An international panel of neurologists has drafted a consensus statement on the diagnosis, prognosis, and treatment of stridor in patients with multiple system atrophy (MSA). The statement was published Oct. 1 in Neurology. In addition to reviewing the literature on the topic and providing recommendations, the authors described several areas for future research.

MSA is a rare neurodegenerative disorder that entails autonomic failure, cerebellar ataxia, and parkinsonism. Laryngeal stridor has a high positive predictive value in the diagnosis of MSA, but consensus about its definition and clinical implications had not been established previously. The Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) delle Scienze Neurologiche di Bologna (Italy) convened a consensus conference of experts in 2017 to determine diagnostic criteria for stridor in MSA, define its prognostic value, suggest treatment options, and indicate subjects for future research. The neurologists reviewed studies of any design that reported original data. They based their statements on 34 published articles, most of which were class III or IV.

The authors defined stridor in MSA as “a strained, high-pitched, harsh respiratory sound, mainly inspiratory, caused by laryngeal dysfunction leading to narrowing of the rima glottidis.” Stridor may occur exclusively during sleep or during sleep and wakefulness. It may be recognized during a clinical examination, through witness report, or through an audio recording. Neurologists may consider laryngoscopy to exclude mechanical lesions or functional vocal cord abnormalities related to other neurologic conditions, wrote the authors. Drug-induced sleep endoscopy and video polysomnography also may be considered.

Whether stridor, or certain features of stridor, affects survival in MSA is uncertain. “Stridor within 3 years of motor or autonomic symptom onset may shorten survival,” according to the statement. “However, identification of stridor onset may be difficult.” Moreover, stridor during wakefulness is considered to reflect a more advanced stage of disease, compared with stridor during sleep. Although stridor can be distressing for the patient and his or her caregivers, its influence on health-related quality of life has yet to be determined, according to the statement.

Continuous positive airway pressure (CPAP) during sleep can be a useful symptomatic treatment and should be considered a first-line therapy for stridor, wrote the authors. Tracheostomy, another effective symptomatic treatment, bypasses upper-airway obstruction at the larynx. “Persistent and severe stridor may require tracheostomy,” according to the statement. It is not certain whether CPAP improves survival in patients with MSA and stridor, and tracheostomy may improve survival. The literature contains insufficient evidence about whether minimally invasive procedures or botulinum toxin injections are effective symptomatic treatments for stridor, wrote the authors.

During their review of the literature, the authors identified what they considered to be several research gaps. The diagnosis of stridor remains challenging, and investigators should develop a questionnaire for detecting stridor, they wrote. A smartphone application also could be developed to recognize stridor automatically. “The relationship between stridor and other breathing disorders (i.e., central apneas and breathing rate abnormalities) and their respective contributions to disease prognosis and survival should be determined through a multicenter prospective study,” according to the statement. Finally, randomized controlled trials comparing CPAP and tracheostomy for various degrees of stridor could guide physicians’ choice of treatment.

The IRCCS funded the study. One of the authors is a section editor for Neurology, and other authors reported receiving honoraria from various companies such as Novartis, Sanofi, and UCB.

[email protected]

SOURCE: Cortelli P et al. Neurology. 2019;93(14):630-9.

An international panel of neurologists has drafted a consensus statement on the diagnosis, prognosis, and treatment of stridor in patients with multiple system atrophy (MSA). The statement was published Oct. 1 in Neurology. In addition to reviewing the literature on the topic and providing recommendations, the authors described several areas for future research.

MSA is a rare neurodegenerative disorder that entails autonomic failure, cerebellar ataxia, and parkinsonism. Laryngeal stridor has a high positive predictive value in the diagnosis of MSA, but consensus about its definition and clinical implications had not been established previously. The Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) delle Scienze Neurologiche di Bologna (Italy) convened a consensus conference of experts in 2017 to determine diagnostic criteria for stridor in MSA, define its prognostic value, suggest treatment options, and indicate subjects for future research. The neurologists reviewed studies of any design that reported original data. They based their statements on 34 published articles, most of which were class III or IV.

The authors defined stridor in MSA as “a strained, high-pitched, harsh respiratory sound, mainly inspiratory, caused by laryngeal dysfunction leading to narrowing of the rima glottidis.” Stridor may occur exclusively during sleep or during sleep and wakefulness. It may be recognized during a clinical examination, through witness report, or through an audio recording. Neurologists may consider laryngoscopy to exclude mechanical lesions or functional vocal cord abnormalities related to other neurologic conditions, wrote the authors. Drug-induced sleep endoscopy and video polysomnography also may be considered.

Whether stridor, or certain features of stridor, affects survival in MSA is uncertain. “Stridor within 3 years of motor or autonomic symptom onset may shorten survival,” according to the statement. “However, identification of stridor onset may be difficult.” Moreover, stridor during wakefulness is considered to reflect a more advanced stage of disease, compared with stridor during sleep. Although stridor can be distressing for the patient and his or her caregivers, its influence on health-related quality of life has yet to be determined, according to the statement.

Continuous positive airway pressure (CPAP) during sleep can be a useful symptomatic treatment and should be considered a first-line therapy for stridor, wrote the authors. Tracheostomy, another effective symptomatic treatment, bypasses upper-airway obstruction at the larynx. “Persistent and severe stridor may require tracheostomy,” according to the statement. It is not certain whether CPAP improves survival in patients with MSA and stridor, and tracheostomy may improve survival. The literature contains insufficient evidence about whether minimally invasive procedures or botulinum toxin injections are effective symptomatic treatments for stridor, wrote the authors.

During their review of the literature, the authors identified what they considered to be several research gaps. The diagnosis of stridor remains challenging, and investigators should develop a questionnaire for detecting stridor, they wrote. A smartphone application also could be developed to recognize stridor automatically. “The relationship between stridor and other breathing disorders (i.e., central apneas and breathing rate abnormalities) and their respective contributions to disease prognosis and survival should be determined through a multicenter prospective study,” according to the statement. Finally, randomized controlled trials comparing CPAP and tracheostomy for various degrees of stridor could guide physicians’ choice of treatment.

The IRCCS funded the study. One of the authors is a section editor for Neurology, and other authors reported receiving honoraria from various companies such as Novartis, Sanofi, and UCB.

[email protected]

SOURCE: Cortelli P et al. Neurology. 2019;93(14):630-9.

An international panel of neurologists has drafted a consensus statement on the diagnosis, prognosis, and treatment of stridor in patients with multiple system atrophy (MSA). The statement was published Oct. 1 in Neurology. In addition to reviewing the literature on the topic and providing recommendations, the authors described several areas for future research.

MSA is a rare neurodegenerative disorder that entails autonomic failure, cerebellar ataxia, and parkinsonism. Laryngeal stridor has a high positive predictive value in the diagnosis of MSA, but consensus about its definition and clinical implications had not been established previously. The Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) delle Scienze Neurologiche di Bologna (Italy) convened a consensus conference of experts in 2017 to determine diagnostic criteria for stridor in MSA, define its prognostic value, suggest treatment options, and indicate subjects for future research. The neurologists reviewed studies of any design that reported original data. They based their statements on 34 published articles, most of which were class III or IV.

The authors defined stridor in MSA as “a strained, high-pitched, harsh respiratory sound, mainly inspiratory, caused by laryngeal dysfunction leading to narrowing of the rima glottidis.” Stridor may occur exclusively during sleep or during sleep and wakefulness. It may be recognized during a clinical examination, through witness report, or through an audio recording. Neurologists may consider laryngoscopy to exclude mechanical lesions or functional vocal cord abnormalities related to other neurologic conditions, wrote the authors. Drug-induced sleep endoscopy and video polysomnography also may be considered.

Whether stridor, or certain features of stridor, affects survival in MSA is uncertain. “Stridor within 3 years of motor or autonomic symptom onset may shorten survival,” according to the statement. “However, identification of stridor onset may be difficult.” Moreover, stridor during wakefulness is considered to reflect a more advanced stage of disease, compared with stridor during sleep. Although stridor can be distressing for the patient and his or her caregivers, its influence on health-related quality of life has yet to be determined, according to the statement.

Continuous positive airway pressure (CPAP) during sleep can be a useful symptomatic treatment and should be considered a first-line therapy for stridor, wrote the authors. Tracheostomy, another effective symptomatic treatment, bypasses upper-airway obstruction at the larynx. “Persistent and severe stridor may require tracheostomy,” according to the statement. It is not certain whether CPAP improves survival in patients with MSA and stridor, and tracheostomy may improve survival. The literature contains insufficient evidence about whether minimally invasive procedures or botulinum toxin injections are effective symptomatic treatments for stridor, wrote the authors.

During their review of the literature, the authors identified what they considered to be several research gaps. The diagnosis of stridor remains challenging, and investigators should develop a questionnaire for detecting stridor, they wrote. A smartphone application also could be developed to recognize stridor automatically. “The relationship between stridor and other breathing disorders (i.e., central apneas and breathing rate abnormalities) and their respective contributions to disease prognosis and survival should be determined through a multicenter prospective study,” according to the statement. Finally, randomized controlled trials comparing CPAP and tracheostomy for various degrees of stridor could guide physicians’ choice of treatment.

The IRCCS funded the study. One of the authors is a section editor for Neurology, and other authors reported receiving honoraria from various companies such as Novartis, Sanofi, and UCB.

[email protected]

SOURCE: Cortelli P et al. Neurology. 2019;93(14):630-9.

Patients with thrombotic antiphospholipid syndrome (APS) may have a greater risk of recurrent thrombosis when taking rivaroxaban instead of a vitamin K antagonist, suggests a recent trial conducted in Spain.

Stroke was also more common among those taking rivaroxaban, while major bleeding was slightly less common, reported lead author Josep Ordi-Ros, MD, PhD, of Vall d’Hebrón University Hospital Research Institute in Barcelona, and colleagues in Annals of Internal Medicine.

“Two randomized, controlled trials comparing rivaroxaban with warfarin suggested that rivaroxaban may be efficacious in patients with previous venous thromboembolism who are receiving standard-intensity anticoagulation but showed an increased thrombotic risk in those with triple-positive antiphospholipid antibodies,” the investigators wrote. However, they also noted that these findings required a cautious interpretation because of study limitations, such as premature termination caused by an excess of study events and the use of a laboratory surrogate marker as a primary outcome.

To learn more, the investigators performed an open-label, phase 3 trial involving 190 patients with thrombotic APS. Patients were randomized in a 1:1 ratio to receive either rivaroxaban (20 mg per day, or 15 mg per day for patients with a creatinine clearance of 30-49 mL/min per 1.73 m²) or an adjusted dosage of vitamin K antagonists (target international normalized ratio of 2.0-3.0, or 3.1-4.0 for those with a history of recurrent thrombosis).

Patients underwent evaluations every month for the first 3 months and then every 3 months thereafter, each of which involved a variety of laboratory diagnostics such as checks for antinuclear antibodies and lupus anticoagulant, among others. Statistical analyses aimed to determine if rivaroxaban was noninferior to therapy with vitamin K antagonists based on parameters drawn from previous meta-analyses, as no studies had compared the two types of treatment when the present study was designed.

