Physician payment models that include productivity bonuses are widespread, says Reshma Gupta, MD, MSHPM.

“These payment models are thought to affect clinician behavior, with productivity bonuses incentivizing clinicians to do more. While new policies aim to reduce total costs of care, little is known about the association between physician payment models and the culture of delivering high-value care,” said Dr. Gupta, the medical director for quality improvement at UCLA Health in Los Angeles.

To find out if hospitalist reimbursement models are associated with high-value culture in university, community, and safety-net hospitals, internal medicine hospitalists from 12 hospitals across California completed a cross-sectional survey assessing their perceptions of high-value care culture within their institutions. Dr. Gupta and colleagues summarized the results.

The study found that nearly 30% of hospitalists who were sampled reported payment with productivity bonuses, while only 5% of hospitalists sampled reported quality or value-based bonuses, Dr. Gupta said. “Hospitalists who reported payment with productivity bonuses were more likely to report lower high-value care culture within their programs.”

Hospitalist leaders interested in improving high-value care culture can use the High Value Care Culture Survey (http://www.highvaluecareculturesurvey.com) to quickly assess the culture within their programs, diagnose areas of opportunity and target improvement efforts.

“They can test new physician payment models within their programs and evaluate their high-value care culture to identify areas of opportunity for improvement,” Dr. Gupta said.

Reference

1. Gupta R et al. Association between hospitalist productivity payments and high-value care culture. J Hosp Med. 2019;1;16-21.

Physician payment models that include productivity bonuses are widespread, says Reshma Gupta, MD, MSHPM.

“These payment models are thought to affect clinician behavior, with productivity bonuses incentivizing clinicians to do more. While new policies aim to reduce total costs of care, little is known about the association between physician payment models and the culture of delivering high-value care,” said Dr. Gupta, the medical director for quality improvement at UCLA Health in Los Angeles.

To find out if hospitalist reimbursement models are associated with high-value culture in university, community, and safety-net hospitals, internal medicine hospitalists from 12 hospitals across California completed a cross-sectional survey assessing their perceptions of high-value care culture within their institutions. Dr. Gupta and colleagues summarized the results.

The study found that nearly 30% of hospitalists who were sampled reported payment with productivity bonuses, while only 5% of hospitalists sampled reported quality or value-based bonuses, Dr. Gupta said. “Hospitalists who reported payment with productivity bonuses were more likely to report lower high-value care culture within their programs.”

Hospitalist leaders interested in improving high-value care culture can use the High Value Care Culture Survey (http://www.highvaluecareculturesurvey.com) to quickly assess the culture within their programs, diagnose areas of opportunity and target improvement efforts.

“They can test new physician payment models within their programs and evaluate their high-value care culture to identify areas of opportunity for improvement,” Dr. Gupta said.

Reference

1. Gupta R et al. Association between hospitalist productivity payments and high-value care culture. J Hosp Med. 2019;1;16-21.

Physician payment models that include productivity bonuses are widespread, says Reshma Gupta, MD, MSHPM.

“These payment models are thought to affect clinician behavior, with productivity bonuses incentivizing clinicians to do more. While new policies aim to reduce total costs of care, little is known about the association between physician payment models and the culture of delivering high-value care,” said Dr. Gupta, the medical director for quality improvement at UCLA Health in Los Angeles.

To find out if hospitalist reimbursement models are associated with high-value culture in university, community, and safety-net hospitals, internal medicine hospitalists from 12 hospitals across California completed a cross-sectional survey assessing their perceptions of high-value care culture within their institutions. Dr. Gupta and colleagues summarized the results.

The study found that nearly 30% of hospitalists who were sampled reported payment with productivity bonuses, while only 5% of hospitalists sampled reported quality or value-based bonuses, Dr. Gupta said. “Hospitalists who reported payment with productivity bonuses were more likely to report lower high-value care culture within their programs.”

Hospitalist leaders interested in improving high-value care culture can use the High Value Care Culture Survey (http://www.highvaluecareculturesurvey.com) to quickly assess the culture within their programs, diagnose areas of opportunity and target improvement efforts.

“They can test new physician payment models within their programs and evaluate their high-value care culture to identify areas of opportunity for improvement,” Dr. Gupta said.

Reference

1. Gupta R et al. Association between hospitalist productivity payments and high-value care culture. J Hosp Med. 2019;1;16-21.

Randomized trials are needed to determine the optimal treatment approach for early stage follicular lymphoma (FL), according to researchers.

Patho/Wikimedia Commons/CC BY-SA 3.0(http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons

A retrospective study showed similar outcomes among patients who received radiotherapy, immunochemotherapy, combined modality treatment (CMT), and watchful waiting (WW).

There were some differences in progression-free survival (PFS) according to treatment approach. However, there were no significant differences in overall survival (OS) between any of the active treatments or between patients who received active treatment and those managed with WW.

Joshua W. D. Tobin, MD, of Princess Alexandra Hospital in Brisbane, Queensland, Australia, and colleagues conducted this research and reported the results in Blood Advances.

The researchers analyzed 365 patients with newly diagnosed, stage I/II FL. The patients had a median age of 63 years and more than half were men. They were diagnosed between 2005 and 2017, and the median follow-up was 45 months.

Most patients (n = 280) received active treatment, but 85 were managed with WW. The WW patients were older and had more extranodal involvement.

Types of active treatment included radiotherapy alone (n = 171), immunochemotherapy alone (n = 63), and CMT (n = 46). Compared with the other groups, patients who received radiotherapy alone had less bulk, fewer nodal sites, and fewer B symptoms, and were more likely to have stage I disease. Patients who received CMT had fewer B symptoms and lower FLIPI scores compared with patients who received immunochemotherapy.

The immunochemotherapy regimens used were largely rituximab based. In all, 106 patients received rituximab (alone or in combination) for induction, and 49 received maintenance rituximab (37 in the immunochemotherapy group and 12 in the CMT group).

Results

Response rates were similar among the active treatment groups. The overall response rate was 95% in the radiotherapy group, 96% in the immunochemotherapy group, and 95% in the CMT group (P = .87).

There was a significant difference in PFS between the radiotherapy, immunochemotherapy, and CMT groups (P = .023), but there was no difference in OS between these groups (P = .38).

There was no significant difference in PFS between the immunochemotherapy and CMT groups (hazard ratio [HR], 1.78; P = .24), so the researchers combined these groups into a single group called “systemic therapy.” The patients treated with systemic therapy had PFS (HR, 1.32; P = .96) and OS (HR, 0.46; P = .21) similar to that of patients treated with radiotherapy alone.

Maintenance rituximab was associated with prolonged PFS among patients treated with systemic therapy (HR, 0.24; P = .017). However, there was no significant difference in OS between patients who received maintenance and those who did not (HR, 0.89; P = .90).

Relapse was less common among patients who received maintenance, and there were no cases of transformation in that group. Relapse occurred in 24.6% of the radiotherapy group, 18.3% of the systemic therapy group, and 4.1% of the group that received systemic therapy plus maintenance (P = .006). Transformation was less likely in the systemic therapy group (1.8%) than in the radiotherapy (6.4%) and WW (9.4%) groups (HR, 0.20; P = .034).

Overall, the active treatment group had better PFS than the WW group (HR, 0.52; P = .002), but there was no significant difference in OS between the groups (HR, 0.94; P = .90).

“Based on our comparable OS between WW and actively treated patients, WW could be considered as an initial management strategy in early stage FL,” Dr. Tobin and colleagues wrote. “However, long-term follow-up is required to determine if a survival benefit exists favoring active treatment.”

The researchers reported relationships with many pharmaceutical companies.

jensmith@mdedge.com

SOURCE: Tobin JWD et al. Blood Adv. 2019 Oct 8;3(19):2804-11.

Randomized trials are needed to determine the optimal treatment approach for early stage follicular lymphoma (FL), according to researchers.

Patho/Wikimedia Commons/CC BY-SA 3.0(http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons

A retrospective study showed similar outcomes among patients who received radiotherapy, immunochemotherapy, combined modality treatment (CMT), and watchful waiting (WW).

There were some differences in progression-free survival (PFS) according to treatment approach. However, there were no significant differences in overall survival (OS) between any of the active treatments or between patients who received active treatment and those managed with WW.

Joshua W. D. Tobin, MD, of Princess Alexandra Hospital in Brisbane, Queensland, Australia, and colleagues conducted this research and reported the results in Blood Advances.

The researchers analyzed 365 patients with newly diagnosed, stage I/II FL. The patients had a median age of 63 years and more than half were men. They were diagnosed between 2005 and 2017, and the median follow-up was 45 months.

Most patients (n = 280) received active treatment, but 85 were managed with WW. The WW patients were older and had more extranodal involvement.

Types of active treatment included radiotherapy alone (n = 171), immunochemotherapy alone (n = 63), and CMT (n = 46). Compared with the other groups, patients who received radiotherapy alone had less bulk, fewer nodal sites, and fewer B symptoms, and were more likely to have stage I disease. Patients who received CMT had fewer B symptoms and lower FLIPI scores compared with patients who received immunochemotherapy.

The immunochemotherapy regimens used were largely rituximab based. In all, 106 patients received rituximab (alone or in combination) for induction, and 49 received maintenance rituximab (37 in the immunochemotherapy group and 12 in the CMT group).

Results

Response rates were similar among the active treatment groups. The overall response rate was 95% in the radiotherapy group, 96% in the immunochemotherapy group, and 95% in the CMT group (P = .87).

There was a significant difference in PFS between the radiotherapy, immunochemotherapy, and CMT groups (P = .023), but there was no difference in OS between these groups (P = .38).

There was no significant difference in PFS between the immunochemotherapy and CMT groups (hazard ratio [HR], 1.78; P = .24), so the researchers combined these groups into a single group called “systemic therapy.” The patients treated with systemic therapy had PFS (HR, 1.32; P = .96) and OS (HR, 0.46; P = .21) similar to that of patients treated with radiotherapy alone.

Maintenance rituximab was associated with prolonged PFS among patients treated with systemic therapy (HR, 0.24; P = .017). However, there was no significant difference in OS between patients who received maintenance and those who did not (HR, 0.89; P = .90).

Relapse was less common among patients who received maintenance, and there were no cases of transformation in that group. Relapse occurred in 24.6% of the radiotherapy group, 18.3% of the systemic therapy group, and 4.1% of the group that received systemic therapy plus maintenance (P = .006). Transformation was less likely in the systemic therapy group (1.8%) than in the radiotherapy (6.4%) and WW (9.4%) groups (HR, 0.20; P = .034).

Overall, the active treatment group had better PFS than the WW group (HR, 0.52; P = .002), but there was no significant difference in OS between the groups (HR, 0.94; P = .90).

“Based on our comparable OS between WW and actively treated patients, WW could be considered as an initial management strategy in early stage FL,” Dr. Tobin and colleagues wrote. “However, long-term follow-up is required to determine if a survival benefit exists favoring active treatment.”

The researchers reported relationships with many pharmaceutical companies.

jensmith@mdedge.com

SOURCE: Tobin JWD et al. Blood Adv. 2019 Oct 8;3(19):2804-11.

Randomized trials are needed to determine the optimal treatment approach for early stage follicular lymphoma (FL), according to researchers.

Patho/Wikimedia Commons/CC BY-SA 3.0(http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons

A retrospective study showed similar outcomes among patients who received radiotherapy, immunochemotherapy, combined modality treatment (CMT), and watchful waiting (WW).

There were some differences in progression-free survival (PFS) according to treatment approach. However, there were no significant differences in overall survival (OS) between any of the active treatments or between patients who received active treatment and those managed with WW.

Joshua W. D. Tobin, MD, of Princess Alexandra Hospital in Brisbane, Queensland, Australia, and colleagues conducted this research and reported the results in Blood Advances.

The researchers analyzed 365 patients with newly diagnosed, stage I/II FL. The patients had a median age of 63 years and more than half were men. They were diagnosed between 2005 and 2017, and the median follow-up was 45 months.

Most patients (n = 280) received active treatment, but 85 were managed with WW. The WW patients were older and had more extranodal involvement.

Types of active treatment included radiotherapy alone (n = 171), immunochemotherapy alone (n = 63), and CMT (n = 46). Compared with the other groups, patients who received radiotherapy alone had less bulk, fewer nodal sites, and fewer B symptoms, and were more likely to have stage I disease. Patients who received CMT had fewer B symptoms and lower FLIPI scores compared with patients who received immunochemotherapy.

The immunochemotherapy regimens used were largely rituximab based. In all, 106 patients received rituximab (alone or in combination) for induction, and 49 received maintenance rituximab (37 in the immunochemotherapy group and 12 in the CMT group).

Results

Response rates were similar among the active treatment groups. The overall response rate was 95% in the radiotherapy group, 96% in the immunochemotherapy group, and 95% in the CMT group (P = .87).

There was a significant difference in PFS between the radiotherapy, immunochemotherapy, and CMT groups (P = .023), but there was no difference in OS between these groups (P = .38).

There was no significant difference in PFS between the immunochemotherapy and CMT groups (hazard ratio [HR], 1.78; P = .24), so the researchers combined these groups into a single group called “systemic therapy.” The patients treated with systemic therapy had PFS (HR, 1.32; P = .96) and OS (HR, 0.46; P = .21) similar to that of patients treated with radiotherapy alone.

