Get rid of “incident-to” billing and have nurse practitioners and physician assistant bill Medicare under their own numbers – that’s the unanimous recommendation the Medicare Payment Advisory Commission made in its June report to Congress.

TheaDesign/Thinkstock

Incident-to billing occurs when an advanced practicing registered nurse (APRN) or a physician assistant (PA) performs a service but bills Medicare under the physician’s national provider number and receives full physician fee schedule payment, as opposed to 85% of the fee under their own number.

“Medicare beneficiaries increasingly use APRNs and PAs for both primary and specialty care,” according to MedPAC’s June report. “APRNs are furnishing a larger share and a greater variety of services for Medicare beneficiaries than they did in the past. Despite this growing reliance, Medicare does not have a full accounting of the services delivered and beneficiaries treated.”

Currently, identical coding requirements obscure whether the physician or the APRN/PA is providing the service, making it difficult to track volume and quality.

MedPAC estimated that, in 2016, 17% of all nurse practitioners billed all their services as incident to, as that was the number of nurse practitioners who never appeared in the performing provider field for reimbursement but ordered services/drugs or at least one Medicare fee-for-service beneficiary.

Another 34% billed some of their services as incident to as their name appeared at least once in the performing provider they ordered services/drugs for, but ordered more services/drugs for patients where they were not listed as the performing provider.

That leaves just about half (49%) who did not billing their services as incident to.

Requiring APRNs and PAs to bill directly for all of their services provided would update Medicare’s payment policies to better reflect current clinical practice, according to the MedPAC report. “In addition to improving policy makers’ foundational knowledge of who provides care for Medicare beneficiaries, direct billing could create substantial benefits for the Medicare program, beneficiaries, clinicians, and researchers that range from improving the accuracy of the physician fee schedule, reducing expenditures, enhancing program integrity, and allowing for better comparisons between cost and quality of care provided by physicians and APRNs/PAs.”

At their October 2018 meeting, MedPAC commissioners discussed how to appropriately compensate APRNs and PAs, should incident-to billing be eliminated; they ultimately recommended maintaining the 85% rate.

The American Academy of Family Practitioners spoke out against the idea of eliminating incident-to billing.

However, lowering all APRN/PA payments to 85% of what physicians make would impact doctors in a negative way, according to AAFP President Michael Munger, MD.

Dr. Munger described primary care as a team sport, and “this is certainly going to be felt in terms of the overall mission of delivering quality care.”

Access to care also could be reduced along with the reduced payment level.

“You have to make business decisions at the end of the day,” he said in an interview. “You need to make sure that you can have adequate revenue to offset expenses, and if you are going to take a 15% cut in your revenue in, you have to look at where your expenses are, and obviously salary is your No. 1 expense. If you are not able to count on this revenue and you can’t afford to have NPs and PAs as part of the team, it is going to become an access issue for patients.”

The MedPAC commissioner saw it differently.

“Most of these clinicians are already paid at this lower rate, and yet the supply of these clinicians has increased dramatically over the last several years,” the report states, adding that the salary differential between these clinicians and physicians “is large enough that employing them likely would remain attractive even if all of their services were paid at 85% of physician fee schedule rates.”

MedPAC, as an advisory body to Congress, makes no disclosures.

gtwachtman@mdedge.com

Get rid of “incident-to” billing and have nurse practitioners and physician assistant bill Medicare under their own numbers – that’s the unanimous recommendation the Medicare Payment Advisory Commission made in its June report to Congress.

TheaDesign/Thinkstock

Incident-to billing occurs when an advanced practicing registered nurse (APRN) or a physician assistant (PA) performs a service but bills Medicare under the physician’s national provider number and receives full physician fee schedule payment, as opposed to 85% of the fee under their own number.

“Medicare beneficiaries increasingly use APRNs and PAs for both primary and specialty care,” according to MedPAC’s June report. “APRNs are furnishing a larger share and a greater variety of services for Medicare beneficiaries than they did in the past. Despite this growing reliance, Medicare does not have a full accounting of the services delivered and beneficiaries treated.”

Currently, identical coding requirements obscure whether the physician or the APRN/PA is providing the service, making it difficult to track volume and quality.

MedPAC estimated that, in 2016, 17% of all nurse practitioners billed all their services as incident to, as that was the number of nurse practitioners who never appeared in the performing provider field for reimbursement but ordered services/drugs or at least one Medicare fee-for-service beneficiary.

Another 34% billed some of their services as incident to as their name appeared at least once in the performing provider they ordered services/drugs for, but ordered more services/drugs for patients where they were not listed as the performing provider.

That leaves just about half (49%) who did not billing their services as incident to.

Requiring APRNs and PAs to bill directly for all of their services provided would update Medicare’s payment policies to better reflect current clinical practice, according to the MedPAC report. “In addition to improving policy makers’ foundational knowledge of who provides care for Medicare beneficiaries, direct billing could create substantial benefits for the Medicare program, beneficiaries, clinicians, and researchers that range from improving the accuracy of the physician fee schedule, reducing expenditures, enhancing program integrity, and allowing for better comparisons between cost and quality of care provided by physicians and APRNs/PAs.”

At their October 2018 meeting, MedPAC commissioners discussed how to appropriately compensate APRNs and PAs, should incident-to billing be eliminated; they ultimately recommended maintaining the 85% rate.

The American Academy of Family Practitioners spoke out against the idea of eliminating incident-to billing.

However, lowering all APRN/PA payments to 85% of what physicians make would impact doctors in a negative way, according to AAFP President Michael Munger, MD.

Dr. Munger described primary care as a team sport, and “this is certainly going to be felt in terms of the overall mission of delivering quality care.”

Access to care also could be reduced along with the reduced payment level.

“You have to make business decisions at the end of the day,” he said in an interview. “You need to make sure that you can have adequate revenue to offset expenses, and if you are going to take a 15% cut in your revenue in, you have to look at where your expenses are, and obviously salary is your No. 1 expense. If you are not able to count on this revenue and you can’t afford to have NPs and PAs as part of the team, it is going to become an access issue for patients.”

The MedPAC commissioner saw it differently.

“Most of these clinicians are already paid at this lower rate, and yet the supply of these clinicians has increased dramatically over the last several years,” the report states, adding that the salary differential between these clinicians and physicians “is large enough that employing them likely would remain attractive even if all of their services were paid at 85% of physician fee schedule rates.”

MedPAC, as an advisory body to Congress, makes no disclosures.

gtwachtman@mdedge.com

Get rid of “incident-to” billing and have nurse practitioners and physician assistant bill Medicare under their own numbers – that’s the unanimous recommendation the Medicare Payment Advisory Commission made in its June report to Congress.

TheaDesign/Thinkstock

Incident-to billing occurs when an advanced practicing registered nurse (APRN) or a physician assistant (PA) performs a service but bills Medicare under the physician’s national provider number and receives full physician fee schedule payment, as opposed to 85% of the fee under their own number.

“Medicare beneficiaries increasingly use APRNs and PAs for both primary and specialty care,” according to MedPAC’s June report. “APRNs are furnishing a larger share and a greater variety of services for Medicare beneficiaries than they did in the past. Despite this growing reliance, Medicare does not have a full accounting of the services delivered and beneficiaries treated.”

Currently, identical coding requirements obscure whether the physician or the APRN/PA is providing the service, making it difficult to track volume and quality.

MedPAC estimated that, in 2016, 17% of all nurse practitioners billed all their services as incident to, as that was the number of nurse practitioners who never appeared in the performing provider field for reimbursement but ordered services/drugs or at least one Medicare fee-for-service beneficiary.

Another 34% billed some of their services as incident to as their name appeared at least once in the performing provider they ordered services/drugs for, but ordered more services/drugs for patients where they were not listed as the performing provider.

That leaves just about half (49%) who did not billing their services as incident to.

Requiring APRNs and PAs to bill directly for all of their services provided would update Medicare’s payment policies to better reflect current clinical practice, according to the MedPAC report. “In addition to improving policy makers’ foundational knowledge of who provides care for Medicare beneficiaries, direct billing could create substantial benefits for the Medicare program, beneficiaries, clinicians, and researchers that range from improving the accuracy of the physician fee schedule, reducing expenditures, enhancing program integrity, and allowing for better comparisons between cost and quality of care provided by physicians and APRNs/PAs.”

At their October 2018 meeting, MedPAC commissioners discussed how to appropriately compensate APRNs and PAs, should incident-to billing be eliminated; they ultimately recommended maintaining the 85% rate.

The American Academy of Family Practitioners spoke out against the idea of eliminating incident-to billing.

However, lowering all APRN/PA payments to 85% of what physicians make would impact doctors in a negative way, according to AAFP President Michael Munger, MD.

Dr. Munger described primary care as a team sport, and “this is certainly going to be felt in terms of the overall mission of delivering quality care.”

Access to care also could be reduced along with the reduced payment level.

“You have to make business decisions at the end of the day,” he said in an interview. “You need to make sure that you can have adequate revenue to offset expenses, and if you are going to take a 15% cut in your revenue in, you have to look at where your expenses are, and obviously salary is your No. 1 expense. If you are not able to count on this revenue and you can’t afford to have NPs and PAs as part of the team, it is going to become an access issue for patients.”

The MedPAC commissioner saw it differently.

“Most of these clinicians are already paid at this lower rate, and yet the supply of these clinicians has increased dramatically over the last several years,” the report states, adding that the salary differential between these clinicians and physicians “is large enough that employing them likely would remain attractive even if all of their services were paid at 85% of physician fee schedule rates.”

MedPAC, as an advisory body to Congress, makes no disclosures.

gtwachtman@mdedge.com

AMSTERDAM – A new clinical prediction model can determine the risk of venous thromboembolism in patients with leukemia, according to investigators.

Will Pass/MDedge News

The scoring system, which incorporates historical, morphological, and cytologic factors, was internally validated at multiple time points over the course of a year, reported lead author, Alejandro Lazo-Langner, MD, of the University of Western Ontario, London.

“It is important that we can predict or anticipate which patients [with acute leukemia] will develop venous thrombosis so that we can develop preventions and aim for better surveillance strategies,” Dr. Lazo-Langner said at the annual congress of the European Hematology Association. Venous thromboembolism (VTE) risk modeling is available for patients with solid tumors, but a similar prognostic tool for leukemia patients has been missing.

To fill this practice gap, Dr. Lazo-Langner and colleagues conducted a retrospective cohort study involving 501 patients with acute leukemia who were diagnosed between 2006 and 2017. Of these patients, 427 (85.2%) had myeloid lineage and 74 (14.8%) had lymphoblastic disease. VTE outcomes of interest included proximal lower- and upper-extremity deep vein thrombosis; pulmonary embolism; and thrombosis of unusual sites, such as splanchnic and cerebral. Patients were followed until last follow-up, VTE, or death. Single variable and multiple variable logistic regression were used sequentially to evaluate and confirm potential predictive factors, with nonparametric bootstrapping for internal validation.

After last follow-up, 77 patients (15.3%) had developed VTE; specifically, 44 patients had upper-extremity deep vein thrombosis, 28 had lower-extremity deep vein thrombosis or pulmonary embolism, and 5 had cerebral vein thrombosis. The median time from leukemia diagnosis to VTE was approximately 2 months (64 days). Out of 20 possible predictive factors, 7 were included in the multivariable model, and 3 constitute the final model. These three factors are platelet count greater than 50 x 10⁹/L at time of diagnosis (1 point), lymphoblastic leukemia (2 points), and previous history of venous thromboembolism (3 points).

Dr. Lazo-Langner explained that leukemia patients at high risk of VTE are those with a score of 3 or more points. Using this risk threshold, the investigators found that the overall cumulative incidence of VTE in the high-risk group was 44.0%, compared with 10.5% in the low-risk group. Temporal analysis showed a widening disparity between the two groups, from 3 months (28.8% vs. 6.3%), to 6 months (41.1% vs. 7.9%), and 12 months (42.5% vs. 9.3%).

When asked if treatment type was evaluated, Dr. Lazo-Langner said that treatment type was evaluated but proved unfruitful for the model, which is designed for universal use in leukemia.

“We did include a number of different chemotherapy regimens,” he said. “The problem is, because we included both AML [acute myeloid leukemia] and ALL [acute lymphoblastic leukemia] lineage, and the cornerstone of treatment is different for both lineages. It’s difficult to actually include what kind of chemotherapy [patients had]. For instance, it is known that anthracyclines increase risk of thrombosis, but in both lineages, you use anthracyclines, so you really cannot use that as a predictor.”

Looking to the future, the next step will be validation in other cohorts. If this is successful, then Dr. Lazo-Langner speculated that clinicians could use the scoring system to direct monitoring and treatment. For example, patients with high scores and low platelet counts could receive earlier transfusional support, while all high-risk patients could be placed under more intensive surveillance and given additional education about thrombosis.

“I think recognizing symptoms early is important,” Dr. Lazo-Langner said, “and that would be training not only clinicians, but also nursing personnel and the patients themselves to be aware of the symptoms, so they can actually recognize them sooner.”

The study was funded by the Canadian Institutes of Health Research. Dr. Lazo-Langner is an investigator with the Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network.

SOURCE: Lazo-Langner A et al. EHA 2019, Abstract S1642.

AMSTERDAM – A new clinical prediction model can determine the risk of venous thromboembolism in patients with leukemia, according to investigators.

Will Pass/MDedge News

The scoring system, which incorporates historical, morphological, and cytologic factors, was internally validated at multiple time points over the course of a year, reported lead author, Alejandro Lazo-Langner, MD, of the University of Western Ontario, London.