After 3 years of follow-up, almost twice as many patients in the rivaroxaban group had experienced recurrent thrombosis (11.6% vs. 6.3%), although this finding lacked statistical significance for both noninferiority of rivaroxaban (P = .29) and superiority of vitamin K antagonists (P = .20). Still, supporting a similar trend toward differences in efficacy, stroke was more common in the rivaroxaban group, in which nine events occurred, compared with none in the vitamin K antagonist group. In contrast, major bleeding was slightly less common with rivaroxaban than vitamin K antagonists (6.3% vs. 7.4%).

“In conclusion, rivaroxaban did not demonstrate noninferiority to dose-adjusted vitamin K antagonists for secondary thromboprophylaxis in patients with thrombotic APS,” the investigators wrote. “Instead, our results indicate a recurrent thrombotic rate that is nearly double, albeit without statistical significance.”

The study was funded by Bayer Hispania. One coauthor reported additional relationships with Pfizer, Lilly, Janssen, and others.

SOURCE: Ordi-Ros J et al. Ann Intern Med. 2019 Oct 15. doi: 10.7326/M19-0291.

Patients with thrombotic antiphospholipid syndrome (APS) may have a greater risk of recurrent thrombosis when taking rivaroxaban instead of a vitamin K antagonist, suggests a recent trial conducted in Spain.

Stroke was also more common among those taking rivaroxaban, while major bleeding was slightly less common, reported lead author Josep Ordi-Ros, MD, PhD, of Vall d’Hebrón University Hospital Research Institute in Barcelona, and colleagues in Annals of Internal Medicine.

“Two randomized, controlled trials comparing rivaroxaban with warfarin suggested that rivaroxaban may be efficacious in patients with previous venous thromboembolism who are receiving standard-intensity anticoagulation but showed an increased thrombotic risk in those with triple-positive antiphospholipid antibodies,” the investigators wrote. However, they also noted that these findings required a cautious interpretation because of study limitations, such as premature termination caused by an excess of study events and the use of a laboratory surrogate marker as a primary outcome.

To learn more, the investigators performed an open-label, phase 3 trial involving 190 patients with thrombotic APS. Patients were randomized in a 1:1 ratio to receive either rivaroxaban (20 mg per day, or 15 mg per day for patients with a creatinine clearance of 30-49 mL/min per 1.73 m²) or an adjusted dosage of vitamin K antagonists (target international normalized ratio of 2.0-3.0, or 3.1-4.0 for those with a history of recurrent thrombosis).

Patients underwent evaluations every month for the first 3 months and then every 3 months thereafter, each of which involved a variety of laboratory diagnostics such as checks for antinuclear antibodies and lupus anticoagulant, among others. Statistical analyses aimed to determine if rivaroxaban was noninferior to therapy with vitamin K antagonists based on parameters drawn from previous meta-analyses, as no studies had compared the two types of treatment when the present study was designed.

After 3 years of follow-up, almost twice as many patients in the rivaroxaban group had experienced recurrent thrombosis (11.6% vs. 6.3%), although this finding lacked statistical significance for both noninferiority of rivaroxaban (P = .29) and superiority of vitamin K antagonists (P = .20). Still, supporting a similar trend toward differences in efficacy, stroke was more common in the rivaroxaban group, in which nine events occurred, compared with none in the vitamin K antagonist group. In contrast, major bleeding was slightly less common with rivaroxaban than vitamin K antagonists (6.3% vs. 7.4%).

“In conclusion, rivaroxaban did not demonstrate noninferiority to dose-adjusted vitamin K antagonists for secondary thromboprophylaxis in patients with thrombotic APS,” the investigators wrote. “Instead, our results indicate a recurrent thrombotic rate that is nearly double, albeit without statistical significance.”

The study was funded by Bayer Hispania. One coauthor reported additional relationships with Pfizer, Lilly, Janssen, and others.

SOURCE: Ordi-Ros J et al. Ann Intern Med. 2019 Oct 15. doi: 10.7326/M19-0291.

Patients with thrombotic antiphospholipid syndrome (APS) may have a greater risk of recurrent thrombosis when taking rivaroxaban instead of a vitamin K antagonist, suggests a recent trial conducted in Spain.

Stroke was also more common among those taking rivaroxaban, while major bleeding was slightly less common, reported lead author Josep Ordi-Ros, MD, PhD, of Vall d’Hebrón University Hospital Research Institute in Barcelona, and colleagues in Annals of Internal Medicine.

“Two randomized, controlled trials comparing rivaroxaban with warfarin suggested that rivaroxaban may be efficacious in patients with previous venous thromboembolism who are receiving standard-intensity anticoagulation but showed an increased thrombotic risk in those with triple-positive antiphospholipid antibodies,” the investigators wrote. However, they also noted that these findings required a cautious interpretation because of study limitations, such as premature termination caused by an excess of study events and the use of a laboratory surrogate marker as a primary outcome.

To learn more, the investigators performed an open-label, phase 3 trial involving 190 patients with thrombotic APS. Patients were randomized in a 1:1 ratio to receive either rivaroxaban (20 mg per day, or 15 mg per day for patients with a creatinine clearance of 30-49 mL/min per 1.73 m²) or an adjusted dosage of vitamin K antagonists (target international normalized ratio of 2.0-3.0, or 3.1-4.0 for those with a history of recurrent thrombosis).

Patients underwent evaluations every month for the first 3 months and then every 3 months thereafter, each of which involved a variety of laboratory diagnostics such as checks for antinuclear antibodies and lupus anticoagulant, among others. Statistical analyses aimed to determine if rivaroxaban was noninferior to therapy with vitamin K antagonists based on parameters drawn from previous meta-analyses, as no studies had compared the two types of treatment when the present study was designed.

After 3 years of follow-up, almost twice as many patients in the rivaroxaban group had experienced recurrent thrombosis (11.6% vs. 6.3%), although this finding lacked statistical significance for both noninferiority of rivaroxaban (P = .29) and superiority of vitamin K antagonists (P = .20). Still, supporting a similar trend toward differences in efficacy, stroke was more common in the rivaroxaban group, in which nine events occurred, compared with none in the vitamin K antagonist group. In contrast, major bleeding was slightly less common with rivaroxaban than vitamin K antagonists (6.3% vs. 7.4%).

“In conclusion, rivaroxaban did not demonstrate noninferiority to dose-adjusted vitamin K antagonists for secondary thromboprophylaxis in patients with thrombotic APS,” the investigators wrote. “Instead, our results indicate a recurrent thrombotic rate that is nearly double, albeit without statistical significance.”

The study was funded by Bayer Hispania. One coauthor reported additional relationships with Pfizer, Lilly, Janssen, and others.

SOURCE: Ordi-Ros J et al. Ann Intern Med. 2019 Oct 15. doi: 10.7326/M19-0291.

More conservative oxygen therapy during mechanical ventilation in intensive care does not appear to increase the number of ventilator-free days or reduce mortality, according to a study published online in the New England Journal of Medicine.

Diane Mackle of the Medical Research Institute of New Zealand and her co-authors wrote that hyperoxemia in adults undergoing mechanical ventilation has been associated with increased mortality, as well as fewer days free of ventilation, but there was a lack of data to guide oxygen administration.

In a parallel-group trial, 1,000 adults who were expected to require mechanical ventilation – with an intention-to-treat population of 965 – were randomized either to conservative oxygen therapy or usual therapy. For the conservative therapy, the upper limit of the pulse oximetry alarm would sound when levels reached 97% and the F10₂ was decreased to 0.21 if the pulse oximetry was above the acceptable lower limit, while usual therapy involved no specific limiting measures. In both groups, the default lower limit for oxygen saturation was 90%.

At day 28 after ventilation, there was no significant difference between the conservative and usual care groups in the number of ventilator-free days (21.3 days vs. 22.1 days). The patients in the conservative oxygen group spent a median of 29 hours receiving an F10₂ level of 0.21, compared with 1 hour in the usual care group.

The mortality rate at day 180 was 35.7% in the conservative oxygen group, and 34.5% in the usual-oxygen group (HR 1.05, 95% CI 0.85 – 1.30). Researchers also saw no differences between the two groups in paid employment and cognitive function.

In patients with suspected hypoxic-ischemic encephalopathy between-group differences were apparent; At day 28, those in the conservative-oxygen group had a median of 21.1 ventilator-free days, compared with none in the usual-oxygen group. The usual-oxygen group also had a higher 180-day mortality rate than those in the conservative-oxygen group (43% vs. 59%).

“Our data are suggestive of a possible benefit of conservative oxygen therapy in patients with suspected hypoxic-ischemic encephalopathy,” the authors wrote. “It is biologically plausible that conservative oxygen therapy reduces the incidence of secondary brain damage after resuscitation from cardiac arrest, and observational data suggest that exposure to hyperoxemia in such patients may be harmful.”

The authors noted that their trial did not rule out the possibility of benefit or harm had they used a more liberal oxygen regimen in their usual-care group, and that different conservative regimens might also have achieved different outcomes.

The study was funded by the New Zealand Health Research Council. Six authors declared research support for the trial from the study funder, and two declared unrelated research grants from private industry. No other conflicts of interest were declared.

SOURCE: Mackle D et al. NJEM 2019, October 14. DOI:10.1056/NEJMoa1903297.

More conservative oxygen therapy during mechanical ventilation in intensive care does not appear to increase the number of ventilator-free days or reduce mortality, according to a study published online in the New England Journal of Medicine.

Diane Mackle of the Medical Research Institute of New Zealand and her co-authors wrote that hyperoxemia in adults undergoing mechanical ventilation has been associated with increased mortality, as well as fewer days free of ventilation, but there was a lack of data to guide oxygen administration.

In a parallel-group trial, 1,000 adults who were expected to require mechanical ventilation – with an intention-to-treat population of 965 – were randomized either to conservative oxygen therapy or usual therapy. For the conservative therapy, the upper limit of the pulse oximetry alarm would sound when levels reached 97% and the F10₂ was decreased to 0.21 if the pulse oximetry was above the acceptable lower limit, while usual therapy involved no specific limiting measures. In both groups, the default lower limit for oxygen saturation was 90%.

At day 28 after ventilation, there was no significant difference between the conservative and usual care groups in the number of ventilator-free days (21.3 days vs. 22.1 days). The patients in the conservative oxygen group spent a median of 29 hours receiving an F10₂ level of 0.21, compared with 1 hour in the usual care group.

The mortality rate at day 180 was 35.7% in the conservative oxygen group, and 34.5% in the usual-oxygen group (HR 1.05, 95% CI 0.85 – 1.30). Researchers also saw no differences between the two groups in paid employment and cognitive function.

In patients with suspected hypoxic-ischemic encephalopathy between-group differences were apparent; At day 28, those in the conservative-oxygen group had a median of 21.1 ventilator-free days, compared with none in the usual-oxygen group. The usual-oxygen group also had a higher 180-day mortality rate than those in the conservative-oxygen group (43% vs. 59%).

