worried that their condition will get worse, and 63% (888/1400) were concerned that their platelet count changes for no apparent reason.

Thirty-seven percent of all patients (511/1400) had reduced their work hours because of ITP, 37% (522/1400) seriously considered reducing their hours, and 21% (294/1400) considered terminating their employment.

Thirty-five percent of patients (491/1400) said obtaining healthy blood counts was their most important treatment goal. Twenty-one percent (299/1400) said increasing their energy levels was most important, and 15% (203/1400) said reducing spontaneous bleeds/bruising was most important.

Photo from EHA

STOCKHOLM—A new survey has revealed patients’ perceptions of immune thrombocytopenia (ITP) and how the condition impacts their quality of life (QOL).

Patients reported delays in diagnosis, lack of support, severe fatigue, and impacts on both emotional well-being and their ability to work.

Interim results of this survey, the ITP World Impact Survey (I-WISh), were presented in a poster (abstract PF654) at the 23rd Congress of the European Hematology Association (EHA).

I-WISh is a cross-sectional survey of ITP patients developed by global ITP experts, patient groups, and Novartis.

Interim results of the survey included patients from 12 countries (Canada, China, Colombia, France, Germany, Italy, India, Japan, Spain, Turkey, UK, and US) who completed an online questionnaire beginning in January 2018.

As of May 14, 2018, 1400 adults (age 18 and older) had completed the survey. Sixty-five percent were female, and they had a mean age of 47.1 years. The patients’ mean length of time with ITP was 110 months.

Most patients (63%) reported a high score for their current health state (5 to 7 on the Likert scale), but 15% reported a low score (1-3).

Most patients were working full-time (45%) or part-time (16%) at the time of the survey. Nineteen percent were retired, 6% were homemakers, 4% were students, and 10% were not seeking employment, on long-term sick leave or disability, or “other.”

Diagnosis

Twenty-two percent of all patients (307/1400) felt they had a delay in their ITP diagnosis caused by waiting for additional tests (49%, 150/307) or referral to a specialist (37%, 114/307).

Three-quarters of patients with a perceived delay (229/307) were anxious throughout diagnosis.

And 66% of all patients (927/1400) wanted more support during their diagnosis.

Symptoms

Patients reported fatigue as one of the most severe symptoms at diagnosis (75%, 627/839) and at survey completion (66%, 480/722).

The other “most severe” symptoms at diagnosis were heavy menstrual bleeding (85%, 353/416) and anxiety surrounding unstable platelet count (78%, 382/487). The other “most severe” symptoms at survey completion were thrombosis (73%, 24/33) and anxiety surrounding unstable platelet count (66%, 284/431).

“Severe fatigue, in particular, was reported by many patients as the most difficult-to-manage symptom of ITP,” said study investigator Nichola Cooper, MD, of Hammersmith Hospital, Imperial College London, in the UK.

“This is an important message for healthcare providers treating patients with this rare disease. ITP is about more than bruising and risk of bleeding.”

QOL

Forty-four percent of respondents (611/1398) said ITP impacted their energy levels more than half the time, and 36% (501/1398) said ITP had a negative impact on their normal capacity to exercise more than half the time.

Half of all patients (697/1400) said ITP had a high impact on their emotional well-being.

Eighty-three percent (1157/1400) said they felt a stable and safe platelet count was important, 64% (900/1400) worried that their condition will get worse, and 63% (888/1400) were concerned that their platelet count changes for no apparent reason.

Thirty-seven percent of all patients (511/1400) had reduced their work hours because of ITP, 37% (522/1400) seriously considered reducing their hours, and 21% (294/1400) considered terminating their employment.

Thirty-five percent of patients (491/1400) said obtaining healthy blood counts was their most important treatment goal. Twenty-one percent (299/1400) said increasing their energy levels was most important, and 15% (203/1400) said reducing spontaneous bleeds/bruising was most important.

Photo from EHA

STOCKHOLM—A new survey has revealed patients’ perceptions of immune thrombocytopenia (ITP) and how the condition impacts their quality of life (QOL).