“It is important that we can predict or anticipate which patients [with acute leukemia] will develop venous thrombosis so that we can develop preventions and aim for better surveillance strategies,” Dr. Lazo-Langner said at the annual congress of the European Hematology Association. Venous thromboembolism (VTE) risk modeling is available for patients with solid tumors, but a similar prognostic tool for leukemia patients has been missing.

To fill this practice gap, Dr. Lazo-Langner and colleagues conducted a retrospective cohort study involving 501 patients with acute leukemia who were diagnosed between 2006 and 2017. Of these patients, 427 (85.2%) had myeloid lineage and 74 (14.8%) had lymphoblastic disease. VTE outcomes of interest included proximal lower- and upper-extremity deep vein thrombosis; pulmonary embolism; and thrombosis of unusual sites, such as splanchnic and cerebral. Patients were followed until last follow-up, VTE, or death. Single variable and multiple variable logistic regression were used sequentially to evaluate and confirm potential predictive factors, with nonparametric bootstrapping for internal validation.

After last follow-up, 77 patients (15.3%) had developed VTE; specifically, 44 patients had upper-extremity deep vein thrombosis, 28 had lower-extremity deep vein thrombosis or pulmonary embolism, and 5 had cerebral vein thrombosis. The median time from leukemia diagnosis to VTE was approximately 2 months (64 days). Out of 20 possible predictive factors, 7 were included in the multivariable model, and 3 constitute the final model. These three factors are platelet count greater than 50 x 10⁹/L at time of diagnosis (1 point), lymphoblastic leukemia (2 points), and previous history of venous thromboembolism (3 points).

Dr. Lazo-Langner explained that leukemia patients at high risk of VTE are those with a score of 3 or more points. Using this risk threshold, the investigators found that the overall cumulative incidence of VTE in the high-risk group was 44.0%, compared with 10.5% in the low-risk group. Temporal analysis showed a widening disparity between the two groups, from 3 months (28.8% vs. 6.3%), to 6 months (41.1% vs. 7.9%), and 12 months (42.5% vs. 9.3%).

When asked if treatment type was evaluated, Dr. Lazo-Langner said that treatment type was evaluated but proved unfruitful for the model, which is designed for universal use in leukemia.

“We did include a number of different chemotherapy regimens,” he said. “The problem is, because we included both AML [acute myeloid leukemia] and ALL [acute lymphoblastic leukemia] lineage, and the cornerstone of treatment is different for both lineages. It’s difficult to actually include what kind of chemotherapy [patients had]. For instance, it is known that anthracyclines increase risk of thrombosis, but in both lineages, you use anthracyclines, so you really cannot use that as a predictor.”

Looking to the future, the next step will be validation in other cohorts. If this is successful, then Dr. Lazo-Langner speculated that clinicians could use the scoring system to direct monitoring and treatment. For example, patients with high scores and low platelet counts could receive earlier transfusional support, while all high-risk patients could be placed under more intensive surveillance and given additional education about thrombosis.

“I think recognizing symptoms early is important,” Dr. Lazo-Langner said, “and that would be training not only clinicians, but also nursing personnel and the patients themselves to be aware of the symptoms, so they can actually recognize them sooner.”

The study was funded by the Canadian Institutes of Health Research. Dr. Lazo-Langner is an investigator with the Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network.

SOURCE: Lazo-Langner A et al. EHA 2019, Abstract S1642.

AMSTERDAM – A new clinical prediction model can determine the risk of venous thromboembolism in patients with leukemia, according to investigators.

Will Pass/MDedge News

The scoring system, which incorporates historical, morphological, and cytologic factors, was internally validated at multiple time points over the course of a year, reported lead author, Alejandro Lazo-Langner, MD, of the University of Western Ontario, London.

“It is important that we can predict or anticipate which patients [with acute leukemia] will develop venous thrombosis so that we can develop preventions and aim for better surveillance strategies,” Dr. Lazo-Langner said at the annual congress of the European Hematology Association. Venous thromboembolism (VTE) risk modeling is available for patients with solid tumors, but a similar prognostic tool for leukemia patients has been missing.

To fill this practice gap, Dr. Lazo-Langner and colleagues conducted a retrospective cohort study involving 501 patients with acute leukemia who were diagnosed between 2006 and 2017. Of these patients, 427 (85.2%) had myeloid lineage and 74 (14.8%) had lymphoblastic disease. VTE outcomes of interest included proximal lower- and upper-extremity deep vein thrombosis; pulmonary embolism; and thrombosis of unusual sites, such as splanchnic and cerebral. Patients were followed until last follow-up, VTE, or death. Single variable and multiple variable logistic regression were used sequentially to evaluate and confirm potential predictive factors, with nonparametric bootstrapping for internal validation.

After last follow-up, 77 patients (15.3%) had developed VTE; specifically, 44 patients had upper-extremity deep vein thrombosis, 28 had lower-extremity deep vein thrombosis or pulmonary embolism, and 5 had cerebral vein thrombosis. The median time from leukemia diagnosis to VTE was approximately 2 months (64 days). Out of 20 possible predictive factors, 7 were included in the multivariable model, and 3 constitute the final model. These three factors are platelet count greater than 50 x 10⁹/L at time of diagnosis (1 point), lymphoblastic leukemia (2 points), and previous history of venous thromboembolism (3 points).

Dr. Lazo-Langner explained that leukemia patients at high risk of VTE are those with a score of 3 or more points. Using this risk threshold, the investigators found that the overall cumulative incidence of VTE in the high-risk group was 44.0%, compared with 10.5% in the low-risk group. Temporal analysis showed a widening disparity between the two groups, from 3 months (28.8% vs. 6.3%), to 6 months (41.1% vs. 7.9%), and 12 months (42.5% vs. 9.3%).

When asked if treatment type was evaluated, Dr. Lazo-Langner said that treatment type was evaluated but proved unfruitful for the model, which is designed for universal use in leukemia.

“We did include a number of different chemotherapy regimens,” he said. “The problem is, because we included both AML [acute myeloid leukemia] and ALL [acute lymphoblastic leukemia] lineage, and the cornerstone of treatment is different for both lineages. It’s difficult to actually include what kind of chemotherapy [patients had]. For instance, it is known that anthracyclines increase risk of thrombosis, but in both lineages, you use anthracyclines, so you really cannot use that as a predictor.”

Looking to the future, the next step will be validation in other cohorts. If this is successful, then Dr. Lazo-Langner speculated that clinicians could use the scoring system to direct monitoring and treatment. For example, patients with high scores and low platelet counts could receive earlier transfusional support, while all high-risk patients could be placed under more intensive surveillance and given additional education about thrombosis.

“I think recognizing symptoms early is important,” Dr. Lazo-Langner said, “and that would be training not only clinicians, but also nursing personnel and the patients themselves to be aware of the symptoms, so they can actually recognize them sooner.”

The study was funded by the Canadian Institutes of Health Research. Dr. Lazo-Langner is an investigator with the Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network.

SOURCE: Lazo-Langner A et al. EHA 2019, Abstract S1642.

SAN ANTONIO – Interventions aimed at educating parents about proper disposal methods for leftover prescription opioids and on explaining the risks of retaining opioids can increase the likelihood that parents will dispose of opioids when their children no longer need them, according to new research.

“Cost-effective disposal methods can nudge parents to dispose of their child’s leftover opioids promptly after use, but risk messaging is needed to best affect both early disposal and planned retention,” concluded Terri Voepel-Lewis, PhD, RN, of the University of Michigan, Ann Arbor, and colleagues.

“Such strategies can effectively reduce the presence of risky leftover medications in the home and decrease the risks posed to children and adolescents,” they wrote in a research poster at the annual meeting of College on Problems of Drug Dependence.

The researchers recruited 517 parents of children prescribed a short course of opioids, excluding children with chronic pain or the inability to report their pain.

The 255 parents randomly assigned to the nudge group received visual instructions on how to properly dispose of drugs while the 262 parents in the control group did not receive information on a disposal method. The groups were otherwise similar in terms of parent education, race/ethnicity, the child’s age and past opioid use, the parents’ past opioid use or misuse, whether opioids were kept in the home and whether the child’s procedure had been orthopedic/sports medicine–related.

Parents also were randomly assigned to routine care or to a Scenario-Tailored Opioid Messaging Program (STOMP). The STOMP group received tailored opioid risk information.

After a baseline survey on the child’s past pain, opioid use, misuse of opioids and risk perceptions, parents completed follow-up surveys at 7 and 14 days on opioid use, child pain, and behaviors related to retaining or disposing of opioids.

Just over a third of parents in the nudge group (34.7%) disposed of leftover opioids immediately after use, compared with 24% in the control group (odds ratio, 1.68; P = .01). Parents with the highest rate of disposal were those in the nudge group who participated in STOMP; they were more than twice as likely to dispose of opioids immediately after they were no longer needed (OR, 2.55; compared with control/non-STOMP).

A higher likelihood of disposal for parents in the nudge group alone, however, barely missed significance (OR, 1.77; P = .06) before adjustment. Parents’ intention to dispose of opioids was significantly different only among those who received STOMP education.

After the researchers controlled for child and parent factors, actual early disposal was significantly more likely in both the nudge and STOMP groups.

“Parental past opioid behaviors (kept an opioid in the home and past misuse) as well as orthopedic/sports medicine procedure were strongly associated with parents’ intention to retain [opioids],” the authors reported.

The study results revealed a divergence in parents’ intentions versus their behavior for one of the intervention groups.

“The nudge intervention improved parents’ prompt disposal of leftover prescription opioids but had no effect on planned retention rates,” the researchers reported. “In contrast, STOMP education had significant effects on early disposal behavior and planned retention. These findings suggest that clear and blunt messaging about the risks that opioids pose to household members is needed to reduce the presence of leftover opioids in the home.”

Additional findings regarding parents’ past behaviors suggested that those who have kept leftover opioids or previously misused them may see the risks of doing so as low, the authors noted.

“Importantly, parents’ past prescription opioid retention behavior doubled the risk for planned retention, and their past opioid misuse more than tripled the risk,” the researchers wrote. “Assessing parents’ past behaviors and enhancing their perceptions of the real risks posed to children are important targets for risk reduction.”

The National Institute on Drug Addiction funded the research. The authors reported having no conflicts of interest.

SAN ANTONIO – Interventions aimed at educating parents about proper disposal methods for leftover prescription opioids and on explaining the risks of retaining opioids can increase the likelihood that parents will dispose of opioids when their children no longer need them, according to new research.

“Cost-effective disposal methods can nudge parents to dispose of their child’s leftover opioids promptly after use, but risk messaging is needed to best affect both early disposal and planned retention,” concluded Terri Voepel-Lewis, PhD, RN, of the University of Michigan, Ann Arbor, and colleagues.

“Such strategies can effectively reduce the presence of risky leftover medications in the home and decrease the risks posed to children and adolescents,” they wrote in a research poster at the annual meeting of College on Problems of Drug Dependence.

The researchers recruited 517 parents of children prescribed a short course of opioids, excluding children with chronic pain or the inability to report their pain.

The 255 parents randomly assigned to the nudge group received visual instructions on how to properly dispose of drugs while the 262 parents in the control group did not receive information on a disposal method. The groups were otherwise similar in terms of parent education, race/ethnicity, the child’s age and past opioid use, the parents’ past opioid use or misuse, whether opioids were kept in the home and whether the child’s procedure had been orthopedic/sports medicine–related.

Parents also were randomly assigned to routine care or to a Scenario-Tailored Opioid Messaging Program (STOMP). The STOMP group received tailored opioid risk information.

After a baseline survey on the child’s past pain, opioid use, misuse of opioids and risk perceptions, parents completed follow-up surveys at 7 and 14 days on opioid use, child pain, and behaviors related to retaining or disposing of opioids.

Just over a third of parents in the nudge group (34.7%) disposed of leftover opioids immediately after use, compared with 24% in the control group (odds ratio, 1.68; P = .01). Parents with the highest rate of disposal were those in the nudge group who participated in STOMP; they were more than twice as likely to dispose of opioids immediately after they were no longer needed (OR, 2.55; compared with control/non-STOMP).

A higher likelihood of disposal for parents in the nudge group alone, however, barely missed significance (OR, 1.77; P = .06) before adjustment. Parents’ intention to dispose of opioids was significantly different only among those who received STOMP education.

After the researchers controlled for child and parent factors, actual early disposal was significantly more likely in both the nudge and STOMP groups.

“Parental past opioid behaviors (kept an opioid in the home and past misuse) as well as orthopedic/sports medicine procedure were strongly associated with parents’ intention to retain [opioids],” the authors reported.

The study results revealed a divergence in parents’ intentions versus their behavior for one of the intervention groups.

“The nudge intervention improved parents’ prompt disposal of leftover prescription opioids but had no effect on planned retention rates,” the researchers reported. “In contrast, STOMP education had significant effects on early disposal behavior and planned retention. These findings suggest that clear and blunt messaging about the risks that opioids pose to household members is needed to reduce the presence of leftover opioids in the home.”

Additional findings regarding parents’ past behaviors suggested that those who have kept leftover opioids or previously misused them may see the risks of doing so as low, the authors noted.

“Importantly, parents’ past prescription opioid retention behavior doubled the risk for planned retention, and their past opioid misuse more than tripled the risk,” the researchers wrote. “Assessing parents’ past behaviors and enhancing their perceptions of the real risks posed to children are important targets for risk reduction.”

The National Institute on Drug Addiction funded the research. The authors reported having no conflicts of interest.

SAN ANTONIO – Interventions aimed at educating parents about proper disposal methods for leftover prescription opioids and on explaining the risks of retaining opioids can increase the likelihood that parents will dispose of opioids when their children no longer need them, according to new research.