“Our data are suggestive of a possible benefit of conservative oxygen therapy in patients with suspected hypoxic-ischemic encephalopathy,” the authors wrote. “It is biologically plausible that conservative oxygen therapy reduces the incidence of secondary brain damage after resuscitation from cardiac arrest, and observational data suggest that exposure to hyperoxemia in such patients may be harmful.”

The authors noted that their trial did not rule out the possibility of benefit or harm had they used a more liberal oxygen regimen in their usual-care group, and that different conservative regimens might also have achieved different outcomes.

The study was funded by the New Zealand Health Research Council. Six authors declared research support for the trial from the study funder, and two declared unrelated research grants from private industry. No other conflicts of interest were declared.

SOURCE: Mackle D et al. NJEM 2019, October 14. DOI:10.1056/NEJMoa1903297.

More conservative oxygen therapy during mechanical ventilation in intensive care does not appear to increase the number of ventilator-free days or reduce mortality, according to a study published online in the New England Journal of Medicine.

Diane Mackle of the Medical Research Institute of New Zealand and her co-authors wrote that hyperoxemia in adults undergoing mechanical ventilation has been associated with increased mortality, as well as fewer days free of ventilation, but there was a lack of data to guide oxygen administration.

In a parallel-group trial, 1,000 adults who were expected to require mechanical ventilation – with an intention-to-treat population of 965 – were randomized either to conservative oxygen therapy or usual therapy. For the conservative therapy, the upper limit of the pulse oximetry alarm would sound when levels reached 97% and the F10₂ was decreased to 0.21 if the pulse oximetry was above the acceptable lower limit, while usual therapy involved no specific limiting measures. In both groups, the default lower limit for oxygen saturation was 90%.

At day 28 after ventilation, there was no significant difference between the conservative and usual care groups in the number of ventilator-free days (21.3 days vs. 22.1 days). The patients in the conservative oxygen group spent a median of 29 hours receiving an F10₂ level of 0.21, compared with 1 hour in the usual care group.

The mortality rate at day 180 was 35.7% in the conservative oxygen group, and 34.5% in the usual-oxygen group (HR 1.05, 95% CI 0.85 – 1.30). Researchers also saw no differences between the two groups in paid employment and cognitive function.

In patients with suspected hypoxic-ischemic encephalopathy between-group differences were apparent; At day 28, those in the conservative-oxygen group had a median of 21.1 ventilator-free days, compared with none in the usual-oxygen group. The usual-oxygen group also had a higher 180-day mortality rate than those in the conservative-oxygen group (43% vs. 59%).

“Our data are suggestive of a possible benefit of conservative oxygen therapy in patients with suspected hypoxic-ischemic encephalopathy,” the authors wrote. “It is biologically plausible that conservative oxygen therapy reduces the incidence of secondary brain damage after resuscitation from cardiac arrest, and observational data suggest that exposure to hyperoxemia in such patients may be harmful.”

The authors noted that their trial did not rule out the possibility of benefit or harm had they used a more liberal oxygen regimen in their usual-care group, and that different conservative regimens might also have achieved different outcomes.

The study was funded by the New Zealand Health Research Council. Six authors declared research support for the trial from the study funder, and two declared unrelated research grants from private industry. No other conflicts of interest were declared.

SOURCE: Mackle D et al. NJEM 2019, October 14. DOI:10.1056/NEJMoa1903297.

ST. LOUIS – Getting an MRI first for suspected stroke, instead of a CT, saves money by avoiding unnecessary admissions and might lead to better outcomes, according to a review from Johns Hopkins University, Baltimore.

MRI as the first scan leads to “a definitive diagnoses sooner and helps you manage the person more rapidly and appropriately, without negatively affecting outcomes even in stroke patients who receive endovascular therapy,” said neurologist and senior investigator Argye Hillis, MD, director of the Center of Excellence in Stroke Detection and Diagnosis at Hopkins. “Consider skipping the CT and getting an MRI, and get the MRI while they are still in the emergency room.”

Almost all emergency departments in the United States are set up to get a CT first, but MRI is known to be the better study, according to the researchers. MRI is much more sensitive to stroke, especially in the first 24 hours, and pinpoints the location and extent of the damage. It can detect causes of stroke invisible to CT, with no radiation, and rule out stroke entirely, whereas CT can rule out only intracranial bleeding. Increasingly in Europe, MRI is the first study in suspected stroke, and new EDs in the United States are being designed with an in-house MRI, or one nearby.

The ED at Hopkins’ main campus in downtown Baltimore already has an MRI, and uses it first whenever possible. The problem has been that MRI techs are available only during weekdays, so physicians have to default back to CT at night and on weekends. The impetus for the review, presented at the annual meeting of the American Neurological Association, was to see if savings from unnecessary admissions prevented by MRI would be enough to offset the cost of around-the-clock staffing for the MRI scanner.

Dr. Hillis and her team reviewed 320 patients with suspected ischemic stroke who were seen at the main campus in 2018 and had CT in the ED, and then definitive diagnosis by MRI, which is the usual approach in most U.S. hospitals.

A total of 134 patients had a final diagnosis on MRI that did not justify admission; techs were available to give 75 of them MRIs in the ED after the CT, and those patients were sent home. Techs were not available, however, for 59 patients and since the CT was not able to rule out stroke, those patients were admitted. The cost of those 59 admissions was $814,016.

The cost of the noncontrast CTs for the 75 patients who were sent home after definitive MRI imaging was $28,050, plus an additional $46,072 for those who had CT neck/head angiograms. Altogether, skipping the CT and going straight to the MRI would have saved Hopkins $888,138 in 2018, enough to cover round-the-clock MRI staffing in the ED, which is now the plan at the main campus.

Once the facility moves to 24-and-7 MRI coverage, the next step in the project is to compare stroke outcomes with Johns Hopkins Bayview Medical Center, also in Baltimore, which will continue to do CT first. “We know MRI first is cheaper. We want to see if we have better outcomes. If we find they’re much better, I think many hospitals will say it’s worth the 5 minutes longer it takes to get to the MRI scanner,” Dr. Hillis said.

Stroke mimics among the 134 patients included peripheral nerve palsy and migraine, but also people simply faking it for a hot meal and a warm bed. “Its pretty common, unfortunately,” she said.

The average age for stroke admissions at Hopkins is 55 years, with as many men as women.

There was no industry funding, and Dr. Hillis didn’t have any relevant disclosures.

[email protected]

ST. LOUIS – Getting an MRI first for suspected stroke, instead of a CT, saves money by avoiding unnecessary admissions and might lead to better outcomes, according to a review from Johns Hopkins University, Baltimore.

MRI as the first scan leads to “a definitive diagnoses sooner and helps you manage the person more rapidly and appropriately, without negatively affecting outcomes even in stroke patients who receive endovascular therapy,” said neurologist and senior investigator Argye Hillis, MD, director of the Center of Excellence in Stroke Detection and Diagnosis at Hopkins. “Consider skipping the CT and getting an MRI, and get the MRI while they are still in the emergency room.”

Almost all emergency departments in the United States are set up to get a CT first, but MRI is known to be the better study, according to the researchers. MRI is much more sensitive to stroke, especially in the first 24 hours, and pinpoints the location and extent of the damage. It can detect causes of stroke invisible to CT, with no radiation, and rule out stroke entirely, whereas CT can rule out only intracranial bleeding. Increasingly in Europe, MRI is the first study in suspected stroke, and new EDs in the United States are being designed with an in-house MRI, or one nearby.

The ED at Hopkins’ main campus in downtown Baltimore already has an MRI, and uses it first whenever possible. The problem has been that MRI techs are available only during weekdays, so physicians have to default back to CT at night and on weekends. The impetus for the review, presented at the annual meeting of the American Neurological Association, was to see if savings from unnecessary admissions prevented by MRI would be enough to offset the cost of around-the-clock staffing for the MRI scanner.

Dr. Hillis and her team reviewed 320 patients with suspected ischemic stroke who were seen at the main campus in 2018 and had CT in the ED, and then definitive diagnosis by MRI, which is the usual approach in most U.S. hospitals.

A total of 134 patients had a final diagnosis on MRI that did not justify admission; techs were available to give 75 of them MRIs in the ED after the CT, and those patients were sent home. Techs were not available, however, for 59 patients and since the CT was not able to rule out stroke, those patients were admitted. The cost of those 59 admissions was $814,016.

The cost of the noncontrast CTs for the 75 patients who were sent home after definitive MRI imaging was $28,050, plus an additional $46,072 for those who had CT neck/head angiograms. Altogether, skipping the CT and going straight to the MRI would have saved Hopkins $888,138 in 2018, enough to cover round-the-clock MRI staffing in the ED, which is now the plan at the main campus.

Once the facility moves to 24-and-7 MRI coverage, the next step in the project is to compare stroke outcomes with Johns Hopkins Bayview Medical Center, also in Baltimore, which will continue to do CT first. “We know MRI first is cheaper. We want to see if we have better outcomes. If we find they’re much better, I think many hospitals will say it’s worth the 5 minutes longer it takes to get to the MRI scanner,” Dr. Hillis said.

Stroke mimics among the 134 patients included peripheral nerve palsy and migraine, but also people simply faking it for a hot meal and a warm bed. “Its pretty common, unfortunately,” she said.

The average age for stroke admissions at Hopkins is 55 years, with as many men as women.

There was no industry funding, and Dr. Hillis didn’t have any relevant disclosures.

[email protected]

ST. LOUIS – Getting an MRI first for suspected stroke, instead of a CT, saves money by avoiding unnecessary admissions and might lead to better outcomes, according to a review from Johns Hopkins University, Baltimore.

MRI as the first scan leads to “a definitive diagnoses sooner and helps you manage the person more rapidly and appropriately, without negatively affecting outcomes even in stroke patients who receive endovascular therapy,” said neurologist and senior investigator Argye Hillis, MD, director of the Center of Excellence in Stroke Detection and Diagnosis at Hopkins. “Consider skipping the CT and getting an MRI, and get the MRI while they are still in the emergency room.”

Almost all emergency departments in the United States are set up to get a CT first, but MRI is known to be the better study, according to the researchers. MRI is much more sensitive to stroke, especially in the first 24 hours, and pinpoints the location and extent of the damage. It can detect causes of stroke invisible to CT, with no radiation, and rule out stroke entirely, whereas CT can rule out only intracranial bleeding. Increasingly in Europe, MRI is the first study in suspected stroke, and new EDs in the United States are being designed with an in-house MRI, or one nearby.

The ED at Hopkins’ main campus in downtown Baltimore already has an MRI, and uses it first whenever possible. The problem has been that MRI techs are available only during weekdays, so physicians have to default back to CT at night and on weekends. The impetus for the review, presented at the annual meeting of the American Neurological Association, was to see if savings from unnecessary admissions prevented by MRI would be enough to offset the cost of around-the-clock staffing for the MRI scanner.

