Jim Kling

At a single robotic-assisted pulmonary lobectomy center, patients with public insurance or combined public and private insurance fared worse than those with private insurance, according to a new retrospective analysis.

The study used public insurance status as a marker for low socioeconomic status (SES) and suggests that patients with combined insurance may constitute a separate population that deserves more attention.

Lower SES has been linked to later stage diagnoses and worse outcomes in NSCLC. Private insurance is a generally-accepted indicator of higher SES, while public insurance like Medicare or Medicaid, alone or in combination with private supplementary insurance, is an indicator of lower SES.

Although previous studies have found associations between patients having public health insurance and experiencing later-stage diagnoses and worse overall survival, there have been few studies of surgical outcomes, and almost no research has examined combination health insurance, according to Allison O. Dumitriu Carcoana, who presented the research during a poster session at the European Lung Cancer Congress 2023.

“This is an important insurance subgroup for us because the majority of our patients fall into this subgroup by being over 65 years old and thus qualifying for Medicare while also paying for a private supplement,” said Ms. Dumitriu Carcoana, who is a medical student at University of South Florida Health Morsani College of Medicine, Tampa.

A previous analysis by the group found an association between private insurance status and better discharge status, as well as higher 5-year overall survival. After accumulating an additional 278 patients, the researchers examined 10-year survival outcomes.

In the new analysis, 52% of 711 participants had combination insurance, while 28% had private insurance, and 20% had public insurance. The subgroups all had similar demographic and histological characteristics. The study was unique in that it found no between-group differences in higher stage at diagnosis, whereas previous studies have found a greater risk of higher stage diagnosis among individuals with public insurance. As expected, patients in the combined insurance group had a higher mean age (P less than .0001) and higher Charlson comorbidity index scores (P = .0014), which in turn was associated with lower 10-year survival. The group also had the highest percentage of former smokers, while the public insurance group had the highest percentage of current smokers (P = .0003).

At both 5 and 10 years, the private insurance group had better OS than the group with public (P less than .001) and the combination insurance group (P = .08). Public health insurance was associated with worse OS at 5 years (hazard ratio, 1.83; P less than .005) but not at 10 years (HR, 1.18; P = .51), while combination insurance was associated with worse OS at 10 years (HR, 1.72; P = .02).

“We think that patients with public health insurance having the worst 5-year overall survival, despite their lower ages and fewer comorbid conditions, compared with patients with combination insurance, highlights the impact of lower socioeconomic status on health outcomes. These patients had the same tumor characteristics, BMI, sex, and race as our patients in the other two insurance groups. The only other significant risk factor [the group had besides having a higher proportion of patients with lower socioeconomic status was that it had a higher proportion of current smokers]. But the multivariate analyses showed that insurance status was an independent predictor of survival, regardless of smoking status or other comorbidities,” said Ms. Dumitriu Carcoana.

“At 10 years post-operatively, the survival curves have shifted and the combination patients had the worst 10-year overall survival. We attribute this to their higher number of comorbid conditions and increased age. In practice, [this means that] the group of patients with public insurance type, but no supplement, should be identified clinically, and the clinical team can initiate a discussion,” Ms. Dumitriu Carcoana said.

“Do these patients feel that they can make follow-up appointments, keep up with medication costs, and make the right lifestyle decisions postoperatively on their current insurance plan? If not, can they afford a private supplement? In our cohort specifically, it may also be important to do more preoperative counseling on the importance of smoking cessation,” she added.

The study is interesting, but it has some important limitations, according to Raja Flores, MD, who was not involved with the study. The authors stated that there was no difference between the insurance groups with respect to mortality or cancer stage, which is the most important predictor of survival. However, the poster didn't include details of the authors' analysis, making it difficult to interpret, Dr. Flores said.

The fact that the study includes a single surgeon has some disadvantages in terms of broader applicability, but it also controls for surgical technique. “Different surgeons have different ways of doing things, so if you had the same surgeon doing it the same way every time, you can look at other variables like insurance (status) and stage,” said Dr. Flores.

The results may also provide an argument against using robotic surgery in patients who do not have insurance, especially since they have not been proven to be better than standard minimally invasive surgery with no robotic assistance. With uninsured patients, “you’re using taxpayer money for a more expensive procedure that isn’t proving to be any better,” Dr. Flores explained.

The study was performed at a single center and cannot prove causation due to its retrospective nature.

Ms. Dumitriu Carcoana and Dr. Flores have no relevant financial disclosures.

*This article was updated on 4/13/2023.

At a single robotic-assisted pulmonary lobectomy center, patients with public insurance or combined public and private insurance fared worse than those with private insurance, according to a new retrospective analysis.

The study used public insurance status as a marker for low socioeconomic status (SES) and suggests that patients with combined insurance may constitute a separate population that deserves more attention.

Lower SES has been linked to later stage diagnoses and worse outcomes in NSCLC. Private insurance is a generally-accepted indicator of higher SES, while public insurance like Medicare or Medicaid, alone or in combination with private supplementary insurance, is an indicator of lower SES.

Although previous studies have found associations between patients having public health insurance and experiencing later-stage diagnoses and worse overall survival, there have been few studies of surgical outcomes, and almost no research has examined combination health insurance, according to Allison O. Dumitriu Carcoana, who presented the research during a poster session at the European Lung Cancer Congress 2023.

“This is an important insurance subgroup for us because the majority of our patients fall into this subgroup by being over 65 years old and thus qualifying for Medicare while also paying for a private supplement,” said Ms. Dumitriu Carcoana, who is a medical student at University of South Florida Health Morsani College of Medicine, Tampa.

A previous analysis by the group found an association between private insurance status and better discharge status, as well as higher 5-year overall survival. After accumulating an additional 278 patients, the researchers examined 10-year survival outcomes.

In the new analysis, 52% of 711 participants had combination insurance, while 28% had private insurance, and 20% had public insurance. The subgroups all had similar demographic and histological characteristics. The study was unique in that it found no between-group differences in higher stage at diagnosis, whereas previous studies have found a greater risk of higher stage diagnosis among individuals with public insurance. As expected, patients in the combined insurance group had a higher mean age (P less than .0001) and higher Charlson comorbidity index scores (P = .0014), which in turn was associated with lower 10-year survival. The group also had the highest percentage of former smokers, while the public insurance group had the highest percentage of current smokers (P = .0003).

At both 5 and 10 years, the private insurance group had better OS than the group with public (P less than .001) and the combination insurance group (P = .08). Public health insurance was associated with worse OS at 5 years (hazard ratio, 1.83; P less than .005) but not at 10 years (HR, 1.18; P = .51), while combination insurance was associated with worse OS at 10 years (HR, 1.72; P = .02).

“We think that patients with public health insurance having the worst 5-year overall survival, despite their lower ages and fewer comorbid conditions, compared with patients with combination insurance, highlights the impact of lower socioeconomic status on health outcomes. These patients had the same tumor characteristics, BMI, sex, and race as our patients in the other two insurance groups. The only other significant risk factor [the group had besides having a higher proportion of patients with lower socioeconomic status was that it had a higher proportion of current smokers]. But the multivariate analyses showed that insurance status was an independent predictor of survival, regardless of smoking status or other comorbidities,” said Ms. Dumitriu Carcoana.

“At 10 years post-operatively, the survival curves have shifted and the combination patients had the worst 10-year overall survival. We attribute this to their higher number of comorbid conditions and increased age. In practice, [this means that] the group of patients with public insurance type, but no supplement, should be identified clinically, and the clinical team can initiate a discussion,” Ms. Dumitriu Carcoana said.

“Do these patients feel that they can make follow-up appointments, keep up with medication costs, and make the right lifestyle decisions postoperatively on their current insurance plan? If not, can they afford a private supplement? In our cohort specifically, it may also be important to do more preoperative counseling on the importance of smoking cessation,” she added.

The study is interesting, but it has some important limitations, according to Raja Flores, MD, who was not involved with the study. The authors stated that there was no difference between the insurance groups with respect to mortality or cancer stage, which is the most important predictor of survival. However, the poster didn't include details of the authors' analysis, making it difficult to interpret, Dr. Flores said.

The fact that the study includes a single surgeon has some disadvantages in terms of broader applicability, but it also controls for surgical technique. “Different surgeons have different ways of doing things, so if you had the same surgeon doing it the same way every time, you can look at other variables like insurance (status) and stage,” said Dr. Flores.

The results may also provide an argument against using robotic surgery in patients who do not have insurance, especially since they have not been proven to be better than standard minimally invasive surgery with no robotic assistance. With uninsured patients, “you’re using taxpayer money for a more expensive procedure that isn’t proving to be any better,” Dr. Flores explained.

The study was performed at a single center and cannot prove causation due to its retrospective nature.

Ms. Dumitriu Carcoana and Dr. Flores have no relevant financial disclosures.

*This article was updated on 4/13/2023.

At a single robotic-assisted pulmonary lobectomy center, patients with public insurance or combined public and private insurance fared worse than those with private insurance, according to a new retrospective analysis.

The study used public insurance status as a marker for low socioeconomic status (SES) and suggests that patients with combined insurance may constitute a separate population that deserves more attention.

Lower SES has been linked to later stage diagnoses and worse outcomes in NSCLC. Private insurance is a generally-accepted indicator of higher SES, while public insurance like Medicare or Medicaid, alone or in combination with private supplementary insurance, is an indicator of lower SES.

Although previous studies have found associations between patients having public health insurance and experiencing later-stage diagnoses and worse overall survival, there have been few studies of surgical outcomes, and almost no research has examined combination health insurance, according to Allison O. Dumitriu Carcoana, who presented the research during a poster session at the European Lung Cancer Congress 2023.

“This is an important insurance subgroup for us because the majority of our patients fall into this subgroup by being over 65 years old and thus qualifying for Medicare while also paying for a private supplement,” said Ms. Dumitriu Carcoana, who is a medical student at University of South Florida Health Morsani College of Medicine, Tampa.

A previous analysis by the group found an association between private insurance status and better discharge status, as well as higher 5-year overall survival. After accumulating an additional 278 patients, the researchers examined 10-year survival outcomes.