“Cost-effective disposal methods can nudge parents to dispose of their child’s leftover opioids promptly after use, but risk messaging is needed to best affect both early disposal and planned retention,” concluded Terri Voepel-Lewis, PhD, RN, of the University of Michigan, Ann Arbor, and colleagues.

“Such strategies can effectively reduce the presence of risky leftover medications in the home and decrease the risks posed to children and adolescents,” they wrote in a research poster at the annual meeting of College on Problems of Drug Dependence.

The researchers recruited 517 parents of children prescribed a short course of opioids, excluding children with chronic pain or the inability to report their pain.

The 255 parents randomly assigned to the nudge group received visual instructions on how to properly dispose of drugs while the 262 parents in the control group did not receive information on a disposal method. The groups were otherwise similar in terms of parent education, race/ethnicity, the child’s age and past opioid use, the parents’ past opioid use or misuse, whether opioids were kept in the home and whether the child’s procedure had been orthopedic/sports medicine–related.

Parents also were randomly assigned to routine care or to a Scenario-Tailored Opioid Messaging Program (STOMP). The STOMP group received tailored opioid risk information.

After a baseline survey on the child’s past pain, opioid use, misuse of opioids and risk perceptions, parents completed follow-up surveys at 7 and 14 days on opioid use, child pain, and behaviors related to retaining or disposing of opioids.

Just over a third of parents in the nudge group (34.7%) disposed of leftover opioids immediately after use, compared with 24% in the control group (odds ratio, 1.68; P = .01). Parents with the highest rate of disposal were those in the nudge group who participated in STOMP; they were more than twice as likely to dispose of opioids immediately after they were no longer needed (OR, 2.55; compared with control/non-STOMP).

A higher likelihood of disposal for parents in the nudge group alone, however, barely missed significance (OR, 1.77; P = .06) before adjustment. Parents’ intention to dispose of opioids was significantly different only among those who received STOMP education.

After the researchers controlled for child and parent factors, actual early disposal was significantly more likely in both the nudge and STOMP groups.

“Parental past opioid behaviors (kept an opioid in the home and past misuse) as well as orthopedic/sports medicine procedure were strongly associated with parents’ intention to retain [opioids],” the authors reported.

The study results revealed a divergence in parents’ intentions versus their behavior for one of the intervention groups.

“The nudge intervention improved parents’ prompt disposal of leftover prescription opioids but had no effect on planned retention rates,” the researchers reported. “In contrast, STOMP education had significant effects on early disposal behavior and planned retention. These findings suggest that clear and blunt messaging about the risks that opioids pose to household members is needed to reduce the presence of leftover opioids in the home.”

Additional findings regarding parents’ past behaviors suggested that those who have kept leftover opioids or previously misused them may see the risks of doing so as low, the authors noted.

“Importantly, parents’ past prescription opioid retention behavior doubled the risk for planned retention, and their past opioid misuse more than tripled the risk,” the researchers wrote. “Assessing parents’ past behaviors and enhancing their perceptions of the real risks posed to children are important targets for risk reduction.”

The National Institute on Drug Addiction funded the research. The authors reported having no conflicts of interest.

To the Editor:

Granuloma annulare (GA) is a common dermatosis that usually presents with dermal papules and annular plaques in a symmetric distribution.¹ The etiology is unknown, but a delayed-type hypersensitivity reaction is the favored pathogenesis. Several systemic associations have been reported with generalized GA including diabetes mellitus, hyperlipidemia, autoimmune thyroiditis, rheumatoid arthritis, and lymphoproliferative malignancies, as well as other malignancies and viral infections such as human immunodeficiency virus and hepatitis C. Localized GA often is self-limiting, but generalized disease can be chronic and progressive. Although asymptomatic in most cases, the lesions can be cosmetically bothersome, and many patients desire treatment. There are few well-controlled studies of treatment, and most are limited to case reports and series. A review of GA treatment noted only 3 randomized studies: 2 relating to photodynamic therapy and 1 to cryosurgery. Well-accepted therapies, such as topical and intralesional corticosteroids, antimalarials, immunosuppressants, antibiotics, and phototherapy, are substantiated by lesser-quality evidence.¹ Phototherapy has been studied for the treatment of GA and other disorders with altered dermal matrix deposition for which there are limited effective treatment options. UV irradiation promotes degradation of structural components of the dermis and inhibition of collagen production.² Granuloma annulare generally is resistant to therapy. We report a case of generalized GA of long duration that responded well to phototherapy with narrowband UVB (NB-UVB).

A 60-year-old woman presented with generalized GA of 4 years’ duration that was confirmed on biopsy on 2 occasions (Figure 1). The lesions were asymptomatic but disfiguring and consisted of extensive pink, thin, annular plaques and papules on the torso, arms, and legs (Figure 2A). Apart from mild depression for which she was being treated with paroxetine and trazodone, she was otherwise healthy without evidence of thyroid disease, hyperlipidemia, or diabetes mellitus. Prior treatments for GA had included tapering courses of prednisone (up to 30 mg/d, tapered by 5 mg every 4 days) and betamethasone dipropionate cream 0.05%. She was started on NB-UVB therapy 5 times weekly in incremental doses with no adjuvant therapy. After 100 treatments, there was notable improvement with lesions becoming paler and flatter, with some involuting completely (Figure 2B). The frequency of treatment was reduced to 3 times weekly with continued improvement. An NB-UVB device was used containing 48 TL 100W/01-FS72 lamps with a mean irradiance of 2.9 mW/cm². Her starting dose was 90 mJ/cm². The cumulative dose after 100 treatments was 35,600 mJ/cm². Apart from occasional mild erythema, there were no adverse effects.

To the Editor:

Granuloma annulare (GA) is a common dermatosis that usually presents with dermal papules and annular plaques in a symmetric distribution.¹ The etiology is unknown, but a delayed-type hypersensitivity reaction is the favored pathogenesis. Several systemic associations have been reported with generalized GA including diabetes mellitus, hyperlipidemia, autoimmune thyroiditis, rheumatoid arthritis, and lymphoproliferative malignancies, as well as other malignancies and viral infections such as human immunodeficiency virus and hepatitis C. Localized GA often is self-limiting, but generalized disease can be chronic and progressive. Although asymptomatic in most cases, the lesions can be cosmetically bothersome, and many patients desire treatment. There are few well-controlled studies of treatment, and most are limited to case reports and series. A review of GA treatment noted only 3 randomized studies: 2 relating to photodynamic therapy and 1 to cryosurgery. Well-accepted therapies, such as topical and intralesional corticosteroids, antimalarials, immunosuppressants, antibiotics, and phototherapy, are substantiated by lesser-quality evidence.¹ Phototherapy has been studied for the treatment of GA and other disorders with altered dermal matrix deposition for which there are limited effective treatment options. UV irradiation promotes degradation of structural components of the dermis and inhibition of collagen production.² Granuloma annulare generally is resistant to therapy. We report a case of generalized GA of long duration that responded well to phototherapy with narrowband UVB (NB-UVB).

A 60-year-old woman presented with generalized GA of 4 years’ duration that was confirmed on biopsy on 2 occasions (Figure 1). The lesions were asymptomatic but disfiguring and consisted of extensive pink, thin, annular plaques and papules on the torso, arms, and legs (Figure 2A). Apart from mild depression for which she was being treated with paroxetine and trazodone, she was otherwise healthy without evidence of thyroid disease, hyperlipidemia, or diabetes mellitus. Prior treatments for GA had included tapering courses of prednisone (up to 30 mg/d, tapered by 5 mg every 4 days) and betamethasone dipropionate cream 0.05%. She was started on NB-UVB therapy 5 times weekly in incremental doses with no adjuvant therapy. After 100 treatments, there was notable improvement with lesions becoming paler and flatter, with some involuting completely (Figure 2B). The frequency of treatment was reduced to 3 times weekly with continued improvement. An NB-UVB device was used containing 48 TL 100W/01-FS72 lamps with a mean irradiance of 2.9 mW/cm². Her starting dose was 90 mJ/cm². The cumulative dose after 100 treatments was 35,600 mJ/cm². Apart from occasional mild erythema, there were no adverse effects.

To the Editor:

Granuloma annulare (GA) is a common dermatosis that usually presents with dermal papules and annular plaques in a symmetric distribution.¹ The etiology is unknown, but a delayed-type hypersensitivity reaction is the favored pathogenesis. Several systemic associations have been reported with generalized GA including diabetes mellitus, hyperlipidemia, autoimmune thyroiditis, rheumatoid arthritis, and lymphoproliferative malignancies, as well as other malignancies and viral infections such as human immunodeficiency virus and hepatitis C. Localized GA often is self-limiting, but generalized disease can be chronic and progressive. Although asymptomatic in most cases, the lesions can be cosmetically bothersome, and many patients desire treatment. There are few well-controlled studies of treatment, and most are limited to case reports and series. A review of GA treatment noted only 3 randomized studies: 2 relating to photodynamic therapy and 1 to cryosurgery. Well-accepted therapies, such as topical and intralesional corticosteroids, antimalarials, immunosuppressants, antibiotics, and phototherapy, are substantiated by lesser-quality evidence.¹ Phototherapy has been studied for the treatment of GA and other disorders with altered dermal matrix deposition for which there are limited effective treatment options. UV irradiation promotes degradation of structural components of the dermis and inhibition of collagen production.² Granuloma annulare generally is resistant to therapy. We report a case of generalized GA of long duration that responded well to phototherapy with narrowband UVB (NB-UVB).

A 60-year-old woman presented with generalized GA of 4 years’ duration that was confirmed on biopsy on 2 occasions (Figure 1). The lesions were asymptomatic but disfiguring and consisted of extensive pink, thin, annular plaques and papules on the torso, arms, and legs (Figure 2A). Apart from mild depression for which she was being treated with paroxetine and trazodone, she was otherwise healthy without evidence of thyroid disease, hyperlipidemia, or diabetes mellitus. Prior treatments for GA had included tapering courses of prednisone (up to 30 mg/d, tapered by 5 mg every 4 days) and betamethasone dipropionate cream 0.05%. She was started on NB-UVB therapy 5 times weekly in incremental doses with no adjuvant therapy. After 100 treatments, there was notable improvement with lesions becoming paler and flatter, with some involuting completely (Figure 2B). The frequency of treatment was reduced to 3 times weekly with continued improvement. An NB-UVB device was used containing 48 TL 100W/01-FS72 lamps with a mean irradiance of 2.9 mW/cm². Her starting dose was 90 mJ/cm². The cumulative dose after 100 treatments was 35,600 mJ/cm². Apart from occasional mild erythema, there were no adverse effects.

LJUBLJANA, SLOVENIA – The dogma of the “Golden Hour” for the immediate management of pediatric sepsis has been oversold and actually is based upon weak evidence, Luregn J. Schlapbach, MD, asserted at the annual meeting of the European Society for Paediatric Infectious Diseases.

The true Golden Hour – that is, the time frame within which it’s imperative to administer the sepsis bundle comprised of appropriate antibiotics, fluids, and inotropes – is probably more like 3 hours.

Bruce Jancin/MDedge News

“The evidence suggests that up to 3 hours you don’t really have a big difference in outcomes for sepsis. If you recognize shock there’s no question: You should not even wait 1 hour. But if you’re not certain, it may be better to give up to 3 hours to work up the child and get the senior clinician involved before you make decisions about treatment. So I’m not advocating to delay anything, I’m advocating that if you’re not sure this is sepsis, allow yourself an hour or 2 to make a proper investigation,” said Dr. Schlapbach, a pediatric intensivist at the Child Health Research Center at the University of Queensland in South Brisbane, Australia.

The problem with a 1-hour mandate for delivery of the sepsis bundle, as recommended in guidelines by the Surviving Sepsis Campaign and the American College of Critical Care Medicine, and endorsed in quality improvement initiatives, is that the time pressure pushes physicians to overprescribe antibiotics to children who don’t actually have a serious bacterial infection. And that, he noted, contributes to the growing problem of antimicrobial resistance.

“You may have a child where you’re not too sure. Usually you would have done a urine culture because UTI [urinary tract infection] is quite a common cause of these infections, and many of these kids aren’t necessarily septic. But if people tell you that within 1 hour you need to treat, are you going to take the time to do the urine culture, or are you just going to decide to treat?” he asked rhetorically.

Dr. Schlapbach is a world-renowned pediatric sepsis researcher. He is far from alone in his reservations about the Golden Hour mandate.

“This is one of the reasons why IDSA [the Infectious Diseases Society of America] has not endorsed the Surviving Sepsis Campaign,” according to the physician, who noted that, in a position statement, IDSA officials have declared that discrimination of sepsis from noninfectious conditions remains a challenge, and that a 60-minute time to antibiotics may jeopardize patient reassessment (Clin Infect Dis. 2018 May 15;66[10]:1631-5).

Dr. Schlapbach highlighted other recent developments in pediatric sepsis.

The definition of adult sepsis has changed, and the pediatric version needs to as well

The revised definition of sepsis, known as Sepsis-3, issued by the International Sepsis Definition Task Force in 2016 notably dropped systemic inflammatory response syndrome (SIRS), as a requirement for sepsis (JAMA. 2016;315[8]:801-10). The revised definition characterizes sepsis as a dysregulated host response to infection resulting in life-threatening organ dysfunction. But Sepsis-3 is based entirely on adult data and is not considered applicable to children.

The current Pediatric Sepsis Consensus Conference definition dates back to 2005. A comprehensive revision is getting underway. It, too, is likely to drop SIRS into the wastebasket, Dr. Schlapbach said.

“It is probably time to abandon the old view of sepsis disease progression, which proposes a progression from infection to SIRS to severe sepsis with organ dysfunction to septic shock, because most children with infection do manifest signs of SIRS, such as tachycardia, tachypnea, and fever, and these probably should be considered as more of an adaptive rather than a maladaptive response,” he explained.