Dr. Hillis and her team reviewed 320 patients with suspected ischemic stroke who were seen at the main campus in 2018 and had CT in the ED, and then definitive diagnosis by MRI, which is the usual approach in most U.S. hospitals.

A total of 134 patients had a final diagnosis on MRI that did not justify admission; techs were available to give 75 of them MRIs in the ED after the CT, and those patients were sent home. Techs were not available, however, for 59 patients and since the CT was not able to rule out stroke, those patients were admitted. The cost of those 59 admissions was $814,016.

The cost of the noncontrast CTs for the 75 patients who were sent home after definitive MRI imaging was $28,050, plus an additional $46,072 for those who had CT neck/head angiograms. Altogether, skipping the CT and going straight to the MRI would have saved Hopkins $888,138 in 2018, enough to cover round-the-clock MRI staffing in the ED, which is now the plan at the main campus.

Once the facility moves to 24-and-7 MRI coverage, the next step in the project is to compare stroke outcomes with Johns Hopkins Bayview Medical Center, also in Baltimore, which will continue to do CT first. “We know MRI first is cheaper. We want to see if we have better outcomes. If we find they’re much better, I think many hospitals will say it’s worth the 5 minutes longer it takes to get to the MRI scanner,” Dr. Hillis said.

Stroke mimics among the 134 patients included peripheral nerve palsy and migraine, but also people simply faking it for a hot meal and a warm bed. “Its pretty common, unfortunately,” she said.

The average age for stroke admissions at Hopkins is 55 years, with as many men as women.

There was no industry funding, and Dr. Hillis didn’t have any relevant disclosures.

[email protected]

Q)I have a patient with a discharge diagnosis of community-acquired acute kidney injury. What does this mean? What do I do now?

Acute kidney injury (AKI) refers to an abrupt decrease in kidney function that is possibly reversible or in which harm to the kidney can be modified.^1,2 AKI encompasses a broad spectrum of conditions affecting the kidney—including acute renal failure, since even “failure” can sometimes be reversed.¹ Criteria for AKI and its severity can be found in the Table.¹

AKI can be either community-acquired (CA-AKI) or hospital-acquired (HA-AKI).^1,2 In the United States, CA-AKI occurs less frequently than HA-AKI, although cases are likely underreported.¹ Evaluation and management are similar for both.

The etiology of the AKI must be determined before treatment of the cause or precipitating factor can be attempted. Causes of AKI can be classified as prerenal (up to 70% of cases), intrinsic, or postrenal.¹

Most AKI cases have a prerenal origin.³ Prerenal AKI occurs when there is inadequate blood flow to the kidneys, leading to a rise in blood urea nitrogen (BUN) and serum creatinine (SCr) levels. Reduced blood flow can be caused by

• Diuretic dosing
• Polypharmacy (diuretics, angiotensin-converting enzyme inhibitors [ACEIs]/ angiotensin receptor blockers [ARBs], and/or NSAIDs are common culprits)
• Congestive heart failure exacerbation
• Volume depletion through vomiting or diarrhea
• Massive blood loss (trauma).³

Postrenal causes of AKI include any type of obstructive uropathy. Intrinsic causes involve any condition within the kidney, including interstitial nephritis or acute tubular necrosis. Use of antibiotics (eg, high-dose penicillin or vancomycin) is included in this category.

Obtaining an accurate medical history and examining the patient’s fluid status are critical. Although numerous novel biomarkers have been investigated for detection of AKI, none are yet in wide use. The primary assessment measures remain a serum panel to evaluate SCr and BUN levels; an electrolyte panel to assess for abnormalities; a complete blood count to assess for anemia caused by a less likely source; urinalysis; and imaging to assess for abnormalities or structural changes.

Urinalysis. Urine often holds the key to diagnosis of AKI. Notably in a prerenal injury, its specific gravity will be elevated, but the rest of the urine will likely be bland.³

Continue to: Urinalysis is helpful for...

Urinalysis is helpful for ruling out intrinsic causes of AKI. Patients with intrarenal AKI will have abnormal urine sediment; for example, red blood cell casts are found in glomerulonephritis; granular casts in cases of acute tubular necrosis; and white blood cell casts and eosinophils in acute interstitial nephritis.⁴

Imaging. The most commonly used imaging for AKI is retroperitoneal ultrasonography of the kidneys, ureters, and bladder, which provides information on the size and shape of the kidneys and can detect stones or masses. It also detects the presence or absence of hydronephrosis, which can occur in postrenal injuries.

Currently, no definitive therapy or pharmacologic agent is approved for AKI; treatment focuses on reversing the cause of the injury. In the immediate aftermath of AKI, it is important to avoid potentially nephrotoxic medications, including NSAIDs. Minimize the use of diuretics and avoid ACEIs and ARB therapy; these can be reintroduced after lab results confirm that the AKI has resolved with a stabilized SCr.

Practice guidelines recommend prompt follow-up at 3 months in most cases of AKI.¹ Providers should obtain a metabolic panel and perform a urinalysis to evaluate for chronic kidney disease (CKD), because almost one-third of patients with an AKI episode are newly classified with CKD in the following year.⁵ Earlier follow-up (< 3 months) is warranted if the patient has a significant comorbidity, such as congestive heart failure.^1,2—CS

Christopher Sjoberg, CNN-NP
Idaho Nephrology Associates, Boise
Adjunct Faculty, Boise State University

Q)I have a patient with a discharge diagnosis of community-acquired acute kidney injury. What does this mean? What do I do now?

Acute kidney injury (AKI) refers to an abrupt decrease in kidney function that is possibly reversible or in which harm to the kidney can be modified.^1,2 AKI encompasses a broad spectrum of conditions affecting the kidney—including acute renal failure, since even “failure” can sometimes be reversed.¹ Criteria for AKI and its severity can be found in the Table.¹

AKI can be either community-acquired (CA-AKI) or hospital-acquired (HA-AKI).^1,2 In the United States, CA-AKI occurs less frequently than HA-AKI, although cases are likely underreported.¹ Evaluation and management are similar for both.

The etiology of the AKI must be determined before treatment of the cause or precipitating factor can be attempted. Causes of AKI can be classified as prerenal (up to 70% of cases), intrinsic, or postrenal.¹

Most AKI cases have a prerenal origin.³ Prerenal AKI occurs when there is inadequate blood flow to the kidneys, leading to a rise in blood urea nitrogen (BUN) and serum creatinine (SCr) levels. Reduced blood flow can be caused by

• Diuretic dosing
• Polypharmacy (diuretics, angiotensin-converting enzyme inhibitors [ACEIs]/ angiotensin receptor blockers [ARBs], and/or NSAIDs are common culprits)
• Congestive heart failure exacerbation
• Volume depletion through vomiting or diarrhea
• Massive blood loss (trauma).³

Postrenal causes of AKI include any type of obstructive uropathy. Intrinsic causes involve any condition within the kidney, including interstitial nephritis or acute tubular necrosis. Use of antibiotics (eg, high-dose penicillin or vancomycin) is included in this category.

Obtaining an accurate medical history and examining the patient’s fluid status are critical. Although numerous novel biomarkers have been investigated for detection of AKI, none are yet in wide use. The primary assessment measures remain a serum panel to evaluate SCr and BUN levels; an electrolyte panel to assess for abnormalities; a complete blood count to assess for anemia caused by a less likely source; urinalysis; and imaging to assess for abnormalities or structural changes.

Urinalysis. Urine often holds the key to diagnosis of AKI. Notably in a prerenal injury, its specific gravity will be elevated, but the rest of the urine will likely be bland.³

Continue to: Urinalysis is helpful for...

Urinalysis is helpful for ruling out intrinsic causes of AKI. Patients with intrarenal AKI will have abnormal urine sediment; for example, red blood cell casts are found in glomerulonephritis; granular casts in cases of acute tubular necrosis; and white blood cell casts and eosinophils in acute interstitial nephritis.⁴

Imaging. The most commonly used imaging for AKI is retroperitoneal ultrasonography of the kidneys, ureters, and bladder, which provides information on the size and shape of the kidneys and can detect stones or masses. It also detects the presence or absence of hydronephrosis, which can occur in postrenal injuries.

Currently, no definitive therapy or pharmacologic agent is approved for AKI; treatment focuses on reversing the cause of the injury. In the immediate aftermath of AKI, it is important to avoid potentially nephrotoxic medications, including NSAIDs. Minimize the use of diuretics and avoid ACEIs and ARB therapy; these can be reintroduced after lab results confirm that the AKI has resolved with a stabilized SCr.

Practice guidelines recommend prompt follow-up at 3 months in most cases of AKI.¹ Providers should obtain a metabolic panel and perform a urinalysis to evaluate for chronic kidney disease (CKD), because almost one-third of patients with an AKI episode are newly classified with CKD in the following year.⁵ Earlier follow-up (< 3 months) is warranted if the patient has a significant comorbidity, such as congestive heart failure.^1,2—CS

Christopher Sjoberg, CNN-NP
Idaho Nephrology Associates, Boise
Adjunct Faculty, Boise State University

Q)I have a patient with a discharge diagnosis of community-acquired acute kidney injury. What does this mean? What do I do now?

Acute kidney injury (AKI) refers to an abrupt decrease in kidney function that is possibly reversible or in which harm to the kidney can be modified.^1,2 AKI encompasses a broad spectrum of conditions affecting the kidney—including acute renal failure, since even “failure” can sometimes be reversed.¹ Criteria for AKI and its severity can be found in the Table.¹

AKI can be either community-acquired (CA-AKI) or hospital-acquired (HA-AKI).^1,2 In the United States, CA-AKI occurs less frequently than HA-AKI, although cases are likely underreported.¹ Evaluation and management are similar for both.

The etiology of the AKI must be determined before treatment of the cause or precipitating factor can be attempted. Causes of AKI can be classified as prerenal (up to 70% of cases), intrinsic, or postrenal.¹

Most AKI cases have a prerenal origin.³ Prerenal AKI occurs when there is inadequate blood flow to the kidneys, leading to a rise in blood urea nitrogen (BUN) and serum creatinine (SCr) levels. Reduced blood flow can be caused by

• Diuretic dosing
• Polypharmacy (diuretics, angiotensin-converting enzyme inhibitors [ACEIs]/ angiotensin receptor blockers [ARBs], and/or NSAIDs are common culprits)
• Congestive heart failure exacerbation
• Volume depletion through vomiting or diarrhea
• Massive blood loss (trauma).³

Postrenal causes of AKI include any type of obstructive uropathy. Intrinsic causes involve any condition within the kidney, including interstitial nephritis or acute tubular necrosis. Use of antibiotics (eg, high-dose penicillin or vancomycin) is included in this category.

Obtaining an accurate medical history and examining the patient’s fluid status are critical. Although numerous novel biomarkers have been investigated for detection of AKI, none are yet in wide use. The primary assessment measures remain a serum panel to evaluate SCr and BUN levels; an electrolyte panel to assess for abnormalities; a complete blood count to assess for anemia caused by a less likely source; urinalysis; and imaging to assess for abnormalities or structural changes.