In the new analysis, 52% of 711 participants had combination insurance, while 28% had private insurance, and 20% had public insurance. The subgroups all had similar demographic and histological characteristics. The study was unique in that it found no between-group differences in higher stage at diagnosis, whereas previous studies have found a greater risk of higher stage diagnosis among individuals with public insurance. As expected, patients in the combined insurance group had a higher mean age (P less than .0001) and higher Charlson comorbidity index scores (P = .0014), which in turn was associated with lower 10-year survival. The group also had the highest percentage of former smokers, while the public insurance group had the highest percentage of current smokers (P = .0003).

At both 5 and 10 years, the private insurance group had better OS than the group with public (P less than .001) and the combination insurance group (P = .08). Public health insurance was associated with worse OS at 5 years (hazard ratio, 1.83; P less than .005) but not at 10 years (HR, 1.18; P = .51), while combination insurance was associated with worse OS at 10 years (HR, 1.72; P = .02).

“We think that patients with public health insurance having the worst 5-year overall survival, despite their lower ages and fewer comorbid conditions, compared with patients with combination insurance, highlights the impact of lower socioeconomic status on health outcomes. These patients had the same tumor characteristics, BMI, sex, and race as our patients in the other two insurance groups. The only other significant risk factor [the group had besides having a higher proportion of patients with lower socioeconomic status was that it had a higher proportion of current smokers]. But the multivariate analyses showed that insurance status was an independent predictor of survival, regardless of smoking status or other comorbidities,” said Ms. Dumitriu Carcoana.

“At 10 years post-operatively, the survival curves have shifted and the combination patients had the worst 10-year overall survival. We attribute this to their higher number of comorbid conditions and increased age. In practice, [this means that] the group of patients with public insurance type, but no supplement, should be identified clinically, and the clinical team can initiate a discussion,” Ms. Dumitriu Carcoana said.

“Do these patients feel that they can make follow-up appointments, keep up with medication costs, and make the right lifestyle decisions postoperatively on their current insurance plan? If not, can they afford a private supplement? In our cohort specifically, it may also be important to do more preoperative counseling on the importance of smoking cessation,” she added.

The study is interesting, but it has some important limitations, according to Raja Flores, MD, who was not involved with the study. The authors stated that there was no difference between the insurance groups with respect to mortality or cancer stage, which is the most important predictor of survival. However, the poster didn't include details of the authors' analysis, making it difficult to interpret, Dr. Flores said.

The fact that the study includes a single surgeon has some disadvantages in terms of broader applicability, but it also controls for surgical technique. “Different surgeons have different ways of doing things, so if you had the same surgeon doing it the same way every time, you can look at other variables like insurance (status) and stage,” said Dr. Flores.

The results may also provide an argument against using robotic surgery in patients who do not have insurance, especially since they have not been proven to be better than standard minimally invasive surgery with no robotic assistance. With uninsured patients, “you’re using taxpayer money for a more expensive procedure that isn’t proving to be any better,” Dr. Flores explained.

The study was performed at a single center and cannot prove causation due to its retrospective nature.

Ms. Dumitriu Carcoana and Dr. Flores have no relevant financial disclosures.

*This article was updated on 4/13/2023.

A comparison of Food and Drug Administration and European Medicines Agency approvals of immune checkpoint inhibitors in the field of thoracic cancer found significantly longer approval times at the European agency, as well as some examples of different perspectives on biomarkers.

The findings of this new study suggest that patients in Europe may face delayed access to new therapies, the authors wrote in a poster presentation at the European Lung Cancer Congress 2023.

They also noted that some FDA approvals occurred before pivotal trial data became available, which can leave doubt about efficacy.

“Effective cancer management relies on availability of therapies which improve patient outcomes, such as immunotherapy. The two largest regulators involved in approving immunotherapies are the FDA and the EMA and therefore we aimed to compare the approval timings between both to see if a difference in approval timings was present,” coauthor Aakash Desai, MD, said in an interview.

Previously, the researchers conducted a study of cancer approval patterns at the FDA and EMA between 2010 and 2019, and found U.S. patients gain access to new cancer therapeutics more quickly than do European patients. Of 89 new therapies approved in that time span, the FDA approval occurred first in 85 cases (95%), though just 72% were submitted to FDA first. The median increased time it took for EMA approval compared with the FDA was 241 days. Thirty-nine percent of U.S. approvals came before the publication of the pivotal clinical trial, versus 9% of EMA approvals.

The new study focuses on thoracic oncology, where lung cancer is the leading cause of death. “As such, prompt approval timings for immunotherapies are crucial for effective treatment. Furthermore, lung cancer immunotherapies target certain biomarkers, of which, PD1 and PD-L1 are key,” said Dr. Desai, a fellow at Mayo Clinic, Rochester, Minn.

Still, Dr. Desai sounded a note of caution. “Just because a therapy is approved more quickly does not necessarily mean it is efficacious, as the clinical trials involving these drugs may not have been completed or fully reported at the time of authorization. [Drug developers] need to have a more global and coordinated approach to evaluating evidence and approval of drugs so the care received by a particular patient is not a factor of where they live,” he said.

The researchers surveyed approvals of seven immune checkpoint inhibitors (ICIs) approved by both the FDA and the EMA for thoracic malignancies, including non–small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and mesothelioma. The FDA approved 22 indications for the novel ICIs in thoracic malignancies, compared with 16 indications at the EMA. The difference in median approval times was larger for SCLC (179 versus 308 days) and mesothelioma (39 versus 280 days) than for NSCLC (242 versus 272 days).

“There are two discrepancies in biomarker requirements between the FDA and EMA, whereby the FDA has a broader requirement, despite these being ranked fairly consistently in terms of evidence of benefit by [European Society for Medical Oncology Magnitude of Clinical Benefit Scale and National Comprehensive Cancer Network] frameworks,” said Dr. Desai. In the case of atezolizumab for adjuvant NSCLC, the FDA required PDL1 levels of 1% or higher, while the EMA required 50% or higher. For durvalumab in unresectable NSCLC, the FDA had no PDL1 requirement, while the EMA required 1% or higher.

Dr. Desai suggested a need for further investigation into the differences between the two agencies. Asked why the two agencies might have different views on the biomarkers, Dr. Desai responded: “That is the million-dollar question. My guess is [the] EMA weighs subgroup data more than [the] FDA.”

Dr. Desai has no relevant financial disclosures.

A comparison of Food and Drug Administration and European Medicines Agency approvals of immune checkpoint inhibitors in the field of thoracic cancer found significantly longer approval times at the European agency, as well as some examples of different perspectives on biomarkers.

The findings of this new study suggest that patients in Europe may face delayed access to new therapies, the authors wrote in a poster presentation at the European Lung Cancer Congress 2023.

They also noted that some FDA approvals occurred before pivotal trial data became available, which can leave doubt about efficacy.

“Effective cancer management relies on availability of therapies which improve patient outcomes, such as immunotherapy. The two largest regulators involved in approving immunotherapies are the FDA and the EMA and therefore we aimed to compare the approval timings between both to see if a difference in approval timings was present,” coauthor Aakash Desai, MD, said in an interview.

Previously, the researchers conducted a study of cancer approval patterns at the FDA and EMA between 2010 and 2019, and found U.S. patients gain access to new cancer therapeutics more quickly than do European patients. Of 89 new therapies approved in that time span, the FDA approval occurred first in 85 cases (95%), though just 72% were submitted to FDA first. The median increased time it took for EMA approval compared with the FDA was 241 days. Thirty-nine percent of U.S. approvals came before the publication of the pivotal clinical trial, versus 9% of EMA approvals.

The new study focuses on thoracic oncology, where lung cancer is the leading cause of death. “As such, prompt approval timings for immunotherapies are crucial for effective treatment. Furthermore, lung cancer immunotherapies target certain biomarkers, of which, PD1 and PD-L1 are key,” said Dr. Desai, a fellow at Mayo Clinic, Rochester, Minn.

Still, Dr. Desai sounded a note of caution. “Just because a therapy is approved more quickly does not necessarily mean it is efficacious, as the clinical trials involving these drugs may not have been completed or fully reported at the time of authorization. [Drug developers] need to have a more global and coordinated approach to evaluating evidence and approval of drugs so the care received by a particular patient is not a factor of where they live,” he said.

The researchers surveyed approvals of seven immune checkpoint inhibitors (ICIs) approved by both the FDA and the EMA for thoracic malignancies, including non–small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and mesothelioma. The FDA approved 22 indications for the novel ICIs in thoracic malignancies, compared with 16 indications at the EMA. The difference in median approval times was larger for SCLC (179 versus 308 days) and mesothelioma (39 versus 280 days) than for NSCLC (242 versus 272 days).

“There are two discrepancies in biomarker requirements between the FDA and EMA, whereby the FDA has a broader requirement, despite these being ranked fairly consistently in terms of evidence of benefit by [European Society for Medical Oncology Magnitude of Clinical Benefit Scale and National Comprehensive Cancer Network] frameworks,” said Dr. Desai. In the case of atezolizumab for adjuvant NSCLC, the FDA required PDL1 levels of 1% or higher, while the EMA required 50% or higher. For durvalumab in unresectable NSCLC, the FDA had no PDL1 requirement, while the EMA required 1% or higher.

Dr. Desai suggested a need for further investigation into the differences between the two agencies. Asked why the two agencies might have different views on the biomarkers, Dr. Desai responded: “That is the million-dollar question. My guess is [the] EMA weighs subgroup data more than [the] FDA.”

Dr. Desai has no relevant financial disclosures.

A comparison of Food and Drug Administration and European Medicines Agency approvals of immune checkpoint inhibitors in the field of thoracic cancer found significantly longer approval times at the European agency, as well as some examples of different perspectives on biomarkers.

The findings of this new study suggest that patients in Europe may face delayed access to new therapies, the authors wrote in a poster presentation at the European Lung Cancer Congress 2023.

They also noted that some FDA approvals occurred before pivotal trial data became available, which can leave doubt about efficacy.

“Effective cancer management relies on availability of therapies which improve patient outcomes, such as immunotherapy. The two largest regulators involved in approving immunotherapies are the FDA and the EMA and therefore we aimed to compare the approval timings between both to see if a difference in approval timings was present,” coauthor Aakash Desai, MD, said in an interview.