The goal of the pediatric sepsis redefinition project is to come up with something more useful for clinicians than the Sepsis-3 definition. While the Sepsis-3 concept of a dysregulated host response to infection sounds nice, he explained, “we don’t actually know what it is.

“One of the challenges that you all know as pediatricians is that children who develop sepsis get sick very, very quickly. We all have memories of children who we saw and may have discharged, and they were dead 12 hours later,” he noted.

Indeed, he and others have shown in multiple studies that up to 50% of pediatric deaths caused by sepsis happen within 24 hours of presentation.

“So whatever happens, it happens very quickly. The true question for us is actually how and why do children progress from no organ dysfunction, where the mortality is close to zero, to organ dysfunction, where all of a sudden mortality jumps up dramatically. It’s this progression that we don’t understand at all,” according to Dr. Schlapbach.

The genetic contribution to fulminant sepsis in children may be substantial

One-third of pediatric sepsis deaths in high-income countries happen in previously healthy children. In a proof-of-concept study, Dr. Schlapbach and coinvestigators in the Swiss Pediatric Sepsis Study Group conducted exome-sequencing genetic studies in eight previously healthy children with no family history of immunodeficiency who died of severe sepsis because of community-acquired Pseudomonas aeruginosa infection. Two of the eight had rare loss-of-function mutations in genes known to cause primary immunodeficiencies. The investigators proposed that unusually severe sepsis in previously healthy children warrants exome sequencing to look for underlying previously undetected primary immunodeficiencies. That’s important information for survivors and/or affected families to have, they argued (Front Immunol. 2016 Sep 20;7:357. eCollection 2016).

“There are some indications that the genetic contribution in children with sepsis may be larger than previously assumed,” he said.

The longstanding practice of fluid bolus therapy for resuscitation in pediatric sepsis is being reexamined

The FEAST (Fluid Expansion As Supportive Therapy) study, a randomized trial of more than 3,000 children with severe febrile illness and impaired perfusion in sub-Saharan Africa, turned heads with its finding that fluid boluses significantly increased 48-hour mortality (BMC Med. 2013 Mar 14;11:67).

Indeed, the FEAST findings, supported by mechanistic animal studies, were sufficiently compelling that the use of fluid boluses in both pediatric and adult septic shock is now under scrutiny in two major randomized trials: RIFTS (the Restrictive IV Fluid Trial in Severe Sepsis and Septic Shock), and CLOVERS (Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis). Stay tuned.

Dr. Schlapbach reported having no financial conflicts regarding his presentation.

bjancin@mdedge.com

LJUBLJANA, SLOVENIA – The dogma of the “Golden Hour” for the immediate management of pediatric sepsis has been oversold and actually is based upon weak evidence, Luregn J. Schlapbach, MD, asserted at the annual meeting of the European Society for Paediatric Infectious Diseases.

The true Golden Hour – that is, the time frame within which it’s imperative to administer the sepsis bundle comprised of appropriate antibiotics, fluids, and inotropes – is probably more like 3 hours.

Bruce Jancin/MDedge News

“The evidence suggests that up to 3 hours you don’t really have a big difference in outcomes for sepsis. If you recognize shock there’s no question: You should not even wait 1 hour. But if you’re not certain, it may be better to give up to 3 hours to work up the child and get the senior clinician involved before you make decisions about treatment. So I’m not advocating to delay anything, I’m advocating that if you’re not sure this is sepsis, allow yourself an hour or 2 to make a proper investigation,” said Dr. Schlapbach, a pediatric intensivist at the Child Health Research Center at the University of Queensland in South Brisbane, Australia.

The problem with a 1-hour mandate for delivery of the sepsis bundle, as recommended in guidelines by the Surviving Sepsis Campaign and the American College of Critical Care Medicine, and endorsed in quality improvement initiatives, is that the time pressure pushes physicians to overprescribe antibiotics to children who don’t actually have a serious bacterial infection. And that, he noted, contributes to the growing problem of antimicrobial resistance.

“You may have a child where you’re not too sure. Usually you would have done a urine culture because UTI [urinary tract infection] is quite a common cause of these infections, and many of these kids aren’t necessarily septic. But if people tell you that within 1 hour you need to treat, are you going to take the time to do the urine culture, or are you just going to decide to treat?” he asked rhetorically.

Dr. Schlapbach is a world-renowned pediatric sepsis researcher. He is far from alone in his reservations about the Golden Hour mandate.

“This is one of the reasons why IDSA [the Infectious Diseases Society of America] has not endorsed the Surviving Sepsis Campaign,” according to the physician, who noted that, in a position statement, IDSA officials have declared that discrimination of sepsis from noninfectious conditions remains a challenge, and that a 60-minute time to antibiotics may jeopardize patient reassessment (Clin Infect Dis. 2018 May 15;66[10]:1631-5).

Dr. Schlapbach highlighted other recent developments in pediatric sepsis.

The definition of adult sepsis has changed, and the pediatric version needs to as well

The revised definition of sepsis, known as Sepsis-3, issued by the International Sepsis Definition Task Force in 2016 notably dropped systemic inflammatory response syndrome (SIRS), as a requirement for sepsis (JAMA. 2016;315[8]:801-10). The revised definition characterizes sepsis as a dysregulated host response to infection resulting in life-threatening organ dysfunction. But Sepsis-3 is based entirely on adult data and is not considered applicable to children.

The current Pediatric Sepsis Consensus Conference definition dates back to 2005. A comprehensive revision is getting underway. It, too, is likely to drop SIRS into the wastebasket, Dr. Schlapbach said.

“It is probably time to abandon the old view of sepsis disease progression, which proposes a progression from infection to SIRS to severe sepsis with organ dysfunction to septic shock, because most children with infection do manifest signs of SIRS, such as tachycardia, tachypnea, and fever, and these probably should be considered as more of an adaptive rather than a maladaptive response,” he explained.

The goal of the pediatric sepsis redefinition project is to come up with something more useful for clinicians than the Sepsis-3 definition. While the Sepsis-3 concept of a dysregulated host response to infection sounds nice, he explained, “we don’t actually know what it is.

“One of the challenges that you all know as pediatricians is that children who develop sepsis get sick very, very quickly. We all have memories of children who we saw and may have discharged, and they were dead 12 hours later,” he noted.

Indeed, he and others have shown in multiple studies that up to 50% of pediatric deaths caused by sepsis happen within 24 hours of presentation.

“So whatever happens, it happens very quickly. The true question for us is actually how and why do children progress from no organ dysfunction, where the mortality is close to zero, to organ dysfunction, where all of a sudden mortality jumps up dramatically. It’s this progression that we don’t understand at all,” according to Dr. Schlapbach.

The genetic contribution to fulminant sepsis in children may be substantial

One-third of pediatric sepsis deaths in high-income countries happen in previously healthy children. In a proof-of-concept study, Dr. Schlapbach and coinvestigators in the Swiss Pediatric Sepsis Study Group conducted exome-sequencing genetic studies in eight previously healthy children with no family history of immunodeficiency who died of severe sepsis because of community-acquired Pseudomonas aeruginosa infection. Two of the eight had rare loss-of-function mutations in genes known to cause primary immunodeficiencies. The investigators proposed that unusually severe sepsis in previously healthy children warrants exome sequencing to look for underlying previously undetected primary immunodeficiencies. That’s important information for survivors and/or affected families to have, they argued (Front Immunol. 2016 Sep 20;7:357. eCollection 2016).

“There are some indications that the genetic contribution in children with sepsis may be larger than previously assumed,” he said.

The longstanding practice of fluid bolus therapy for resuscitation in pediatric sepsis is being reexamined

The FEAST (Fluid Expansion As Supportive Therapy) study, a randomized trial of more than 3,000 children with severe febrile illness and impaired perfusion in sub-Saharan Africa, turned heads with its finding that fluid boluses significantly increased 48-hour mortality (BMC Med. 2013 Mar 14;11:67).

Indeed, the FEAST findings, supported by mechanistic animal studies, were sufficiently compelling that the use of fluid boluses in both pediatric and adult septic shock is now under scrutiny in two major randomized trials: RIFTS (the Restrictive IV Fluid Trial in Severe Sepsis and Septic Shock), and CLOVERS (Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis). Stay tuned.

Dr. Schlapbach reported having no financial conflicts regarding his presentation.

bjancin@mdedge.com

LJUBLJANA, SLOVENIA – The dogma of the “Golden Hour” for the immediate management of pediatric sepsis has been oversold and actually is based upon weak evidence, Luregn J. Schlapbach, MD, asserted at the annual meeting of the European Society for Paediatric Infectious Diseases.

The true Golden Hour – that is, the time frame within which it’s imperative to administer the sepsis bundle comprised of appropriate antibiotics, fluids, and inotropes – is probably more like 3 hours.

Bruce Jancin/MDedge News

“The evidence suggests that up to 3 hours you don’t really have a big difference in outcomes for sepsis. If you recognize shock there’s no question: You should not even wait 1 hour. But if you’re not certain, it may be better to give up to 3 hours to work up the child and get the senior clinician involved before you make decisions about treatment. So I’m not advocating to delay anything, I’m advocating that if you’re not sure this is sepsis, allow yourself an hour or 2 to make a proper investigation,” said Dr. Schlapbach, a pediatric intensivist at the Child Health Research Center at the University of Queensland in South Brisbane, Australia.

The problem with a 1-hour mandate for delivery of the sepsis bundle, as recommended in guidelines by the Surviving Sepsis Campaign and the American College of Critical Care Medicine, and endorsed in quality improvement initiatives, is that the time pressure pushes physicians to overprescribe antibiotics to children who don’t actually have a serious bacterial infection. And that, he noted, contributes to the growing problem of antimicrobial resistance.

“You may have a child where you’re not too sure. Usually you would have done a urine culture because UTI [urinary tract infection] is quite a common cause of these infections, and many of these kids aren’t necessarily septic. But if people tell you that within 1 hour you need to treat, are you going to take the time to do the urine culture, or are you just going to decide to treat?” he asked rhetorically.

Dr. Schlapbach is a world-renowned pediatric sepsis researcher. He is far from alone in his reservations about the Golden Hour mandate.

“This is one of the reasons why IDSA [the Infectious Diseases Society of America] has not endorsed the Surviving Sepsis Campaign,” according to the physician, who noted that, in a position statement, IDSA officials have declared that discrimination of sepsis from noninfectious conditions remains a challenge, and that a 60-minute time to antibiotics may jeopardize patient reassessment (Clin Infect Dis. 2018 May 15;66[10]:1631-5).

Dr. Schlapbach highlighted other recent developments in pediatric sepsis.

The definition of adult sepsis has changed, and the pediatric version needs to as well

The revised definition of sepsis, known as Sepsis-3, issued by the International Sepsis Definition Task Force in 2016 notably dropped systemic inflammatory response syndrome (SIRS), as a requirement for sepsis (JAMA. 2016;315[8]:801-10). The revised definition characterizes sepsis as a dysregulated host response to infection resulting in life-threatening organ dysfunction. But Sepsis-3 is based entirely on adult data and is not considered applicable to children.

The current Pediatric Sepsis Consensus Conference definition dates back to 2005. A comprehensive revision is getting underway. It, too, is likely to drop SIRS into the wastebasket, Dr. Schlapbach said.

“It is probably time to abandon the old view of sepsis disease progression, which proposes a progression from infection to SIRS to severe sepsis with organ dysfunction to septic shock, because most children with infection do manifest signs of SIRS, such as tachycardia, tachypnea, and fever, and these probably should be considered as more of an adaptive rather than a maladaptive response,” he explained.

The goal of the pediatric sepsis redefinition project is to come up with something more useful for clinicians than the Sepsis-3 definition. While the Sepsis-3 concept of a dysregulated host response to infection sounds nice, he explained, “we don’t actually know what it is.

“One of the challenges that you all know as pediatricians is that children who develop sepsis get sick very, very quickly. We all have memories of children who we saw and may have discharged, and they were dead 12 hours later,” he noted.

Indeed, he and others have shown in multiple studies that up to 50% of pediatric deaths caused by sepsis happen within 24 hours of presentation.

“So whatever happens, it happens very quickly. The true question for us is actually how and why do children progress from no organ dysfunction, where the mortality is close to zero, to organ dysfunction, where all of a sudden mortality jumps up dramatically. It’s this progression that we don’t understand at all,” according to Dr. Schlapbach.

The genetic contribution to fulminant sepsis in children may be substantial

One-third of pediatric sepsis deaths in high-income countries happen in previously healthy children. In a proof-of-concept study, Dr. Schlapbach and coinvestigators in the Swiss Pediatric Sepsis Study Group conducted exome-sequencing genetic studies in eight previously healthy children with no family history of immunodeficiency who died of severe sepsis because of community-acquired Pseudomonas aeruginosa infection. Two of the eight had rare loss-of-function mutations in genes known to cause primary immunodeficiencies. The investigators proposed that unusually severe sepsis in previously healthy children warrants exome sequencing to look for underlying previously undetected primary immunodeficiencies. That’s important information for survivors and/or affected families to have, they argued (Front Immunol. 2016 Sep 20;7:357. eCollection 2016).

“There are some indications that the genetic contribution in children with sepsis may be larger than previously assumed,” he said.

The longstanding practice of fluid bolus therapy for resuscitation in pediatric sepsis is being reexamined

The FEAST (Fluid Expansion As Supportive Therapy) study, a randomized trial of more than 3,000 children with severe febrile illness and impaired perfusion in sub-Saharan Africa, turned heads with its finding that fluid boluses significantly increased 48-hour mortality (BMC Med. 2013 Mar 14;11:67).