Patients reported delays in diagnosis, lack of support, severe fatigue, and impacts on both emotional well-being and their ability to work.

Interim results of this survey, the ITP World Impact Survey (I-WISh), were presented in a poster (abstract PF654) at the 23rd Congress of the European Hematology Association (EHA).

I-WISh is a cross-sectional survey of ITP patients developed by global ITP experts, patient groups, and Novartis.

Interim results of the survey included patients from 12 countries (Canada, China, Colombia, France, Germany, Italy, India, Japan, Spain, Turkey, UK, and US) who completed an online questionnaire beginning in January 2018.

As of May 14, 2018, 1400 adults (age 18 and older) had completed the survey. Sixty-five percent were female, and they had a mean age of 47.1 years. The patients’ mean length of time with ITP was 110 months.

Most patients (63%) reported a high score for their current health state (5 to 7 on the Likert scale), but 15% reported a low score (1-3).

Most patients were working full-time (45%) or part-time (16%) at the time of the survey. Nineteen percent were retired, 6% were homemakers, 4% were students, and 10% were not seeking employment, on long-term sick leave or disability, or “other.”

Diagnosis

Twenty-two percent of all patients (307/1400) felt they had a delay in their ITP diagnosis caused by waiting for additional tests (49%, 150/307) or referral to a specialist (37%, 114/307).

Three-quarters of patients with a perceived delay (229/307) were anxious throughout diagnosis.

And 66% of all patients (927/1400) wanted more support during their diagnosis.

Symptoms

Patients reported fatigue as one of the most severe symptoms at diagnosis (75%, 627/839) and at survey completion (66%, 480/722).

The other “most severe” symptoms at diagnosis were heavy menstrual bleeding (85%, 353/416) and anxiety surrounding unstable platelet count (78%, 382/487). The other “most severe” symptoms at survey completion were thrombosis (73%, 24/33) and anxiety surrounding unstable platelet count (66%, 284/431).

“Severe fatigue, in particular, was reported by many patients as the most difficult-to-manage symptom of ITP,” said study investigator Nichola Cooper, MD, of Hammersmith Hospital, Imperial College London, in the UK.

“This is an important message for healthcare providers treating patients with this rare disease. ITP is about more than bruising and risk of bleeding.”

QOL

Forty-four percent of respondents (611/1398) said ITP impacted their energy levels more than half the time, and 36% (501/1398) said ITP had a negative impact on their normal capacity to exercise more than half the time.

Half of all patients (697/1400) said ITP had a high impact on their emotional well-being.

Eighty-three percent (1157/1400) said they felt a stable and safe platelet count was important, 64% (900/1400) worried that their condition will get worse, and 63% (888/1400) were concerned that their platelet count changes for no apparent reason.

Thirty-seven percent of all patients (511/1400) had reduced their work hours because of ITP, 37% (522/1400) seriously considered reducing their hours, and 21% (294/1400) considered terminating their employment.

Thirty-five percent of patients (491/1400) said obtaining healthy blood counts was their most important treatment goal. Twenty-one percent (299/1400) said increasing their energy levels was most important, and 15% (203/1400) said reducing spontaneous bleeds/bruising was most important.

The recent crises of the separation of stressed children from their equally stressed parents at this country’s southern border raises the specter of emotional and cognitive reactions within these children – the negative ramifications of which will manifest themselves for years to come.

Stress is ubiquitous. Children experience stress in the normal everyday frustrations that come their way: going to day care for a few hours and leaving mommy, the tripping and falling as they learn to walk, a toy breaking. These stresses help a child develop the capacity for emotional regulation and are termed “tolerable stress.” There is, however, a big difference between tolerable stress and toxic stress.

When the stress reaction in response to perceived or actual danger is beyond tolerable levels by virtue of its quality, intensity, and longevity, it saps the body’s ability to rally or handle the trauma that is being faced because of depleted neurotransmitters that normally assist the body to fight or flee from danger. Unfortunately, that’s not the end of the story: As the stressor persists, it has the capacity to produce long-term alterations in the resilience of the brain and body of the young child. This change often is irreversible.