Urinalysis. Urine often holds the key to diagnosis of AKI. Notably in a prerenal injury, its specific gravity will be elevated, but the rest of the urine will likely be bland.³

Continue to: Urinalysis is helpful for...

Urinalysis is helpful for ruling out intrinsic causes of AKI. Patients with intrarenal AKI will have abnormal urine sediment; for example, red blood cell casts are found in glomerulonephritis; granular casts in cases of acute tubular necrosis; and white blood cell casts and eosinophils in acute interstitial nephritis.⁴

Imaging. The most commonly used imaging for AKI is retroperitoneal ultrasonography of the kidneys, ureters, and bladder, which provides information on the size and shape of the kidneys and can detect stones or masses. It also detects the presence or absence of hydronephrosis, which can occur in postrenal injuries.

Currently, no definitive therapy or pharmacologic agent is approved for AKI; treatment focuses on reversing the cause of the injury. In the immediate aftermath of AKI, it is important to avoid potentially nephrotoxic medications, including NSAIDs. Minimize the use of diuretics and avoid ACEIs and ARB therapy; these can be reintroduced after lab results confirm that the AKI has resolved with a stabilized SCr.

Practice guidelines recommend prompt follow-up at 3 months in most cases of AKI.¹ Providers should obtain a metabolic panel and perform a urinalysis to evaluate for chronic kidney disease (CKD), because almost one-third of patients with an AKI episode are newly classified with CKD in the following year.⁵ Earlier follow-up (< 3 months) is warranted if the patient has a significant comorbidity, such as congestive heart failure.^1,2—CS

Christopher Sjoberg, CNN-NP
Idaho Nephrology Associates, Boise
Adjunct Faculty, Boise State University

CHICAGO – Although advanced renal dysfunction is a major contraindication for open repair of complex thoracoabdominal aneurysms (TAAA) and pararenal aneurysms (PRA), a single-center study of patients who had branched-fenestrated endovascular aneurysm repair (B-FEVAR) found that those with severe or moderate dysfunction and those with normal kidney function had similar results, according to a study reported at the annual meeting of the Midwestern Vascular Surgery Society.

“In our series of patients with stage 4 and 5 chronic kidney disease, branched-fenestration aneurysm repair for pararenal and thoracoabdominal aneurysm was associated with acceptable morbidity and mortality,” said Luis C. Cajas-Monson, MD, of the Mayo Clinic in Rochester, Minn. “Although often a contraindication for open repair, B-FEVAR could be a safe alternative for TAAA patients with poor renal function.”

The study evaluated 231 patients who had B-FEVAR for the following etiologies: 80 for PRA; 89 for Type I to III TAAA; and 62 for type IV TAAA. The patients had at least 1 year of follow-up. A small percentage of patients (4%; n = 9) had stage IV or V chronic kidney disease; the remainder had stage I to III CKD. The study compared results in the lower- and higher-stage CKD groups.

“The frequency of endovascular aortic aneurysm repair continues to increase, and it has advanced to treating more complex aortic pathology,” Dr. Cajas-Monson said. “There appears to be no significant decline in renal function with complex EVAR.” He noted that in open TAAA repair, the more severe the chronic kidney disease state, the worse the outcomes.

The Mayo researchers set out to evaluate the impact of renal function on survival after B-FEVAR for TAAA and PRA. “We hypothesized that renal function is not a significant factor in early and late survival after B-FEVAR,” Dr. Cajas-Monson said. TAAA patients represented 65% of the study population, with 59% having Extent I to III and 41% having Extent IV disease.

Dr. Cajas-Monson noted that demographics were comparable between the higher- and lower-stage CKD groups, with the exception of higher baseline creatinine levels in the CKD 4/5 patients: 3.14 vs. 1.13 (P less than .001). Operative outcomes and length of stay were also similar.

The higher-stage group had a higher overall rate of major adverse events, but given the small sample size this was not found to be significantly different (44% vs. 29%; P = .26). However, there were no events of perioperative death, stroke, paraplegia or estimated blood loss greater than 1 L in the higher-stage patients, while the lower-stage group had low percentages of these events.

Three-year survival was 84% in the lower-stage group and 75% in the higher-stage group.

Dr. Cajas-Monson acknowledged that the small sample size was a limitation of the study. “Further evaluation of patients with renal dysfunction is needed to validate our initial findings,” he said.

This abstract of this study was published in the Journal of Vascular Surgery (2019. 70 [3]:e67).

Dr. Cajas-Monson had no financial relationships to disclose.

SOURCE: Cajas-Monson LC et al. Midwestern Vascular 2019, Abstract 19.

CHICAGO – Although advanced renal dysfunction is a major contraindication for open repair of complex thoracoabdominal aneurysms (TAAA) and pararenal aneurysms (PRA), a single-center study of patients who had branched-fenestrated endovascular aneurysm repair (B-FEVAR) found that those with severe or moderate dysfunction and those with normal kidney function had similar results, according to a study reported at the annual meeting of the Midwestern Vascular Surgery Society.

“In our series of patients with stage 4 and 5 chronic kidney disease, branched-fenestration aneurysm repair for pararenal and thoracoabdominal aneurysm was associated with acceptable morbidity and mortality,” said Luis C. Cajas-Monson, MD, of the Mayo Clinic in Rochester, Minn. “Although often a contraindication for open repair, B-FEVAR could be a safe alternative for TAAA patients with poor renal function.”

The study evaluated 231 patients who had B-FEVAR for the following etiologies: 80 for PRA; 89 for Type I to III TAAA; and 62 for type IV TAAA. The patients had at least 1 year of follow-up. A small percentage of patients (4%; n = 9) had stage IV or V chronic kidney disease; the remainder had stage I to III CKD. The study compared results in the lower- and higher-stage CKD groups.

“The frequency of endovascular aortic aneurysm repair continues to increase, and it has advanced to treating more complex aortic pathology,” Dr. Cajas-Monson said. “There appears to be no significant decline in renal function with complex EVAR.” He noted that in open TAAA repair, the more severe the chronic kidney disease state, the worse the outcomes.

The Mayo researchers set out to evaluate the impact of renal function on survival after B-FEVAR for TAAA and PRA. “We hypothesized that renal function is not a significant factor in early and late survival after B-FEVAR,” Dr. Cajas-Monson said. TAAA patients represented 65% of the study population, with 59% having Extent I to III and 41% having Extent IV disease.

Dr. Cajas-Monson noted that demographics were comparable between the higher- and lower-stage CKD groups, with the exception of higher baseline creatinine levels in the CKD 4/5 patients: 3.14 vs. 1.13 (P less than .001). Operative outcomes and length of stay were also similar.

The higher-stage group had a higher overall rate of major adverse events, but given the small sample size this was not found to be significantly different (44% vs. 29%; P = .26). However, there were no events of perioperative death, stroke, paraplegia or estimated blood loss greater than 1 L in the higher-stage patients, while the lower-stage group had low percentages of these events.

Three-year survival was 84% in the lower-stage group and 75% in the higher-stage group.

Dr. Cajas-Monson acknowledged that the small sample size was a limitation of the study. “Further evaluation of patients with renal dysfunction is needed to validate our initial findings,” he said.

This abstract of this study was published in the Journal of Vascular Surgery (2019. 70 [3]:e67).

Dr. Cajas-Monson had no financial relationships to disclose.

SOURCE: Cajas-Monson LC et al. Midwestern Vascular 2019, Abstract 19.

CHICAGO – Although advanced renal dysfunction is a major contraindication for open repair of complex thoracoabdominal aneurysms (TAAA) and pararenal aneurysms (PRA), a single-center study of patients who had branched-fenestrated endovascular aneurysm repair (B-FEVAR) found that those with severe or moderate dysfunction and those with normal kidney function had similar results, according to a study reported at the annual meeting of the Midwestern Vascular Surgery Society.

“In our series of patients with stage 4 and 5 chronic kidney disease, branched-fenestration aneurysm repair for pararenal and thoracoabdominal aneurysm was associated with acceptable morbidity and mortality,” said Luis C. Cajas-Monson, MD, of the Mayo Clinic in Rochester, Minn. “Although often a contraindication for open repair, B-FEVAR could be a safe alternative for TAAA patients with poor renal function.”

The study evaluated 231 patients who had B-FEVAR for the following etiologies: 80 for PRA; 89 for Type I to III TAAA; and 62 for type IV TAAA. The patients had at least 1 year of follow-up. A small percentage of patients (4%; n = 9) had stage IV or V chronic kidney disease; the remainder had stage I to III CKD. The study compared results in the lower- and higher-stage CKD groups.

“The frequency of endovascular aortic aneurysm repair continues to increase, and it has advanced to treating more complex aortic pathology,” Dr. Cajas-Monson said. “There appears to be no significant decline in renal function with complex EVAR.” He noted that in open TAAA repair, the more severe the chronic kidney disease state, the worse the outcomes.

The Mayo researchers set out to evaluate the impact of renal function on survival after B-FEVAR for TAAA and PRA. “We hypothesized that renal function is not a significant factor in early and late survival after B-FEVAR,” Dr. Cajas-Monson said. TAAA patients represented 65% of the study population, with 59% having Extent I to III and 41% having Extent IV disease.

Dr. Cajas-Monson noted that demographics were comparable between the higher- and lower-stage CKD groups, with the exception of higher baseline creatinine levels in the CKD 4/5 patients: 3.14 vs. 1.13 (P less than .001). Operative outcomes and length of stay were also similar.

The higher-stage group had a higher overall rate of major adverse events, but given the small sample size this was not found to be significantly different (44% vs. 29%; P = .26). However, there were no events of perioperative death, stroke, paraplegia or estimated blood loss greater than 1 L in the higher-stage patients, while the lower-stage group had low percentages of these events.

Three-year survival was 84% in the lower-stage group and 75% in the higher-stage group.

Dr. Cajas-Monson acknowledged that the small sample size was a limitation of the study. “Further evaluation of patients with renal dysfunction is needed to validate our initial findings,” he said.

This abstract of this study was published in the Journal of Vascular Surgery (2019. 70 [3]:e67).

Dr. Cajas-Monson had no financial relationships to disclose.

SOURCE: Cajas-Monson LC et al. Midwestern Vascular 2019, Abstract 19.

BARCELONA – Checkpoint inhibition with nivolumab led to a clinically meaningful, but not statistically significant, improvement in overall survival, compared with sorafenib for the first-line treatment of advanced hepatocellular carcinoma (HCC) in the phase 3 CheckMate 459 study.

Median overall survival (OS), the primary study endpoint, was 16.4 months in 371 patients randomized to receive the programmed death-1 (PD-1) inhibitor nivolumab, and 14.7 months in 372 patients who received the tyrosine kinase inhibitor sorafenib – the current standard for advanced HCC therapy (hazard ratio, 0.85; P = .0752), Thomas Yau, MD, reported at the European Society for Medical Oncology Congress.