Maintenance rituximab was associated with prolonged PFS among patients treated with systemic therapy (HR, 0.24; P = .017). However, there was no significant difference in OS between patients who received maintenance and those who did not (HR, 0.89; P = .90).

Relapse was less common among patients who received maintenance, and there were no cases of transformation in that group. Relapse occurred in 24.6% of the radiotherapy group, 18.3% of the systemic therapy group, and 4.1% of the group that received systemic therapy plus maintenance (P = .006). Transformation was less likely in the systemic therapy group (1.8%) than in the radiotherapy (6.4%) and WW (9.4%) groups (HR, 0.20; P = .034).

Overall, the active treatment group had better PFS than the WW group (HR, 0.52; P = .002), but there was no significant difference in OS between the groups (HR, 0.94; P = .90).

“Based on our comparable OS between WW and actively treated patients, WW could be considered as an initial management strategy in early stage FL,” Dr. Tobin and colleagues wrote. “However, long-term follow-up is required to determine if a survival benefit exists favoring active treatment.”

The researchers reported relationships with many pharmaceutical companies.

jensmith@mdedge.com

SOURCE: Tobin JWD et al. Blood Adv. 2019 Oct 8;3(19):2804-11.

STOCKHOLM – The Age-Related Multiple Sclerosis Severity (ARMSS) score can be used to create a measurement that predicts a patient’s future level of disability, according to research presented at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. The resulting measurement is stable, not highly sensitive to age, and appropriate for research applications. “It could give a clinician an earlier indication of the potential disease course of a patient,” said Ryan Ramanujam, PhD, assistant professor of translational neuroepidemiology at Karolinska Institutet in Stockholm.

Researchers who study MS use various scores to measure disease severity, including the Expanded Disability Status Scale (EDSS) and the MS Severity Scale (MSSS). These scores cannot predict a patient’s future status, however, and they do not remain stable throughout the course of a patient’s disease. Fitting a linear model over a series of scores over time can provide a misleading impression of a patient’s disease progression. “What we need is a metric to give a holistic overview of disease course, regardless of when it’s measured in a patient’s disease progression,” said Dr. Ramanujam. Such a measurement could aid the search for genes that affect MS severity, he added.
 

Examining disability by patient age

Dr. Ramanujam and colleagues constructed their measure using the ARMSS score, which ranks EDSS score by age instead of by disease duration. The ARMSS score ranges from 0 to 10, and the median value is 5 for all patients at a given age. Investigators can calculate the score using a previously published global matrix of values for ARMSS and MSSS available in the R package ms.sev.

The investigators found that the ARMSS score is slightly superior to the MSSS in detecting small increases in EDSS. One benefit of the ARMSS score, compared with the MSSS, is that it allows investigators to study patients for whom time of disease onset is unknown. The ARMSS score also removes potential systematic bias that might result from a neurologist’s retrospective assignment of date of disease onset, said Dr. Ramanujam.

He and his colleagues used ARMSS to compare patients’ disease course with what is expected for that patient (i.e., an ARMSS that remains stable at 5). They extracted data for 15,831 patients participating in the Swedish MS registry, including age and EDSS score at each neurological visit. Eligible patients had serial EDSS scores for 10 years. Dr. Ramanujam and colleagues included 4,514 patients in their analysis.
 

Measures at 2 years correlated with those at 10 years

The researchers created what they called the ARMSS integral by calculating the ARMSS score’s change from 5 at each examination (e.g., −0.5 or 1). “The ARMSS integral can be thought of as the cumulative disability that a patient accrues over his or her disease course, relative to the average patient, who had the disease for the same ages,” said Dr. Ramanujam. At 2 years of follow-up and at 10 years of follow-up, the distribution of ARMSS integrals for the study population followed a normal pattern.

Next, the investigators sought to compare patients by standardizing their follow-up time. To do this, they calculated what they called the ARMSS-rate by dividing each patient’s ARMSS integral by the number of years of follow-up. The ARMSS-rate offers a “snapshot of disease severity and progression,” said Dr. Ramanujam. When the researchers compared ARMSS-rates at 2 years and 10 years for each patient, they found that the measure was “extremely stable over time and strongly correlated with future disability.” The correlation improved slightly when the researchers compared ARMSS-rates at 4 years and 10 years.

The investigators then categorized patients based on their ARMSS-rate at 2 years (e.g., 0 to 1, 1 to 2, 2 to 3). When they compared the values in these categories with the median ARMSS-rates for the same individuals over the subsequent 8 years, they found strong group-level correlations.

To analyze correlations on an individual level, Dr. Ramanujam and colleagues examined the ability of different metrics at the time closest to 2 years of follow-up to predict those measured at 10 years. They assigned the value 1 to the most severe quartile of outcomes and the value 0 to all other quartiles. For predictors and outcomes, the investigators examined ARMSS-rate and the integral of progression index, which they calculated using the integral of EDSS. They also included EDSS at 10 years as an outcome for progression index.

For predicting the subsequent 8 years of ARMSS-rates, ARMSS-rate at 2 years had an area under the curve (AUC) of 0.921. When the investigators performed the same analysis using a cohort of patients with MS from British Columbia, Canada, they obtained an AUC of 0.887. Progression index at 2 years had an AUC of 0.61 for predicting the most severe quartile of the next 8 years. Compared with this result, ARMSS integral up to 2 years was slightly better at predicting EDSS at 10 years, said Dr. Ramanujam. The progression index poorly predicted the most severe quartile of EDSS at 10 years.

The main limitation of the ARMSS integral and ARMSS-rate is that they are based on EDSS, he added. The EDSS gives great weight to mobility and largely does not measure cognitive disability. “Future metrics could therefore include additional data such as MRI, Symbol Digit Modalities Test, or neurofilament light levels,” said Dr. Ramanujam. “Also, self-assessment could be one area to improve in the future.”

Dr. Ramanujam had no conflicts of interest to disclose. He receives funding from the MultipleMS Project, which is part of the EU Horizon 2020 Framework.

egreb@mdedge.com

SOURCE: Manouchehrinia A et al. ECTRIMS 2019. Abstract 218.

STOCKHOLM – The Age-Related Multiple Sclerosis Severity (ARMSS) score can be used to create a measurement that predicts a patient’s future level of disability, according to research presented at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. The resulting measurement is stable, not highly sensitive to age, and appropriate for research applications. “It could give a clinician an earlier indication of the potential disease course of a patient,” said Ryan Ramanujam, PhD, assistant professor of translational neuroepidemiology at Karolinska Institutet in Stockholm.

Researchers who study MS use various scores to measure disease severity, including the Expanded Disability Status Scale (EDSS) and the MS Severity Scale (MSSS). These scores cannot predict a patient’s future status, however, and they do not remain stable throughout the course of a patient’s disease. Fitting a linear model over a series of scores over time can provide a misleading impression of a patient’s disease progression. “What we need is a metric to give a holistic overview of disease course, regardless of when it’s measured in a patient’s disease progression,” said Dr. Ramanujam. Such a measurement could aid the search for genes that affect MS severity, he added.
 

Examining disability by patient age

Dr. Ramanujam and colleagues constructed their measure using the ARMSS score, which ranks EDSS score by age instead of by disease duration. The ARMSS score ranges from 0 to 10, and the median value is 5 for all patients at a given age. Investigators can calculate the score using a previously published global matrix of values for ARMSS and MSSS available in the R package ms.sev.

The investigators found that the ARMSS score is slightly superior to the MSSS in detecting small increases in EDSS. One benefit of the ARMSS score, compared with the MSSS, is that it allows investigators to study patients for whom time of disease onset is unknown. The ARMSS score also removes potential systematic bias that might result from a neurologist’s retrospective assignment of date of disease onset, said Dr. Ramanujam.

He and his colleagues used ARMSS to compare patients’ disease course with what is expected for that patient (i.e., an ARMSS that remains stable at 5). They extracted data for 15,831 patients participating in the Swedish MS registry, including age and EDSS score at each neurological visit. Eligible patients had serial EDSS scores for 10 years. Dr. Ramanujam and colleagues included 4,514 patients in their analysis.
 

Measures at 2 years correlated with those at 10 years

The researchers created what they called the ARMSS integral by calculating the ARMSS score’s change from 5 at each examination (e.g., −0.5 or 1). “The ARMSS integral can be thought of as the cumulative disability that a patient accrues over his or her disease course, relative to the average patient, who had the disease for the same ages,” said Dr. Ramanujam. At 2 years of follow-up and at 10 years of follow-up, the distribution of ARMSS integrals for the study population followed a normal pattern.

Next, the investigators sought to compare patients by standardizing their follow-up time. To do this, they calculated what they called the ARMSS-rate by dividing each patient’s ARMSS integral by the number of years of follow-up. The ARMSS-rate offers a “snapshot of disease severity and progression,” said Dr. Ramanujam. When the researchers compared ARMSS-rates at 2 years and 10 years for each patient, they found that the measure was “extremely stable over time and strongly correlated with future disability.” The correlation improved slightly when the researchers compared ARMSS-rates at 4 years and 10 years.

The investigators then categorized patients based on their ARMSS-rate at 2 years (e.g., 0 to 1, 1 to 2, 2 to 3). When they compared the values in these categories with the median ARMSS-rates for the same individuals over the subsequent 8 years, they found strong group-level correlations.

To analyze correlations on an individual level, Dr. Ramanujam and colleagues examined the ability of different metrics at the time closest to 2 years of follow-up to predict those measured at 10 years. They assigned the value 1 to the most severe quartile of outcomes and the value 0 to all other quartiles. For predictors and outcomes, the investigators examined ARMSS-rate and the integral of progression index, which they calculated using the integral of EDSS. They also included EDSS at 10 years as an outcome for progression index.

For predicting the subsequent 8 years of ARMSS-rates, ARMSS-rate at 2 years had an area under the curve (AUC) of 0.921. When the investigators performed the same analysis using a cohort of patients with MS from British Columbia, Canada, they obtained an AUC of 0.887. Progression index at 2 years had an AUC of 0.61 for predicting the most severe quartile of the next 8 years. Compared with this result, ARMSS integral up to 2 years was slightly better at predicting EDSS at 10 years, said Dr. Ramanujam. The progression index poorly predicted the most severe quartile of EDSS at 10 years.

The main limitation of the ARMSS integral and ARMSS-rate is that they are based on EDSS, he added. The EDSS gives great weight to mobility and largely does not measure cognitive disability. “Future metrics could therefore include additional data such as MRI, Symbol Digit Modalities Test, or neurofilament light levels,” said Dr. Ramanujam. “Also, self-assessment could be one area to improve in the future.”

Dr. Ramanujam had no conflicts of interest to disclose. He receives funding from the MultipleMS Project, which is part of the EU Horizon 2020 Framework.

egreb@mdedge.com

SOURCE: Manouchehrinia A et al. ECTRIMS 2019. Abstract 218.

STOCKHOLM – The Age-Related Multiple Sclerosis Severity (ARMSS) score can be used to create a measurement that predicts a patient’s future level of disability, according to research presented at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. The resulting measurement is stable, not highly sensitive to age, and appropriate for research applications. “It could give a clinician an earlier indication of the potential disease course of a patient,” said Ryan Ramanujam, PhD, assistant professor of translational neuroepidemiology at Karolinska Institutet in Stockholm.

Researchers who study MS use various scores to measure disease severity, including the Expanded Disability Status Scale (EDSS) and the MS Severity Scale (MSSS). These scores cannot predict a patient’s future status, however, and they do not remain stable throughout the course of a patient’s disease. Fitting a linear model over a series of scores over time can provide a misleading impression of a patient’s disease progression. “What we need is a metric to give a holistic overview of disease course, regardless of when it’s measured in a patient’s disease progression,” said Dr. Ramanujam. Such a measurement could aid the search for genes that affect MS severity, he added.
 

Examining disability by patient age

Dr. Ramanujam and colleagues constructed their measure using the ARMSS score, which ranks EDSS score by age instead of by disease duration. The ARMSS score ranges from 0 to 10, and the median value is 5 for all patients at a given age. Investigators can calculate the score using a previously published global matrix of values for ARMSS and MSSS available in the R package ms.sev.

The investigators found that the ARMSS score is slightly superior to the MSSS in detecting small increases in EDSS. One benefit of the ARMSS score, compared with the MSSS, is that it allows investigators to study patients for whom time of disease onset is unknown. The ARMSS score also removes potential systematic bias that might result from a neurologist’s retrospective assignment of date of disease onset, said Dr. Ramanujam.

He and his colleagues used ARMSS to compare patients’ disease course with what is expected for that patient (i.e., an ARMSS that remains stable at 5). They extracted data for 15,831 patients participating in the Swedish MS registry, including age and EDSS score at each neurological visit. Eligible patients had serial EDSS scores for 10 years. Dr. Ramanujam and colleagues included 4,514 patients in their analysis.
 

Measures at 2 years correlated with those at 10 years

The researchers created what they called the ARMSS integral by calculating the ARMSS score’s change from 5 at each examination (e.g., −0.5 or 1). “The ARMSS integral can be thought of as the cumulative disability that a patient accrues over his or her disease course, relative to the average patient, who had the disease for the same ages,” said Dr. Ramanujam. At 2 years of follow-up and at 10 years of follow-up, the distribution of ARMSS integrals for the study population followed a normal pattern.