Previously, the researchers conducted a study of cancer approval patterns at the FDA and EMA between 2010 and 2019, and found U.S. patients gain access to new cancer therapeutics more quickly than do European patients. Of 89 new therapies approved in that time span, the FDA approval occurred first in 85 cases (95%), though just 72% were submitted to FDA first. The median increased time it took for EMA approval compared with the FDA was 241 days. Thirty-nine percent of U.S. approvals came before the publication of the pivotal clinical trial, versus 9% of EMA approvals.

The new study focuses on thoracic oncology, where lung cancer is the leading cause of death. “As such, prompt approval timings for immunotherapies are crucial for effective treatment. Furthermore, lung cancer immunotherapies target certain biomarkers, of which, PD1 and PD-L1 are key,” said Dr. Desai, a fellow at Mayo Clinic, Rochester, Minn.

Still, Dr. Desai sounded a note of caution. “Just because a therapy is approved more quickly does not necessarily mean it is efficacious, as the clinical trials involving these drugs may not have been completed or fully reported at the time of authorization. [Drug developers] need to have a more global and coordinated approach to evaluating evidence and approval of drugs so the care received by a particular patient is not a factor of where they live,” he said.

The researchers surveyed approvals of seven immune checkpoint inhibitors (ICIs) approved by both the FDA and the EMA for thoracic malignancies, including non–small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and mesothelioma. The FDA approved 22 indications for the novel ICIs in thoracic malignancies, compared with 16 indications at the EMA. The difference in median approval times was larger for SCLC (179 versus 308 days) and mesothelioma (39 versus 280 days) than for NSCLC (242 versus 272 days).

“There are two discrepancies in biomarker requirements between the FDA and EMA, whereby the FDA has a broader requirement, despite these being ranked fairly consistently in terms of evidence of benefit by [European Society for Medical Oncology Magnitude of Clinical Benefit Scale and National Comprehensive Cancer Network] frameworks,” said Dr. Desai. In the case of atezolizumab for adjuvant NSCLC, the FDA required PDL1 levels of 1% or higher, while the EMA required 50% or higher. For durvalumab in unresectable NSCLC, the FDA had no PDL1 requirement, while the EMA required 1% or higher.

Dr. Desai suggested a need for further investigation into the differences between the two agencies. Asked why the two agencies might have different views on the biomarkers, Dr. Desai responded: “That is the million-dollar question. My guess is [the] EMA weighs subgroup data more than [the] FDA.”

Dr. Desai has no relevant financial disclosures.

A large, systematic review of phase III randomized, controlled trials in metastatic non–small cell lung cancer found quality of life (QoL) improvements in progression-free survival (PFS), but not overall survival (OS), among patients treated with targeted therapy.

The authors, including Fabio Salomone of the University of Naples Federico II, department of clinical medicine and surgery, also observed trends toward an association between QoL improvement and PFS among patients treated with chemotherapy and immunotherapy.

The new research was presented during a poster session at European Lung Cancer Congress 2023.

“The findings of the study support the thesis that QoL and survival in patients with NSCLC are linked. Although this is documented in the literature, this study sums up the evidence of a large number of RCTs, and provides detail in the QoL/survival relationship by treatment type. The subgroup analysis by treatment type is a key strength of the study showing that the QoL/survival link is stronger and more reliable in target(ed) therapies,” George Kypriotakis, PhD, who was not involved with the study, said in an interview.

Combining efficacy and quality of life improvement is an important consideration in clinical practice. “It is important that clinicians provide therapies that are also palliative and improve QoL,” said Dr. Kypriotakis, assistant professor of behavioral sciences at University of Texas MD Anderson Cancer Center, Houston. He noted that the finding of a PFS benefit is a good indicator of overall benefit, which is important since OS outcomes require a larger number of patients and longer follow-up to determine.

“PFS can still be a valid surrogate for OS, especially when it is positively associated with QoL,” noted Dr. Kypriotakis.

The study included 81 trials. Sixteen of the studies investigated immunotherapy, 50 investigated targeted therapy, and 17 investigated chemotherapy regimens. Thirty-seven percent of the trials found an improvement in QoL in the treatment arm compared with the control arm, 59.3% found no difference between arms, and 3.7% found a worse QoL in the treatment arm. There was no statistically significant association between an improvement in OS and QoL among the trials (P = .368).
 

Improved QoL tied to improved PFS

The researchers found an association between improved QoL and improved PFS. Among 60 trials that showed improved PFS, 43.3% found a superior QoL in the treatment arm, 53.3% showed no difference, and 3.3% showed reduced QoL. Among 20 trials that found no improvement in PFS, 20% demonstrated an improved QoL, 75% found no change, and 5% showed worse QoL (P = .0473).

A subanalysis of 48 targeted therapy trials found a correlation between PFS and QoL improvement (P = .0196). Among 25 trials involving patients receiving epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibitors showing an improved PFS, 60% showed improved QoL, 36% showed no difference, and 4% showed worsening (P = .0077). Seven of these trials showed no PFS benefit and no change in QoL.
 

Industry sponsorship may affect QOL results

The researchers found potential evidence that industry sponsorship may lead to a spin on QoL outcomes. Among 51 trials that showed no QoL benefit associated with treatment, the description of the QoL outcome in 37 industry-sponsored was judged to be neutral and coherent with the study findings in 26 cases, but unjustifiably favorable in 11 cases. Among 14 with nonprofit support, descriptions of QoL results were found to be neutral in all cases (P = .0232).

“Obviously, industry may be motivated to overemphasize treatment benefits, especially in measures that also have a qualitative/subjective dimension such as QoL. Assuming that the authors used a reliable criterion to evaluate “inappropriateness,” industry may be more likely to emphasize QoL improvements as a surrogate for OS, especially when seeking drug approval,” Dr. Kypriotakis said.

The study is retrospective and cannot prove causation.

Dr. Salomone and Dr. Kypriotakis have no relevant financial disclosures.

A large, systematic review of phase III randomized, controlled trials in metastatic non–small cell lung cancer found quality of life (QoL) improvements in progression-free survival (PFS), but not overall survival (OS), among patients treated with targeted therapy.

The authors, including Fabio Salomone of the University of Naples Federico II, department of clinical medicine and surgery, also observed trends toward an association between QoL improvement and PFS among patients treated with chemotherapy and immunotherapy.

The new research was presented during a poster session at European Lung Cancer Congress 2023.

“The findings of the study support the thesis that QoL and survival in patients with NSCLC are linked. Although this is documented in the literature, this study sums up the evidence of a large number of RCTs, and provides detail in the QoL/survival relationship by treatment type. The subgroup analysis by treatment type is a key strength of the study showing that the QoL/survival link is stronger and more reliable in target(ed) therapies,” George Kypriotakis, PhD, who was not involved with the study, said in an interview.

Combining efficacy and quality of life improvement is an important consideration in clinical practice. “It is important that clinicians provide therapies that are also palliative and improve QoL,” said Dr. Kypriotakis, assistant professor of behavioral sciences at University of Texas MD Anderson Cancer Center, Houston. He noted that the finding of a PFS benefit is a good indicator of overall benefit, which is important since OS outcomes require a larger number of patients and longer follow-up to determine.

“PFS can still be a valid surrogate for OS, especially when it is positively associated with QoL,” noted Dr. Kypriotakis.

The study included 81 trials. Sixteen of the studies investigated immunotherapy, 50 investigated targeted therapy, and 17 investigated chemotherapy regimens. Thirty-seven percent of the trials found an improvement in QoL in the treatment arm compared with the control arm, 59.3% found no difference between arms, and 3.7% found a worse QoL in the treatment arm. There was no statistically significant association between an improvement in OS and QoL among the trials (P = .368).
 

Improved QoL tied to improved PFS

The researchers found an association between improved QoL and improved PFS. Among 60 trials that showed improved PFS, 43.3% found a superior QoL in the treatment arm, 53.3% showed no difference, and 3.3% showed reduced QoL. Among 20 trials that found no improvement in PFS, 20% demonstrated an improved QoL, 75% found no change, and 5% showed worse QoL (P = .0473).

A subanalysis of 48 targeted therapy trials found a correlation between PFS and QoL improvement (P = .0196). Among 25 trials involving patients receiving epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibitors showing an improved PFS, 60% showed improved QoL, 36% showed no difference, and 4% showed worsening (P = .0077). Seven of these trials showed no PFS benefit and no change in QoL.
 

Industry sponsorship may affect QOL results

The researchers found potential evidence that industry sponsorship may lead to a spin on QoL outcomes. Among 51 trials that showed no QoL benefit associated with treatment, the description of the QoL outcome in 37 industry-sponsored was judged to be neutral and coherent with the study findings in 26 cases, but unjustifiably favorable in 11 cases. Among 14 with nonprofit support, descriptions of QoL results were found to be neutral in all cases (P = .0232).

“Obviously, industry may be motivated to overemphasize treatment benefits, especially in measures that also have a qualitative/subjective dimension such as QoL. Assuming that the authors used a reliable criterion to evaluate “inappropriateness,” industry may be more likely to emphasize QoL improvements as a surrogate for OS, especially when seeking drug approval,” Dr. Kypriotakis said.

The study is retrospective and cannot prove causation.

Dr. Salomone and Dr. Kypriotakis have no relevant financial disclosures.

A large, systematic review of phase III randomized, controlled trials in metastatic non–small cell lung cancer found quality of life (QoL) improvements in progression-free survival (PFS), but not overall survival (OS), among patients treated with targeted therapy.

The authors, including Fabio Salomone of the University of Naples Federico II, department of clinical medicine and surgery, also observed trends toward an association between QoL improvement and PFS among patients treated with chemotherapy and immunotherapy.

The new research was presented during a poster session at European Lung Cancer Congress 2023.

“The findings of the study support the thesis that QoL and survival in patients with NSCLC are linked. Although this is documented in the literature, this study sums up the evidence of a large number of RCTs, and provides detail in the QoL/survival relationship by treatment type. The subgroup analysis by treatment type is a key strength of the study showing that the QoL/survival link is stronger and more reliable in target(ed) therapies,” George Kypriotakis, PhD, who was not involved with the study, said in an interview.