The median OS seen with nivolumab is the longest ever reported in a first-line phase 3 HCC trial, but the difference between the arms did not meet the predefined threshold for statistical significance (HR, 0.84 and P = .419). However, clinical benefit was observed across predefined subgroups of patients, including those with hepatitis infection and those with vascular invasion and/or extrahepatic spread, said Dr. Yau of the University of Hong Kong.

The overall response rates (ORR) were 15% and 7% in the nivolumab and sorafenib arms, with 14 and 5 patients in each group experiencing a complete response (CR), respectively, he said.

At 12 and 24 months, the OS rates in the groups were 59.7% vs. 55.1%, and 36.5% vs. 33.1%, respectively. Median progression-free survival (PFS) was similar in the groups, at 3.7 and 3.8 months, respectively, and analysis by baseline tumor programmed death-ligand 1 (PD-L1) expression showed that ORR was 28% vs. 9% with PD-L1 expression of 1% or greater in the groups, respectively, and 12% vs. 7% among those with PD-L1 expression less than 1%.

Additionally, nivolumab had a more tolerable safety profile; grade 3/4 treatment-related adverse events were reported in 22% and 49% of patients in the groups, respectively, and led to discontinuation in 4% and 8%, respectively. No new safety signals were observed, Dr. Yau said.

Participants in the multicenter study were systemic therapy–naive adults with advanced disease. They were randomized 1:1 to receive intravenous nivolumab at a dose of 240 mg every 2 weeks or oral sorafenib at a dose of 400 mg twice daily, and were followed for at least 22.8 months.

“These results are important in the treatment of hepatocellular carcinoma, as there have been no significant advances over sorafenib in the first-line setting in more than a decade,” Dr. Yau said in an ESMO press release. “HCC is often diagnosed in the advanced stage, where effective treatment options are limited. The encouraging efficacy and favorable safety profile seen with nivolumab demonstrates the potential benefit of immunotherapy as a first-line treatment for patients with this aggressive cancer.”

He further noted that the OS benefit seen in this study is “particularly impactful considering the high frequency of subsequent use of systemic therapy, including immunotherapy, in the sorafenib arm,” and that the OS impact is bolstered by patient-reported outcomes suggesting improved quality of life in the nivolumab arm.

Nevertheless, the fact that CheckMate 459 did not meet its primary OS endpoint means the findings are unlikely to change the current standard of care, according to Angela Lamarca, MD, PhD, consultant medical oncologist and honorary senior lecturer at the Christie NHS Foundation Trust, University of Manchester (England).

She added, however, that the findings do underscore a potential role for immunotherapy in the first-line treatment of advanced HCC and noted that the clinically meaningful improvement in response rates with nivolumab, along with the checkpoint inhibitor’s favorable safety profile in this study, raise the possibility of its selection in this setting.

“In a hypothetical scenario in which both options ... were available and reimbursed, and if quality of life was shown to be better with nivolumab ... clinicians and patients may favor the option with a more tolerable safety profile,” she said in the press release.

She added, however, that at this point conclusions should be made cautiously and the high cost of immunotherapy should be considered.

Dr. Lamarca also highlighted the finding that patients with high PD-L1 expression had an increased response rate only in the nivolumab arm. This suggests a potential role for PD-L1 expression as a predictive biomarker in advanced HCC, but more research is needed to better understand how to select patients for immunotherapy, she said, adding that the lack of a reliable biomarker may have contributed to the study’s failure to show improved OS with nivolumab.

“In addition, the study design with a ‘high’ predefined threshold of statistical significance is generating confusion in the community, with potentially beneficial therapies generating statistically negative studies,” she noted.

CheckMate 459 was funded by Bristol-Myers Squibb. Dr. Yau is an advisor and/or consultant to Bristol-Myers Squibb, and reported honoraria from the company to his institution. Dr. Lamarca reported honoraria, consultation fees, travel funding, and/or education funding from Eisai, Nutricia, Ipsen, Pfizer, Bayer, AAA, Sirtex, Delcath, Novartis, and Mylan, as well as participation in company-sponsored speaker bureaus for Pfizer, Ipsen, Merck, and Incyte.

SOURCE: Yau T et al. ESMO 2019, Abstract LBA38-PR
 

BARCELONA – Checkpoint inhibition with nivolumab led to a clinically meaningful, but not statistically significant, improvement in overall survival, compared with sorafenib for the first-line treatment of advanced hepatocellular carcinoma (HCC) in the phase 3 CheckMate 459 study.

Median overall survival (OS), the primary study endpoint, was 16.4 months in 371 patients randomized to receive the programmed death-1 (PD-1) inhibitor nivolumab, and 14.7 months in 372 patients who received the tyrosine kinase inhibitor sorafenib – the current standard for advanced HCC therapy (hazard ratio, 0.85; P = .0752), Thomas Yau, MD, reported at the European Society for Medical Oncology Congress.

The median OS seen with nivolumab is the longest ever reported in a first-line phase 3 HCC trial, but the difference between the arms did not meet the predefined threshold for statistical significance (HR, 0.84 and P = .419). However, clinical benefit was observed across predefined subgroups of patients, including those with hepatitis infection and those with vascular invasion and/or extrahepatic spread, said Dr. Yau of the University of Hong Kong.

The overall response rates (ORR) were 15% and 7% in the nivolumab and sorafenib arms, with 14 and 5 patients in each group experiencing a complete response (CR), respectively, he said.

At 12 and 24 months, the OS rates in the groups were 59.7% vs. 55.1%, and 36.5% vs. 33.1%, respectively. Median progression-free survival (PFS) was similar in the groups, at 3.7 and 3.8 months, respectively, and analysis by baseline tumor programmed death-ligand 1 (PD-L1) expression showed that ORR was 28% vs. 9% with PD-L1 expression of 1% or greater in the groups, respectively, and 12% vs. 7% among those with PD-L1 expression less than 1%.

Additionally, nivolumab had a more tolerable safety profile; grade 3/4 treatment-related adverse events were reported in 22% and 49% of patients in the groups, respectively, and led to discontinuation in 4% and 8%, respectively. No new safety signals were observed, Dr. Yau said.

Participants in the multicenter study were systemic therapy–naive adults with advanced disease. They were randomized 1:1 to receive intravenous nivolumab at a dose of 240 mg every 2 weeks or oral sorafenib at a dose of 400 mg twice daily, and were followed for at least 22.8 months.

“These results are important in the treatment of hepatocellular carcinoma, as there have been no significant advances over sorafenib in the first-line setting in more than a decade,” Dr. Yau said in an ESMO press release. “HCC is often diagnosed in the advanced stage, where effective treatment options are limited. The encouraging efficacy and favorable safety profile seen with nivolumab demonstrates the potential benefit of immunotherapy as a first-line treatment for patients with this aggressive cancer.”

He further noted that the OS benefit seen in this study is “particularly impactful considering the high frequency of subsequent use of systemic therapy, including immunotherapy, in the sorafenib arm,” and that the OS impact is bolstered by patient-reported outcomes suggesting improved quality of life in the nivolumab arm.

Nevertheless, the fact that CheckMate 459 did not meet its primary OS endpoint means the findings are unlikely to change the current standard of care, according to Angela Lamarca, MD, PhD, consultant medical oncologist and honorary senior lecturer at the Christie NHS Foundation Trust, University of Manchester (England).

She added, however, that the findings do underscore a potential role for immunotherapy in the first-line treatment of advanced HCC and noted that the clinically meaningful improvement in response rates with nivolumab, along with the checkpoint inhibitor’s favorable safety profile in this study, raise the possibility of its selection in this setting.

“In a hypothetical scenario in which both options ... were available and reimbursed, and if quality of life was shown to be better with nivolumab ... clinicians and patients may favor the option with a more tolerable safety profile,” she said in the press release.

She added, however, that at this point conclusions should be made cautiously and the high cost of immunotherapy should be considered.

Dr. Lamarca also highlighted the finding that patients with high PD-L1 expression had an increased response rate only in the nivolumab arm. This suggests a potential role for PD-L1 expression as a predictive biomarker in advanced HCC, but more research is needed to better understand how to select patients for immunotherapy, she said, adding that the lack of a reliable biomarker may have contributed to the study’s failure to show improved OS with nivolumab.

“In addition, the study design with a ‘high’ predefined threshold of statistical significance is generating confusion in the community, with potentially beneficial therapies generating statistically negative studies,” she noted.

CheckMate 459 was funded by Bristol-Myers Squibb. Dr. Yau is an advisor and/or consultant to Bristol-Myers Squibb, and reported honoraria from the company to his institution. Dr. Lamarca reported honoraria, consultation fees, travel funding, and/or education funding from Eisai, Nutricia, Ipsen, Pfizer, Bayer, AAA, Sirtex, Delcath, Novartis, and Mylan, as well as participation in company-sponsored speaker bureaus for Pfizer, Ipsen, Merck, and Incyte.

SOURCE: Yau T et al. ESMO 2019, Abstract LBA38-PR
 

BARCELONA – Checkpoint inhibition with nivolumab led to a clinically meaningful, but not statistically significant, improvement in overall survival, compared with sorafenib for the first-line treatment of advanced hepatocellular carcinoma (HCC) in the phase 3 CheckMate 459 study.

Median overall survival (OS), the primary study endpoint, was 16.4 months in 371 patients randomized to receive the programmed death-1 (PD-1) inhibitor nivolumab, and 14.7 months in 372 patients who received the tyrosine kinase inhibitor sorafenib – the current standard for advanced HCC therapy (hazard ratio, 0.85; P = .0752), Thomas Yau, MD, reported at the European Society for Medical Oncology Congress.

The median OS seen with nivolumab is the longest ever reported in a first-line phase 3 HCC trial, but the difference between the arms did not meet the predefined threshold for statistical significance (HR, 0.84 and P = .419). However, clinical benefit was observed across predefined subgroups of patients, including those with hepatitis infection and those with vascular invasion and/or extrahepatic spread, said Dr. Yau of the University of Hong Kong.

The overall response rates (ORR) were 15% and 7% in the nivolumab and sorafenib arms, with 14 and 5 patients in each group experiencing a complete response (CR), respectively, he said.

At 12 and 24 months, the OS rates in the groups were 59.7% vs. 55.1%, and 36.5% vs. 33.1%, respectively. Median progression-free survival (PFS) was similar in the groups, at 3.7 and 3.8 months, respectively, and analysis by baseline tumor programmed death-ligand 1 (PD-L1) expression showed that ORR was 28% vs. 9% with PD-L1 expression of 1% or greater in the groups, respectively, and 12% vs. 7% among those with PD-L1 expression less than 1%.

Additionally, nivolumab had a more tolerable safety profile; grade 3/4 treatment-related adverse events were reported in 22% and 49% of patients in the groups, respectively, and led to discontinuation in 4% and 8%, respectively. No new safety signals were observed, Dr. Yau said.

Participants in the multicenter study were systemic therapy–naive adults with advanced disease. They were randomized 1:1 to receive intravenous nivolumab at a dose of 240 mg every 2 weeks or oral sorafenib at a dose of 400 mg twice daily, and were followed for at least 22.8 months.