Next, the investigators sought to compare patients by standardizing their follow-up time. To do this, they calculated what they called the ARMSS-rate by dividing each patient’s ARMSS integral by the number of years of follow-up. The ARMSS-rate offers a “snapshot of disease severity and progression,” said Dr. Ramanujam. When the researchers compared ARMSS-rates at 2 years and 10 years for each patient, they found that the measure was “extremely stable over time and strongly correlated with future disability.” The correlation improved slightly when the researchers compared ARMSS-rates at 4 years and 10 years.

The investigators then categorized patients based on their ARMSS-rate at 2 years (e.g., 0 to 1, 1 to 2, 2 to 3). When they compared the values in these categories with the median ARMSS-rates for the same individuals over the subsequent 8 years, they found strong group-level correlations.

To analyze correlations on an individual level, Dr. Ramanujam and colleagues examined the ability of different metrics at the time closest to 2 years of follow-up to predict those measured at 10 years. They assigned the value 1 to the most severe quartile of outcomes and the value 0 to all other quartiles. For predictors and outcomes, the investigators examined ARMSS-rate and the integral of progression index, which they calculated using the integral of EDSS. They also included EDSS at 10 years as an outcome for progression index.

For predicting the subsequent 8 years of ARMSS-rates, ARMSS-rate at 2 years had an area under the curve (AUC) of 0.921. When the investigators performed the same analysis using a cohort of patients with MS from British Columbia, Canada, they obtained an AUC of 0.887. Progression index at 2 years had an AUC of 0.61 for predicting the most severe quartile of the next 8 years. Compared with this result, ARMSS integral up to 2 years was slightly better at predicting EDSS at 10 years, said Dr. Ramanujam. The progression index poorly predicted the most severe quartile of EDSS at 10 years.

The main limitation of the ARMSS integral and ARMSS-rate is that they are based on EDSS, he added. The EDSS gives great weight to mobility and largely does not measure cognitive disability. “Future metrics could therefore include additional data such as MRI, Symbol Digit Modalities Test, or neurofilament light levels,” said Dr. Ramanujam. “Also, self-assessment could be one area to improve in the future.”

Dr. Ramanujam had no conflicts of interest to disclose. He receives funding from the MultipleMS Project, which is part of the EU Horizon 2020 Framework.

egreb@mdedge.com

SOURCE: Manouchehrinia A et al. ECTRIMS 2019. Abstract 218.

Kidneys from donors with hepatitis C virus (HCV) infection function well despite adverse quality assessment and are a valuable resource for transplantation candidates independent of HCV status, according to the findings of a large U.S. registry study.

Mohammed Haneefa Nizamudeen/Getty Images

A total of 260 HCV-viremic kidneys were transplanted in the first quarter of 2019, with 105 additional viremic kidneys being discarded, according to a report in the Journal of the American Society of Nephrology by Vishnu S. Potluri, MD, of the University of Pennsylvania, Philadelphia, and colleagues.

Donor HCV viremia was defined as an HCV nucleic acid test–positive result reported to the Organ Procurement and Transplantation Network (OPTN). Donors who were HCV negative in this test were labeled as HCV nonviremic. Kidney transplantation recipients were defined as either HCV seropositive or seronegative based on HCV antibody testing.

During the first quarter of 2019, 74% of HCV-viremic kidneys were transplanted into seronegative recipients, which is a major change from how HCV-viremic kidneys were allocated a few years ago, according to the researchers. The results of small trials showing the benefits of such transplantations and the success of direct-acting antiviral therapy (DAA) on clearing HCV infections were indicated as likely responsible for the change.

HCV-viremic kidneys had similar function, compared with HCV-nonviremic kidneys, when matched on the donor elements included in the Kidney Profile Donor Index (KDPI), excluding HCV, they added. In addition, the 12-month estimated glomerular filtration rate (eGFR) was similar between the seropositive and seronegative recipients, respectively 65.4 and 71.1 mL/min per 1.73 m² (P = .05), which suggests that recipient HCV serostatus does not negatively affect 1-year graft function using HCV-viremic kidneys in the era of DAA treatments, according to the authors.

Also, among HCV-seropositive recipients of HCV-viremic kidneys, seven (3.4%) died by 1 year post transplantation, while none of the HCV-seronegative recipients of HCV-viremic kidneys experienced graft failure or death.

“These striking results provide important additional evidence that the KDPI, with its current negative weighting for HCV status, does not accurately assess the quality of kidneys from HCV-viremic donors,” the authors wrote.

“HCV-viremic kidneys are a valuable resource for transplantation. Disincentives for accepting these organs should be addressed by the transplantation community,” Dr. Potluri and colleagues concluded.

This work was supported in part by the Health Resources and Services Administration of the U.S. Department of Health & Human Services. The various authors reported grant funding and advisory board participation with a number of pharmaceutical companies.

mlesney@mdedge.com

SOURCE: Potluri VS et al. J Am Soc Nephrol. 2019;30:1939-51.

Kidneys from donors with hepatitis C virus (HCV) infection function well despite adverse quality assessment and are a valuable resource for transplantation candidates independent of HCV status, according to the findings of a large U.S. registry study.

Mohammed Haneefa Nizamudeen/Getty Images

A total of 260 HCV-viremic kidneys were transplanted in the first quarter of 2019, with 105 additional viremic kidneys being discarded, according to a report in the Journal of the American Society of Nephrology by Vishnu S. Potluri, MD, of the University of Pennsylvania, Philadelphia, and colleagues.

Donor HCV viremia was defined as an HCV nucleic acid test–positive result reported to the Organ Procurement and Transplantation Network (OPTN). Donors who were HCV negative in this test were labeled as HCV nonviremic. Kidney transplantation recipients were defined as either HCV seropositive or seronegative based on HCV antibody testing.

During the first quarter of 2019, 74% of HCV-viremic kidneys were transplanted into seronegative recipients, which is a major change from how HCV-viremic kidneys were allocated a few years ago, according to the researchers. The results of small trials showing the benefits of such transplantations and the success of direct-acting antiviral therapy (DAA) on clearing HCV infections were indicated as likely responsible for the change.

HCV-viremic kidneys had similar function, compared with HCV-nonviremic kidneys, when matched on the donor elements included in the Kidney Profile Donor Index (KDPI), excluding HCV, they added. In addition, the 12-month estimated glomerular filtration rate (eGFR) was similar between the seropositive and seronegative recipients, respectively 65.4 and 71.1 mL/min per 1.73 m² (P = .05), which suggests that recipient HCV serostatus does not negatively affect 1-year graft function using HCV-viremic kidneys in the era of DAA treatments, according to the authors.

Also, among HCV-seropositive recipients of HCV-viremic kidneys, seven (3.4%) died by 1 year post transplantation, while none of the HCV-seronegative recipients of HCV-viremic kidneys experienced graft failure or death.

“These striking results provide important additional evidence that the KDPI, with its current negative weighting for HCV status, does not accurately assess the quality of kidneys from HCV-viremic donors,” the authors wrote.

“HCV-viremic kidneys are a valuable resource for transplantation. Disincentives for accepting these organs should be addressed by the transplantation community,” Dr. Potluri and colleagues concluded.

This work was supported in part by the Health Resources and Services Administration of the U.S. Department of Health & Human Services. The various authors reported grant funding and advisory board participation with a number of pharmaceutical companies.

mlesney@mdedge.com

SOURCE: Potluri VS et al. J Am Soc Nephrol. 2019;30:1939-51.

Kidneys from donors with hepatitis C virus (HCV) infection function well despite adverse quality assessment and are a valuable resource for transplantation candidates independent of HCV status, according to the findings of a large U.S. registry study.

Mohammed Haneefa Nizamudeen/Getty Images

A total of 260 HCV-viremic kidneys were transplanted in the first quarter of 2019, with 105 additional viremic kidneys being discarded, according to a report in the Journal of the American Society of Nephrology by Vishnu S. Potluri, MD, of the University of Pennsylvania, Philadelphia, and colleagues.

Donor HCV viremia was defined as an HCV nucleic acid test–positive result reported to the Organ Procurement and Transplantation Network (OPTN). Donors who were HCV negative in this test were labeled as HCV nonviremic. Kidney transplantation recipients were defined as either HCV seropositive or seronegative based on HCV antibody testing.

During the first quarter of 2019, 74% of HCV-viremic kidneys were transplanted into seronegative recipients, which is a major change from how HCV-viremic kidneys were allocated a few years ago, according to the researchers. The results of small trials showing the benefits of such transplantations and the success of direct-acting antiviral therapy (DAA) on clearing HCV infections were indicated as likely responsible for the change.

HCV-viremic kidneys had similar function, compared with HCV-nonviremic kidneys, when matched on the donor elements included in the Kidney Profile Donor Index (KDPI), excluding HCV, they added. In addition, the 12-month estimated glomerular filtration rate (eGFR) was similar between the seropositive and seronegative recipients, respectively 65.4 and 71.1 mL/min per 1.73 m² (P = .05), which suggests that recipient HCV serostatus does not negatively affect 1-year graft function using HCV-viremic kidneys in the era of DAA treatments, according to the authors.

Also, among HCV-seropositive recipients of HCV-viremic kidneys, seven (3.4%) died by 1 year post transplantation, while none of the HCV-seronegative recipients of HCV-viremic kidneys experienced graft failure or death.

“These striking results provide important additional evidence that the KDPI, with its current negative weighting for HCV status, does not accurately assess the quality of kidneys from HCV-viremic donors,” the authors wrote.

“HCV-viremic kidneys are a valuable resource for transplantation. Disincentives for accepting these organs should be addressed by the transplantation community,” Dr. Potluri and colleagues concluded.

This work was supported in part by the Health Resources and Services Administration of the U.S. Department of Health & Human Services. The various authors reported grant funding and advisory board participation with a number of pharmaceutical companies.

mlesney@mdedge.com

SOURCE: Potluri VS et al. J Am Soc Nephrol. 2019;30:1939-51.

STOCKHOLM – Cognitive rehabilitation to address memory deficits in multiple sclerosis (MS) can take a page from efforts to help those with other conditions, but practitioners and patients should realize that more intensive interventions are likely to be of greater benefit in MS.

“High-intensive memory-strategy interventions exert the largest effects on hippocampal memory function” in addressing the memory problems frequently seen in MS, Piet Bouman reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Hippocampal pathology can underlie the high-impact memory deficits that are seen frequently in patients with MS, noted Mr. Bouman, a doctoral student at Amsterdam University Medical Centers, and his collaborators. However, they observed, which strategies might best ameliorate hippocampal memory loss for those with MS is an open question.

To address this knowledge gap, Mr. Bouman and his coauthors conducted a systematic review and meta-analysis that aimed to determine which memory interventions in current use most help hippocampal memory functioning. The authors did not limit the review to MS, but included other conditions where hippocampal lesions, atrophy, or changes in connection or functioning may affect memory. These include healthy aging, mild cognitive impairment, and Alzheimer’s disease.

Included in the search for studies were those that used either cognitive or exercise interventions and also evaluated both visuospatial and verbal memory using validated measures, such as the Brief Visuospatial Memory Test or the California Verbal Learning Test.

After reviewing an initial 6,697 articles, the authors used Cochrane criteria to eliminate studies that were at high risk of bias. In the end, 141 studies were selected for the final review, and 82 of these were included in the meta-analysis. Eighteen studies involving 895 individuals addressed healthy aging; 39 studies enrolled 2,256 patients with mild cognitive impairment; 8 studies enrolled 223 patients with Alzheimer’s disease; and 26 studies involving 1,174 patients looked at cognitive impairment in the MS population.

To express the efficacy of the interventions across the various studies, Mr. Bouman and collaborators used the ratio of the difference in mean outcomes between groups and the standard deviation in outcome among participants. This ratio, commonly used to harmonize data in meta-analyses, is termed standardized mean difference.

Individuals representing the healthy aging population saw the most benefit from interventions to address memory loss, with a standardized mean difference of 0.48. Patients with mild cognitive impairment saw a standardized mean difference of 0.46, followed by patients with Alzheimer’s disease with a standardized mean difference of 0.43. Patients with MS lagged far behind in their response to interventions to improve memory, with a standardized mean difference of 0.34.

Looking at the different kinds of interventions, exercise interventions showed moderate effectiveness, with a standardized mean difference of 0.46. By contrast, high intensity cognitive training working on memory strategies was the most effective intervention, said Mr. Bouman and his coauthors: This intervention showed a standardized mean difference of 1.03.

Among the varying conditions associated with hippocampal memory loss, MS-related memory problems saw the least response to intervention, “which might be a result of a more widespread pattern of cognitive decline in MS,” noted Mr. Bouman and coauthors.

“Future studies should work from the realization that memory rehabilitation in MS might require a different approach” than that used in healthy aging, mild cognitive impairment, and Alzheimer’s disease, wrote the authors.

Their review revealed “persistent methodological flaws” in the literature, they noted. These included small sample sizes and selection bias.

Mr. Bouman reported that he had no disclosures. One coauthor reported financial relationships with Sanofi Genzyme, Merck-Serono and Biogen Idec. Another reported financial relationships with Merck-Serono, Bogen, Novartis, Genzyme, and Teva Pharmaceuticals.
 

koakes@mdedge.com

SOURCE: Bouman P et al. ECTRIMS 2019. Abstract P1439.

STOCKHOLM – Cognitive rehabilitation to address memory deficits in multiple sclerosis (MS) can take a page from efforts to help those with other conditions, but practitioners and patients should realize that more intensive interventions are likely to be of greater benefit in MS.