Combining efficacy and quality of life improvement is an important consideration in clinical practice. “It is important that clinicians provide therapies that are also palliative and improve QoL,” said Dr. Kypriotakis, assistant professor of behavioral sciences at University of Texas MD Anderson Cancer Center, Houston. He noted that the finding of a PFS benefit is a good indicator of overall benefit, which is important since OS outcomes require a larger number of patients and longer follow-up to determine.

“PFS can still be a valid surrogate for OS, especially when it is positively associated with QoL,” noted Dr. Kypriotakis.

The study included 81 trials. Sixteen of the studies investigated immunotherapy, 50 investigated targeted therapy, and 17 investigated chemotherapy regimens. Thirty-seven percent of the trials found an improvement in QoL in the treatment arm compared with the control arm, 59.3% found no difference between arms, and 3.7% found a worse QoL in the treatment arm. There was no statistically significant association between an improvement in OS and QoL among the trials (P = .368).
 

Improved QoL tied to improved PFS

The researchers found an association between improved QoL and improved PFS. Among 60 trials that showed improved PFS, 43.3% found a superior QoL in the treatment arm, 53.3% showed no difference, and 3.3% showed reduced QoL. Among 20 trials that found no improvement in PFS, 20% demonstrated an improved QoL, 75% found no change, and 5% showed worse QoL (P = .0473).

A subanalysis of 48 targeted therapy trials found a correlation between PFS and QoL improvement (P = .0196). Among 25 trials involving patients receiving epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibitors showing an improved PFS, 60% showed improved QoL, 36% showed no difference, and 4% showed worsening (P = .0077). Seven of these trials showed no PFS benefit and no change in QoL.
 

Industry sponsorship may affect QOL results

The researchers found potential evidence that industry sponsorship may lead to a spin on QoL outcomes. Among 51 trials that showed no QoL benefit associated with treatment, the description of the QoL outcome in 37 industry-sponsored was judged to be neutral and coherent with the study findings in 26 cases, but unjustifiably favorable in 11 cases. Among 14 with nonprofit support, descriptions of QoL results were found to be neutral in all cases (P = .0232).

“Obviously, industry may be motivated to overemphasize treatment benefits, especially in measures that also have a qualitative/subjective dimension such as QoL. Assuming that the authors used a reliable criterion to evaluate “inappropriateness,” industry may be more likely to emphasize QoL improvements as a surrogate for OS, especially when seeking drug approval,” Dr. Kypriotakis said.

The study is retrospective and cannot prove causation.

Dr. Salomone and Dr. Kypriotakis have no relevant financial disclosures.

It’s been over 2 decades since 37-year-old Joshua Denton was diagnosed with ulcerative colitis.

Controlling the physical symptoms of comorbidities, such as inflammatory bowel disease, have been possible, but he was surprised when depression and anxiety set in.

“You’re dealing with what I call the anxiety of the unknown. What does this mean?” said Mr. Denton, who serves as a patient advocate with Color of Crohn’s & Chronic Illness, a nonprofit group aimed at improving quality of life for racial-ethnic minorities. “When you understand that it’s autoimmune that is chronic and incurable, you’re wondering, ‘Am I going to have a chance to get better in terms of my quality-of-life? Is it going to get worse?’ It indirectly builds this level of anxiety.”

Mr. Denton described a level of anxiety and depression that other patients living with inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, described in a recent survey from the American Gastroenterological Association. Survey results, released in March, show how emotional and social challenges are top of mind for patients living with IBD, but not so much for gastroenterologists who said they’re more concerned about treating physical health than emotional health and believe mental health is sufficiently addressed in their patients’ IBD care.

In response, the AGA has launched the My IBD Life campaign to provide resources to patients and help their health care providers become active partners in psychosocial care.

Discussions about mental health challenges are difficult for both physician and patients. For patients, they may be unwilling to talk to their physicians out of concern of being a burden, while physicians may be reluctant to pry or intrude. “I want to dispel the myth to the patients (and tell them) that your doctor actually would love to know, but is afraid to pry. And to the doctor: Your patient wants you to know, but is afraid to be a burden,” said Laurie A. Keefer, PhD, a psychologist at Icahn School of Medicine at Mount Sinai, New York, who specializes in the psychosocial care of patients with chronic digestive diseases and serves as an adviser to the My IBD Life campaign, which was launched to support both patients living with IBD and their health care providers.

But “prying” in this way is important, Dr. Keefer said. Depression and anxiety can have wide-ranging effects on patient outcomes. Depressed patients may not follow through with medication refills or may be more accepting of disability, while anxiety can lead to worries about colonoscopies or surgeries, which can lead to avoidance. “I always tell GI providers, if you can’t figure out why someone never follows through with that test or that procedure, consider anxiety before you assume that it’s just nonadherence. Anxiety and depression really affect how somebody follows the requirements they need to manage their disease,” said Dr. Keefer.
 

Rates of anxiety among patients are increasing

The survey included 1,026 adults (18-59 years) with IBD and of these, 63% reported having comorbid conditions, such as anxiety (36%) and depression (35%). These rates are significantly higher than in the general population – at 19% and 8%, respectively. The rate of anxiety among patients with IBD has increased since AGA conducted a similar survey in 2017.

Patients reported that they were most concerned with the ways that IBD affects their mental health or emotional health and day-to-day life. Many said their providers were more concerned about treating them physically than emotionally and expressed a need for additional information on IBD treatment options (37%) and medications (35%). They also desired more information about the impact on emotional and mental health (25%), which has increased since the 2017 survey.

The No. 1 concern for patients was the need to consider bathroom logistics when away from home (7.03 on a scale of 1-10). The second most popular concern was mental and emotional health with a rating of 6.51 on a 1-10 scale. Thirty percent requested more information about diet and 27% asked for more information about general IBD symptoms.

Both patients and providers were less satisfied with emotional and social care than physical care for IBD. Among patients, women and those between ages 18 and 39 said they were the least satisfied with their care.

“We must always consider the mind and body together when managing a chronic disease, and IBD is no exception,” Dr. Keefer said. “We also know that failure to address emotional concerns in IBD leads to poorer disease outcomes, not just reduced quality of life.”

The surveys also highlighted different experiences among communities. For instance, people of color, particularly those in the Black community, were more likely to report that their IBD journey was impacted by their personal identity, whether by race, ethnicity, culture, sexual orientation, gender identity, or age.

In contrast, a companion survey of 117 gastroenterologists found that providers are focused on physical health over emotional health (8.34 on a scale of 1-10), but they reported having sufficiently addressed concerns their patients may have expressed about mental health issues. At the same time, many also said they feel more equipped to treat their patients physically rather than emotionally.

The provider survey showed their biggest challenge was in securing insurance authorizations for medications.

Mr. Denton encourages all patients to be as transparent as possible with their providers and family members.

“I firmly believe you cannot internalize the experience and keep it to yourself. I strongly encourage other patients with IBD to continue to push themselves to be as transparent as possible with their loved ones and health care professionals, because the more we talk about it, the more we can humanize the experience and allow people that aren’t health care professionals to have a more empathetic understanding of what we’re dealing with which in turn, hopefully, will provide better support and resources,” Mr. Denton said.

The My IBD Life website provides resources for patients to navigate a range of common scenarios, including conversations about new medications, workplace concerns, intimacy and relationships, vacations and travel, and medical procedures and surgeries. An interactive 3D graphic demonstrates how IBD affects the body, and videos of patients highlight personal experiences and ways to build emotional resilience.

The My IBD Life campaign is supported by an independent grant from Bristol Myers Squibb.

It’s been over 2 decades since 37-year-old Joshua Denton was diagnosed with ulcerative colitis.

Controlling the physical symptoms of comorbidities, such as inflammatory bowel disease, have been possible, but he was surprised when depression and anxiety set in.

“You’re dealing with what I call the anxiety of the unknown. What does this mean?” said Mr. Denton, who serves as a patient advocate with Color of Crohn’s & Chronic Illness, a nonprofit group aimed at improving quality of life for racial-ethnic minorities. “When you understand that it’s autoimmune that is chronic and incurable, you’re wondering, ‘Am I going to have a chance to get better in terms of my quality-of-life? Is it going to get worse?’ It indirectly builds this level of anxiety.”

Mr. Denton described a level of anxiety and depression that other patients living with inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, described in a recent survey from the American Gastroenterological Association. Survey results, released in March, show how emotional and social challenges are top of mind for patients living with IBD, but not so much for gastroenterologists who said they’re more concerned about treating physical health than emotional health and believe mental health is sufficiently addressed in their patients’ IBD care.

In response, the AGA has launched the My IBD Life campaign to provide resources to patients and help their health care providers become active partners in psychosocial care.

Discussions about mental health challenges are difficult for both physician and patients. For patients, they may be unwilling to talk to their physicians out of concern of being a burden, while physicians may be reluctant to pry or intrude. “I want to dispel the myth to the patients (and tell them) that your doctor actually would love to know, but is afraid to pry. And to the doctor: Your patient wants you to know, but is afraid to be a burden,” said Laurie A. Keefer, PhD, a psychologist at Icahn School of Medicine at Mount Sinai, New York, who specializes in the psychosocial care of patients with chronic digestive diseases and serves as an adviser to the My IBD Life campaign, which was launched to support both patients living with IBD and their health care providers.

But “prying” in this way is important, Dr. Keefer said. Depression and anxiety can have wide-ranging effects on patient outcomes. Depressed patients may not follow through with medication refills or may be more accepting of disability, while anxiety can lead to worries about colonoscopies or surgeries, which can lead to avoidance. “I always tell GI providers, if you can’t figure out why someone never follows through with that test or that procedure, consider anxiety before you assume that it’s just nonadherence. Anxiety and depression really affect how somebody follows the requirements they need to manage their disease,” said Dr. Keefer.
 

Rates of anxiety among patients are increasing

The survey included 1,026 adults (18-59 years) with IBD and of these, 63% reported having comorbid conditions, such as anxiety (36%) and depression (35%). These rates are significantly higher than in the general population – at 19% and 8%, respectively. The rate of anxiety among patients with IBD has increased since AGA conducted a similar survey in 2017.