“These results are important in the treatment of hepatocellular carcinoma, as there have been no significant advances over sorafenib in the first-line setting in more than a decade,” Dr. Yau said in an ESMO press release. “HCC is often diagnosed in the advanced stage, where effective treatment options are limited. The encouraging efficacy and favorable safety profile seen with nivolumab demonstrates the potential benefit of immunotherapy as a first-line treatment for patients with this aggressive cancer.”

He further noted that the OS benefit seen in this study is “particularly impactful considering the high frequency of subsequent use of systemic therapy, including immunotherapy, in the sorafenib arm,” and that the OS impact is bolstered by patient-reported outcomes suggesting improved quality of life in the nivolumab arm.

Nevertheless, the fact that CheckMate 459 did not meet its primary OS endpoint means the findings are unlikely to change the current standard of care, according to Angela Lamarca, MD, PhD, consultant medical oncologist and honorary senior lecturer at the Christie NHS Foundation Trust, University of Manchester (England).

She added, however, that the findings do underscore a potential role for immunotherapy in the first-line treatment of advanced HCC and noted that the clinically meaningful improvement in response rates with nivolumab, along with the checkpoint inhibitor’s favorable safety profile in this study, raise the possibility of its selection in this setting.

“In a hypothetical scenario in which both options ... were available and reimbursed, and if quality of life was shown to be better with nivolumab ... clinicians and patients may favor the option with a more tolerable safety profile,” she said in the press release.

She added, however, that at this point conclusions should be made cautiously and the high cost of immunotherapy should be considered.

Dr. Lamarca also highlighted the finding that patients with high PD-L1 expression had an increased response rate only in the nivolumab arm. This suggests a potential role for PD-L1 expression as a predictive biomarker in advanced HCC, but more research is needed to better understand how to select patients for immunotherapy, she said, adding that the lack of a reliable biomarker may have contributed to the study’s failure to show improved OS with nivolumab.

“In addition, the study design with a ‘high’ predefined threshold of statistical significance is generating confusion in the community, with potentially beneficial therapies generating statistically negative studies,” she noted.

CheckMate 459 was funded by Bristol-Myers Squibb. Dr. Yau is an advisor and/or consultant to Bristol-Myers Squibb, and reported honoraria from the company to his institution. Dr. Lamarca reported honoraria, consultation fees, travel funding, and/or education funding from Eisai, Nutricia, Ipsen, Pfizer, Bayer, AAA, Sirtex, Delcath, Novartis, and Mylan, as well as participation in company-sponsored speaker bureaus for Pfizer, Ipsen, Merck, and Incyte.

SOURCE: Yau T et al. ESMO 2019, Abstract LBA38-PR
 

Working memory (WM)—the function that allows us to temporarily store information and use it for cognitive tasks like learning, reasoning, and comprehension—is thought to play an important role in managing anxiety and intrusive symptoms of posttraumatic stress disorder (PTSD). Researchers have found inefficient filtering of threatening material from WM and increased storage of task-irrelevant threat distractors are associated with elevated anxiety. Thus, veterans with high levels of anxiety may disproportionately allocate cognitive resources toward threatening stimuli, and have trouble keeping threatening thoughts from entering WM and staying there. People with PTSD also have been shown to have problems using WM in emotional contexts, making it hard for them to deal with stressful situations in work and personal life. Some research has suggested that WM training that incorporates affective stimuli may increase the ability to use WM in emotional contexts. In a pilot study, researchers from Medical College of Wisconsin and University of Wisconsin-Milwaukee expanded on that possibility by testing 2 kinds of WM training in 21 veterans with elevated PTSD symptoms.

Participants completed a pretest, 15 sessions of at-home computerized training, a posttest, and a 1-month follow-up session. The computerized tests included tasks to measure WM capacity, such as solving math questions while trying to remember a set of unrelated numbers. The participants were then assigned to active emotional WM training (n-back) or control emotional WM training (1-back). The n-back training involved constant updating of information stored in WM and shifting between visual and auditory stimuli using 8 different faces and 8 different negative words. The training sessions started at the 1-back level and increased in difficulty level by level with performance with > 95% accuracy, or were scaled back with performance with < 75% accuracy. The control training was the same but consisted only of 1 level.

Overall, the researchers say, contrary to their hypothesis, they did not find a significant difference in results from the 2 groups. But they did find that both trainings had an overall “significant and sizable” impact on PTSD symptoms in both groups: 73% of the n-back group and 60% of the 1-back group had a reduction of ≥ 10 points on the PTSD Checklist total scores, which the researchers say is considered a clinically meaningful change. Moreover, both groups showed a clinically meaningful reduction in symptoms at follow-up: 55% and 40%, respectively.

It was interesting, the researchers say, that both groups showed improvement, especially with the 1-back intervention, which they had used as a “minimally effective” control condition. They also note that, anecdotally, the participants found both interventions “quite challenging.” It may be that in this population even the 1-back intervention is enough to detectably reduce symptoms, the researchers say. They were also encouraged to see that the n-back condition (marginally) outperformed the 1-back condition in improving reexperiencing symptoms, theoretically the most relevant training target of WM-focused intervention. The researchers  believe that their study yields useful pilot data, suggesting that n-back training can have a clinical impact primarily by reducing reexperiencing symptoms, which are highly likely to indicate the presence of impaired WM functioning.

Working memory (WM)—the function that allows us to temporarily store information and use it for cognitive tasks like learning, reasoning, and comprehension—is thought to play an important role in managing anxiety and intrusive symptoms of posttraumatic stress disorder (PTSD). Researchers have found inefficient filtering of threatening material from WM and increased storage of task-irrelevant threat distractors are associated with elevated anxiety. Thus, veterans with high levels of anxiety may disproportionately allocate cognitive resources toward threatening stimuli, and have trouble keeping threatening thoughts from entering WM and staying there. People with PTSD also have been shown to have problems using WM in emotional contexts, making it hard for them to deal with stressful situations in work and personal life. Some research has suggested that WM training that incorporates affective stimuli may increase the ability to use WM in emotional contexts. In a pilot study, researchers from Medical College of Wisconsin and University of Wisconsin-Milwaukee expanded on that possibility by testing 2 kinds of WM training in 21 veterans with elevated PTSD symptoms.

Participants completed a pretest, 15 sessions of at-home computerized training, a posttest, and a 1-month follow-up session. The computerized tests included tasks to measure WM capacity, such as solving math questions while trying to remember a set of unrelated numbers. The participants were then assigned to active emotional WM training (n-back) or control emotional WM training (1-back). The n-back training involved constant updating of information stored in WM and shifting between visual and auditory stimuli using 8 different faces and 8 different negative words. The training sessions started at the 1-back level and increased in difficulty level by level with performance with > 95% accuracy, or were scaled back with performance with < 75% accuracy. The control training was the same but consisted only of 1 level.

Overall, the researchers say, contrary to their hypothesis, they did not find a significant difference in results from the 2 groups. But they did find that both trainings had an overall “significant and sizable” impact on PTSD symptoms in both groups: 73% of the n-back group and 60% of the 1-back group had a reduction of ≥ 10 points on the PTSD Checklist total scores, which the researchers say is considered a clinically meaningful change. Moreover, both groups showed a clinically meaningful reduction in symptoms at follow-up: 55% and 40%, respectively.

It was interesting, the researchers say, that both groups showed improvement, especially with the 1-back intervention, which they had used as a “minimally effective” control condition. They also note that, anecdotally, the participants found both interventions “quite challenging.” It may be that in this population even the 1-back intervention is enough to detectably reduce symptoms, the researchers say. They were also encouraged to see that the n-back condition (marginally) outperformed the 1-back condition in improving reexperiencing symptoms, theoretically the most relevant training target of WM-focused intervention. The researchers  believe that their study yields useful pilot data, suggesting that n-back training can have a clinical impact primarily by reducing reexperiencing symptoms, which are highly likely to indicate the presence of impaired WM functioning.

Working memory (WM)—the function that allows us to temporarily store information and use it for cognitive tasks like learning, reasoning, and comprehension—is thought to play an important role in managing anxiety and intrusive symptoms of posttraumatic stress disorder (PTSD). Researchers have found inefficient filtering of threatening material from WM and increased storage of task-irrelevant threat distractors are associated with elevated anxiety. Thus, veterans with high levels of anxiety may disproportionately allocate cognitive resources toward threatening stimuli, and have trouble keeping threatening thoughts from entering WM and staying there. People with PTSD also have been shown to have problems using WM in emotional contexts, making it hard for them to deal with stressful situations in work and personal life. Some research has suggested that WM training that incorporates affective stimuli may increase the ability to use WM in emotional contexts. In a pilot study, researchers from Medical College of Wisconsin and University of Wisconsin-Milwaukee expanded on that possibility by testing 2 kinds of WM training in 21 veterans with elevated PTSD symptoms.

Participants completed a pretest, 15 sessions of at-home computerized training, a posttest, and a 1-month follow-up session. The computerized tests included tasks to measure WM capacity, such as solving math questions while trying to remember a set of unrelated numbers. The participants were then assigned to active emotional WM training (n-back) or control emotional WM training (1-back). The n-back training involved constant updating of information stored in WM and shifting between visual and auditory stimuli using 8 different faces and 8 different negative words. The training sessions started at the 1-back level and increased in difficulty level by level with performance with > 95% accuracy, or were scaled back with performance with < 75% accuracy. The control training was the same but consisted only of 1 level.

Overall, the researchers say, contrary to their hypothesis, they did not find a significant difference in results from the 2 groups. But they did find that both trainings had an overall “significant and sizable” impact on PTSD symptoms in both groups: 73% of the n-back group and 60% of the 1-back group had a reduction of ≥ 10 points on the PTSD Checklist total scores, which the researchers say is considered a clinically meaningful change. Moreover, both groups showed a clinically meaningful reduction in symptoms at follow-up: 55% and 40%, respectively.

It was interesting, the researchers say, that both groups showed improvement, especially with the 1-back intervention, which they had used as a “minimally effective” control condition. They also note that, anecdotally, the participants found both interventions “quite challenging.” It may be that in this population even the 1-back intervention is enough to detectably reduce symptoms, the researchers say. They were also encouraged to see that the n-back condition (marginally) outperformed the 1-back condition in improving reexperiencing symptoms, theoretically the most relevant training target of WM-focused intervention. The researchers  believe that their study yields useful pilot data, suggesting that n-back training can have a clinical impact primarily by reducing reexperiencing symptoms, which are highly likely to indicate the presence of impaired WM functioning.

MADRID – Psoriasis patients on adalimumab for up to 10 years in the prospective, observational, international, real-world ESPRIT registry had a sharply reduced likelihood of all-cause mortality, compared with the age- and sex-matched general population in participating countries, Diamant T. Thaci, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

“If someone tells you that you as a dermatologist can save patient lives by controlling psoriasis, you may not believe it. But look at this standardized mortality ratio data,” said Dr. Thaci, professor of dermatology and head of the Comprehensive Center for Inflammation Medicine at the University of Luebeck (Germany).