“High-intensive memory-strategy interventions exert the largest effects on hippocampal memory function” in addressing the memory problems frequently seen in MS, Piet Bouman reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Hippocampal pathology can underlie the high-impact memory deficits that are seen frequently in patients with MS, noted Mr. Bouman, a doctoral student at Amsterdam University Medical Centers, and his collaborators. However, they observed, which strategies might best ameliorate hippocampal memory loss for those with MS is an open question.

To address this knowledge gap, Mr. Bouman and his coauthors conducted a systematic review and meta-analysis that aimed to determine which memory interventions in current use most help hippocampal memory functioning. The authors did not limit the review to MS, but included other conditions where hippocampal lesions, atrophy, or changes in connection or functioning may affect memory. These include healthy aging, mild cognitive impairment, and Alzheimer’s disease.

Included in the search for studies were those that used either cognitive or exercise interventions and also evaluated both visuospatial and verbal memory using validated measures, such as the Brief Visuospatial Memory Test or the California Verbal Learning Test.

After reviewing an initial 6,697 articles, the authors used Cochrane criteria to eliminate studies that were at high risk of bias. In the end, 141 studies were selected for the final review, and 82 of these were included in the meta-analysis. Eighteen studies involving 895 individuals addressed healthy aging; 39 studies enrolled 2,256 patients with mild cognitive impairment; 8 studies enrolled 223 patients with Alzheimer’s disease; and 26 studies involving 1,174 patients looked at cognitive impairment in the MS population.

To express the efficacy of the interventions across the various studies, Mr. Bouman and collaborators used the ratio of the difference in mean outcomes between groups and the standard deviation in outcome among participants. This ratio, commonly used to harmonize data in meta-analyses, is termed standardized mean difference.

Individuals representing the healthy aging population saw the most benefit from interventions to address memory loss, with a standardized mean difference of 0.48. Patients with mild cognitive impairment saw a standardized mean difference of 0.46, followed by patients with Alzheimer’s disease with a standardized mean difference of 0.43. Patients with MS lagged far behind in their response to interventions to improve memory, with a standardized mean difference of 0.34.

Looking at the different kinds of interventions, exercise interventions showed moderate effectiveness, with a standardized mean difference of 0.46. By contrast, high intensity cognitive training working on memory strategies was the most effective intervention, said Mr. Bouman and his coauthors: This intervention showed a standardized mean difference of 1.03.

Among the varying conditions associated with hippocampal memory loss, MS-related memory problems saw the least response to intervention, “which might be a result of a more widespread pattern of cognitive decline in MS,” noted Mr. Bouman and coauthors.

“Future studies should work from the realization that memory rehabilitation in MS might require a different approach” than that used in healthy aging, mild cognitive impairment, and Alzheimer’s disease, wrote the authors.

Their review revealed “persistent methodological flaws” in the literature, they noted. These included small sample sizes and selection bias.

Mr. Bouman reported that he had no disclosures. One coauthor reported financial relationships with Sanofi Genzyme, Merck-Serono and Biogen Idec. Another reported financial relationships with Merck-Serono, Bogen, Novartis, Genzyme, and Teva Pharmaceuticals.
 

koakes@mdedge.com

SOURCE: Bouman P et al. ECTRIMS 2019. Abstract P1439.

STOCKHOLM – Cognitive rehabilitation to address memory deficits in multiple sclerosis (MS) can take a page from efforts to help those with other conditions, but practitioners and patients should realize that more intensive interventions are likely to be of greater benefit in MS.

“High-intensive memory-strategy interventions exert the largest effects on hippocampal memory function” in addressing the memory problems frequently seen in MS, Piet Bouman reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Hippocampal pathology can underlie the high-impact memory deficits that are seen frequently in patients with MS, noted Mr. Bouman, a doctoral student at Amsterdam University Medical Centers, and his collaborators. However, they observed, which strategies might best ameliorate hippocampal memory loss for those with MS is an open question.

To address this knowledge gap, Mr. Bouman and his coauthors conducted a systematic review and meta-analysis that aimed to determine which memory interventions in current use most help hippocampal memory functioning. The authors did not limit the review to MS, but included other conditions where hippocampal lesions, atrophy, or changes in connection or functioning may affect memory. These include healthy aging, mild cognitive impairment, and Alzheimer’s disease.

Included in the search for studies were those that used either cognitive or exercise interventions and also evaluated both visuospatial and verbal memory using validated measures, such as the Brief Visuospatial Memory Test or the California Verbal Learning Test.

After reviewing an initial 6,697 articles, the authors used Cochrane criteria to eliminate studies that were at high risk of bias. In the end, 141 studies were selected for the final review, and 82 of these were included in the meta-analysis. Eighteen studies involving 895 individuals addressed healthy aging; 39 studies enrolled 2,256 patients with mild cognitive impairment; 8 studies enrolled 223 patients with Alzheimer’s disease; and 26 studies involving 1,174 patients looked at cognitive impairment in the MS population.

To express the efficacy of the interventions across the various studies, Mr. Bouman and collaborators used the ratio of the difference in mean outcomes between groups and the standard deviation in outcome among participants. This ratio, commonly used to harmonize data in meta-analyses, is termed standardized mean difference.

Individuals representing the healthy aging population saw the most benefit from interventions to address memory loss, with a standardized mean difference of 0.48. Patients with mild cognitive impairment saw a standardized mean difference of 0.46, followed by patients with Alzheimer’s disease with a standardized mean difference of 0.43. Patients with MS lagged far behind in their response to interventions to improve memory, with a standardized mean difference of 0.34.

Looking at the different kinds of interventions, exercise interventions showed moderate effectiveness, with a standardized mean difference of 0.46. By contrast, high intensity cognitive training working on memory strategies was the most effective intervention, said Mr. Bouman and his coauthors: This intervention showed a standardized mean difference of 1.03.

Among the varying conditions associated with hippocampal memory loss, MS-related memory problems saw the least response to intervention, “which might be a result of a more widespread pattern of cognitive decline in MS,” noted Mr. Bouman and coauthors.

“Future studies should work from the realization that memory rehabilitation in MS might require a different approach” than that used in healthy aging, mild cognitive impairment, and Alzheimer’s disease, wrote the authors.

Their review revealed “persistent methodological flaws” in the literature, they noted. These included small sample sizes and selection bias.

Mr. Bouman reported that he had no disclosures. One coauthor reported financial relationships with Sanofi Genzyme, Merck-Serono and Biogen Idec. Another reported financial relationships with Merck-Serono, Bogen, Novartis, Genzyme, and Teva Pharmaceuticals.
 

koakes@mdedge.com

SOURCE: Bouman P et al. ECTRIMS 2019. Abstract P1439.

Older patients with immune thrombotic thrombocytopenic purpura (iTTP) more often have an atypical neurological presentation, which could result in a delayed diagnosis, according to authors of a recent retrospective analysis.

“Practitioners should be aware of this in order to shorten the time to treatment, which could improve the prognosis in older iTTP patients,” Paul Coppo, MD, PhD, of Hôpital Saint-Antoine, Paris, and coauthors wrote in Blood.

The older patients also had increased 1-month and 1-year mortality compared with younger patients, and had more than a threefold risk of long-term mortality compared with elderly patients without iTTP, according to the study report.

The analysis included 411 patients with iTTP entered into a national registry in France between 2000 and 2016. Seventy-one patients were 60 years of age or older.

Time from hospital admission to diagnosis was 3 days for those older patients, versus just 1 day for patients under 60 years of age (P = .0001), Dr. Coppo and colleagues reported.

Clinical records were available for 67 of the older iTTP patients, of whom 17 had no evidence of delayed diagnosis. The remainder had a “possible diagnostic delay,” according to the report; among those, the iTTP diagnosis was preceded by neurological manifestations in 26 cases, and transient ischemic stroke that usually led to focal deficiency or aphasia in 14 cases. Other features preceding the diagnosis included malaise, behavioral abnormalities, seizure, and dizziness.

Many of these findings are “not specific to a disease, and they are less alarming than in young patients,” the researchers wrote. “In this context, the presence of a thrombocytopenia with anemia should alert physicians to this possible rare diagnosis.”

Older patients also presented with less pronounced cytopenias compared with younger patients, which could have contributed to a late diagnosis, they added.

Older age is a known risk factor for mortality related to iTTP. In the present study, rates of 1-month mortality were 37% for patients aged 60 years and older, and 9% for those younger than age 60 (P less than .0001). The 1-year mortality rates were 49% and 11% for older and younger patients, respectively (P less than .0001).

Compared with older individuals without iTTP from a different study, older iTTP patients had a lower long-term survival rate. iTTP remained an independent risk factor for death even after adjustment for age, sex, and some comorbidities (hazard ratio, 3.44; 95% confidence interval, 2.02-5.87).

The study was partly funded by a grant from the French Ministry of Health. Dr. Coppo reported that he is a clinical advisory board member for Alexion, Ablynx (now part of Sanofi), Shire, and Octapharma. Two other co-authors reported participating in advisory boards for Ablynx.

SOURCE: Prevel R et al. Blood. 2019 Sep 17. doi: 10.1182/blood.2019000748.

Older patients with immune thrombotic thrombocytopenic purpura (iTTP) more often have an atypical neurological presentation, which could result in a delayed diagnosis, according to authors of a recent retrospective analysis.

“Practitioners should be aware of this in order to shorten the time to treatment, which could improve the prognosis in older iTTP patients,” Paul Coppo, MD, PhD, of Hôpital Saint-Antoine, Paris, and coauthors wrote in Blood.

The older patients also had increased 1-month and 1-year mortality compared with younger patients, and had more than a threefold risk of long-term mortality compared with elderly patients without iTTP, according to the study report.

The analysis included 411 patients with iTTP entered into a national registry in France between 2000 and 2016. Seventy-one patients were 60 years of age or older.

Time from hospital admission to diagnosis was 3 days for those older patients, versus just 1 day for patients under 60 years of age (P = .0001), Dr. Coppo and colleagues reported.

Clinical records were available for 67 of the older iTTP patients, of whom 17 had no evidence of delayed diagnosis. The remainder had a “possible diagnostic delay,” according to the report; among those, the iTTP diagnosis was preceded by neurological manifestations in 26 cases, and transient ischemic stroke that usually led to focal deficiency or aphasia in 14 cases. Other features preceding the diagnosis included malaise, behavioral abnormalities, seizure, and dizziness.

Many of these findings are “not specific to a disease, and they are less alarming than in young patients,” the researchers wrote. “In this context, the presence of a thrombocytopenia with anemia should alert physicians to this possible rare diagnosis.”

Older patients also presented with less pronounced cytopenias compared with younger patients, which could have contributed to a late diagnosis, they added.

Older age is a known risk factor for mortality related to iTTP. In the present study, rates of 1-month mortality were 37% for patients aged 60 years and older, and 9% for those younger than age 60 (P less than .0001). The 1-year mortality rates were 49% and 11% for older and younger patients, respectively (P less than .0001).

Compared with older individuals without iTTP from a different study, older iTTP patients had a lower long-term survival rate. iTTP remained an independent risk factor for death even after adjustment for age, sex, and some comorbidities (hazard ratio, 3.44; 95% confidence interval, 2.02-5.87).

The study was partly funded by a grant from the French Ministry of Health. Dr. Coppo reported that he is a clinical advisory board member for Alexion, Ablynx (now part of Sanofi), Shire, and Octapharma. Two other co-authors reported participating in advisory boards for Ablynx.

SOURCE: Prevel R et al. Blood. 2019 Sep 17. doi: 10.1182/blood.2019000748.

Older patients with immune thrombotic thrombocytopenic purpura (iTTP) more often have an atypical neurological presentation, which could result in a delayed diagnosis, according to authors of a recent retrospective analysis.

“Practitioners should be aware of this in order to shorten the time to treatment, which could improve the prognosis in older iTTP patients,” Paul Coppo, MD, PhD, of Hôpital Saint-Antoine, Paris, and coauthors wrote in Blood.

The older patients also had increased 1-month and 1-year mortality compared with younger patients, and had more than a threefold risk of long-term mortality compared with elderly patients without iTTP, according to the study report.

The analysis included 411 patients with iTTP entered into a national registry in France between 2000 and 2016. Seventy-one patients were 60 years of age or older.

Time from hospital admission to diagnosis was 3 days for those older patients, versus just 1 day for patients under 60 years of age (P = .0001), Dr. Coppo and colleagues reported.

Clinical records were available for 67 of the older iTTP patients, of whom 17 had no evidence of delayed diagnosis. The remainder had a “possible diagnostic delay,” according to the report; among those, the iTTP diagnosis was preceded by neurological manifestations in 26 cases, and transient ischemic stroke that usually led to focal deficiency or aphasia in 14 cases. Other features preceding the diagnosis included malaise, behavioral abnormalities, seizure, and dizziness.

Many of these findings are “not specific to a disease, and they are less alarming than in young patients,” the researchers wrote. “In this context, the presence of a thrombocytopenia with anemia should alert physicians to this possible rare diagnosis.”

Older patients also presented with less pronounced cytopenias compared with younger patients, which could have contributed to a late diagnosis, they added.

Older age is a known risk factor for mortality related to iTTP. In the present study, rates of 1-month mortality were 37% for patients aged 60 years and older, and 9% for those younger than age 60 (P less than .0001). The 1-year mortality rates were 49% and 11% for older and younger patients, respectively (P less than .0001).