Indeed, the FEAST findings, supported by mechanistic animal studies, were sufficiently compelling that the use of fluid boluses in both pediatric and adult septic shock is now under scrutiny in two major randomized trials: RIFTS (the Restrictive IV Fluid Trial in Severe Sepsis and Septic Shock), and CLOVERS (Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis). Stay tuned.

Dr. Schlapbach reported having no financial conflicts regarding his presentation.

bjancin@mdedge.com

MILAN – Among the dermatologic adverse effects of immune checkpoint inhibitor therapy, bullous disorders are relatively infrequent but associated with a high likelihood of treatment interruption, according to results of a single-center study described at the World Congress of Dermatology.

Bullous disorders were seen in about 1% of patients receiving anti-PD-1 or anti-PD-L1 therapy in the single-center retrospective review, and nearly all required systemic steroids and were associated with interruptions and discontinuations of the anti-cancer treatment, reported Jonathan Leventhal, MD, director of the oncodermatology clinic at Yale University, New Haven, Conn.

“This series highlights a very important, clinically relevant, cutaneous immune-related adverse event,” Dr. Leventhal said in an oral presentation at the congress. “These disorders manifested in most patients as bullous pemphigoid, occurred several months after starting therapy, and at a frequency rate of 1%” among all patients treated with these agents, “at least in our institution.”

The retrospective review presented by Dr. Leventhal was based on medical records of patients evaluated at Yale New Haven Hospital between 2016 and 2018. This included a total of 853 patients who received anti-PD-1/PD-L1 therapy, of whom 98 (11.5%) were evaluated at the oncodermatology clinic or inpatient consultative service.

Nine patients – five men, four women – developed bullous disorders, representing about 1% of patients treated with PD-1/PD-L1 blocking therapy, according to Dr. Leventhal. The mean age of the patients was 67.4 years. Seven of the nine patients had received PD-1 inhibitors, while two received PD-L1 inhibitors, for tumors of the lung in four cases, melanoma in two, genitourinary tumors in two, and acute myeloid leukemia in one.

“The time from rash onset to first administration of the drug was over 6 months, which is quite long compared to a lot of the other (checkpoint inhibitor–associated) toxicities that we see more commonly, which often occur in several weeks to just a few months,” Dr. Leventhal said.

Of the 853 patients in this retrospective study, 463 (54.3%) were treated with nivolumab (Opdivo) and 242 (28.4%) were treated with pembrolizumab (Keytruda), both PD-1 blockers. Of the remainder, 112 (13.1%) received the PD-L1 blockers atezolizumab (Tecentriq), 29 (3.4%) received durvalumab (Imfinzi), and 7 (0.8%) received avelumab (Bavencio), Dr. Leventhal reported.

All these patients presented with both pruritus and vesiculobullous eruptions seen mainly on the trunk and extremities, while two patients had oral ulcerations. Other presentations included urticarial-predominant bullous pemphigoid, dyshidrosiform pemphigoid, and lichenoid papules and vesicles. The diagnosis was bullous pemphigoid in seven of nine cases, Dr. Leventhal said.

The best management approach for immune-related bullous disorders would be use of high-potency topical steroids to avoid systemic steroids and avoid interruptions in checkpoint inhibitor therapy, he pointed out. However, eight of the nine patients in this retrospective series required systemic steroids due to progression of the bullae, he added.

Several notable cases were described, including one patient refractory to prednisone and omalizumab who eventually achieved control with methotrexate, a second patient who was well controlled with omalizumab monotherapy and able to resume treatment with an anti PD-1 inhibitor, and another patient who responded to prednisone and dapsone maintenance therapy.

The immunotherapy treatment for cancer was interrupted in four of nine patients due to the bullous disorders, and was permanently discontinued in another four, Dr. Leventhal said.

It’s not clear why patients receiving cancer immunotherapy treatment develop bullous pemphigoid. However, the 180-kd bullous pemphigoid antigen (BP180) is expressed in melanoma and non-small cell lung cancer, which may lead to production of antibodies against tumor cell antigens that also impact the skin, according to Dr. Leventhal.

Further studies are needed to evaluate whether immune-related bullous disorders have any prognostic significance in cancer patients, he added.

Dr. Leventhal reported that he had no relevant disclosures.

MILAN – Among the dermatologic adverse effects of immune checkpoint inhibitor therapy, bullous disorders are relatively infrequent but associated with a high likelihood of treatment interruption, according to results of a single-center study described at the World Congress of Dermatology.

Bullous disorders were seen in about 1% of patients receiving anti-PD-1 or anti-PD-L1 therapy in the single-center retrospective review, and nearly all required systemic steroids and were associated with interruptions and discontinuations of the anti-cancer treatment, reported Jonathan Leventhal, MD, director of the oncodermatology clinic at Yale University, New Haven, Conn.

“This series highlights a very important, clinically relevant, cutaneous immune-related adverse event,” Dr. Leventhal said in an oral presentation at the congress. “These disorders manifested in most patients as bullous pemphigoid, occurred several months after starting therapy, and at a frequency rate of 1%” among all patients treated with these agents, “at least in our institution.”

The retrospective review presented by Dr. Leventhal was based on medical records of patients evaluated at Yale New Haven Hospital between 2016 and 2018. This included a total of 853 patients who received anti-PD-1/PD-L1 therapy, of whom 98 (11.5%) were evaluated at the oncodermatology clinic or inpatient consultative service.

Nine patients – five men, four women – developed bullous disorders, representing about 1% of patients treated with PD-1/PD-L1 blocking therapy, according to Dr. Leventhal. The mean age of the patients was 67.4 years. Seven of the nine patients had received PD-1 inhibitors, while two received PD-L1 inhibitors, for tumors of the lung in four cases, melanoma in two, genitourinary tumors in two, and acute myeloid leukemia in one.

“The time from rash onset to first administration of the drug was over 6 months, which is quite long compared to a lot of the other (checkpoint inhibitor–associated) toxicities that we see more commonly, which often occur in several weeks to just a few months,” Dr. Leventhal said.

Of the 853 patients in this retrospective study, 463 (54.3%) were treated with nivolumab (Opdivo) and 242 (28.4%) were treated with pembrolizumab (Keytruda), both PD-1 blockers. Of the remainder, 112 (13.1%) received the PD-L1 blockers atezolizumab (Tecentriq), 29 (3.4%) received durvalumab (Imfinzi), and 7 (0.8%) received avelumab (Bavencio), Dr. Leventhal reported.

All these patients presented with both pruritus and vesiculobullous eruptions seen mainly on the trunk and extremities, while two patients had oral ulcerations. Other presentations included urticarial-predominant bullous pemphigoid, dyshidrosiform pemphigoid, and lichenoid papules and vesicles. The diagnosis was bullous pemphigoid in seven of nine cases, Dr. Leventhal said.

The best management approach for immune-related bullous disorders would be use of high-potency topical steroids to avoid systemic steroids and avoid interruptions in checkpoint inhibitor therapy, he pointed out. However, eight of the nine patients in this retrospective series required systemic steroids due to progression of the bullae, he added.

Several notable cases were described, including one patient refractory to prednisone and omalizumab who eventually achieved control with methotrexate, a second patient who was well controlled with omalizumab monotherapy and able to resume treatment with an anti PD-1 inhibitor, and another patient who responded to prednisone and dapsone maintenance therapy.

The immunotherapy treatment for cancer was interrupted in four of nine patients due to the bullous disorders, and was permanently discontinued in another four, Dr. Leventhal said.

It’s not clear why patients receiving cancer immunotherapy treatment develop bullous pemphigoid. However, the 180-kd bullous pemphigoid antigen (BP180) is expressed in melanoma and non-small cell lung cancer, which may lead to production of antibodies against tumor cell antigens that also impact the skin, according to Dr. Leventhal.

Further studies are needed to evaluate whether immune-related bullous disorders have any prognostic significance in cancer patients, he added.

Dr. Leventhal reported that he had no relevant disclosures.

MILAN – Among the dermatologic adverse effects of immune checkpoint inhibitor therapy, bullous disorders are relatively infrequent but associated with a high likelihood of treatment interruption, according to results of a single-center study described at the World Congress of Dermatology.

Bullous disorders were seen in about 1% of patients receiving anti-PD-1 or anti-PD-L1 therapy in the single-center retrospective review, and nearly all required systemic steroids and were associated with interruptions and discontinuations of the anti-cancer treatment, reported Jonathan Leventhal, MD, director of the oncodermatology clinic at Yale University, New Haven, Conn.

“This series highlights a very important, clinically relevant, cutaneous immune-related adverse event,” Dr. Leventhal said in an oral presentation at the congress. “These disorders manifested in most patients as bullous pemphigoid, occurred several months after starting therapy, and at a frequency rate of 1%” among all patients treated with these agents, “at least in our institution.”

The retrospective review presented by Dr. Leventhal was based on medical records of patients evaluated at Yale New Haven Hospital between 2016 and 2018. This included a total of 853 patients who received anti-PD-1/PD-L1 therapy, of whom 98 (11.5%) were evaluated at the oncodermatology clinic or inpatient consultative service.

Nine patients – five men, four women – developed bullous disorders, representing about 1% of patients treated with PD-1/PD-L1 blocking therapy, according to Dr. Leventhal. The mean age of the patients was 67.4 years. Seven of the nine patients had received PD-1 inhibitors, while two received PD-L1 inhibitors, for tumors of the lung in four cases, melanoma in two, genitourinary tumors in two, and acute myeloid leukemia in one.

“The time from rash onset to first administration of the drug was over 6 months, which is quite long compared to a lot of the other (checkpoint inhibitor–associated) toxicities that we see more commonly, which often occur in several weeks to just a few months,” Dr. Leventhal said.

Of the 853 patients in this retrospective study, 463 (54.3%) were treated with nivolumab (Opdivo) and 242 (28.4%) were treated with pembrolizumab (Keytruda), both PD-1 blockers. Of the remainder, 112 (13.1%) received the PD-L1 blockers atezolizumab (Tecentriq), 29 (3.4%) received durvalumab (Imfinzi), and 7 (0.8%) received avelumab (Bavencio), Dr. Leventhal reported.

All these patients presented with both pruritus and vesiculobullous eruptions seen mainly on the trunk and extremities, while two patients had oral ulcerations. Other presentations included urticarial-predominant bullous pemphigoid, dyshidrosiform pemphigoid, and lichenoid papules and vesicles. The diagnosis was bullous pemphigoid in seven of nine cases, Dr. Leventhal said.

The best management approach for immune-related bullous disorders would be use of high-potency topical steroids to avoid systemic steroids and avoid interruptions in checkpoint inhibitor therapy, he pointed out. However, eight of the nine patients in this retrospective series required systemic steroids due to progression of the bullae, he added.

Several notable cases were described, including one patient refractory to prednisone and omalizumab who eventually achieved control with methotrexate, a second patient who was well controlled with omalizumab monotherapy and able to resume treatment with an anti PD-1 inhibitor, and another patient who responded to prednisone and dapsone maintenance therapy.

The immunotherapy treatment for cancer was interrupted in four of nine patients due to the bullous disorders, and was permanently discontinued in another four, Dr. Leventhal said.

It’s not clear why patients receiving cancer immunotherapy treatment develop bullous pemphigoid. However, the 180-kd bullous pemphigoid antigen (BP180) is expressed in melanoma and non-small cell lung cancer, which may lead to production of antibodies against tumor cell antigens that also impact the skin, according to Dr. Leventhal.

Further studies are needed to evaluate whether immune-related bullous disorders have any prognostic significance in cancer patients, he added.

Dr. Leventhal reported that he had no relevant disclosures.

MADRID – Tocilizumab (Actemra) preserved lung function in patients with early systemic sclerosis (SSc), according to a secondary endpoint analysis of the phase 3, double-blind, randomized, controlled focuSSced trial.

Vidyard Video

After 48 weeks, a significantly lower proportion of patients treated with tocilizumab than placebo experienced any decline in lung function from baseline (50.5% versus 70.3% (P = .015), as defined by the percentage increase in predicted forced vital capacity (%pFVC). When only patients with interstitial lung disease (ILD) were considered, the respective percentages were 51.7% and 75.5% (P = .003).

In SSc-ILD patients, a clinically meaningful decline of 10% or more of the %pFVC in lung function was seen in 24.5% given placebo but in just 8.6% of those treated with tocilizumab.

“ILD is a major complication of scleroderma; it has high morbidity and mortality ... and it’s largely irreversible,” Dinesh Khanna, MD, said at the European Congress of Rheumatology.

“In this day and age, when we treat ILD, we wait for a patient to develop clinical ILD,” added Dr. Khanna, director of the scleroderma program at the University of Michigan, Ann Arbor. Clinical ILD can be defined by symptoms, abnormal pulmonary function tests, and marked abnormalities on high resolution computed tomography (HRCT) scans. He indicated that if improving ILD was not possible, then the next best thing would be to stabilize the disease and ensure there was no worsening in lung function.

As yet, there are no disease-modifying treatments available to treat SSc but there are “ample data that interleukin-6 plays a very important role in the pathogenesis of scleroderma,” Dr. Khanna observed. Tocilizumab is a humanized monoclonal antibody against the interleukin-6 receptor.

Data from the phase 2 faSScinate trial showed initial promise for the drug in SSc where a numerical, but not statistically significant, improvement in skin thickening was seen, and the results had hinted at a possible benefit on lung function (Lancet. 2016 Jun 25;387:2630-40).

However, in the phase 3 focuSSced trial, there was no statistically significant difference in the change from baseline to week 48 modified Rodnan skin score (mRSS) between tocilizumab and placebo, which was the primary endpoint. The least square mean change in mRSS was –6.14 for tocilizumab and –4.41 for placebo (P = .0983).