Scientists and the lay public have begun to actively discuss the impact of adverse childhood experiences and their causal link to irreversible negative adult health outcomes. We now know without a doubt the impact of toxic versus tolerable stress on the hypothalamic-pituitary-adrenal axis of the young child. We are aware that the brain of a young child is particularly vulnerable to stress during critical and sensitive periods of development and that downstream effects of early trauma show up as disorganized behavior and cognitive underperformance.

Development plays a central role in children’s behavioral response to separation from parents. Infants develop a sense of stranger anxiety and the primacy of one central figure between ages 8 and 10 months. The baby chooses the parent over strangers for comfort and care. Roughly between ages 3 and 4, a child develops an internal representation of the parent as the primary figure in their lives so that they can tolerate short periods of being away from the primary caregiver for, let’s say, half a day. They depend on the parent for all their physical and emotional needs, which includes the need for a stable, nurturing, and predictable presence.

Familiarity of the environment, family rituals, consistency of daily routines provided by the parent help neural pathways responsible for the biologic unfolding of developmental milestones. Only recently, the science of early brain development and the role of early childhood trauma on brain biology has caught up with the longitudinal observational studies of bereaved children who lost their parents under circumstances of acute stress (the blitzkrieg, the Yom Kippur War, the Hungarian orphans) followed by the chronic stress phase of no primary caregiver for months to years. These observational studies coupled by the emerging neuroscience of early brain development and trauma are powerful informants of what is tolerable stress for children and what is not.

As a psychiatrist and expert in early child development, I am concerned about these long-term effects on migrant children. Research shows that young children who are nonverbal react to the stress of separation by death or absence of parents with anxiety; frantically seeking the parent/comforting familiar caregiver. Gradually as that possibility fades, with their limited ability to verbalize needs, episodic weeping can give way to disorganized behavior, despondence, and finally apathy and regression of milestones and cognitive abilities already achieved. The separation is merely the proxy face of other disasters that are probably co-occurring for the child/family and multiplies the dose of the stress: loss of siblings, loss of familiar physical elements of the landscape, loss of adequate physical sustenance, loss of routine, loss of consistency, increased vulnerability for physical illness, and the list goes on.

By age 2 and above, children are more vocal in their desire for reunification and will weep inconsolably upon separation. At this time their bodies and the psychological lens through which they view the world is changing irrevocably. Stress hormones, noxious at high levels such as cortisol/adrenocorticotropic hormone and glutamate rise to levels that no longer respond to the traditional negative feedback loop of the body and reach levels that lead to cell death in areas of the brain responsible for modulating emotions that can permanently change brain architecture.

Psychologically, the child seeks out the parent by any means (crying, flailing, tantruming). When no positive outcome occurs, this is replaced by an unwillingness to engage with the world, or the child engages but by behavior that is aggressive, disorganized, and regressed. In their own way, young children’s mistrust of the world leads to a variety of behaviors that impede normal development: rejection of others, disengagement from social connections by quietly sitting in a corner, being unwilling to eat or sleeping fitfully.

As separation from the primary caregiver continues, there is a deepening sense of hopelessness. Generally, no amount of physical props (toys, playgrounds) without the human familiar faces can rectify the feeling of abandonment and hopelessness that children in these conditions face. Assuming they are no strangers to trauma experienced through the lives of their asylum-seeking parents, this separation refreshes all the wounds of days gone by. At least in those moments of initial trauma, they had the parent as a buffer. But with this new separation, they are left to emotionally fend for themselves with no tools to manage their emotions.

We have to deal with the aftereffects of so many natural disasters that cannot be avoided: earthquakes, tornadoes, tsunamis that displace children and families with horrific outcomes. Did we really need a man-made disaster that will irrevocably change the brains and behaviors of a generation of children who just happen to be on our southern borders because of an accident of birth? If parents abandoned their children this way it would be called child abuse. Deliberate policy decisions that have such dire effects on children also take on the label of child abuse.