Compared with older individuals without iTTP from a different study, older iTTP patients had a lower long-term survival rate. iTTP remained an independent risk factor for death even after adjustment for age, sex, and some comorbidities (hazard ratio, 3.44; 95% confidence interval, 2.02-5.87).

The study was partly funded by a grant from the French Ministry of Health. Dr. Coppo reported that he is a clinical advisory board member for Alexion, Ablynx (now part of Sanofi), Shire, and Octapharma. Two other co-authors reported participating in advisory boards for Ablynx.

SOURCE: Prevel R et al. Blood. 2019 Sep 17. doi: 10.1182/blood.2019000748.

Choose your answer in the poll below. To check the accuracy of your answer, see PURLs: A Better Approach to the Diagnosis of PE.

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The correct answer is b.) 14%

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Choose your answer in the poll below. To check the accuracy of your answer, see PURLs: A Better Approach to the Diagnosis of PE.

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The correct answer is b.) 14%

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Choose your answer in the poll below. To check the accuracy of your answer, see PURLs: A Better Approach to the Diagnosis of PE.

[polldaddy:10428150]

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The correct answer is b.) 14%

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About a year ago, I had the opportunity to don the honorary regalia of the American College of Chest Physicians as its 81st President. On that memorable day on the dais in San Antonio, I used the example of James Surowiecki’s book, “The Wisdom of Crowds: Why the Many Are Smarter than the Few and How Collective Wisdom Shapes Business, Economics, Societies, and Nations” to explain how we would use the collective wisdom of our members, our committee and NetWork members, and our talented association staff to build and shape CHEST over the coming year. For those of you not familiar with this concept, Surowiecki, a business columnist for New Yorker, outlines the concept that large groups of people are actually smarter than an elite few at solving the problems of an organization, fostering innovation, collectively coming to wise decisions, or even predicting the future. In channeling the lessons from the book, it has become obvious that listening to our members and partners, rather than trying to make all decisions from the top down, has been an effective method for coming to wise decisions about the strategy and operation of CHEST. Now that it’s already time to hand the responsibility of the organization as President over to my friend and colleague Dr. Stephanie Levine, I’ve reflected on actually how effectively we have listened and how smart the collective crowd has been in moving the success of CHEST forward.

We heard from members that it was difficult to know how to get involved and what happens at the highest leadership levels of the organization. This prompted the development of podcasts dubbed “The Inside Scoop,” recorded live approximately every 2 months and featured various leaders of the organization with an informal way for members to better understand how to become involved in CHEST activities and to feel the pulse of activity of the association between the time the annual meeting ends and the next one begins.

The crowd informed us that communication at the Board of Regents level could be better. To address this, regular communications were sent out to the Board of Regents to update them on activities and discussion of issues between scheduled board meetings, as well as providing board members the opportunity to have access to the minutes of phone calls of the “5Ps,” calls that included the Immediate Past, President-Elect, President-Designate, and current President of the association, as well as the CHEST Foundation President.

We were told by members through focus groups and surveys, then again told by experts we invited to the June board meetings from education, business, design, and venture capital sectors (and who were naïve to CHEST as an association) that we needed to double down on virtual educational offerings to learners across the health-care delivery team and to revamp its information technology infrastructure. To that end, a digital strategy work group was convened with expertise in information technology, social media, and marketing to inventory all digital assets of the College and make recommendations for not just improvement, but for a complete transformation of digital technology created and promulgated by CHEST. The board then approved a budget of nearly $1 million to upgrade and rebuild the user experience within CHEST’s digital environment, including its learning management system. We also opened a multimedia studio at CHEST headquarters, increased the numbers of serious educational gaming opportunities at the annual meeting, and are developing a line of serious game platforms that will allow for “edutainment” opportunities for our members and other learners around the world using various digital platforms.

Colleagues from around the world reminded us that 20% of CHEST membership was international and that our strategic plan included an international strategy. Thanks to the support of our colleagues around the world, we were able to enjoy a tremendously successful CHEST Congress in Bangkok, Thailand, in April, and a smaller regional meeting in June in Athens, Greece. Efforts of the Governance Committee have reshaped the structure of international representation, making it more relevant and allowing its members to have a stronger voice to the Board of Regents. Plans are underway for the next CHEST Congress in June 2020 in Bologna, Italy, to be held in collaboration with the Italian Chapter of CHEST in that country.

In an era when the majority of association annual meetings across multiple specialties are driving toward parity with similar looks, marketing, formats, and expectations, we listened to the needs and desires of attendees of last year’s meeting and have improved CHEST 2019 in New Orleans even more. With the most simulation courses ever delivered at an annual meeting, more serious game opportunities, CHEST Challenge finals, a new innovation competition called “FISH Bowl,” and even a medical escape room, CHEST volunteer leaders and organization staff have worked hard to provide a world class meeting that has a different look and feel from all the others. Plus, the crowd also told us that having CME and MOC credit available for the entire meeting was another variable that was desired, and has now been achieved.

The wisdom of the proverbial crowd of membership has spoken in terms of the need for philanthropic efforts in our specialty. The CHEST Foundation has responded by awarding tens of thousands of dollars to our members to recognize cutting-edge research, community service efforts, and, in addition, has allowed dozens of providers early on in training or in their career to attend the annual meeting with the help of travel grants.

CHEST guidelines continue to be updated and new ones created based on input from expert panel teams. The CHEST journal submission process, review turnaround times, and quality of manuscripts have improved each year thanks to useful feedback from authors and readers. Publications such as CHEST Physician are modified each year based upon feedback from our readers. Critiques from the board review courses have been the driving force keeping live learning formats and the electronic SEEK board preparation questions current and accurate when the science is constantly changing.

Truly, the collective wisdom of our members, talented clinicians and researchers, and colleagues in industry has provided incredibly valuable input to the CHEST leadership team. You have spoken, and we have been listening. Thanks to each of you who have reached out to me during this year as President. Traveling to four continents this past year to better understand the needs of members who are clinicians, educators, researchers, and caregivers positioned in each geographic region has been enlightening, educational, and transformative for me and my family. Your meaningful feedback, keen insights, and passion for outstanding patient care, impactful educational experiences, and life-changing research have helped push CHEST to a higher level of excellence and to offer unparalleled experiences for our members to ultimately provide the very best care to patients.

About a year ago, I had the opportunity to don the honorary regalia of the American College of Chest Physicians as its 81st President. On that memorable day on the dais in San Antonio, I used the example of James Surowiecki’s book, “The Wisdom of Crowds: Why the Many Are Smarter than the Few and How Collective Wisdom Shapes Business, Economics, Societies, and Nations” to explain how we would use the collective wisdom of our members, our committee and NetWork members, and our talented association staff to build and shape CHEST over the coming year. For those of you not familiar with this concept, Surowiecki, a business columnist for New Yorker, outlines the concept that large groups of people are actually smarter than an elite few at solving the problems of an organization, fostering innovation, collectively coming to wise decisions, or even predicting the future. In channeling the lessons from the book, it has become obvious that listening to our members and partners, rather than trying to make all decisions from the top down, has been an effective method for coming to wise decisions about the strategy and operation of CHEST. Now that it’s already time to hand the responsibility of the organization as President over to my friend and colleague Dr. Stephanie Levine, I’ve reflected on actually how effectively we have listened and how smart the collective crowd has been in moving the success of CHEST forward.

We heard from members that it was difficult to know how to get involved and what happens at the highest leadership levels of the organization. This prompted the development of podcasts dubbed “The Inside Scoop,” recorded live approximately every 2 months and featured various leaders of the organization with an informal way for members to better understand how to become involved in CHEST activities and to feel the pulse of activity of the association between the time the annual meeting ends and the next one begins.

The crowd informed us that communication at the Board of Regents level could be better. To address this, regular communications were sent out to the Board of Regents to update them on activities and discussion of issues between scheduled board meetings, as well as providing board members the opportunity to have access to the minutes of phone calls of the “5Ps,” calls that included the Immediate Past, President-Elect, President-Designate, and current President of the association, as well as the CHEST Foundation President.

We were told by members through focus groups and surveys, then again told by experts we invited to the June board meetings from education, business, design, and venture capital sectors (and who were naïve to CHEST as an association) that we needed to double down on virtual educational offerings to learners across the health-care delivery team and to revamp its information technology infrastructure. To that end, a digital strategy work group was convened with expertise in information technology, social media, and marketing to inventory all digital assets of the College and make recommendations for not just improvement, but for a complete transformation of digital technology created and promulgated by CHEST. The board then approved a budget of nearly $1 million to upgrade and rebuild the user experience within CHEST’s digital environment, including its learning management system. We also opened a multimedia studio at CHEST headquarters, increased the numbers of serious educational gaming opportunities at the annual meeting, and are developing a line of serious game platforms that will allow for “edutainment” opportunities for our members and other learners around the world using various digital platforms.

Colleagues from around the world reminded us that 20% of CHEST membership was international and that our strategic plan included an international strategy. Thanks to the support of our colleagues around the world, we were able to enjoy a tremendously successful CHEST Congress in Bangkok, Thailand, in April, and a smaller regional meeting in June in Athens, Greece. Efforts of the Governance Committee have reshaped the structure of international representation, making it more relevant and allowing its members to have a stronger voice to the Board of Regents. Plans are underway for the next CHEST Congress in June 2020 in Bologna, Italy, to be held in collaboration with the Italian Chapter of CHEST in that country.

In an era when the majority of association annual meetings across multiple specialties are driving toward parity with similar looks, marketing, formats, and expectations, we listened to the needs and desires of attendees of last year’s meeting and have improved CHEST 2019 in New Orleans even more. With the most simulation courses ever delivered at an annual meeting, more serious game opportunities, CHEST Challenge finals, a new innovation competition called “FISH Bowl,” and even a medical escape room, CHEST volunteer leaders and organization staff have worked hard to provide a world class meeting that has a different look and feel from all the others. Plus, the crowd also told us that having CME and MOC credit available for the entire meeting was another variable that was desired, and has now been achieved.

The wisdom of the proverbial crowd of membership has spoken in terms of the need for philanthropic efforts in our specialty. The CHEST Foundation has responded by awarding tens of thousands of dollars to our members to recognize cutting-edge research, community service efforts, and, in addition, has allowed dozens of providers early on in training or in their career to attend the annual meeting with the help of travel grants.

CHEST guidelines continue to be updated and new ones created based on input from expert panel teams. The CHEST journal submission process, review turnaround times, and quality of manuscripts have improved each year thanks to useful feedback from authors and readers. Publications such as CHEST Physician are modified each year based upon feedback from our readers. Critiques from the board review courses have been the driving force keeping live learning formats and the electronic SEEK board preparation questions current and accurate when the science is constantly changing.

Truly, the collective wisdom of our members, talented clinicians and researchers, and colleagues in industry has provided incredibly valuable input to the CHEST leadership team. You have spoken, and we have been listening. Thanks to each of you who have reached out to me during this year as President. Traveling to four continents this past year to better understand the needs of members who are clinicians, educators, researchers, and caregivers positioned in each geographic region has been enlightening, educational, and transformative for me and my family. Your meaningful feedback, keen insights, and passion for outstanding patient care, impactful educational experiences, and life-changing research have helped push CHEST to a higher level of excellence and to offer unparalleled experiences for our members to ultimately provide the very best care to patients.

About a year ago, I had the opportunity to don the honorary regalia of the American College of Chest Physicians as its 81st President. On that memorable day on the dais in San Antonio, I used the example of James Surowiecki’s book, “The Wisdom of Crowds: Why the Many Are Smarter than the Few and How Collective Wisdom Shapes Business, Economics, Societies, and Nations” to explain how we would use the collective wisdom of our members, our committee and NetWork members, and our talented association staff to build and shape CHEST over the coming year. For those of you not familiar with this concept, Surowiecki, a business columnist for New Yorker, outlines the concept that large groups of people are actually smarter than an elite few at solving the problems of an organization, fostering innovation, collectively coming to wise decisions, or even predicting the future. In channeling the lessons from the book, it has become obvious that listening to our members and partners, rather than trying to make all decisions from the top down, has been an effective method for coming to wise decisions about the strategy and operation of CHEST. Now that it’s already time to hand the responsibility of the organization as President over to my friend and colleague Dr. Stephanie Levine, I’ve reflected on actually how effectively we have listened and how smart the collective crowd has been in moving the success of CHEST forward.

We heard from members that it was difficult to know how to get involved and what happens at the highest leadership levels of the organization. This prompted the development of podcasts dubbed “The Inside Scoop,” recorded live approximately every 2 months and featured various leaders of the organization with an informal way for members to better understand how to become involved in CHEST activities and to feel the pulse of activity of the association between the time the annual meeting ends and the next one begins.

The crowd informed us that communication at the Board of Regents level could be better. To address this, regular communications were sent out to the Board of Regents to update them on activities and discussion of issues between scheduled board meetings, as well as providing board members the opportunity to have access to the minutes of phone calls of the “5Ps,” calls that included the Immediate Past, President-Elect, President-Designate, and current President of the association, as well as the CHEST Foundation President.