A total of 205 patients with SSc were studied and randomized, 1:1 in a double-blind fashion, to receive either a once-weekly, subcutaneous dose of 162 mg tocilizumab or a weekly subcutaneous placebo injection for 48 weeks.

For inclusion in the study, patients had to have SSc that met American College of Rheumatology and European League Against Rheumatism (EULAR) criteria and be diagnosed less than 60 months previously. Patients had to have an mRSS of 10-35 units and active disease with one or more of the following: C-reactive protein of 6 mg/L or higher; erythrocyte sedimentation rate of 28 mm/h or higher; and platelet count of330 x 10⁹ L.


“What was astonishing in the trial was that every patient had HRCT at baseline and at the end of the study,” Dr. Khanna reported. These scans showed that 64% of patients had evidence of ILD at baseline and that those treated with tocilizumab had less evidence of fibrosis at week 48 versus placebo, indicating a stabilization rather than worsening of disease.

A time to treatment failure analysis also favored tocilizumab over placebo, but there were no significant changes in patient-reported outcomes.

Dr. Khanna’s slides stated that “given that the primary endpoint for mRSS was not met, all other P values are presented for information purposes only and cannot be considered statistically significant despite the strength of the evidence.” During the Q&A after his presentation, he noted that it was unlikely that the study’s sponsors (Roche/Genentech) will now pursue a license for tocilizumab in SSc.

Nevertheless, Dr. Khanna concluded, “we have the opportunity, based on these data, to treat these patients early on, where you can preserve the lung function, which is a paradigm shift versus waiting for the lung function to decline, become clinically meaningful, significant, and then treat this patient population.”

Roche/Genentech sponsored the study. Dr. Khanna acts as a consultant to Roche/Genentech and eight other pharmaceutical companies. He owns stock in Eicos Sciences.

SOURCE: Khanna D et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):202-3. Abstract OP0245, doi: 10.1136/annrheumdis-2019-eular.2120

MADRID – Tocilizumab (Actemra) preserved lung function in patients with early systemic sclerosis (SSc), according to a secondary endpoint analysis of the phase 3, double-blind, randomized, controlled focuSSced trial.

Vidyard Video

After 48 weeks, a significantly lower proportion of patients treated with tocilizumab than placebo experienced any decline in lung function from baseline (50.5% versus 70.3% (P = .015), as defined by the percentage increase in predicted forced vital capacity (%pFVC). When only patients with interstitial lung disease (ILD) were considered, the respective percentages were 51.7% and 75.5% (P = .003).

In SSc-ILD patients, a clinically meaningful decline of 10% or more of the %pFVC in lung function was seen in 24.5% given placebo but in just 8.6% of those treated with tocilizumab.

“ILD is a major complication of scleroderma; it has high morbidity and mortality ... and it’s largely irreversible,” Dinesh Khanna, MD, said at the European Congress of Rheumatology.

“In this day and age, when we treat ILD, we wait for a patient to develop clinical ILD,” added Dr. Khanna, director of the scleroderma program at the University of Michigan, Ann Arbor. Clinical ILD can be defined by symptoms, abnormal pulmonary function tests, and marked abnormalities on high resolution computed tomography (HRCT) scans. He indicated that if improving ILD was not possible, then the next best thing would be to stabilize the disease and ensure there was no worsening in lung function.

As yet, there are no disease-modifying treatments available to treat SSc but there are “ample data that interleukin-6 plays a very important role in the pathogenesis of scleroderma,” Dr. Khanna observed. Tocilizumab is a humanized monoclonal antibody against the interleukin-6 receptor.

Data from the phase 2 faSScinate trial showed initial promise for the drug in SSc where a numerical, but not statistically significant, improvement in skin thickening was seen, and the results had hinted at a possible benefit on lung function (Lancet. 2016 Jun 25;387:2630-40).

However, in the phase 3 focuSSced trial, there was no statistically significant difference in the change from baseline to week 48 modified Rodnan skin score (mRSS) between tocilizumab and placebo, which was the primary endpoint. The least square mean change in mRSS was –6.14 for tocilizumab and –4.41 for placebo (P = .0983).

A total of 205 patients with SSc were studied and randomized, 1:1 in a double-blind fashion, to receive either a once-weekly, subcutaneous dose of 162 mg tocilizumab or a weekly subcutaneous placebo injection for 48 weeks.

For inclusion in the study, patients had to have SSc that met American College of Rheumatology and European League Against Rheumatism (EULAR) criteria and be diagnosed less than 60 months previously. Patients had to have an mRSS of 10-35 units and active disease with one or more of the following: C-reactive protein of 6 mg/L or higher; erythrocyte sedimentation rate of 28 mm/h or higher; and platelet count of330 x 10⁹ L.


“What was astonishing in the trial was that every patient had HRCT at baseline and at the end of the study,” Dr. Khanna reported. These scans showed that 64% of patients had evidence of ILD at baseline and that those treated with tocilizumab had less evidence of fibrosis at week 48 versus placebo, indicating a stabilization rather than worsening of disease.

A time to treatment failure analysis also favored tocilizumab over placebo, but there were no significant changes in patient-reported outcomes.

Dr. Khanna’s slides stated that “given that the primary endpoint for mRSS was not met, all other P values are presented for information purposes only and cannot be considered statistically significant despite the strength of the evidence.” During the Q&A after his presentation, he noted that it was unlikely that the study’s sponsors (Roche/Genentech) will now pursue a license for tocilizumab in SSc.

Nevertheless, Dr. Khanna concluded, “we have the opportunity, based on these data, to treat these patients early on, where you can preserve the lung function, which is a paradigm shift versus waiting for the lung function to decline, become clinically meaningful, significant, and then treat this patient population.”

Roche/Genentech sponsored the study. Dr. Khanna acts as a consultant to Roche/Genentech and eight other pharmaceutical companies. He owns stock in Eicos Sciences.

SOURCE: Khanna D et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):202-3. Abstract OP0245, doi: 10.1136/annrheumdis-2019-eular.2120

MADRID – Tocilizumab (Actemra) preserved lung function in patients with early systemic sclerosis (SSc), according to a secondary endpoint analysis of the phase 3, double-blind, randomized, controlled focuSSced trial.

Vidyard Video

After 48 weeks, a significantly lower proportion of patients treated with tocilizumab than placebo experienced any decline in lung function from baseline (50.5% versus 70.3% (P = .015), as defined by the percentage increase in predicted forced vital capacity (%pFVC). When only patients with interstitial lung disease (ILD) were considered, the respective percentages were 51.7% and 75.5% (P = .003).

In SSc-ILD patients, a clinically meaningful decline of 10% or more of the %pFVC in lung function was seen in 24.5% given placebo but in just 8.6% of those treated with tocilizumab.

“ILD is a major complication of scleroderma; it has high morbidity and mortality ... and it’s largely irreversible,” Dinesh Khanna, MD, said at the European Congress of Rheumatology.

“In this day and age, when we treat ILD, we wait for a patient to develop clinical ILD,” added Dr. Khanna, director of the scleroderma program at the University of Michigan, Ann Arbor. Clinical ILD can be defined by symptoms, abnormal pulmonary function tests, and marked abnormalities on high resolution computed tomography (HRCT) scans. He indicated that if improving ILD was not possible, then the next best thing would be to stabilize the disease and ensure there was no worsening in lung function.

As yet, there are no disease-modifying treatments available to treat SSc but there are “ample data that interleukin-6 plays a very important role in the pathogenesis of scleroderma,” Dr. Khanna observed. Tocilizumab is a humanized monoclonal antibody against the interleukin-6 receptor.

Data from the phase 2 faSScinate trial showed initial promise for the drug in SSc where a numerical, but not statistically significant, improvement in skin thickening was seen, and the results had hinted at a possible benefit on lung function (Lancet. 2016 Jun 25;387:2630-40).

However, in the phase 3 focuSSced trial, there was no statistically significant difference in the change from baseline to week 48 modified Rodnan skin score (mRSS) between tocilizumab and placebo, which was the primary endpoint. The least square mean change in mRSS was –6.14 for tocilizumab and –4.41 for placebo (P = .0983).

A total of 205 patients with SSc were studied and randomized, 1:1 in a double-blind fashion, to receive either a once-weekly, subcutaneous dose of 162 mg tocilizumab or a weekly subcutaneous placebo injection for 48 weeks.

For inclusion in the study, patients had to have SSc that met American College of Rheumatology and European League Against Rheumatism (EULAR) criteria and be diagnosed less than 60 months previously. Patients had to have an mRSS of 10-35 units and active disease with one or more of the following: C-reactive protein of 6 mg/L or higher; erythrocyte sedimentation rate of 28 mm/h or higher; and platelet count of330 x 10⁹ L.


“What was astonishing in the trial was that every patient had HRCT at baseline and at the end of the study,” Dr. Khanna reported. These scans showed that 64% of patients had evidence of ILD at baseline and that those treated with tocilizumab had less evidence of fibrosis at week 48 versus placebo, indicating a stabilization rather than worsening of disease.

A time to treatment failure analysis also favored tocilizumab over placebo, but there were no significant changes in patient-reported outcomes.

Dr. Khanna’s slides stated that “given that the primary endpoint for mRSS was not met, all other P values are presented for information purposes only and cannot be considered statistically significant despite the strength of the evidence.” During the Q&A after his presentation, he noted that it was unlikely that the study’s sponsors (Roche/Genentech) will now pursue a license for tocilizumab in SSc.

Nevertheless, Dr. Khanna concluded, “we have the opportunity, based on these data, to treat these patients early on, where you can preserve the lung function, which is a paradigm shift versus waiting for the lung function to decline, become clinically meaningful, significant, and then treat this patient population.”

Roche/Genentech sponsored the study. Dr. Khanna acts as a consultant to Roche/Genentech and eight other pharmaceutical companies. He owns stock in Eicos Sciences.

SOURCE: Khanna D et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):202-3. Abstract OP0245, doi: 10.1136/annrheumdis-2019-eular.2120

Clinical question: Do repeated quick Sepsis-Related Organ Failure Assessment (qSOFA) measurements improve predictive validity for sepsis using in-hospital mortality, compared with a single qSOFA measurement at the time a clinician first suspects infection?

Background: Sepsis in hospitalized patients is associated with poor outcomes, but it is not clear how to best identify patients at risk. For non-ICU patients, the qSOFA score (made up of three simple clinical variables: respiratory rate greater than or equal to 22 breaths/minute, systolic blood pressure less than or equal to 100 mm Hg, and Glasgow Coma Scale score less than 15) has predictive validity for important outcomes including in-hospital mortality. qSOFA is relatively new in clinical practice, and the optimal utilization of the score has not yet been defined.

Study design: Retrospective Cohort Study.

Setting: All adult medical and surgical encounters in the ED, hospital ward, postanesthesia care unit (PACU), and ICU at 12 hospitals in Pennsylvania in 2012.

Synopsis: Kievlan et al. studied whether repeated qSOFA scores improved prediction of in-hospital mortality and allowed identification of specific clinical trajectories. The study included approximately 37,600 encounters. Authors abstracted demographic data, vital signs, laboratory results, and antibiotic/culture orders. An infection cohort was identified by a combination of orders for body fluid culture and antibiotics. The qSOFA scores were gathered at 6-hour intervals from the culture/antibiotic event (suspected sepsis). Scores were low (0), moderate (1), or high (greater than or equal to 2). Mean initial qSOFA scores were greater for patients who died, and remained higher during the 48-hours after suspected infection. Mortality was less than 2% in patients with an initial low qSOFA. 25% of patients with an initial moderate qSOFA had subsequent higher qSOFAs, and they had higher mortality, compared with patients with subsequent low qSOFA scores (16% vs. 4%).

Only those patients with initial qSOFA scores at the time of suspected infection were included, and missing data was common. The results may not be applicable to hospitals with a different sepsis case mix from the those of study institutions.

Bottom line: Repeated qSOFA measurements improve predictive validity for in-hospital mortality for patients with sepsis. Patients with low initial qSOFA scores have a low chance (less than 2%) of in-hospital mortality. Further studies are needed to determine how repeat qSOFA measurements can be used to improve management of patients with sepsis.

Citation: Kievlan DR et al. Evaluation of repeated quick sepsis-related organ failure assessment measurements among patients with suspected infection. Crit Care Med. 2018. doi: 10.1097/CCM.0000000000003360.
 

Dr. Linker is an assistant professor of medicine in the division of hospital medicine at Mount Sinai Hospital, New York.

Clinical question: Do repeated quick Sepsis-Related Organ Failure Assessment (qSOFA) measurements improve predictive validity for sepsis using in-hospital mortality, compared with a single qSOFA measurement at the time a clinician first suspects infection?

Background: Sepsis in hospitalized patients is associated with poor outcomes, but it is not clear how to best identify patients at risk. For non-ICU patients, the qSOFA score (made up of three simple clinical variables: respiratory rate greater than or equal to 22 breaths/minute, systolic blood pressure less than or equal to 100 mm Hg, and Glasgow Coma Scale score less than 15) has predictive validity for important outcomes including in-hospital mortality. qSOFA is relatively new in clinical practice, and the optimal utilization of the score has not yet been defined.

Study design: Retrospective Cohort Study.

Setting: All adult medical and surgical encounters in the ED, hospital ward, postanesthesia care unit (PACU), and ICU at 12 hospitals in Pennsylvania in 2012.