Although images of my years as a young parent of three boys are turning a sepia color in faded memory, in my new role as a grandmother observing my son and his wife so in love with their 2-year-old reinforces how much mutual dependency of a child and parent on each other strengthens the very fabric of life. Children are our future and are the building blocks of a just and humane society.

As of this writing, the administration has vowed to end these separations. But how will children who have been separated be reunited with their families?

The education of decision makers about the far-reaching emotional and physical consequences on normative childhood development must be a top priority for all scientists and professionals interested in kids and families: I think that means all of us.
 

Dr. Sood is professor of psychiatry and pediatrics, and senior professor of child mental health policy at the Virginia Treatment Center at Virginia Commonwealth University, Richmond. She also is affiliated with the department of psychiatry at VCU and Children’s Hospital of Richmond.

The recent crises of the separation of stressed children from their equally stressed parents at this country’s southern border raises the specter of emotional and cognitive reactions within these children – the negative ramifications of which will manifest themselves for years to come.

Stress is ubiquitous. Children experience stress in the normal everyday frustrations that come their way: going to day care for a few hours and leaving mommy, the tripping and falling as they learn to walk, a toy breaking. These stresses help a child develop the capacity for emotional regulation and are termed “tolerable stress.” There is, however, a big difference between tolerable stress and toxic stress.

When the stress reaction in response to perceived or actual danger is beyond tolerable levels by virtue of its quality, intensity, and longevity, it saps the body’s ability to rally or handle the trauma that is being faced because of depleted neurotransmitters that normally assist the body to fight or flee from danger. Unfortunately, that’s not the end of the story: As the stressor persists, it has the capacity to produce long-term alterations in the resilience of the brain and body of the young child. This change often is irreversible.

Scientists and the lay public have begun to actively discuss the impact of adverse childhood experiences and their causal link to irreversible negative adult health outcomes. We now know without a doubt the impact of toxic versus tolerable stress on the hypothalamic-pituitary-adrenal axis of the young child. We are aware that the brain of a young child is particularly vulnerable to stress during critical and sensitive periods of development and that downstream effects of early trauma show up as disorganized behavior and cognitive underperformance.

Development plays a central role in children’s behavioral response to separation from parents. Infants develop a sense of stranger anxiety and the primacy of one central figure between ages 8 and 10 months. The baby chooses the parent over strangers for comfort and care. Roughly between ages 3 and 4, a child develops an internal representation of the parent as the primary figure in their lives so that they can tolerate short periods of being away from the primary caregiver for, let’s say, half a day. They depend on the parent for all their physical and emotional needs, which includes the need for a stable, nurturing, and predictable presence.

Familiarity of the environment, family rituals, consistency of daily routines provided by the parent help neural pathways responsible for the biologic unfolding of developmental milestones. Only recently, the science of early brain development and the role of early childhood trauma on brain biology has caught up with the longitudinal observational studies of bereaved children who lost their parents under circumstances of acute stress (the blitzkrieg, the Yom Kippur War, the Hungarian orphans) followed by the chronic stress phase of no primary caregiver for months to years. These observational studies coupled by the emerging neuroscience of early brain development and trauma are powerful informants of what is tolerable stress for children and what is not.

As a psychiatrist and expert in early child development, I am concerned about these long-term effects on migrant children. Research shows that young children who are nonverbal react to the stress of separation by death or absence of parents with anxiety; frantically seeking the parent/comforting familiar caregiver. Gradually as that possibility fades, with their limited ability to verbalize needs, episodic weeping can give way to disorganized behavior, despondence, and finally apathy and regression of milestones and cognitive abilities already achieved. The separation is merely the proxy face of other disasters that are probably co-occurring for the child/family and multiplies the dose of the stress: loss of siblings, loss of familiar physical elements of the landscape, loss of adequate physical sustenance, loss of routine, loss of consistency, increased vulnerability for physical illness, and the list goes on.