We were told by members through focus groups and surveys, then again told by experts we invited to the June board meetings from education, business, design, and venture capital sectors (and who were naïve to CHEST as an association) that we needed to double down on virtual educational offerings to learners across the health-care delivery team and to revamp its information technology infrastructure. To that end, a digital strategy work group was convened with expertise in information technology, social media, and marketing to inventory all digital assets of the College and make recommendations for not just improvement, but for a complete transformation of digital technology created and promulgated by CHEST. The board then approved a budget of nearly $1 million to upgrade and rebuild the user experience within CHEST’s digital environment, including its learning management system. We also opened a multimedia studio at CHEST headquarters, increased the numbers of serious educational gaming opportunities at the annual meeting, and are developing a line of serious game platforms that will allow for “edutainment” opportunities for our members and other learners around the world using various digital platforms.

Colleagues from around the world reminded us that 20% of CHEST membership was international and that our strategic plan included an international strategy. Thanks to the support of our colleagues around the world, we were able to enjoy a tremendously successful CHEST Congress in Bangkok, Thailand, in April, and a smaller regional meeting in June in Athens, Greece. Efforts of the Governance Committee have reshaped the structure of international representation, making it more relevant and allowing its members to have a stronger voice to the Board of Regents. Plans are underway for the next CHEST Congress in June 2020 in Bologna, Italy, to be held in collaboration with the Italian Chapter of CHEST in that country.

In an era when the majority of association annual meetings across multiple specialties are driving toward parity with similar looks, marketing, formats, and expectations, we listened to the needs and desires of attendees of last year’s meeting and have improved CHEST 2019 in New Orleans even more. With the most simulation courses ever delivered at an annual meeting, more serious game opportunities, CHEST Challenge finals, a new innovation competition called “FISH Bowl,” and even a medical escape room, CHEST volunteer leaders and organization staff have worked hard to provide a world class meeting that has a different look and feel from all the others. Plus, the crowd also told us that having CME and MOC credit available for the entire meeting was another variable that was desired, and has now been achieved.

The wisdom of the proverbial crowd of membership has spoken in terms of the need for philanthropic efforts in our specialty. The CHEST Foundation has responded by awarding tens of thousands of dollars to our members to recognize cutting-edge research, community service efforts, and, in addition, has allowed dozens of providers early on in training or in their career to attend the annual meeting with the help of travel grants.

CHEST guidelines continue to be updated and new ones created based on input from expert panel teams. The CHEST journal submission process, review turnaround times, and quality of manuscripts have improved each year thanks to useful feedback from authors and readers. Publications such as CHEST Physician are modified each year based upon feedback from our readers. Critiques from the board review courses have been the driving force keeping live learning formats and the electronic SEEK board preparation questions current and accurate when the science is constantly changing.

Truly, the collective wisdom of our members, talented clinicians and researchers, and colleagues in industry has provided incredibly valuable input to the CHEST leadership team. You have spoken, and we have been listening. Thanks to each of you who have reached out to me during this year as President. Traveling to four continents this past year to better understand the needs of members who are clinicians, educators, researchers, and caregivers positioned in each geographic region has been enlightening, educational, and transformative for me and my family. Your meaningful feedback, keen insights, and passion for outstanding patient care, impactful educational experiences, and life-changing research have helped push CHEST to a higher level of excellence and to offer unparalleled experiences for our members to ultimately provide the very best care to patients.

The role of imaging for interstitial lung disease (ILD) is of paramount importance. With the growth of high resolution chest computed tomography (HRCT) imaging techniques, we are able to visualize nuances between individual ILDs more critically. HRCT is an essential component of an initial ILD evaluation and also has become part of the armamentarium of tools used for routine management of these patients. The technology of HRCT scans has evolved over the years, most recently with the advent of quantitative HRCT (qCT). The technology employs texture-based classification, which identifies and quantifies different radiographic findings. The arrival of qCT scanning has been slowly emerging as a new player in the ILD world. What exactly is qCT, and what role can, and will it serve for our ILD patients?

Quantitative CT scanning has been introduced since the 1980s, but only within the last 15 years has its use for ILD taken form. Human interpretation of CTs is fraught with subjectivity, based on the interpreting radiologist’s training, experience, and individual visual perception of images. This can result in significant variability in radiographic interpretations and, ultimately, affects a patient’s diagnosis, disease monitoring, treatment, and prognosis. Semiquantitative visual scoring by radiologists is highly variable, especially in areas with limited availability of chest radiologists. qCT employs an automated histogram signature technique that utilizes density and texture-based analysis of the lung parenchyma. Utilizing machine learning from pathologically confirmed datasets, computer programs were trained with specialized thoracic radiologists to distinguish some commonly found radiographic abnormalities into four major groups: ground glass, reticular, honeycombing, and emphysema. In addition, these categories are quantified and spatially depicted on an analysis (Bartholmai, et al. J Thorac Imaging. 2013;28[5]:298). Various computer programs have been built to streamline the process and expedite the interpretation of an individual’s HRCT scan. The more commonly familiar program, CALIPER (Computer-Aided Lung Informatics for Pathology Evaluation and Ratings), has been used in multiple research studies of qCT in ILD and IPF. Each patient’s CT scan is uploaded to the program, and a breakdown of the patient’s lungs into each category is presented. Not only is each abnormality quantified and precisely defined, it is also color-coded by segments to help with visual interpretation by the physician.

The benefit of qCT lies not only in the automated, objective evaluation of interstitial lung disease, but also in its possible use in prognostication and mortality prediction. Neither use has been fully validated as of yet. However, growing evidence shows a promising role in both realms. Thus far, there have been some studies correlating PFT data with qCT findings. A follow-up study of the Scleroderma Lung Study II examined qCT changes over 24 months and correlated those findings with PFTs and patient-reported outcomes. Patients in this study were either treated with cyclophosphamide (CYC) for 1 year/placebo 1 year vs mycophenolate mofetil (MMF) for 2 years. A large portion of patients receiving CYC or MMF had a significant correlation between improved or stable qCT scores and their FVC and TLC. Neither CYC nor MMF was superior in qCT scores, aligning with the findings of the study, which showed noninferiority of MMF compared with CYC (Goldin, et al. Ann Am Thorac Soc. 2018 Nov;15[11]:1286). Interestingly, the improvement of ground glass is often viewed by physicians as positive, since this finding is typically thought of as active inflammation. However, if qCT determines that the fibrosis score actually increases over time, despite an improvement in ground glass, this may more accurately reflect the development of subtle fibrosis that is not easily appreciated by the human eye (Goldin, et al. Ann Am Thorac Soc. 2018 Nov;15[11]:1286). In this context, it is feasible that parenchymal changes occur prior to deterioration on PFTs. Diffusing capacity for carbon monoxide (DLCO) correlates largely with the extent of lung involvement on qCT, but DLCO is not a specific biomarker in predicting severity of ILD (ie, because pHTN or anemia can confound DLCO). Forced vital capacity (FVC) in certain diseases may also confound CT correlation (ie, muscle weakness or extrathoracic restriction from skin disease in systemic sclerosis). The usefulness of PFT data as a clinical endpoint in research studies may be replaced by qCTs more consistent and precise detection of disease modification.

IPF has been an interesting area of exploration for the role of qCT in disease monitoring and possible prognostication. It is known that the presence of honeycombing on HRCT is associated with increased mortality. Patients with a progressive fibrotic ILD have similar mortality rates to those with IPF (Adegunsoye, et al. Ann Am Thorac Soc. 2019 May;16[5]:580). The ability to correlate radiographic findings with mortality could potentially become an important marker of clinical deterioration, especially in those patients who are unable to perform PFTs. In addition, it can also be beneficial in those with co-existent emphysema, since PFTs may be confounded by this overlap. Nakagawa and colleagues proposed a computer-aided method for qCT analysis of honeycombing in patients with IPF. The algorithm for the qCT analysis also has specific parameters to exclude emphysematous lesions on imaging. The %honeycomb area (HA) was correlated with a composite physiologic index derived from PFTs (calculated from FEV1, FVC and DLCO). This tool can accurately quantify the percentage of honeycombing and aid in monitoring IPF. Using this protocol, Nakagawa was able to demonstrate a significant correlation with 3-year mortality, with a marked difference found when using a cutoff value of 4.8% (Nakagawa, et al. Plos One. 2019 Mar; 14[3]:e0214278). Furthermore, patient survival in IPF has been compared against the CALIPER program and PFTs. Mortality for patients was significantly associated with pulmonary vessel volume (PVV), an innovative tool that quantified the volume of the pulmonary artery and veins, which may become a new parameter used for disease monitoring. Using qCT in addition to PFTs provides more tangible evidence to help monitor patients with IPF, guide treatment decisions, and plan for transplant or palliative care. The growing use of PVV in qCT has yet to be fully elucidated, but it does have a promising role (Jacob, et al. Eur Respir J. 2017;49[1]. doi: 10.1183/13993003.01011-2016).

Despite the positive outlook for qCT, there are major issues that limit its widespread use. During the image acquisition process, there is a lack of consistency and quality control, stemming from multiple different manufacturers of CT scan machines, reconstitution methods, radiation doses, and noise or inspiratory efforts of patients. The Radiologic Society of North America (RSNA) is attempting to fix this issue by creating a standardized protocol for collecting images used for qCT (Castillo-Saldana, et al. J Thorac Imaging. 2019 Aug 7. doi: 10.1097/RTI.0000000000000440). In order to move forward with adaptation of qCT, a standardized approach and handling of images needs to be created.

Quantitative CT is an exciting new prospect for the care of patients with ILD. As these patients, and their management, becomes more complex, expanding the toolbox for physicians is much needed. It will be fascinating to see how the role of qCT takes shape over the coming years.
 

Dr. D’Annunzio is with Westmed Medical Group, Rye, N.Y.; Dr. Nayar is a Pulmonary/Critical Care Fellow at NYU School of Medicine; and Dr. Patel is with Columbia University Medical Center.

The role of imaging for interstitial lung disease (ILD) is of paramount importance. With the growth of high resolution chest computed tomography (HRCT) imaging techniques, we are able to visualize nuances between individual ILDs more critically. HRCT is an essential component of an initial ILD evaluation and also has become part of the armamentarium of tools used for routine management of these patients. The technology of HRCT scans has evolved over the years, most recently with the advent of quantitative HRCT (qCT). The technology employs texture-based classification, which identifies and quantifies different radiographic findings. The arrival of qCT scanning has been slowly emerging as a new player in the ILD world. What exactly is qCT, and what role can, and will it serve for our ILD patients?

Quantitative CT scanning has been introduced since the 1980s, but only within the last 15 years has its use for ILD taken form. Human interpretation of CTs is fraught with subjectivity, based on the interpreting radiologist’s training, experience, and individual visual perception of images. This can result in significant variability in radiographic interpretations and, ultimately, affects a patient’s diagnosis, disease monitoring, treatment, and prognosis. Semiquantitative visual scoring by radiologists is highly variable, especially in areas with limited availability of chest radiologists. qCT employs an automated histogram signature technique that utilizes density and texture-based analysis of the lung parenchyma. Utilizing machine learning from pathologically confirmed datasets, computer programs were trained with specialized thoracic radiologists to distinguish some commonly found radiographic abnormalities into four major groups: ground glass, reticular, honeycombing, and emphysema. In addition, these categories are quantified and spatially depicted on an analysis (Bartholmai, et al. J Thorac Imaging. 2013;28[5]:298). Various computer programs have been built to streamline the process and expedite the interpretation of an individual’s HRCT scan. The more commonly familiar program, CALIPER (Computer-Aided Lung Informatics for Pathology Evaluation and Ratings), has been used in multiple research studies of qCT in ILD and IPF. Each patient’s CT scan is uploaded to the program, and a breakdown of the patient’s lungs into each category is presented. Not only is each abnormality quantified and precisely defined, it is also color-coded by segments to help with visual interpretation by the physician.

The benefit of qCT lies not only in the automated, objective evaluation of interstitial lung disease, but also in its possible use in prognostication and mortality prediction. Neither use has been fully validated as of yet. However, growing evidence shows a promising role in both realms. Thus far, there have been some studies correlating PFT data with qCT findings. A follow-up study of the Scleroderma Lung Study II examined qCT changes over 24 months and correlated those findings with PFTs and patient-reported outcomes. Patients in this study were either treated with cyclophosphamide (CYC) for 1 year/placebo 1 year vs mycophenolate mofetil (MMF) for 2 years. A large portion of patients receiving CYC or MMF had a significant correlation between improved or stable qCT scores and their FVC and TLC. Neither CYC nor MMF was superior in qCT scores, aligning with the findings of the study, which showed noninferiority of MMF compared with CYC (Goldin, et al. Ann Am Thorac Soc. 2018 Nov;15[11]:1286). Interestingly, the improvement of ground glass is often viewed by physicians as positive, since this finding is typically thought of as active inflammation. However, if qCT determines that the fibrosis score actually increases over time, despite an improvement in ground glass, this may more accurately reflect the development of subtle fibrosis that is not easily appreciated by the human eye (Goldin, et al. Ann Am Thorac Soc. 2018 Nov;15[11]:1286). In this context, it is feasible that parenchymal changes occur prior to deterioration on PFTs. Diffusing capacity for carbon monoxide (DLCO) correlates largely with the extent of lung involvement on qCT, but DLCO is not a specific biomarker in predicting severity of ILD (ie, because pHTN or anemia can confound DLCO). Forced vital capacity (FVC) in certain diseases may also confound CT correlation (ie, muscle weakness or extrathoracic restriction from skin disease in systemic sclerosis). The usefulness of PFT data as a clinical endpoint in research studies may be replaced by qCTs more consistent and precise detection of disease modification.