Indeed, the standardized mortality ratio in participants in the ESPRIT registry, featuring 6,014 psoriasis patients with a collective 28,161 person-years on adalimumab in routine clinical practice, was 58% lower than expected, based upon published mortality rate data for the general population in the United States, Canada, and the 10 participating European countries. A total of 144 deaths were predicted in the matched general population, yet only 60 deaths occurred in adalimumab-treated registry participants.

This finding is all the more remarkable because ESPRIT participants had high rates of cardiovascular risk factors, as well as a substantial burden of comorbid conditions, as is typical for patients with chronic moderate to severe psoriasis encountered in real-world clinical practice. It’s a different population than enrollees in the long-term, open-label extensions of phase 3, double-blind, randomized, controlled clinical trials of biologics in psoriasis, which at the outset typically excluded patients with baseline substantial comorbidities, he noted.

Moreover, the incidence rates of serious infections, malignancies, and cardiovascular events in ESPRIT participants remained stable over time and well within the range of published rates in psoriasis patients not on biologic therapy.

“All of this underscores the importance of good control of psoriasis,” Dr. Thaci commented.

The ESPRIT registry began enrolling patients and evaluating them every 6 months in 2008, when the vast majority of dermatologists in clinical practice relied upon Physician Global Assessment (PGA) to evaluate treatment efficacy. For this reason, the PGA, rather than the Psoriasis Area and Severity Index, was the main efficacy measure utilized in the registry. The rate of PGA “clear” or “almost clear” was steady over time at 57% at 1 year, 62.1% at 5 years, and 61.5% at 10 years. It should be noted that this was reported in an “as-observed” analysis, which introduces bias favoring a rosier picture of efficacy since by 10 years slightly under half of patients remained on the tumor necrosis factor inhibitor.

However, the primary focus of this ESPRIT analysis was safety, not efficacy. The rate of serious infections was 1.0 event per 100 person-years on adalimumab, compared with published rates of 0.3-2.1 events/100 person-years in psoriasis patients not on a biologic. Malignancies occurred at a rate of 1.3 events/100 person-years in ESPRIT, compared with published rates of 0.5-2.0/100 person-years in psoriasis patients not on biologic therapy. Acute MI occurred at a rate of 0.1 cases/100 person-years in ESPRIT, stroke at 0.2 events/100 person-years, and heart failure at less than 0.1 event/100 person-years, versus a collective rate of 0.6-1.5 events/100 person-years in the comparator population.

Another view of the data is that, at 10 years, 99.4% of ESPRIT participants had not experienced an acute MI, 95.9% hadn’t had a malignancy, and 96.1% remained free of serious infection while on adalimumab, Dr. Thaci continued.

Injection-site reactions, a significant source of concern when adalimumab first reached the marketplace, occurred at a rate of 0.2 events/100 person-years over the course of 10 years. Oral candidiasis, active tuberculosis, demyelinating disorders, and lupus-like reactions were rare, each occurring at an incidence of less than 0.1 event/100 person-years.

Dr. Thaci’s 10-year update from the ongoing registry follows an earlier report of the 5-year results (J Am Acad Dermatol. 2015 Sep;73[3]:410-9.e6).

The ESPRIT registry is sponsored by AbbVie. Dr. Thaci reported serving as a consultant to and/or receiving research grants from that pharmaceutical company and nearly two dozen others.

[email protected]

MADRID – Psoriasis patients on adalimumab for up to 10 years in the prospective, observational, international, real-world ESPRIT registry had a sharply reduced likelihood of all-cause mortality, compared with the age- and sex-matched general population in participating countries, Diamant T. Thaci, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

“If someone tells you that you as a dermatologist can save patient lives by controlling psoriasis, you may not believe it. But look at this standardized mortality ratio data,” said Dr. Thaci, professor of dermatology and head of the Comprehensive Center for Inflammation Medicine at the University of Luebeck (Germany).

Indeed, the standardized mortality ratio in participants in the ESPRIT registry, featuring 6,014 psoriasis patients with a collective 28,161 person-years on adalimumab in routine clinical practice, was 58% lower than expected, based upon published mortality rate data for the general population in the United States, Canada, and the 10 participating European countries. A total of 144 deaths were predicted in the matched general population, yet only 60 deaths occurred in adalimumab-treated registry participants.

This finding is all the more remarkable because ESPRIT participants had high rates of cardiovascular risk factors, as well as a substantial burden of comorbid conditions, as is typical for patients with chronic moderate to severe psoriasis encountered in real-world clinical practice. It’s a different population than enrollees in the long-term, open-label extensions of phase 3, double-blind, randomized, controlled clinical trials of biologics in psoriasis, which at the outset typically excluded patients with baseline substantial comorbidities, he noted.

Moreover, the incidence rates of serious infections, malignancies, and cardiovascular events in ESPRIT participants remained stable over time and well within the range of published rates in psoriasis patients not on biologic therapy.

“All of this underscores the importance of good control of psoriasis,” Dr. Thaci commented.

The ESPRIT registry began enrolling patients and evaluating them every 6 months in 2008, when the vast majority of dermatologists in clinical practice relied upon Physician Global Assessment (PGA) to evaluate treatment efficacy. For this reason, the PGA, rather than the Psoriasis Area and Severity Index, was the main efficacy measure utilized in the registry. The rate of PGA “clear” or “almost clear” was steady over time at 57% at 1 year, 62.1% at 5 years, and 61.5% at 10 years. It should be noted that this was reported in an “as-observed” analysis, which introduces bias favoring a rosier picture of efficacy since by 10 years slightly under half of patients remained on the tumor necrosis factor inhibitor.

However, the primary focus of this ESPRIT analysis was safety, not efficacy. The rate of serious infections was 1.0 event per 100 person-years on adalimumab, compared with published rates of 0.3-2.1 events/100 person-years in psoriasis patients not on a biologic. Malignancies occurred at a rate of 1.3 events/100 person-years in ESPRIT, compared with published rates of 0.5-2.0/100 person-years in psoriasis patients not on biologic therapy. Acute MI occurred at a rate of 0.1 cases/100 person-years in ESPRIT, stroke at 0.2 events/100 person-years, and heart failure at less than 0.1 event/100 person-years, versus a collective rate of 0.6-1.5 events/100 person-years in the comparator population.

Another view of the data is that, at 10 years, 99.4% of ESPRIT participants had not experienced an acute MI, 95.9% hadn’t had a malignancy, and 96.1% remained free of serious infection while on adalimumab, Dr. Thaci continued.

Injection-site reactions, a significant source of concern when adalimumab first reached the marketplace, occurred at a rate of 0.2 events/100 person-years over the course of 10 years. Oral candidiasis, active tuberculosis, demyelinating disorders, and lupus-like reactions were rare, each occurring at an incidence of less than 0.1 event/100 person-years.

Dr. Thaci’s 10-year update from the ongoing registry follows an earlier report of the 5-year results (J Am Acad Dermatol. 2015 Sep;73[3]:410-9.e6).

The ESPRIT registry is sponsored by AbbVie. Dr. Thaci reported serving as a consultant to and/or receiving research grants from that pharmaceutical company and nearly two dozen others.

[email protected]

MADRID – Psoriasis patients on adalimumab for up to 10 years in the prospective, observational, international, real-world ESPRIT registry had a sharply reduced likelihood of all-cause mortality, compared with the age- and sex-matched general population in participating countries, Diamant T. Thaci, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

“If someone tells you that you as a dermatologist can save patient lives by controlling psoriasis, you may not believe it. But look at this standardized mortality ratio data,” said Dr. Thaci, professor of dermatology and head of the Comprehensive Center for Inflammation Medicine at the University of Luebeck (Germany).

Indeed, the standardized mortality ratio in participants in the ESPRIT registry, featuring 6,014 psoriasis patients with a collective 28,161 person-years on adalimumab in routine clinical practice, was 58% lower than expected, based upon published mortality rate data for the general population in the United States, Canada, and the 10 participating European countries. A total of 144 deaths were predicted in the matched general population, yet only 60 deaths occurred in adalimumab-treated registry participants.

This finding is all the more remarkable because ESPRIT participants had high rates of cardiovascular risk factors, as well as a substantial burden of comorbid conditions, as is typical for patients with chronic moderate to severe psoriasis encountered in real-world clinical practice. It’s a different population than enrollees in the long-term, open-label extensions of phase 3, double-blind, randomized, controlled clinical trials of biologics in psoriasis, which at the outset typically excluded patients with baseline substantial comorbidities, he noted.

Moreover, the incidence rates of serious infections, malignancies, and cardiovascular events in ESPRIT participants remained stable over time and well within the range of published rates in psoriasis patients not on biologic therapy.

“All of this underscores the importance of good control of psoriasis,” Dr. Thaci commented.

The ESPRIT registry began enrolling patients and evaluating them every 6 months in 2008, when the vast majority of dermatologists in clinical practice relied upon Physician Global Assessment (PGA) to evaluate treatment efficacy. For this reason, the PGA, rather than the Psoriasis Area and Severity Index, was the main efficacy measure utilized in the registry. The rate of PGA “clear” or “almost clear” was steady over time at 57% at 1 year, 62.1% at 5 years, and 61.5% at 10 years. It should be noted that this was reported in an “as-observed” analysis, which introduces bias favoring a rosier picture of efficacy since by 10 years slightly under half of patients remained on the tumor necrosis factor inhibitor.

However, the primary focus of this ESPRIT analysis was safety, not efficacy. The rate of serious infections was 1.0 event per 100 person-years on adalimumab, compared with published rates of 0.3-2.1 events/100 person-years in psoriasis patients not on a biologic. Malignancies occurred at a rate of 1.3 events/100 person-years in ESPRIT, compared with published rates of 0.5-2.0/100 person-years in psoriasis patients not on biologic therapy. Acute MI occurred at a rate of 0.1 cases/100 person-years in ESPRIT, stroke at 0.2 events/100 person-years, and heart failure at less than 0.1 event/100 person-years, versus a collective rate of 0.6-1.5 events/100 person-years in the comparator population.

Another view of the data is that, at 10 years, 99.4% of ESPRIT participants had not experienced an acute MI, 95.9% hadn’t had a malignancy, and 96.1% remained free of serious infection while on adalimumab, Dr. Thaci continued.

Injection-site reactions, a significant source of concern when adalimumab first reached the marketplace, occurred at a rate of 0.2 events/100 person-years over the course of 10 years. Oral candidiasis, active tuberculosis, demyelinating disorders, and lupus-like reactions were rare, each occurring at an incidence of less than 0.1 event/100 person-years.

Dr. Thaci’s 10-year update from the ongoing registry follows an earlier report of the 5-year results (J Am Acad Dermatol. 2015 Sep;73[3]:410-9.e6).

The ESPRIT registry is sponsored by AbbVie. Dr. Thaci reported serving as a consultant to and/or receiving research grants from that pharmaceutical company and nearly two dozen others.

[email protected]