Synopsis: Kievlan et al. studied whether repeated qSOFA scores improved prediction of in-hospital mortality and allowed identification of specific clinical trajectories. The study included approximately 37,600 encounters. Authors abstracted demographic data, vital signs, laboratory results, and antibiotic/culture orders. An infection cohort was identified by a combination of orders for body fluid culture and antibiotics. The qSOFA scores were gathered at 6-hour intervals from the culture/antibiotic event (suspected sepsis). Scores were low (0), moderate (1), or high (greater than or equal to 2). Mean initial qSOFA scores were greater for patients who died, and remained higher during the 48-hours after suspected infection. Mortality was less than 2% in patients with an initial low qSOFA. 25% of patients with an initial moderate qSOFA had subsequent higher qSOFAs, and they had higher mortality, compared with patients with subsequent low qSOFA scores (16% vs. 4%).

Only those patients with initial qSOFA scores at the time of suspected infection were included, and missing data was common. The results may not be applicable to hospitals with a different sepsis case mix from the those of study institutions.

Bottom line: Repeated qSOFA measurements improve predictive validity for in-hospital mortality for patients with sepsis. Patients with low initial qSOFA scores have a low chance (less than 2%) of in-hospital mortality. Further studies are needed to determine how repeat qSOFA measurements can be used to improve management of patients with sepsis.

Citation: Kievlan DR et al. Evaluation of repeated quick sepsis-related organ failure assessment measurements among patients with suspected infection. Crit Care Med. 2018. doi: 10.1097/CCM.0000000000003360.
 

Dr. Linker is an assistant professor of medicine in the division of hospital medicine at Mount Sinai Hospital, New York.

Clinical question: Do repeated quick Sepsis-Related Organ Failure Assessment (qSOFA) measurements improve predictive validity for sepsis using in-hospital mortality, compared with a single qSOFA measurement at the time a clinician first suspects infection?

Background: Sepsis in hospitalized patients is associated with poor outcomes, but it is not clear how to best identify patients at risk. For non-ICU patients, the qSOFA score (made up of three simple clinical variables: respiratory rate greater than or equal to 22 breaths/minute, systolic blood pressure less than or equal to 100 mm Hg, and Glasgow Coma Scale score less than 15) has predictive validity for important outcomes including in-hospital mortality. qSOFA is relatively new in clinical practice, and the optimal utilization of the score has not yet been defined.

Study design: Retrospective Cohort Study.

Setting: All adult medical and surgical encounters in the ED, hospital ward, postanesthesia care unit (PACU), and ICU at 12 hospitals in Pennsylvania in 2012.

Synopsis: Kievlan et al. studied whether repeated qSOFA scores improved prediction of in-hospital mortality and allowed identification of specific clinical trajectories. The study included approximately 37,600 encounters. Authors abstracted demographic data, vital signs, laboratory results, and antibiotic/culture orders. An infection cohort was identified by a combination of orders for body fluid culture and antibiotics. The qSOFA scores were gathered at 6-hour intervals from the culture/antibiotic event (suspected sepsis). Scores were low (0), moderate (1), or high (greater than or equal to 2). Mean initial qSOFA scores were greater for patients who died, and remained higher during the 48-hours after suspected infection. Mortality was less than 2% in patients with an initial low qSOFA. 25% of patients with an initial moderate qSOFA had subsequent higher qSOFAs, and they had higher mortality, compared with patients with subsequent low qSOFA scores (16% vs. 4%).

Only those patients with initial qSOFA scores at the time of suspected infection were included, and missing data was common. The results may not be applicable to hospitals with a different sepsis case mix from the those of study institutions.

Bottom line: Repeated qSOFA measurements improve predictive validity for in-hospital mortality for patients with sepsis. Patients with low initial qSOFA scores have a low chance (less than 2%) of in-hospital mortality. Further studies are needed to determine how repeat qSOFA measurements can be used to improve management of patients with sepsis.

Citation: Kievlan DR et al. Evaluation of repeated quick sepsis-related organ failure assessment measurements among patients with suspected infection. Crit Care Med. 2018. doi: 10.1097/CCM.0000000000003360.
 

Dr. Linker is an assistant professor of medicine in the division of hospital medicine at Mount Sinai Hospital, New York.

After 20 years on the rise, new cases of diagnosed diabetes mellitus (DM) in the US have declined by 35%, from 1.7 million in 2008 to 1.3 million in 2017, according to CDC researchers. Not only that: The number of people living with diagnosed DM in the US has remained stable for the past 8 years.

The findings represent the longest decline in new DM cases and the longest sustained plateau in existing cases. Between 1990 and 2009, the number of people living with diagnosed diabetes (DD) rose 4.4% per year, peaked at 8.2 per 100 adults, then leveled off at 8 per 100 in 2017. The trends were similar across age groups, racial and ethnic groups, and genders.

In part, the plateau may be due to the fact that people with DM are living longer, the researchers suggest, pointing to recent reports of a decline in cardiovascular and all-cause mortality in adults with DD.

But maybe the work to “stem the tide of type 2 diabetes” is finally having an effect, says Ann Albright, PhD, director of the CDC Division of Diabetes Translation. She stresses the importance of “putting science-proven programs into action,” citing the National Diabetes Prevention Program as a prime example. But she adds, “We must also increase access to affordable, healthier foods, and safe places to be active.”

The news about the decrease in new diabetes cases comes simultaneously with findings from the Restoring Insulin Secretion (RISE) Adult and Pediatric Medication Studies, which found that type 2 diabetes mellitus (T2DM) progression slows during treatment but resumes after treatment stops.

The research, funded by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), was aimed at finding ways to preserve β-cell function. The adult study randomly assigned participants aged 20 to 65 years to receive long-acting insulin (glargine) for 3 months, followed by metformin for 9 months; liraglutide with metformin for 12 months; metformin alone for 12 months; or placebo. Participants’ β-cell function and blood glucose control improved on the treatments, with those in the liraglutide/metformin group showing the most improvement. But the improvements did not persist after treatment ended. “[T]reatment options were equally effective while people were actively on them,” says study chair Dr. Steven Kahn, from the VA Puget Sound Health Care System. “But people need to stay on treatment to maintain the benefits.”

The youth study (participants aged 10-19 years) study compared 3 months of insulin glargine, followed by metformin for 9 months, to metformin alone for 12 months. (Insulin glargine and metformin are the only FDA-approved drugs for young people with T2D )  β-cell function declined in the 2 pediatric treatment groups and even worsened after treatment ended. The studies support earlier evidence that T2DM affects young people differently and more aggressively than it does in adults, NIDDK Director Dr. Griffin Rodgers says.

Other research news is brighter for people at risk for type 1 diabetes mellitus (T1DM): An NIH-funded study found that treatment with teplizumab, an anti-CD3 monoclonal antibody, delayed clinical T1DM by ≥ 2 years.

Previous research had found that teplizumab slows the loss of β cells in people with recent-onset clinical T1DM, but the drug had not been tested in people without clinical disease. The researchers wanted to see whether early intervention would have a benefit for people at high risk. They compared a 14-day course of teplizumab with placebo in 76 participants aged 8 to 49 years who were relatives of people with T1DM, had at ≥ 2 types of DM-related autoantibodies, and had abnormal glucose tolerance.

During the trial, 72% of people on placebo developed clinical DM compared with 43% of those in the treatment group. The median time for the control participants to develop DM was just over 24 months vs 48 months in the teplizumab group. The effects of the drug were greatest in the first year after it was given, when 41% of the participants—mainly in the placebo group—developed clinical diabetes.

At-risk children and adolescents are known to progress to T1DM faster than adults, the researchers note. They say faster progression is associated with a highly active immune system, which may explain the impact of immune system-modulating drugs like teplizumab.

The study “illustrates how decades of research on the biology of T1D can lead to promising treatments that have a real impact on people’s lives,” NIDDK Director Rodgers says.

But the T1DM and T2DM studies, although highlighting areas of effectiveness, also underscore the continued need for new approaches to prevent and treat DM in young people.

Although the drop in new cases of T2DM are still unclear, the CDC researchers suggest that they are driven in part by increased awareness of DM prevention, changes in diet, changes in physical activity, and changes in diagnostic and screening practices. In other words, prevention also remains an urgent need.

After 20 years on the rise, new cases of diagnosed diabetes mellitus (DM) in the US have declined by 35%, from 1.7 million in 2008 to 1.3 million in 2017, according to CDC researchers. Not only that: The number of people living with diagnosed DM in the US has remained stable for the past 8 years.

The findings represent the longest decline in new DM cases and the longest sustained plateau in existing cases. Between 1990 and 2009, the number of people living with diagnosed diabetes (DD) rose 4.4% per year, peaked at 8.2 per 100 adults, then leveled off at 8 per 100 in 2017. The trends were similar across age groups, racial and ethnic groups, and genders.

In part, the plateau may be due to the fact that people with DM are living longer, the researchers suggest, pointing to recent reports of a decline in cardiovascular and all-cause mortality in adults with DD.

But maybe the work to “stem the tide of type 2 diabetes” is finally having an effect, says Ann Albright, PhD, director of the CDC Division of Diabetes Translation. She stresses the importance of “putting science-proven programs into action,” citing the National Diabetes Prevention Program as a prime example. But she adds, “We must also increase access to affordable, healthier foods, and safe places to be active.”

The news about the decrease in new diabetes cases comes simultaneously with findings from the Restoring Insulin Secretion (RISE) Adult and Pediatric Medication Studies, which found that type 2 diabetes mellitus (T2DM) progression slows during treatment but resumes after treatment stops.

The research, funded by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), was aimed at finding ways to preserve β-cell function. The adult study randomly assigned participants aged 20 to 65 years to receive long-acting insulin (glargine) for 3 months, followed by metformin for 9 months; liraglutide with metformin for 12 months; metformin alone for 12 months; or placebo. Participants’ β-cell function and blood glucose control improved on the treatments, with those in the liraglutide/metformin group showing the most improvement. But the improvements did not persist after treatment ended. “[T]reatment options were equally effective while people were actively on them,” says study chair Dr. Steven Kahn, from the VA Puget Sound Health Care System. “But people need to stay on treatment to maintain the benefits.”

The youth study (participants aged 10-19 years) study compared 3 months of insulin glargine, followed by metformin for 9 months, to metformin alone for 12 months. (Insulin glargine and metformin are the only FDA-approved drugs for young people with T2D )  β-cell function declined in the 2 pediatric treatment groups and even worsened after treatment ended. The studies support earlier evidence that T2DM affects young people differently and more aggressively than it does in adults, NIDDK Director Dr. Griffin Rodgers says.

Other research news is brighter for people at risk for type 1 diabetes mellitus (T1DM): An NIH-funded study found that treatment with teplizumab, an anti-CD3 monoclonal antibody, delayed clinical T1DM by ≥ 2 years.

Previous research had found that teplizumab slows the loss of β cells in people with recent-onset clinical T1DM, but the drug had not been tested in people without clinical disease. The researchers wanted to see whether early intervention would have a benefit for people at high risk. They compared a 14-day course of teplizumab with placebo in 76 participants aged 8 to 49 years who were relatives of people with T1DM, had at ≥ 2 types of DM-related autoantibodies, and had abnormal glucose tolerance.

During the trial, 72% of people on placebo developed clinical DM compared with 43% of those in the treatment group. The median time for the control participants to develop DM was just over 24 months vs 48 months in the teplizumab group. The effects of the drug were greatest in the first year after it was given, when 41% of the participants—mainly in the placebo group—developed clinical diabetes.

At-risk children and adolescents are known to progress to T1DM faster than adults, the researchers note. They say faster progression is associated with a highly active immune system, which may explain the impact of immune system-modulating drugs like teplizumab.

The study “illustrates how decades of research on the biology of T1D can lead to promising treatments that have a real impact on people’s lives,” NIDDK Director Rodgers says.

But the T1DM and T2DM studies, although highlighting areas of effectiveness, also underscore the continued need for new approaches to prevent and treat DM in young people.

Although the drop in new cases of T2DM are still unclear, the CDC researchers suggest that they are driven in part by increased awareness of DM prevention, changes in diet, changes in physical activity, and changes in diagnostic and screening practices. In other words, prevention also remains an urgent need.

After 20 years on the rise, new cases of diagnosed diabetes mellitus (DM) in the US have declined by 35%, from 1.7 million in 2008 to 1.3 million in 2017, according to CDC researchers. Not only that: The number of people living with diagnosed DM in the US has remained stable for the past 8 years.

The findings represent the longest decline in new DM cases and the longest sustained plateau in existing cases. Between 1990 and 2009, the number of people living with diagnosed diabetes (DD) rose 4.4% per year, peaked at 8.2 per 100 adults, then leveled off at 8 per 100 in 2017. The trends were similar across age groups, racial and ethnic groups, and genders.

In part, the plateau may be due to the fact that people with DM are living longer, the researchers suggest, pointing to recent reports of a decline in cardiovascular and all-cause mortality in adults with DD.

But maybe the work to “stem the tide of type 2 diabetes” is finally having an effect, says Ann Albright, PhD, director of the CDC Division of Diabetes Translation. She stresses the importance of “putting science-proven programs into action,” citing the National Diabetes Prevention Program as a prime example. But she adds, “We must also increase access to affordable, healthier foods, and safe places to be active.”

The news about the decrease in new diabetes cases comes simultaneously with findings from the Restoring Insulin Secretion (RISE) Adult and Pediatric Medication Studies, which found that type 2 diabetes mellitus (T2DM) progression slows during treatment but resumes after treatment stops.

The research, funded by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), was aimed at finding ways to preserve β-cell function. The adult study randomly assigned participants aged 20 to 65 years to receive long-acting insulin (glargine) for 3 months, followed by metformin for 9 months; liraglutide with metformin for 12 months; metformin alone for 12 months; or placebo. Participants’ β-cell function and blood glucose control improved on the treatments, with those in the liraglutide/metformin group showing the most improvement. But the improvements did not persist after treatment ended. “[T]reatment options were equally effective while people were actively on them,” says study chair Dr. Steven Kahn, from the VA Puget Sound Health Care System. “But people need to stay on treatment to maintain the benefits.”