IPF has been an interesting area of exploration for the role of qCT in disease monitoring and possible prognostication. It is known that the presence of honeycombing on HRCT is associated with increased mortality. Patients with a progressive fibrotic ILD have similar mortality rates to those with IPF (Adegunsoye, et al. Ann Am Thorac Soc. 2019 May;16[5]:580). The ability to correlate radiographic findings with mortality could potentially become an important marker of clinical deterioration, especially in those patients who are unable to perform PFTs. In addition, it can also be beneficial in those with co-existent emphysema, since PFTs may be confounded by this overlap. Nakagawa and colleagues proposed a computer-aided method for qCT analysis of honeycombing in patients with IPF. The algorithm for the qCT analysis also has specific parameters to exclude emphysematous lesions on imaging. The %honeycomb area (HA) was correlated with a composite physiologic index derived from PFTs (calculated from FEV1, FVC and DLCO). This tool can accurately quantify the percentage of honeycombing and aid in monitoring IPF. Using this protocol, Nakagawa was able to demonstrate a significant correlation with 3-year mortality, with a marked difference found when using a cutoff value of 4.8% (Nakagawa, et al. Plos One. 2019 Mar; 14[3]:e0214278). Furthermore, patient survival in IPF has been compared against the CALIPER program and PFTs. Mortality for patients was significantly associated with pulmonary vessel volume (PVV), an innovative tool that quantified the volume of the pulmonary artery and veins, which may become a new parameter used for disease monitoring. Using qCT in addition to PFTs provides more tangible evidence to help monitor patients with IPF, guide treatment decisions, and plan for transplant or palliative care. The growing use of PVV in qCT has yet to be fully elucidated, but it does have a promising role (Jacob, et al. Eur Respir J. 2017;49[1]. doi: 10.1183/13993003.01011-2016).

Despite the positive outlook for qCT, there are major issues that limit its widespread use. During the image acquisition process, there is a lack of consistency and quality control, stemming from multiple different manufacturers of CT scan machines, reconstitution methods, radiation doses, and noise or inspiratory efforts of patients. The Radiologic Society of North America (RSNA) is attempting to fix this issue by creating a standardized protocol for collecting images used for qCT (Castillo-Saldana, et al. J Thorac Imaging. 2019 Aug 7. doi: 10.1097/RTI.0000000000000440). In order to move forward with adaptation of qCT, a standardized approach and handling of images needs to be created.

Quantitative CT is an exciting new prospect for the care of patients with ILD. As these patients, and their management, becomes more complex, expanding the toolbox for physicians is much needed. It will be fascinating to see how the role of qCT takes shape over the coming years.
 

Dr. D’Annunzio is with Westmed Medical Group, Rye, N.Y.; Dr. Nayar is a Pulmonary/Critical Care Fellow at NYU School of Medicine; and Dr. Patel is with Columbia University Medical Center.

The role of imaging for interstitial lung disease (ILD) is of paramount importance. With the growth of high resolution chest computed tomography (HRCT) imaging techniques, we are able to visualize nuances between individual ILDs more critically. HRCT is an essential component of an initial ILD evaluation and also has become part of the armamentarium of tools used for routine management of these patients. The technology of HRCT scans has evolved over the years, most recently with the advent of quantitative HRCT (qCT). The technology employs texture-based classification, which identifies and quantifies different radiographic findings. The arrival of qCT scanning has been slowly emerging as a new player in the ILD world. What exactly is qCT, and what role can, and will it serve for our ILD patients?

Quantitative CT scanning has been introduced since the 1980s, but only within the last 15 years has its use for ILD taken form. Human interpretation of CTs is fraught with subjectivity, based on the interpreting radiologist’s training, experience, and individual visual perception of images. This can result in significant variability in radiographic interpretations and, ultimately, affects a patient’s diagnosis, disease monitoring, treatment, and prognosis. Semiquantitative visual scoring by radiologists is highly variable, especially in areas with limited availability of chest radiologists. qCT employs an automated histogram signature technique that utilizes density and texture-based analysis of the lung parenchyma. Utilizing machine learning from pathologically confirmed datasets, computer programs were trained with specialized thoracic radiologists to distinguish some commonly found radiographic abnormalities into four major groups: ground glass, reticular, honeycombing, and emphysema. In addition, these categories are quantified and spatially depicted on an analysis (Bartholmai, et al. J Thorac Imaging. 2013;28[5]:298). Various computer programs have been built to streamline the process and expedite the interpretation of an individual’s HRCT scan. The more commonly familiar program, CALIPER (Computer-Aided Lung Informatics for Pathology Evaluation and Ratings), has been used in multiple research studies of qCT in ILD and IPF. Each patient’s CT scan is uploaded to the program, and a breakdown of the patient’s lungs into each category is presented. Not only is each abnormality quantified and precisely defined, it is also color-coded by segments to help with visual interpretation by the physician.

The benefit of qCT lies not only in the automated, objective evaluation of interstitial lung disease, but also in its possible use in prognostication and mortality prediction. Neither use has been fully validated as of yet. However, growing evidence shows a promising role in both realms. Thus far, there have been some studies correlating PFT data with qCT findings. A follow-up study of the Scleroderma Lung Study II examined qCT changes over 24 months and correlated those findings with PFTs and patient-reported outcomes. Patients in this study were either treated with cyclophosphamide (CYC) for 1 year/placebo 1 year vs mycophenolate mofetil (MMF) for 2 years. A large portion of patients receiving CYC or MMF had a significant correlation between improved or stable qCT scores and their FVC and TLC. Neither CYC nor MMF was superior in qCT scores, aligning with the findings of the study, which showed noninferiority of MMF compared with CYC (Goldin, et al. Ann Am Thorac Soc. 2018 Nov;15[11]:1286). Interestingly, the improvement of ground glass is often viewed by physicians as positive, since this finding is typically thought of as active inflammation. However, if qCT determines that the fibrosis score actually increases over time, despite an improvement in ground glass, this may more accurately reflect the development of subtle fibrosis that is not easily appreciated by the human eye (Goldin, et al. Ann Am Thorac Soc. 2018 Nov;15[11]:1286). In this context, it is feasible that parenchymal changes occur prior to deterioration on PFTs. Diffusing capacity for carbon monoxide (DLCO) correlates largely with the extent of lung involvement on qCT, but DLCO is not a specific biomarker in predicting severity of ILD (ie, because pHTN or anemia can confound DLCO). Forced vital capacity (FVC) in certain diseases may also confound CT correlation (ie, muscle weakness or extrathoracic restriction from skin disease in systemic sclerosis). The usefulness of PFT data as a clinical endpoint in research studies may be replaced by qCTs more consistent and precise detection of disease modification.

IPF has been an interesting area of exploration for the role of qCT in disease monitoring and possible prognostication. It is known that the presence of honeycombing on HRCT is associated with increased mortality. Patients with a progressive fibrotic ILD have similar mortality rates to those with IPF (Adegunsoye, et al. Ann Am Thorac Soc. 2019 May;16[5]:580). The ability to correlate radiographic findings with mortality could potentially become an important marker of clinical deterioration, especially in those patients who are unable to perform PFTs. In addition, it can also be beneficial in those with co-existent emphysema, since PFTs may be confounded by this overlap. Nakagawa and colleagues proposed a computer-aided method for qCT analysis of honeycombing in patients with IPF. The algorithm for the qCT analysis also has specific parameters to exclude emphysematous lesions on imaging. The %honeycomb area (HA) was correlated with a composite physiologic index derived from PFTs (calculated from FEV1, FVC and DLCO). This tool can accurately quantify the percentage of honeycombing and aid in monitoring IPF. Using this protocol, Nakagawa was able to demonstrate a significant correlation with 3-year mortality, with a marked difference found when using a cutoff value of 4.8% (Nakagawa, et al. Plos One. 2019 Mar; 14[3]:e0214278). Furthermore, patient survival in IPF has been compared against the CALIPER program and PFTs. Mortality for patients was significantly associated with pulmonary vessel volume (PVV), an innovative tool that quantified the volume of the pulmonary artery and veins, which may become a new parameter used for disease monitoring. Using qCT in addition to PFTs provides more tangible evidence to help monitor patients with IPF, guide treatment decisions, and plan for transplant or palliative care. The growing use of PVV in qCT has yet to be fully elucidated, but it does have a promising role (Jacob, et al. Eur Respir J. 2017;49[1]. doi: 10.1183/13993003.01011-2016).

Despite the positive outlook for qCT, there are major issues that limit its widespread use. During the image acquisition process, there is a lack of consistency and quality control, stemming from multiple different manufacturers of CT scan machines, reconstitution methods, radiation doses, and noise or inspiratory efforts of patients. The Radiologic Society of North America (RSNA) is attempting to fix this issue by creating a standardized protocol for collecting images used for qCT (Castillo-Saldana, et al. J Thorac Imaging. 2019 Aug 7. doi: 10.1097/RTI.0000000000000440). In order to move forward with adaptation of qCT, a standardized approach and handling of images needs to be created.

Quantitative CT is an exciting new prospect for the care of patients with ILD. As these patients, and their management, becomes more complex, expanding the toolbox for physicians is much needed. It will be fascinating to see how the role of qCT takes shape over the coming years.
 

Dr. D’Annunzio is with Westmed Medical Group, Rye, N.Y.; Dr. Nayar is a Pulmonary/Critical Care Fellow at NYU School of Medicine; and Dr. Patel is with Columbia University Medical Center.

Application of basic physiology principles at bedside has changed the approach to the treatment of patients with acute respiratory distress syndrome (ARDS) and refractory hypoxemia. Current standard of care for patients with ARDS includes a low tidal volume ventilation strategy (6 mL/kg of ideal body weight), keeping plateau pressures below 30 cm H₂O (Brower RG, et al. N Engl J Med. 2000;342[18]:1301), driving pressures below 15 cm H₂O and adequate positive end-expiratory pressures (PEEP) to keep the alveoli open without overdistension (Villar J, et al. Crit Care Med. 2006;34[5]:1311). However, at this time, despite the awareness of the importance of this intervention, there is no consensus regarding the best method to determine ideal PEEP at the individual patient level.

A thorough understanding of the basic physiologic concepts regarding respiratory pressures is of paramount importance to be able to formulate an opinion. The transpulmonary pressure (or lung distending pressure) is the gradient caused by the difference between alveolar (PA) and pleural pressure (PPL). In order to prevent lung collapse at end-expiration, PA must remain higher than PPL such that the gradient remains outward, preventing end-expiratory collapse and atelectotrauma. To accomplish that, it is necessary to know the end-expiratory PA and PPL. Esophageal balloon pressures (PES) represent central thoracic pressures, but, despite positional and regional variations, they are a good surrogate for average “effective” PPL (Baedorf KE, et al. Med Klin Intensivmed Notfmed. 2018;113[Suppl 1]:13).

Understanding that the value of the PES represents a practical PPL makes it easier to appreciate the potential usefulness of an esophageal balloon to titrate PEEP. The objective of PEEP titration is to prevent de-recruitment, maintain alveolar aeration, and improve the functional size of aerated alveoli. If the applied PEEP is lower than the PPL, the dependent lung regions will collapse. On the other hand, if PEEP is higher than the PPL, the lung would be overdistended, causing barotrauma and hemodynamic compromise.

The question is: Should we use esophageal balloons?Yes, we should.

A single center randomized control trial (EPVent) compared PEEP titration to achieve a positive PL vs standard of care lung protective ventilation (Talmor D, et al. N Engl J Med. 2008;359:2095). The PEEP titration group used significantly higher levels of PEEP, with improved oxygenation and lung compliance. However, there was no significant difference in ventilator-free days or mortality between the groups.

Obese patients are also likely to benefit from PEEP titration guided by an esophageal balloon, as they often have higher levels of intrinsic PEEP. Therefore, the application of higher levels of PEEP to compensate for the higher levels of intrinsic PEEP may help reduce work of breathing and prevent tidal recruitment-de-recruitment and atelectasis. Additionally, low to negative transpulmonary pressures measured using the actual values of PES in obese patients and obese animal models predicted lung collapse and tidal opening and closing (Fumagalli J, et al. Crit Care Med. 2017;45[8]:1374). It is useful to remember that the compliance of the respiratory system (Crs) is the total of the sum of the compliance of the chest wall (Ccw) and the lung compliance (CL). In obese patients, Ccw has a much more significant contribution to the total Crs, and the clinician should be really interested in the CL. At the bedside, esophageal manometry can be very useful to distinguish the contribution of CL and Ccw to the total Crs.

No, we shouldn’t.

Another randomized controlled trial (EPVent-2), by the same group, compared PEEP titration guided by esophageal pressure with empirical PEEP titration, in patients with moderate to severe ARDS (Beitler JR, et al. JAMA. 2019;321[9]:846). The primary outcomes of interest, death, and mechanical ventilator-free days through day 28 were not different between the groups.

Additionally, placement of an esophageal balloon is challenging and operator-dependent. The balloon portion of the esophageal catheter should be positioned in the lower third of the esophagus, behind the heart. Catheter placement is typically performed by inserting it into the stomach to a depth of about 60 cm, and gently pressing on the abdomen and observing a sudden increase in pressure on the ventilator screen. It is then withdrawn to about 40 cm, while looking for cardiac oscillations and pressure change (Talmor D, et al. N Engl J Med. 2008;359:2095). One can see how easily it would be to insert the esophageal balloon incorrectly. A misplaced balloon won’t provide accurate PES and can potentially cause harm.