Patients reported that they were most concerned with the ways that IBD affects their mental health or emotional health and day-to-day life. Many said their providers were more concerned about treating them physically than emotionally and expressed a need for additional information on IBD treatment options (37%) and medications (35%). They also desired more information about the impact on emotional and mental health (25%), which has increased since the 2017 survey.

The No. 1 concern for patients was the need to consider bathroom logistics when away from home (7.03 on a scale of 1-10). The second most popular concern was mental and emotional health with a rating of 6.51 on a 1-10 scale. Thirty percent requested more information about diet and 27% asked for more information about general IBD symptoms.

Both patients and providers were less satisfied with emotional and social care than physical care for IBD. Among patients, women and those between ages 18 and 39 said they were the least satisfied with their care.

“We must always consider the mind and body together when managing a chronic disease, and IBD is no exception,” Dr. Keefer said. “We also know that failure to address emotional concerns in IBD leads to poorer disease outcomes, not just reduced quality of life.”

The surveys also highlighted different experiences among communities. For instance, people of color, particularly those in the Black community, were more likely to report that their IBD journey was impacted by their personal identity, whether by race, ethnicity, culture, sexual orientation, gender identity, or age.

In contrast, a companion survey of 117 gastroenterologists found that providers are focused on physical health over emotional health (8.34 on a scale of 1-10), but they reported having sufficiently addressed concerns their patients may have expressed about mental health issues. At the same time, many also said they feel more equipped to treat their patients physically rather than emotionally.

The provider survey showed their biggest challenge was in securing insurance authorizations for medications.

Mr. Denton encourages all patients to be as transparent as possible with their providers and family members.

“I firmly believe you cannot internalize the experience and keep it to yourself. I strongly encourage other patients with IBD to continue to push themselves to be as transparent as possible with their loved ones and health care professionals, because the more we talk about it, the more we can humanize the experience and allow people that aren’t health care professionals to have a more empathetic understanding of what we’re dealing with which in turn, hopefully, will provide better support and resources,” Mr. Denton said.

The My IBD Life website provides resources for patients to navigate a range of common scenarios, including conversations about new medications, workplace concerns, intimacy and relationships, vacations and travel, and medical procedures and surgeries. An interactive 3D graphic demonstrates how IBD affects the body, and videos of patients highlight personal experiences and ways to build emotional resilience.

The My IBD Life campaign is supported by an independent grant from Bristol Myers Squibb.

It’s been over 2 decades since 37-year-old Joshua Denton was diagnosed with ulcerative colitis.

Controlling the physical symptoms of comorbidities, such as inflammatory bowel disease, have been possible, but he was surprised when depression and anxiety set in.

“You’re dealing with what I call the anxiety of the unknown. What does this mean?” said Mr. Denton, who serves as a patient advocate with Color of Crohn’s & Chronic Illness, a nonprofit group aimed at improving quality of life for racial-ethnic minorities. “When you understand that it’s autoimmune that is chronic and incurable, you’re wondering, ‘Am I going to have a chance to get better in terms of my quality-of-life? Is it going to get worse?’ It indirectly builds this level of anxiety.”

Mr. Denton described a level of anxiety and depression that other patients living with inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, described in a recent survey from the American Gastroenterological Association. Survey results, released in March, show how emotional and social challenges are top of mind for patients living with IBD, but not so much for gastroenterologists who said they’re more concerned about treating physical health than emotional health and believe mental health is sufficiently addressed in their patients’ IBD care.

In response, the AGA has launched the My IBD Life campaign to provide resources to patients and help their health care providers become active partners in psychosocial care.

Discussions about mental health challenges are difficult for both physician and patients. For patients, they may be unwilling to talk to their physicians out of concern of being a burden, while physicians may be reluctant to pry or intrude. “I want to dispel the myth to the patients (and tell them) that your doctor actually would love to know, but is afraid to pry. And to the doctor: Your patient wants you to know, but is afraid to be a burden,” said Laurie A. Keefer, PhD, a psychologist at Icahn School of Medicine at Mount Sinai, New York, who specializes in the psychosocial care of patients with chronic digestive diseases and serves as an adviser to the My IBD Life campaign, which was launched to support both patients living with IBD and their health care providers.

But “prying” in this way is important, Dr. Keefer said. Depression and anxiety can have wide-ranging effects on patient outcomes. Depressed patients may not follow through with medication refills or may be more accepting of disability, while anxiety can lead to worries about colonoscopies or surgeries, which can lead to avoidance. “I always tell GI providers, if you can’t figure out why someone never follows through with that test or that procedure, consider anxiety before you assume that it’s just nonadherence. Anxiety and depression really affect how somebody follows the requirements they need to manage their disease,” said Dr. Keefer.
 

Rates of anxiety among patients are increasing

The survey included 1,026 adults (18-59 years) with IBD and of these, 63% reported having comorbid conditions, such as anxiety (36%) and depression (35%). These rates are significantly higher than in the general population – at 19% and 8%, respectively. The rate of anxiety among patients with IBD has increased since AGA conducted a similar survey in 2017.

Patients reported that they were most concerned with the ways that IBD affects their mental health or emotional health and day-to-day life. Many said their providers were more concerned about treating them physically than emotionally and expressed a need for additional information on IBD treatment options (37%) and medications (35%). They also desired more information about the impact on emotional and mental health (25%), which has increased since the 2017 survey.

The No. 1 concern for patients was the need to consider bathroom logistics when away from home (7.03 on a scale of 1-10). The second most popular concern was mental and emotional health with a rating of 6.51 on a 1-10 scale. Thirty percent requested more information about diet and 27% asked for more information about general IBD symptoms.

Both patients and providers were less satisfied with emotional and social care than physical care for IBD. Among patients, women and those between ages 18 and 39 said they were the least satisfied with their care.

“We must always consider the mind and body together when managing a chronic disease, and IBD is no exception,” Dr. Keefer said. “We also know that failure to address emotional concerns in IBD leads to poorer disease outcomes, not just reduced quality of life.”

The surveys also highlighted different experiences among communities. For instance, people of color, particularly those in the Black community, were more likely to report that their IBD journey was impacted by their personal identity, whether by race, ethnicity, culture, sexual orientation, gender identity, or age.

In contrast, a companion survey of 117 gastroenterologists found that providers are focused on physical health over emotional health (8.34 on a scale of 1-10), but they reported having sufficiently addressed concerns their patients may have expressed about mental health issues. At the same time, many also said they feel more equipped to treat their patients physically rather than emotionally.

The provider survey showed their biggest challenge was in securing insurance authorizations for medications.

Mr. Denton encourages all patients to be as transparent as possible with their providers and family members.

“I firmly believe you cannot internalize the experience and keep it to yourself. I strongly encourage other patients with IBD to continue to push themselves to be as transparent as possible with their loved ones and health care professionals, because the more we talk about it, the more we can humanize the experience and allow people that aren’t health care professionals to have a more empathetic understanding of what we’re dealing with which in turn, hopefully, will provide better support and resources,” Mr. Denton said.

The My IBD Life website provides resources for patients to navigate a range of common scenarios, including conversations about new medications, workplace concerns, intimacy and relationships, vacations and travel, and medical procedures and surgeries. An interactive 3D graphic demonstrates how IBD affects the body, and videos of patients highlight personal experiences and ways to build emotional resilience.

The My IBD Life campaign is supported by an independent grant from Bristol Myers Squibb.

Researchers have identified a novel mutation in a patient with microvillus inclusion disease (MVID) and rapidly developed a specific mouse model to find insights into the disease process.

MVID is characterized by severe diarrhea, generally beginning within a few hours of birth. The condition is caused by inactivating mutations in the gene myosin VB (MYO5B). Affected individuals usually require lifetime use of total parenteral nutrition or small-bowel transplantation.

More than 100 MYO5B mutations have been identified in MVID patients, most of whom inherit two unique mutant alleles. This can lead to variability in phenotypes, which single-mutation animal models have been unable to mimic. Generally, patients have atrophy of microvilli on enterocytes as well as inclusion bodies within enterocytes that contain microvilli.

In the study, published in Cellular and Molecular Gastroenterology and Hepatology, researchers describe genetic sequencing of MYO5B mutations in a patient and both parents. One mutation is predicted to lead to protein truncation (c.1821delG), and the other (c.1555G>A) appeared to be inherited from the patient’s mother. The patient suffered from severe diarrhea after birth and was intermittently feeding intolerant.

The researchers conducted a range of diagnostic tests and biopsies. One particularly interesting finding was expression of the A-kinase anchoring protein 350 in the vicinity of the inclusion, wrote Andreanna Burman and her coauthors at Vanderbilt University, Nashville, Tenn. This protein takes part in a protein-mediating scaffolding pathway, suggesting that it could play a role in the development of the inclusions.

The researchers used multiplexed immunofluorescence (MxIF) staining of a biopsy of the duodenum to look for expression of a range of proteins. They found a striking decrease in enterocytes that express glucose transporter 2, implying that malabsorption might be due at least in part to enterocytes that fail to mature.

The patient also had internalization of apical nutrient transporters, which has been reported in other MVID patients. The researchers also developed a mouse model that incorporated the patient’s novel compound heterozygous genotype, which they cross-bred to produce a tamoxifen-inducible mouse model.

After the tamoxifen injection, the patient-mimicking animals exhibited a severe watery diarrhea, losing 19% of their body weight by day 4. The animals’ intestines showed a similar phenotype to that of the patient.

The apical sodium transporters sodium-glucose cotransporter 1 (SGLT1), apical sodium-dependent bile transporter, and NHE3 were internalized away from the apical membrane of the enterocytes in the patient-mimicking model animals. This structural difference may explain the limited absorption of sodium and water and the resultant watery diarrhea. The researchers also noted disruption of the actinin-4+ terminal web structure, as well as increased SGLT1 localization with lysosome-associated membrane protein 1+ lysosomes within the mouse model enterocytes. This association may indicate degradation of mislocalized proteins, the authors noted, which has also been seen in expanded RAB7+ vesicles within MVID patient tissues.

Other signs pointed to the expansion of immature cells in the upper crypt and lower villus, as well as faster shedding of enterocytes in the villus than in control animals. Scanning electron microscope images also showed immature and disorganized microvilli in the enterocytes of the patient-mimicking mice.