By age 2 and above, children are more vocal in their desire for reunification and will weep inconsolably upon separation. At this time their bodies and the psychological lens through which they view the world is changing irrevocably. Stress hormones, noxious at high levels such as cortisol/adrenocorticotropic hormone and glutamate rise to levels that no longer respond to the traditional negative feedback loop of the body and reach levels that lead to cell death in areas of the brain responsible for modulating emotions that can permanently change brain architecture.

Psychologically, the child seeks out the parent by any means (crying, flailing, tantruming). When no positive outcome occurs, this is replaced by an unwillingness to engage with the world, or the child engages but by behavior that is aggressive, disorganized, and regressed. In their own way, young children’s mistrust of the world leads to a variety of behaviors that impede normal development: rejection of others, disengagement from social connections by quietly sitting in a corner, being unwilling to eat or sleeping fitfully.

As separation from the primary caregiver continues, there is a deepening sense of hopelessness. Generally, no amount of physical props (toys, playgrounds) without the human familiar faces can rectify the feeling of abandonment and hopelessness that children in these conditions face. Assuming they are no strangers to trauma experienced through the lives of their asylum-seeking parents, this separation refreshes all the wounds of days gone by. At least in those moments of initial trauma, they had the parent as a buffer. But with this new separation, they are left to emotionally fend for themselves with no tools to manage their emotions.

We have to deal with the aftereffects of so many natural disasters that cannot be avoided: earthquakes, tornadoes, tsunamis that displace children and families with horrific outcomes. Did we really need a man-made disaster that will irrevocably change the brains and behaviors of a generation of children who just happen to be on our southern borders because of an accident of birth? If parents abandoned their children this way it would be called child abuse. Deliberate policy decisions that have such dire effects on children also take on the label of child abuse.

Although images of my years as a young parent of three boys are turning a sepia color in faded memory, in my new role as a grandmother observing my son and his wife so in love with their 2-year-old reinforces how much mutual dependency of a child and parent on each other strengthens the very fabric of life. Children are our future and are the building blocks of a just and humane society.

As of this writing, the administration has vowed to end these separations. But how will children who have been separated be reunited with their families?

The education of decision makers about the far-reaching emotional and physical consequences on normative childhood development must be a top priority for all scientists and professionals interested in kids and families: I think that means all of us.
 

Dr. Sood is professor of psychiatry and pediatrics, and senior professor of child mental health policy at the Virginia Treatment Center at Virginia Commonwealth University, Richmond. She also is affiliated with the department of psychiatry at VCU and Children’s Hospital of Richmond.

The recent crises of the separation of stressed children from their equally stressed parents at this country’s southern border raises the specter of emotional and cognitive reactions within these children – the negative ramifications of which will manifest themselves for years to come.

Stress is ubiquitous. Children experience stress in the normal everyday frustrations that come their way: going to day care for a few hours and leaving mommy, the tripping and falling as they learn to walk, a toy breaking. These stresses help a child develop the capacity for emotional regulation and are termed “tolerable stress.” There is, however, a big difference between tolerable stress and toxic stress.

When the stress reaction in response to perceived or actual danger is beyond tolerable levels by virtue of its quality, intensity, and longevity, it saps the body’s ability to rally or handle the trauma that is being faced because of depleted neurotransmitters that normally assist the body to fight or flee from danger. Unfortunately, that’s not the end of the story: As the stressor persists, it has the capacity to produce long-term alterations in the resilience of the brain and body of the young child. This change often is irreversible.

Scientists and the lay public have begun to actively discuss the impact of adverse childhood experiences and their causal link to irreversible negative adult health outcomes. We now know without a doubt the impact of toxic versus tolerable stress on the hypothalamic-pituitary-adrenal axis of the young child. We are aware that the brain of a young child is particularly vulnerable to stress during critical and sensitive periods of development and that downstream effects of early trauma show up as disorganized behavior and cognitive underperformance.

Development plays a central role in children’s behavioral response to separation from parents. Infants develop a sense of stranger anxiety and the primacy of one central figure between ages 8 and 10 months. The baby chooses the parent over strangers for comfort and care. Roughly between ages 3 and 4, a child develops an internal representation of the parent as the primary figure in their lives so that they can tolerate short periods of being away from the primary caregiver for, let’s say, half a day. They depend on the parent for all their physical and emotional needs, which includes the need for a stable, nurturing, and predictable presence.