The youth study (participants aged 10-19 years) study compared 3 months of insulin glargine, followed by metformin for 9 months, to metformin alone for 12 months. (Insulin glargine and metformin are the only FDA-approved drugs for young people with T2D )  β-cell function declined in the 2 pediatric treatment groups and even worsened after treatment ended. The studies support earlier evidence that T2DM affects young people differently and more aggressively than it does in adults, NIDDK Director Dr. Griffin Rodgers says.

Other research news is brighter for people at risk for type 1 diabetes mellitus (T1DM): An NIH-funded study found that treatment with teplizumab, an anti-CD3 monoclonal antibody, delayed clinical T1DM by ≥ 2 years.

Previous research had found that teplizumab slows the loss of β cells in people with recent-onset clinical T1DM, but the drug had not been tested in people without clinical disease. The researchers wanted to see whether early intervention would have a benefit for people at high risk. They compared a 14-day course of teplizumab with placebo in 76 participants aged 8 to 49 years who were relatives of people with T1DM, had at ≥ 2 types of DM-related autoantibodies, and had abnormal glucose tolerance.

During the trial, 72% of people on placebo developed clinical DM compared with 43% of those in the treatment group. The median time for the control participants to develop DM was just over 24 months vs 48 months in the teplizumab group. The effects of the drug were greatest in the first year after it was given, when 41% of the participants—mainly in the placebo group—developed clinical diabetes.

At-risk children and adolescents are known to progress to T1DM faster than adults, the researchers note. They say faster progression is associated with a highly active immune system, which may explain the impact of immune system-modulating drugs like teplizumab.

The study “illustrates how decades of research on the biology of T1D can lead to promising treatments that have a real impact on people’s lives,” NIDDK Director Rodgers says.

But the T1DM and T2DM studies, although highlighting areas of effectiveness, also underscore the continued need for new approaches to prevent and treat DM in young people.

Although the drop in new cases of T2DM are still unclear, the CDC researchers suggest that they are driven in part by increased awareness of DM prevention, changes in diet, changes in physical activity, and changes in diagnostic and screening practices. In other words, prevention also remains an urgent need.

SAN FRANCISCO – A new meta-analysis suggests – but does not prove – that black patients with type 2 diabetes may not benefit from the widely heralded cardioprotective effects of the diabetes drugs classified as sodium-glucose transporter 2 inhibitors and glucagonlike peptide–1 receptor agonists.

“Both are excellent classes of medications that improve hemoglobin A_1c, reduce weight, and may have a renal-protective effect. But because there is no clear evidence of [their] cardiovascular benefit in [black] patients, it may remain appropriate to use other [drugs] when metformin fails,” said internist and lead study author Basem Mishriky, MD, of East Carolina University, Greenville, N.C. He spoke after the report was presented at the annual scientific sessions of the American Diabetes Association.

Dr. Mishriky cautioned that the findings of the analysis were not conclusive because the trials included in their analysis had a low number of black patients and were not powered to uncover racial differences.

Recent study results have suggested that sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagonlike peptide–1 receptor (GLP-1R) agonists have significant positive effects on cardiovascular risk. In a 2019 meta-analysis, researchers examined the results of eight trials with 60,082 participants and found that the risk of a composite measure of nonfatal stroke, nonfatal myocardial infarction, and cardiovascular mortality fell by about 12% (SGLT2 inhibitors: hazard ratio, 0.86; 95% confidence interval, 0.74-1.01 and GLP-1R agonists: HR, 0.88, 95% CI, 0.78-0.98). The study was published in Diabetic Medicine (2019;36[4]:444-52).

Dr. Mishriky and his colleagues decided to conduct their analysis after noticing the high number of white patients included in the cardiac safety trials of these medications. “We cannot assume that a drug causes benefit in [black] patients just because it improved outcomes in a population that was predominantly white,” he said. “The onset of the traditional risk factors for cardiovascular disease, such as diabetes, obesity, and hypertension, occur at an earlier age in [black] patients, and there is a high prevalence of sickle cell trait in [black] patients, which is associated with increased risk for diabetes-related complications.”

In addition, some medications, such as angiotensin-converting enzyme inhibitors, may result in lower reductions in blood pressure in black patients, compared with their white counterparts, he noted.

For the new study, Dr. Mishriky and his colleagues included six cardiovascular safety trials of medications in the two classes of drugs (two for SGLT2 inhibitors and four for GLP-1R agonists) that reported statistically significant decreases in cardiovascular risk. The trials included a total of 53,978 patients, of whom 2,794 (5%) were black.

The researchers found no significant evidence of a difference in the incidence of major adverse cardiovascular events (death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke) between the diabetes medications (SGLT2 inhibitors or GLP-1R agonists) and placebo among black patients with type 2 diabetes and cardiovascular disease, Dr. Mishriky said.

When the two classes of drugs were pooled, the cardiovascular risk in patients who took the drugs, compared with those who received placebo, was statistically insignificant (risk ratio, 0.97; 95% CI, 0.68-1.39, P = .88). The risk was also statistically insignificant when the SGLT2 inhibitors and GLP-1R agonists were compared separately with placebo (RR, 1.00; 95% CI, 0.47-2.14; P = .99 and RR, 0.96; 95% CI, 0.61-1.53; P = .87; respectively). A comparison of the results for the SGLT2 inhibitors and the GLP-1R agonists showed no difference either.

Dr Mishriky said the results suggest that alternative medications to SGLT2 inhibitors and GLP-1R agonists, such as pioglitazone (Actos) and dipeptidyl peptidase–4 (DPP-4) inhibitors, might be considered for black patients who fail metformin.

He noted that, given the limitations of the trials included in the analysis, additional trials with SGLT2 inhibitors and GLP-1R agonists were needed to evaluate cardiovascular benefit in black patients.

An expanded version of the meta-analysis will be published soon, he added.

Dr Mishriky and his colleagues reported no relevant disclosures.

SOURCE: Mishriky B et al. ADA 2019, Abstract 242-OR.

SAN FRANCISCO – A new meta-analysis suggests – but does not prove – that black patients with type 2 diabetes may not benefit from the widely heralded cardioprotective effects of the diabetes drugs classified as sodium-glucose transporter 2 inhibitors and glucagonlike peptide–1 receptor agonists.

“Both are excellent classes of medications that improve hemoglobin A_1c, reduce weight, and may have a renal-protective effect. But because there is no clear evidence of [their] cardiovascular benefit in [black] patients, it may remain appropriate to use other [drugs] when metformin fails,” said internist and lead study author Basem Mishriky, MD, of East Carolina University, Greenville, N.C. He spoke after the report was presented at the annual scientific sessions of the American Diabetes Association.

Dr. Mishriky cautioned that the findings of the analysis were not conclusive because the trials included in their analysis had a low number of black patients and were not powered to uncover racial differences.

Recent study results have suggested that sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagonlike peptide–1 receptor (GLP-1R) agonists have significant positive effects on cardiovascular risk. In a 2019 meta-analysis, researchers examined the results of eight trials with 60,082 participants and found that the risk of a composite measure of nonfatal stroke, nonfatal myocardial infarction, and cardiovascular mortality fell by about 12% (SGLT2 inhibitors: hazard ratio, 0.86; 95% confidence interval, 0.74-1.01 and GLP-1R agonists: HR, 0.88, 95% CI, 0.78-0.98). The study was published in Diabetic Medicine (2019;36[4]:444-52).

Dr. Mishriky and his colleagues decided to conduct their analysis after noticing the high number of white patients included in the cardiac safety trials of these medications. “We cannot assume that a drug causes benefit in [black] patients just because it improved outcomes in a population that was predominantly white,” he said. “The onset of the traditional risk factors for cardiovascular disease, such as diabetes, obesity, and hypertension, occur at an earlier age in [black] patients, and there is a high prevalence of sickle cell trait in [black] patients, which is associated with increased risk for diabetes-related complications.”

In addition, some medications, such as angiotensin-converting enzyme inhibitors, may result in lower reductions in blood pressure in black patients, compared with their white counterparts, he noted.

For the new study, Dr. Mishriky and his colleagues included six cardiovascular safety trials of medications in the two classes of drugs (two for SGLT2 inhibitors and four for GLP-1R agonists) that reported statistically significant decreases in cardiovascular risk. The trials included a total of 53,978 patients, of whom 2,794 (5%) were black.

The researchers found no significant evidence of a difference in the incidence of major adverse cardiovascular events (death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke) between the diabetes medications (SGLT2 inhibitors or GLP-1R agonists) and placebo among black patients with type 2 diabetes and cardiovascular disease, Dr. Mishriky said.

When the two classes of drugs were pooled, the cardiovascular risk in patients who took the drugs, compared with those who received placebo, was statistically insignificant (risk ratio, 0.97; 95% CI, 0.68-1.39, P = .88). The risk was also statistically insignificant when the SGLT2 inhibitors and GLP-1R agonists were compared separately with placebo (RR, 1.00; 95% CI, 0.47-2.14; P = .99 and RR, 0.96; 95% CI, 0.61-1.53; P = .87; respectively). A comparison of the results for the SGLT2 inhibitors and the GLP-1R agonists showed no difference either.

Dr Mishriky said the results suggest that alternative medications to SGLT2 inhibitors and GLP-1R agonists, such as pioglitazone (Actos) and dipeptidyl peptidase–4 (DPP-4) inhibitors, might be considered for black patients who fail metformin.

He noted that, given the limitations of the trials included in the analysis, additional trials with SGLT2 inhibitors and GLP-1R agonists were needed to evaluate cardiovascular benefit in black patients.

An expanded version of the meta-analysis will be published soon, he added.

Dr Mishriky and his colleagues reported no relevant disclosures.

SOURCE: Mishriky B et al. ADA 2019, Abstract 242-OR.

SAN FRANCISCO – A new meta-analysis suggests – but does not prove – that black patients with type 2 diabetes may not benefit from the widely heralded cardioprotective effects of the diabetes drugs classified as sodium-glucose transporter 2 inhibitors and glucagonlike peptide–1 receptor agonists.

“Both are excellent classes of medications that improve hemoglobin A_1c, reduce weight, and may have a renal-protective effect. But because there is no clear evidence of [their] cardiovascular benefit in [black] patients, it may remain appropriate to use other [drugs] when metformin fails,” said internist and lead study author Basem Mishriky, MD, of East Carolina University, Greenville, N.C. He spoke after the report was presented at the annual scientific sessions of the American Diabetes Association.

Dr. Mishriky cautioned that the findings of the analysis were not conclusive because the trials included in their analysis had a low number of black patients and were not powered to uncover racial differences.

Recent study results have suggested that sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagonlike peptide–1 receptor (GLP-1R) agonists have significant positive effects on cardiovascular risk. In a 2019 meta-analysis, researchers examined the results of eight trials with 60,082 participants and found that the risk of a composite measure of nonfatal stroke, nonfatal myocardial infarction, and cardiovascular mortality fell by about 12% (SGLT2 inhibitors: hazard ratio, 0.86; 95% confidence interval, 0.74-1.01 and GLP-1R agonists: HR, 0.88, 95% CI, 0.78-0.98). The study was published in Diabetic Medicine (2019;36[4]:444-52).

Dr. Mishriky and his colleagues decided to conduct their analysis after noticing the high number of white patients included in the cardiac safety trials of these medications. “We cannot assume that a drug causes benefit in [black] patients just because it improved outcomes in a population that was predominantly white,” he said. “The onset of the traditional risk factors for cardiovascular disease, such as diabetes, obesity, and hypertension, occur at an earlier age in [black] patients, and there is a high prevalence of sickle cell trait in [black] patients, which is associated with increased risk for diabetes-related complications.”

In addition, some medications, such as angiotensin-converting enzyme inhibitors, may result in lower reductions in blood pressure in black patients, compared with their white counterparts, he noted.

For the new study, Dr. Mishriky and his colleagues included six cardiovascular safety trials of medications in the two classes of drugs (two for SGLT2 inhibitors and four for GLP-1R agonists) that reported statistically significant decreases in cardiovascular risk. The trials included a total of 53,978 patients, of whom 2,794 (5%) were black.

The researchers found no significant evidence of a difference in the incidence of major adverse cardiovascular events (death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke) between the diabetes medications (SGLT2 inhibitors or GLP-1R agonists) and placebo among black patients with type 2 diabetes and cardiovascular disease, Dr. Mishriky said.

When the two classes of drugs were pooled, the cardiovascular risk in patients who took the drugs, compared with those who received placebo, was statistically insignificant (risk ratio, 0.97; 95% CI, 0.68-1.39, P = .88). The risk was also statistically insignificant when the SGLT2 inhibitors and GLP-1R agonists were compared separately with placebo (RR, 1.00; 95% CI, 0.47-2.14; P = .99 and RR, 0.96; 95% CI, 0.61-1.53; P = .87; respectively). A comparison of the results for the SGLT2 inhibitors and the GLP-1R agonists showed no difference either.

Dr Mishriky said the results suggest that alternative medications to SGLT2 inhibitors and GLP-1R agonists, such as pioglitazone (Actos) and dipeptidyl peptidase–4 (DPP-4) inhibitors, might be considered for black patients who fail metformin.

He noted that, given the limitations of the trials included in the analysis, additional trials with SGLT2 inhibitors and GLP-1R agonists were needed to evaluate cardiovascular benefit in black patients.

An expanded version of the meta-analysis will be published soon, he added.

Dr Mishriky and his colleagues reported no relevant disclosures.

SOURCE: Mishriky B et al. ADA 2019, Abstract 242-OR.