Taken together, “these findings are consistent with a deficit in enterocyte maturation in Myo5b(G519R) mice and in the patient with the MYO5B(G519R) mutation,” the authors wrote.

The authors suggest that their approach could be used more generally to quickly create mouse models of patient-specific monogenic congenital disorders.

The authors disclosed no conflicts of interest. The research was funded by the National Foundation of Science, National Institutes of Health, Vanderbilt Digestive Diseases Research Center Pilot and Feasibility grant, an American Physiological Society John F. Perkins, Jr. Research Career Enhancement Award, and a gift from the Christine Volpe Fund.

Researchers have identified a novel mutation in a patient with microvillus inclusion disease (MVID) and rapidly developed a specific mouse model to find insights into the disease process.

MVID is characterized by severe diarrhea, generally beginning within a few hours of birth. The condition is caused by inactivating mutations in the gene myosin VB (MYO5B). Affected individuals usually require lifetime use of total parenteral nutrition or small-bowel transplantation.

More than 100 MYO5B mutations have been identified in MVID patients, most of whom inherit two unique mutant alleles. This can lead to variability in phenotypes, which single-mutation animal models have been unable to mimic. Generally, patients have atrophy of microvilli on enterocytes as well as inclusion bodies within enterocytes that contain microvilli.

In the study, published in Cellular and Molecular Gastroenterology and Hepatology, researchers describe genetic sequencing of MYO5B mutations in a patient and both parents. One mutation is predicted to lead to protein truncation (c.1821delG), and the other (c.1555G>A) appeared to be inherited from the patient’s mother. The patient suffered from severe diarrhea after birth and was intermittently feeding intolerant.

The researchers conducted a range of diagnostic tests and biopsies. One particularly interesting finding was expression of the A-kinase anchoring protein 350 in the vicinity of the inclusion, wrote Andreanna Burman and her coauthors at Vanderbilt University, Nashville, Tenn. This protein takes part in a protein-mediating scaffolding pathway, suggesting that it could play a role in the development of the inclusions.

The researchers used multiplexed immunofluorescence (MxIF) staining of a biopsy of the duodenum to look for expression of a range of proteins. They found a striking decrease in enterocytes that express glucose transporter 2, implying that malabsorption might be due at least in part to enterocytes that fail to mature.

The patient also had internalization of apical nutrient transporters, which has been reported in other MVID patients. The researchers also developed a mouse model that incorporated the patient’s novel compound heterozygous genotype, which they cross-bred to produce a tamoxifen-inducible mouse model.

After the tamoxifen injection, the patient-mimicking animals exhibited a severe watery diarrhea, losing 19% of their body weight by day 4. The animals’ intestines showed a similar phenotype to that of the patient.

The apical sodium transporters sodium-glucose cotransporter 1 (SGLT1), apical sodium-dependent bile transporter, and NHE3 were internalized away from the apical membrane of the enterocytes in the patient-mimicking model animals. This structural difference may explain the limited absorption of sodium and water and the resultant watery diarrhea. The researchers also noted disruption of the actinin-4+ terminal web structure, as well as increased SGLT1 localization with lysosome-associated membrane protein 1+ lysosomes within the mouse model enterocytes. This association may indicate degradation of mislocalized proteins, the authors noted, which has also been seen in expanded RAB7+ vesicles within MVID patient tissues.

Other signs pointed to the expansion of immature cells in the upper crypt and lower villus, as well as faster shedding of enterocytes in the villus than in control animals. Scanning electron microscope images also showed immature and disorganized microvilli in the enterocytes of the patient-mimicking mice.

Taken together, “these findings are consistent with a deficit in enterocyte maturation in Myo5b(G519R) mice and in the patient with the MYO5B(G519R) mutation,” the authors wrote.

The authors suggest that their approach could be used more generally to quickly create mouse models of patient-specific monogenic congenital disorders.

The authors disclosed no conflicts of interest. The research was funded by the National Foundation of Science, National Institutes of Health, Vanderbilt Digestive Diseases Research Center Pilot and Feasibility grant, an American Physiological Society John F. Perkins, Jr. Research Career Enhancement Award, and a gift from the Christine Volpe Fund.

Researchers have identified a novel mutation in a patient with microvillus inclusion disease (MVID) and rapidly developed a specific mouse model to find insights into the disease process.

MVID is characterized by severe diarrhea, generally beginning within a few hours of birth. The condition is caused by inactivating mutations in the gene myosin VB (MYO5B). Affected individuals usually require lifetime use of total parenteral nutrition or small-bowel transplantation.

More than 100 MYO5B mutations have been identified in MVID patients, most of whom inherit two unique mutant alleles. This can lead to variability in phenotypes, which single-mutation animal models have been unable to mimic. Generally, patients have atrophy of microvilli on enterocytes as well as inclusion bodies within enterocytes that contain microvilli.

In the study, published in Cellular and Molecular Gastroenterology and Hepatology, researchers describe genetic sequencing of MYO5B mutations in a patient and both parents. One mutation is predicted to lead to protein truncation (c.1821delG), and the other (c.1555G>A) appeared to be inherited from the patient’s mother. The patient suffered from severe diarrhea after birth and was intermittently feeding intolerant.

The researchers conducted a range of diagnostic tests and biopsies. One particularly interesting finding was expression of the A-kinase anchoring protein 350 in the vicinity of the inclusion, wrote Andreanna Burman and her coauthors at Vanderbilt University, Nashville, Tenn. This protein takes part in a protein-mediating scaffolding pathway, suggesting that it could play a role in the development of the inclusions.

The researchers used multiplexed immunofluorescence (MxIF) staining of a biopsy of the duodenum to look for expression of a range of proteins. They found a striking decrease in enterocytes that express glucose transporter 2, implying that malabsorption might be due at least in part to enterocytes that fail to mature.

The patient also had internalization of apical nutrient transporters, which has been reported in other MVID patients. The researchers also developed a mouse model that incorporated the patient’s novel compound heterozygous genotype, which they cross-bred to produce a tamoxifen-inducible mouse model.

After the tamoxifen injection, the patient-mimicking animals exhibited a severe watery diarrhea, losing 19% of their body weight by day 4. The animals’ intestines showed a similar phenotype to that of the patient.

The apical sodium transporters sodium-glucose cotransporter 1 (SGLT1), apical sodium-dependent bile transporter, and NHE3 were internalized away from the apical membrane of the enterocytes in the patient-mimicking model animals. This structural difference may explain the limited absorption of sodium and water and the resultant watery diarrhea. The researchers also noted disruption of the actinin-4+ terminal web structure, as well as increased SGLT1 localization with lysosome-associated membrane protein 1+ lysosomes within the mouse model enterocytes. This association may indicate degradation of mislocalized proteins, the authors noted, which has also been seen in expanded RAB7+ vesicles within MVID patient tissues.

Other signs pointed to the expansion of immature cells in the upper crypt and lower villus, as well as faster shedding of enterocytes in the villus than in control animals. Scanning electron microscope images also showed immature and disorganized microvilli in the enterocytes of the patient-mimicking mice.

Taken together, “these findings are consistent with a deficit in enterocyte maturation in Myo5b(G519R) mice and in the patient with the MYO5B(G519R) mutation,” the authors wrote.

The authors suggest that their approach could be used more generally to quickly create mouse models of patient-specific monogenic congenital disorders.

The authors disclosed no conflicts of interest. The research was funded by the National Foundation of Science, National Institutes of Health, Vanderbilt Digestive Diseases Research Center Pilot and Feasibility grant, an American Physiological Society John F. Perkins, Jr. Research Career Enhancement Award, and a gift from the Christine Volpe Fund.

An Irish study attempting to get at the root of why men and women delay colon cancer screening found that, despite an uptick in colon cancer cases among younger adults, screening isn’t a priority for some adults while others are under the impression that a healthy diet with regular bowel movements negates the need for regular screening.

The findings are based on a survey of over 2,000 adults who participated in a population-based fecal immunochemical test (FIT) screening program. The authors found that denying the immediacy of the need to be tested and self-exempting from screening because of a belief in a healthy lifestyle were key drivers for opting out of FIT screening.

“What we found was that people who didn’t take part [in the survey] responded much more defensively to the invitation,” said Nicholas Clarke, PhD, a researcher at Dublin City University, who served as the lead author of the study published in the journal Cancer.

The domain of denying immediacy, which covers decisions like putting off a test because of more pressing life events, was associated with a 47% reduction in screening probability. “That’s quite a high percentage. They’re not saying I won’t do it. They’re saying: ‘I’ll wait to get tested for colon cancer until my other health concerns are under control, or until there’s a better test,’ ” he said.

The other suppression category of self-exempting was associated with a 20% reduction in the odds of participation. “They’re saying: ‘I don’t need to be tested because I have enough vegetables in my diet or because I have regular bowel movements,’ ” Dr. Clarke said.

Despite the proven efficacy of screening, many individuals still resist screening. In previous research, Dr. Clarke found that men in Ireland were less likely than women to undergo screening.

FIT works by identifying small amounts of blood in the stool that could suggest the presence of a tumor or precancerous polyps. The test also looks for methylation and DNA mutations that are indicative of precancer polyps or tumors. A positive test calls for a follow-up procedure such as a colonoscopy, where precancerous polyps can be removed to prevent them from developing into tumors.

FIT has similar sensitivity to colonoscopy in detecting cancers (93% vs. 95%), but is less effective with respect to polyps (42% vs. 75%-93%). For average risk adults between 50-75 years old, the U.S Preventive Services Task Force recommends colonoscopy every 10 years; flexible sigmoidoscopy or CT colonography every 5 years, or flexible sigmoidoscopy every 10 years plus fecal immunochemical test (FIT) every year; FIT DNA test every 3 years; guaiac-based fecal occult blood test or FIT test annually.
 

Findings from the new study

In the new study, researchers contacted both 2,299 responders and nonresponders to FIT tests that had been mailed out as part of a Dublin colorectal cancer screening program between 2008 and 2012. Researchers employed the McQueen defensive information processing (DIP) measure, which includes four domains of defensive attitudes that include information avoidance, mental disengagement or denial, suppression through belief that one is immune, and arguing against the evidence.