Final answer: It depends on each individual patient.

Arguments for and against using an esophageal balloon to titrate PEEP in patients with ARDS and refractory hypoxemia are ongoing. Even the two most cited and applied trials on the matter (EPVent and EPVent-2) reported contradictory results. However, when analyzed in depth, both showed better oxygenation with the use of esophageal balloon. EPVent had improvement in oxygenation as its primary endpoint, and it was significant in the esophageal balloon group. EPVent-2 had oxygenation goals, in the form of need for rescue therapies for refractory hypoxemia, as secondary endpoints. Nonetheless, the patients in the esophageal balloon group in EPVent-2 required prone positioning less frequently, had lower use of pulmonary vasodilators, and a lower rate of ECMO consultations. Even though those trials did not show a mortality benefit, both showed an oxygenation benefit.

The ideal single tool that would indicate the “perfect “PEEP for each patient remains to be described. Until then, PEEP titration guided by a combination of ARDSnet PEEP tables, while maintaining a plateau pressure below 30 cm H₂O and considering a driving pressure below 15 cm H₂O should be a clinician’s goal. In patients in the extremes of height and body weight, and/or with conditions that would increase intra-abdominal pressure, such as ascites, a well-placed esophageal balloon while patient is supine might be beneficial.

The truth of the matter is, PEEP should be titrated by a trained intensivist in conjunction with the multidisciplinary ICU team, at patients’ bedside taking into consideration each individual’s unique physiologic and pathophysiologic characteristics at that moment.

Dr. Gallo de Moraes is Assistant Professor of Medicine, and Dr Oeckler is Assistant Professor of Medicine, Division of Pulmonary and Critical Care, Mayo Clinic, Rochester, Minnesota.

Application of basic physiology principles at bedside has changed the approach to the treatment of patients with acute respiratory distress syndrome (ARDS) and refractory hypoxemia. Current standard of care for patients with ARDS includes a low tidal volume ventilation strategy (6 mL/kg of ideal body weight), keeping plateau pressures below 30 cm H₂O (Brower RG, et al. N Engl J Med. 2000;342[18]:1301), driving pressures below 15 cm H₂O and adequate positive end-expiratory pressures (PEEP) to keep the alveoli open without overdistension (Villar J, et al. Crit Care Med. 2006;34[5]:1311). However, at this time, despite the awareness of the importance of this intervention, there is no consensus regarding the best method to determine ideal PEEP at the individual patient level.

A thorough understanding of the basic physiologic concepts regarding respiratory pressures is of paramount importance to be able to formulate an opinion. The transpulmonary pressure (or lung distending pressure) is the gradient caused by the difference between alveolar (PA) and pleural pressure (PPL). In order to prevent lung collapse at end-expiration, PA must remain higher than PPL such that the gradient remains outward, preventing end-expiratory collapse and atelectotrauma. To accomplish that, it is necessary to know the end-expiratory PA and PPL. Esophageal balloon pressures (PES) represent central thoracic pressures, but, despite positional and regional variations, they are a good surrogate for average “effective” PPL (Baedorf KE, et al. Med Klin Intensivmed Notfmed. 2018;113[Suppl 1]:13).

Understanding that the value of the PES represents a practical PPL makes it easier to appreciate the potential usefulness of an esophageal balloon to titrate PEEP. The objective of PEEP titration is to prevent de-recruitment, maintain alveolar aeration, and improve the functional size of aerated alveoli. If the applied PEEP is lower than the PPL, the dependent lung regions will collapse. On the other hand, if PEEP is higher than the PPL, the lung would be overdistended, causing barotrauma and hemodynamic compromise.

The question is: Should we use esophageal balloons?Yes, we should.

A single center randomized control trial (EPVent) compared PEEP titration to achieve a positive PL vs standard of care lung protective ventilation (Talmor D, et al. N Engl J Med. 2008;359:2095). The PEEP titration group used significantly higher levels of PEEP, with improved oxygenation and lung compliance. However, there was no significant difference in ventilator-free days or mortality between the groups.

Obese patients are also likely to benefit from PEEP titration guided by an esophageal balloon, as they often have higher levels of intrinsic PEEP. Therefore, the application of higher levels of PEEP to compensate for the higher levels of intrinsic PEEP may help reduce work of breathing and prevent tidal recruitment-de-recruitment and atelectasis. Additionally, low to negative transpulmonary pressures measured using the actual values of PES in obese patients and obese animal models predicted lung collapse and tidal opening and closing (Fumagalli J, et al. Crit Care Med. 2017;45[8]:1374). It is useful to remember that the compliance of the respiratory system (Crs) is the total of the sum of the compliance of the chest wall (Ccw) and the lung compliance (CL). In obese patients, Ccw has a much more significant contribution to the total Crs, and the clinician should be really interested in the CL. At the bedside, esophageal manometry can be very useful to distinguish the contribution of CL and Ccw to the total Crs.

No, we shouldn’t.

Another randomized controlled trial (EPVent-2), by the same group, compared PEEP titration guided by esophageal pressure with empirical PEEP titration, in patients with moderate to severe ARDS (Beitler JR, et al. JAMA. 2019;321[9]:846). The primary outcomes of interest, death, and mechanical ventilator-free days through day 28 were not different between the groups.

Additionally, placement of an esophageal balloon is challenging and operator-dependent. The balloon portion of the esophageal catheter should be positioned in the lower third of the esophagus, behind the heart. Catheter placement is typically performed by inserting it into the stomach to a depth of about 60 cm, and gently pressing on the abdomen and observing a sudden increase in pressure on the ventilator screen. It is then withdrawn to about 40 cm, while looking for cardiac oscillations and pressure change (Talmor D, et al. N Engl J Med. 2008;359:2095). One can see how easily it would be to insert the esophageal balloon incorrectly. A misplaced balloon won’t provide accurate PES and can potentially cause harm.

Final answer: It depends on each individual patient.

Arguments for and against using an esophageal balloon to titrate PEEP in patients with ARDS and refractory hypoxemia are ongoing. Even the two most cited and applied trials on the matter (EPVent and EPVent-2) reported contradictory results. However, when analyzed in depth, both showed better oxygenation with the use of esophageal balloon. EPVent had improvement in oxygenation as its primary endpoint, and it was significant in the esophageal balloon group. EPVent-2 had oxygenation goals, in the form of need for rescue therapies for refractory hypoxemia, as secondary endpoints. Nonetheless, the patients in the esophageal balloon group in EPVent-2 required prone positioning less frequently, had lower use of pulmonary vasodilators, and a lower rate of ECMO consultations. Even though those trials did not show a mortality benefit, both showed an oxygenation benefit.

The ideal single tool that would indicate the “perfect “PEEP for each patient remains to be described. Until then, PEEP titration guided by a combination of ARDSnet PEEP tables, while maintaining a plateau pressure below 30 cm H₂O and considering a driving pressure below 15 cm H₂O should be a clinician’s goal. In patients in the extremes of height and body weight, and/or with conditions that would increase intra-abdominal pressure, such as ascites, a well-placed esophageal balloon while patient is supine might be beneficial.

The truth of the matter is, PEEP should be titrated by a trained intensivist in conjunction with the multidisciplinary ICU team, at patients’ bedside taking into consideration each individual’s unique physiologic and pathophysiologic characteristics at that moment.

Dr. Gallo de Moraes is Assistant Professor of Medicine, and Dr Oeckler is Assistant Professor of Medicine, Division of Pulmonary and Critical Care, Mayo Clinic, Rochester, Minnesota.

Application of basic physiology principles at bedside has changed the approach to the treatment of patients with acute respiratory distress syndrome (ARDS) and refractory hypoxemia. Current standard of care for patients with ARDS includes a low tidal volume ventilation strategy (6 mL/kg of ideal body weight), keeping plateau pressures below 30 cm H₂O (Brower RG, et al. N Engl J Med. 2000;342[18]:1301), driving pressures below 15 cm H₂O and adequate positive end-expiratory pressures (PEEP) to keep the alveoli open without overdistension (Villar J, et al. Crit Care Med. 2006;34[5]:1311). However, at this time, despite the awareness of the importance of this intervention, there is no consensus regarding the best method to determine ideal PEEP at the individual patient level.

A thorough understanding of the basic physiologic concepts regarding respiratory pressures is of paramount importance to be able to formulate an opinion. The transpulmonary pressure (or lung distending pressure) is the gradient caused by the difference between alveolar (PA) and pleural pressure (PPL). In order to prevent lung collapse at end-expiration, PA must remain higher than PPL such that the gradient remains outward, preventing end-expiratory collapse and atelectotrauma. To accomplish that, it is necessary to know the end-expiratory PA and PPL. Esophageal balloon pressures (PES) represent central thoracic pressures, but, despite positional and regional variations, they are a good surrogate for average “effective” PPL (Baedorf KE, et al. Med Klin Intensivmed Notfmed. 2018;113[Suppl 1]:13).

Understanding that the value of the PES represents a practical PPL makes it easier to appreciate the potential usefulness of an esophageal balloon to titrate PEEP. The objective of PEEP titration is to prevent de-recruitment, maintain alveolar aeration, and improve the functional size of aerated alveoli. If the applied PEEP is lower than the PPL, the dependent lung regions will collapse. On the other hand, if PEEP is higher than the PPL, the lung would be overdistended, causing barotrauma and hemodynamic compromise.

The question is: Should we use esophageal balloons?Yes, we should.

A single center randomized control trial (EPVent) compared PEEP titration to achieve a positive PL vs standard of care lung protective ventilation (Talmor D, et al. N Engl J Med. 2008;359:2095). The PEEP titration group used significantly higher levels of PEEP, with improved oxygenation and lung compliance. However, there was no significant difference in ventilator-free days or mortality between the groups.

Obese patients are also likely to benefit from PEEP titration guided by an esophageal balloon, as they often have higher levels of intrinsic PEEP. Therefore, the application of higher levels of PEEP to compensate for the higher levels of intrinsic PEEP may help reduce work of breathing and prevent tidal recruitment-de-recruitment and atelectasis. Additionally, low to negative transpulmonary pressures measured using the actual values of PES in obese patients and obese animal models predicted lung collapse and tidal opening and closing (Fumagalli J, et al. Crit Care Med. 2017;45[8]:1374). It is useful to remember that the compliance of the respiratory system (Crs) is the total of the sum of the compliance of the chest wall (Ccw) and the lung compliance (CL). In obese patients, Ccw has a much more significant contribution to the total Crs, and the clinician should be really interested in the CL. At the bedside, esophageal manometry can be very useful to distinguish the contribution of CL and Ccw to the total Crs.

No, we shouldn’t.

Another randomized controlled trial (EPVent-2), by the same group, compared PEEP titration guided by esophageal pressure with empirical PEEP titration, in patients with moderate to severe ARDS (Beitler JR, et al. JAMA. 2019;321[9]:846). The primary outcomes of interest, death, and mechanical ventilator-free days through day 28 were not different between the groups.

Additionally, placement of an esophageal balloon is challenging and operator-dependent. The balloon portion of the esophageal catheter should be positioned in the lower third of the esophagus, behind the heart. Catheter placement is typically performed by inserting it into the stomach to a depth of about 60 cm, and gently pressing on the abdomen and observing a sudden increase in pressure on the ventilator screen. It is then withdrawn to about 40 cm, while looking for cardiac oscillations and pressure change (Talmor D, et al. N Engl J Med. 2008;359:2095). One can see how easily it would be to insert the esophageal balloon incorrectly. A misplaced balloon won’t provide accurate PES and can potentially cause harm.

Final answer: It depends on each individual patient.

Arguments for and against using an esophageal balloon to titrate PEEP in patients with ARDS and refractory hypoxemia are ongoing. Even the two most cited and applied trials on the matter (EPVent and EPVent-2) reported contradictory results. However, when analyzed in depth, both showed better oxygenation with the use of esophageal balloon. EPVent had improvement in oxygenation as its primary endpoint, and it was significant in the esophageal balloon group. EPVent-2 had oxygenation goals, in the form of need for rescue therapies for refractory hypoxemia, as secondary endpoints. Nonetheless, the patients in the esophageal balloon group in EPVent-2 required prone positioning less frequently, had lower use of pulmonary vasodilators, and a lower rate of ECMO consultations. Even though those trials did not show a mortality benefit, both showed an oxygenation benefit.

The ideal single tool that would indicate the “perfect “PEEP for each patient remains to be described. Until then, PEEP titration guided by a combination of ARDSnet PEEP tables, while maintaining a plateau pressure below 30 cm H₂O and considering a driving pressure below 15 cm H₂O should be a clinician’s goal. In patients in the extremes of height and body weight, and/or with conditions that would increase intra-abdominal pressure, such as ascites, a well-placed esophageal balloon while patient is supine might be beneficial.

The truth of the matter is, PEEP should be titrated by a trained intensivist in conjunction with the multidisciplinary ICU team, at patients’ bedside taking into consideration each individual’s unique physiologic and pathophysiologic characteristics at that moment.

Dr. Gallo de Moraes is Assistant Professor of Medicine, and Dr Oeckler is Assistant Professor of Medicine, Division of Pulmonary and Critical Care, Mayo Clinic, Rochester, Minnesota.