Familiarity of the environment, family rituals, consistency of daily routines provided by the parent help neural pathways responsible for the biologic unfolding of developmental milestones. Only recently, the science of early brain development and the role of early childhood trauma on brain biology has caught up with the longitudinal observational studies of bereaved children who lost their parents under circumstances of acute stress (the blitzkrieg, the Yom Kippur War, the Hungarian orphans) followed by the chronic stress phase of no primary caregiver for months to years. These observational studies coupled by the emerging neuroscience of early brain development and trauma are powerful informants of what is tolerable stress for children and what is not.

As a psychiatrist and expert in early child development, I am concerned about these long-term effects on migrant children. Research shows that young children who are nonverbal react to the stress of separation by death or absence of parents with anxiety; frantically seeking the parent/comforting familiar caregiver. Gradually as that possibility fades, with their limited ability to verbalize needs, episodic weeping can give way to disorganized behavior, despondence, and finally apathy and regression of milestones and cognitive abilities already achieved. The separation is merely the proxy face of other disasters that are probably co-occurring for the child/family and multiplies the dose of the stress: loss of siblings, loss of familiar physical elements of the landscape, loss of adequate physical sustenance, loss of routine, loss of consistency, increased vulnerability for physical illness, and the list goes on.

By age 2 and above, children are more vocal in their desire for reunification and will weep inconsolably upon separation. At this time their bodies and the psychological lens through which they view the world is changing irrevocably. Stress hormones, noxious at high levels such as cortisol/adrenocorticotropic hormone and glutamate rise to levels that no longer respond to the traditional negative feedback loop of the body and reach levels that lead to cell death in areas of the brain responsible for modulating emotions that can permanently change brain architecture.

Psychologically, the child seeks out the parent by any means (crying, flailing, tantruming). When no positive outcome occurs, this is replaced by an unwillingness to engage with the world, or the child engages but by behavior that is aggressive, disorganized, and regressed. In their own way, young children’s mistrust of the world leads to a variety of behaviors that impede normal development: rejection of others, disengagement from social connections by quietly sitting in a corner, being unwilling to eat or sleeping fitfully.

As separation from the primary caregiver continues, there is a deepening sense of hopelessness. Generally, no amount of physical props (toys, playgrounds) without the human familiar faces can rectify the feeling of abandonment and hopelessness that children in these conditions face. Assuming they are no strangers to trauma experienced through the lives of their asylum-seeking parents, this separation refreshes all the wounds of days gone by. At least in those moments of initial trauma, they had the parent as a buffer. But with this new separation, they are left to emotionally fend for themselves with no tools to manage their emotions.

We have to deal with the aftereffects of so many natural disasters that cannot be avoided: earthquakes, tornadoes, tsunamis that displace children and families with horrific outcomes. Did we really need a man-made disaster that will irrevocably change the brains and behaviors of a generation of children who just happen to be on our southern borders because of an accident of birth? If parents abandoned their children this way it would be called child abuse. Deliberate policy decisions that have such dire effects on children also take on the label of child abuse.

Although images of my years as a young parent of three boys are turning a sepia color in faded memory, in my new role as a grandmother observing my son and his wife so in love with their 2-year-old reinforces how much mutual dependency of a child and parent on each other strengthens the very fabric of life. Children are our future and are the building blocks of a just and humane society.

As of this writing, the administration has vowed to end these separations. But how will children who have been separated be reunited with their families?

The education of decision makers about the far-reaching emotional and physical consequences on normative childhood development must be a top priority for all scientists and professionals interested in kids and families: I think that means all of us.
 

Dr. Sood is professor of psychiatry and pediatrics, and senior professor of child mental health policy at the Virginia Treatment Center at Virginia Commonwealth University, Richmond. She also is affiliated with the department of psychiatry at VCU and Children’s Hospital of Richmond.