In this study, 7,476 men and women in Dublin were invited to participate in a population‐based FIT screening program. In follow-up questionnaires sent to those who did or did not complete FIT, 53% of those who completed FIT screening answered the questionnaire, while 8% of those who did not complete the screening returned the questionnaire. Those who didn’t complete the FIT test had higher DIP scores suggesting more rates of opting out of receiving health information, avoiding doctor visits, prevention avoidance, continually delaying screening, either claiming colon cancer is rare or normalizing cancer risk, and falsely aligning regular bowel movements with good health which was directly associated with less screening.
 

Increasing rates of early onset colorectal cancer

The research may shed light on reasons for increasing rates of early-onset colorectal cancer. “Often younger people feel invincible and as Beverly Green, MD, MPH, pointed out in an editorial on defensive information processing, invincibility is a good example of self-exemption DIP,” Dr. Clarke said.

“I think what’s underlying these two pieces is a lack of awareness of the trajectory of colorectal cancer, but it’s also the future consequences of not taking part [in screening]. A person can have their colorectal cancer for about 10 years before they begin to feel any symptoms from it, and usually at that point, the disease has gone to an advanced stage, so it’s much more difficult to treat, and the person will have much poorer outcomes. If it’s detected at stage 1, the outcomes are far better,” Dr. Clarke said.

Doctors should react calmly to defensiveness and listen to the patient’s concerns. “Informing them of the aim of screening, i.e. to detect it when its precancerous or at the earliest possible stage, is very important. Letting them know they are taking responsibility for their own health and giving them the best chance of a healthy old age may be a good way of counteracting defensiveness,” he said.

Dr. Green noted that nonresponders claiming lack of immediacy could be swayed with the right approach. She has conducted similar research and subjects themselves suggested the use of marketing techniques “like what happens on Amazon. People remind you frequently the same thing when they get a clue that you have an interest in that behavior. Or, they tell you it’s on sale, and you might lose out from that big bargain if you don’t buy it now. There’s a deadline. I think a lot of the things we might do to nudge people are similar to what’s already happening in marketing,” said Dr. Green, who is a family physician and a researcher at the Kaiser Permanente Washington Health Research Institute.

Dr. Clarke and Dr. Green have no relevant financial disclosures.

An Irish study attempting to get at the root of why men and women delay colon cancer screening found that, despite an uptick in colon cancer cases among younger adults, screening isn’t a priority for some adults while others are under the impression that a healthy diet with regular bowel movements negates the need for regular screening.

The findings are based on a survey of over 2,000 adults who participated in a population-based fecal immunochemical test (FIT) screening program. The authors found that denying the immediacy of the need to be tested and self-exempting from screening because of a belief in a healthy lifestyle were key drivers for opting out of FIT screening.

“What we found was that people who didn’t take part [in the survey] responded much more defensively to the invitation,” said Nicholas Clarke, PhD, a researcher at Dublin City University, who served as the lead author of the study published in the journal Cancer.

The domain of denying immediacy, which covers decisions like putting off a test because of more pressing life events, was associated with a 47% reduction in screening probability. “That’s quite a high percentage. They’re not saying I won’t do it. They’re saying: ‘I’ll wait to get tested for colon cancer until my other health concerns are under control, or until there’s a better test,’ ” he said.

The other suppression category of self-exempting was associated with a 20% reduction in the odds of participation. “They’re saying: ‘I don’t need to be tested because I have enough vegetables in my diet or because I have regular bowel movements,’ ” Dr. Clarke said.

Despite the proven efficacy of screening, many individuals still resist screening. In previous research, Dr. Clarke found that men in Ireland were less likely than women to undergo screening.

FIT works by identifying small amounts of blood in the stool that could suggest the presence of a tumor or precancerous polyps. The test also looks for methylation and DNA mutations that are indicative of precancer polyps or tumors. A positive test calls for a follow-up procedure such as a colonoscopy, where precancerous polyps can be removed to prevent them from developing into tumors.

FIT has similar sensitivity to colonoscopy in detecting cancers (93% vs. 95%), but is less effective with respect to polyps (42% vs. 75%-93%). For average risk adults between 50-75 years old, the U.S Preventive Services Task Force recommends colonoscopy every 10 years; flexible sigmoidoscopy or CT colonography every 5 years, or flexible sigmoidoscopy every 10 years plus fecal immunochemical test (FIT) every year; FIT DNA test every 3 years; guaiac-based fecal occult blood test or FIT test annually.
 

Findings from the new study

In the new study, researchers contacted both 2,299 responders and nonresponders to FIT tests that had been mailed out as part of a Dublin colorectal cancer screening program between 2008 and 2012. Researchers employed the McQueen defensive information processing (DIP) measure, which includes four domains of defensive attitudes that include information avoidance, mental disengagement or denial, suppression through belief that one is immune, and arguing against the evidence.

In this study, 7,476 men and women in Dublin were invited to participate in a population‐based FIT screening program. In follow-up questionnaires sent to those who did or did not complete FIT, 53% of those who completed FIT screening answered the questionnaire, while 8% of those who did not complete the screening returned the questionnaire. Those who didn’t complete the FIT test had higher DIP scores suggesting more rates of opting out of receiving health information, avoiding doctor visits, prevention avoidance, continually delaying screening, either claiming colon cancer is rare or normalizing cancer risk, and falsely aligning regular bowel movements with good health which was directly associated with less screening.
 

Increasing rates of early onset colorectal cancer

The research may shed light on reasons for increasing rates of early-onset colorectal cancer. “Often younger people feel invincible and as Beverly Green, MD, MPH, pointed out in an editorial on defensive information processing, invincibility is a good example of self-exemption DIP,” Dr. Clarke said.

“I think what’s underlying these two pieces is a lack of awareness of the trajectory of colorectal cancer, but it’s also the future consequences of not taking part [in screening]. A person can have their colorectal cancer for about 10 years before they begin to feel any symptoms from it, and usually at that point, the disease has gone to an advanced stage, so it’s much more difficult to treat, and the person will have much poorer outcomes. If it’s detected at stage 1, the outcomes are far better,” Dr. Clarke said.

Doctors should react calmly to defensiveness and listen to the patient’s concerns. “Informing them of the aim of screening, i.e. to detect it when its precancerous or at the earliest possible stage, is very important. Letting them know they are taking responsibility for their own health and giving them the best chance of a healthy old age may be a good way of counteracting defensiveness,” he said.

Dr. Green noted that nonresponders claiming lack of immediacy could be swayed with the right approach. She has conducted similar research and subjects themselves suggested the use of marketing techniques “like what happens on Amazon. People remind you frequently the same thing when they get a clue that you have an interest in that behavior. Or, they tell you it’s on sale, and you might lose out from that big bargain if you don’t buy it now. There’s a deadline. I think a lot of the things we might do to nudge people are similar to what’s already happening in marketing,” said Dr. Green, who is a family physician and a researcher at the Kaiser Permanente Washington Health Research Institute.

Dr. Clarke and Dr. Green have no relevant financial disclosures.

An Irish study attempting to get at the root of why men and women delay colon cancer screening found that, despite an uptick in colon cancer cases among younger adults, screening isn’t a priority for some adults while others are under the impression that a healthy diet with regular bowel movements negates the need for regular screening.

The findings are based on a survey of over 2,000 adults who participated in a population-based fecal immunochemical test (FIT) screening program. The authors found that denying the immediacy of the need to be tested and self-exempting from screening because of a belief in a healthy lifestyle were key drivers for opting out of FIT screening.

“What we found was that people who didn’t take part [in the survey] responded much more defensively to the invitation,” said Nicholas Clarke, PhD, a researcher at Dublin City University, who served as the lead author of the study published in the journal Cancer.

The domain of denying immediacy, which covers decisions like putting off a test because of more pressing life events, was associated with a 47% reduction in screening probability. “That’s quite a high percentage. They’re not saying I won’t do it. They’re saying: ‘I’ll wait to get tested for colon cancer until my other health concerns are under control, or until there’s a better test,’ ” he said.

The other suppression category of self-exempting was associated with a 20% reduction in the odds of participation. “They’re saying: ‘I don’t need to be tested because I have enough vegetables in my diet or because I have regular bowel movements,’ ” Dr. Clarke said.

Despite the proven efficacy of screening, many individuals still resist screening. In previous research, Dr. Clarke found that men in Ireland were less likely than women to undergo screening.

FIT works by identifying small amounts of blood in the stool that could suggest the presence of a tumor or precancerous polyps. The test also looks for methylation and DNA mutations that are indicative of precancer polyps or tumors. A positive test calls for a follow-up procedure such as a colonoscopy, where precancerous polyps can be removed to prevent them from developing into tumors.

FIT has similar sensitivity to colonoscopy in detecting cancers (93% vs. 95%), but is less effective with respect to polyps (42% vs. 75%-93%). For average risk adults between 50-75 years old, the U.S Preventive Services Task Force recommends colonoscopy every 10 years; flexible sigmoidoscopy or CT colonography every 5 years, or flexible sigmoidoscopy every 10 years plus fecal immunochemical test (FIT) every year; FIT DNA test every 3 years; guaiac-based fecal occult blood test or FIT test annually.
 

Findings from the new study

In the new study, researchers contacted both 2,299 responders and nonresponders to FIT tests that had been mailed out as part of a Dublin colorectal cancer screening program between 2008 and 2012. Researchers employed the McQueen defensive information processing (DIP) measure, which includes four domains of defensive attitudes that include information avoidance, mental disengagement or denial, suppression through belief that one is immune, and arguing against the evidence.

In this study, 7,476 men and women in Dublin were invited to participate in a population‐based FIT screening program. In follow-up questionnaires sent to those who did or did not complete FIT, 53% of those who completed FIT screening answered the questionnaire, while 8% of those who did not complete the screening returned the questionnaire. Those who didn’t complete the FIT test had higher DIP scores suggesting more rates of opting out of receiving health information, avoiding doctor visits, prevention avoidance, continually delaying screening, either claiming colon cancer is rare or normalizing cancer risk, and falsely aligning regular bowel movements with good health which was directly associated with less screening.
 

Increasing rates of early onset colorectal cancer

The research may shed light on reasons for increasing rates of early-onset colorectal cancer. “Often younger people feel invincible and as Beverly Green, MD, MPH, pointed out in an editorial on defensive information processing, invincibility is a good example of self-exemption DIP,” Dr. Clarke said.

“I think what’s underlying these two pieces is a lack of awareness of the trajectory of colorectal cancer, but it’s also the future consequences of not taking part [in screening]. A person can have their colorectal cancer for about 10 years before they begin to feel any symptoms from it, and usually at that point, the disease has gone to an advanced stage, so it’s much more difficult to treat, and the person will have much poorer outcomes. If it’s detected at stage 1, the outcomes are far better,” Dr. Clarke said.

Doctors should react calmly to defensiveness and listen to the patient’s concerns. “Informing them of the aim of screening, i.e. to detect it when its precancerous or at the earliest possible stage, is very important. Letting them know they are taking responsibility for their own health and giving them the best chance of a healthy old age may be a good way of counteracting defensiveness,” he said.

Dr. Green noted that nonresponders claiming lack of immediacy could be swayed with the right approach. She has conducted similar research and subjects themselves suggested the use of marketing techniques “like what happens on Amazon. People remind you frequently the same thing when they get a clue that you have an interest in that behavior. Or, they tell you it’s on sale, and you might lose out from that big bargain if you don’t buy it now. There’s a deadline. I think a lot of the things we might do to nudge people are similar to what’s already happening in marketing,” said Dr. Green, who is a family physician and a researcher at the Kaiser Permanente Washington Health Research Institute.

Dr. Clarke and Dr. Green have no relevant financial disclosures.

Low serum levels of the hepatitis B core-related antigen (HBcrAg) could be an early biomarker of a functional cure of a hepatitis B infection, according to new findings from a retrospective study.

A drop in HBcrAg predicted the seroclearance of hepatitis B surface antigen (HBsAg), the widely accepted measure of optimal liver-related outcomes in patient care and clinical trials, long before HBsAg levels actually fell.

“In a large retrospective cohort study of chronic hepatitis B patients, we found lower levels of HBcrAg were associated with higher probability of clearing HBsAg,” wrote Tai-Chung Tseng and coauthors at National Taiwan University Hospital in Taipei. “Reduction of HBcrAg developed 10 years before decline of HBsAg in patients with high HBsAg levels at baseline.”

Nearly 300 million people worldwide are estimated to be positive for the HBsAg antigen, a marker of active hepatitis B virus (HBV) infection. Chronic HBV puts individuals at greater risk of cirrhosis, hepatocellular carcinoma (HCC), and other liver complications.

Seroclearance of HBsAg is generally regarded as signaling a functional cure, because it is associated with low viral activity and good clinical outcomes. Patients with low HBsAg levels may transition to complete clearance, while those with levels of 1,000 IU/mL or higher rarely achieve clearance either spontaneously or through treatment.

As with HBsAg, higher serum levels of HBcrAg have been linked to a raised risk of adverse events, including increased viral activity and heightened risk of developing hepatitis B e antigen-negative hepatitis, cirrhosis, and HCC. Lower HBcrAg levels are associated with a greater likelihood of HBsAg seroclearance in chronic hepatitis B patients who discontinued antiviral therapy.

In a study published in Gastroenterology, researchers conducted a retrospective Taiwanese cohort study of 2,614 untreated patients with hepatitis B who underwent long-term follow-up at National Taiwan University Hospital. The median age was 38.2 years, and 60.6% were men. At baseline, 14.8% had HBsAg levels of less than 100 IU/mL, and 47.7% had HBcrAg levels less than 10,000 IU/mL. Most (77.5%) were infected with HBV genotype B. From stored serum samples, the researchers quantified levels of HBV DNA, HBsAg, and HBcrAg and evaluated the relationships with spontaneous HBsAg seroclearance.

Over an average follow-up of about 12 years, 465 patients cleared HBsAg, an incidence of 1.43% per year. Researchers stratified patients by levels of viral markers. Compared to those with the highest HBcrAg levels (> 100,000 IU/mL), lower levels of HBcrAg were associated with greater likelihood of HBsAg clearance.

Specifically, intermediate levels (10,000-99,999 IU/mL) were associated with nearly double the chance of HBsAg clearance (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.44-2.65), and the lowest levels (< 10,000 IU/mL) were associated with just over triple the chance of clearance (HR, 3.15; 95% CI, 2.45-4.05). These associations held up with multivariable analyses, and HBV DNA levels were not significantly associated with HBsAg clearance.

“Not surprisingly, HBsAg levels still serve as a better predictor than the other two biomarkers,” the authors wrote. “Notably, the HBsAg levels are more like a short-term predictor” (within 5 years).

For patients with higher HBsAg levels (> 1,000 IU/mL), it took a median of 16 years to achieve HBsAg clearance. A subanalysis of the 1,539 patients with HbsAg levels > 1,000 IU/mL found that only HBcrAg levels below 10,000 IU/mL predicted HBsAg seroclearance versus 100,000 U/mL or higher (adjusted HR, 1.95; 95% CI, 1.16-3.27).

HBsAg levels began to decline later, often between 5 and 9 years before HBsAg seroclearance occurs. However, HBcrAg levels became undetectable 10-14 years before HBsAg seroclearance. Among patients achieving undetectable levels of HBcrAg, the annual HBsAg seroclearance rate was higher in the second decade of follow-up than in the first decade (3.75% versus 0.97%).

HBcrAg levels reflect the transcriptional activity of covalently closed circular DNA (cccDNA), the authors noted, while HBsAg can come from cccDNA and HBV-DNA integrated into the host genome. Several novel hepatitis B therapies in development target cccDNA transcription, but it isn’t known if the strategy will result in HBsAg clearance.

In the discussion section, the authors speculated about the possible pathology and treatment implications for several chronic hepatitis B scenarios. For example, the finding that HBcrAg clearance usually precedes HBsAg clearance suggests that reduction of cccDNA transcription is a requirement for curing hepatitis B, the authors speculate, but it also suggests that add-on treatment may need to target HBsAg transcribed from the integrated viral genome for a functional cure.

The researchers noted several study limitations, including that the cohort included only Asians largely with HBV genotypes B or C and that “further validation from Caucasian patients infected with genotypes types A or D is mandatory.”

Tai-Chung Tseng disclosed financial conflicts with Fujirebio, Bristol-Myers Squibb, and Gilead Sciences. The remaining authors had no conflicts of interest. The study received grant support from several institutions, including National Taiwan University Hospital.

Low serum levels of the hepatitis B core-related antigen (HBcrAg) could be an early biomarker of a functional cure of a hepatitis B infection, according to new findings from a retrospective study.

A drop in HBcrAg predicted the seroclearance of hepatitis B surface antigen (HBsAg), the widely accepted measure of optimal liver-related outcomes in patient care and clinical trials, long before HBsAg levels actually fell.

“In a large retrospective cohort study of chronic hepatitis B patients, we found lower levels of HBcrAg were associated with higher probability of clearing HBsAg,” wrote Tai-Chung Tseng and coauthors at National Taiwan University Hospital in Taipei. “Reduction of HBcrAg developed 10 years before decline of HBsAg in patients with high HBsAg levels at baseline.”

Nearly 300 million people worldwide are estimated to be positive for the HBsAg antigen, a marker of active hepatitis B virus (HBV) infection. Chronic HBV puts individuals at greater risk of cirrhosis, hepatocellular carcinoma (HCC), and other liver complications.

Seroclearance of HBsAg is generally regarded as signaling a functional cure, because it is associated with low viral activity and good clinical outcomes. Patients with low HBsAg levels may transition to complete clearance, while those with levels of 1,000 IU/mL or higher rarely achieve clearance either spontaneously or through treatment.

As with HBsAg, higher serum levels of HBcrAg have been linked to a raised risk of adverse events, including increased viral activity and heightened risk of developing hepatitis B e antigen-negative hepatitis, cirrhosis, and HCC. Lower HBcrAg levels are associated with a greater likelihood of HBsAg seroclearance in chronic hepatitis B patients who discontinued antiviral therapy.

In a study published in Gastroenterology, researchers conducted a retrospective Taiwanese cohort study of 2,614 untreated patients with hepatitis B who underwent long-term follow-up at National Taiwan University Hospital. The median age was 38.2 years, and 60.6% were men. At baseline, 14.8% had HBsAg levels of less than 100 IU/mL, and 47.7% had HBcrAg levels less than 10,000 IU/mL. Most (77.5%) were infected with HBV genotype B. From stored serum samples, the researchers quantified levels of HBV DNA, HBsAg, and HBcrAg and evaluated the relationships with spontaneous HBsAg seroclearance.

Over an average follow-up of about 12 years, 465 patients cleared HBsAg, an incidence of 1.43% per year. Researchers stratified patients by levels of viral markers. Compared to those with the highest HBcrAg levels (> 100,000 IU/mL), lower levels of HBcrAg were associated with greater likelihood of HBsAg clearance.

Specifically, intermediate levels (10,000-99,999 IU/mL) were associated with nearly double the chance of HBsAg clearance (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.44-2.65), and the lowest levels (< 10,000 IU/mL) were associated with just over triple the chance of clearance (HR, 3.15; 95% CI, 2.45-4.05). These associations held up with multivariable analyses, and HBV DNA levels were not significantly associated with HBsAg clearance.

“Not surprisingly, HBsAg levels still serve as a better predictor than the other two biomarkers,” the authors wrote. “Notably, the HBsAg levels are more like a short-term predictor” (within 5 years).

For patients with higher HBsAg levels (> 1,000 IU/mL), it took a median of 16 years to achieve HBsAg clearance. A subanalysis of the 1,539 patients with HbsAg levels > 1,000 IU/mL found that only HBcrAg levels below 10,000 IU/mL predicted HBsAg seroclearance versus 100,000 U/mL or higher (adjusted HR, 1.95; 95% CI, 1.16-3.27).

HBsAg levels began to decline later, often between 5 and 9 years before HBsAg seroclearance occurs. However, HBcrAg levels became undetectable 10-14 years before HBsAg seroclearance. Among patients achieving undetectable levels of HBcrAg, the annual HBsAg seroclearance rate was higher in the second decade of follow-up than in the first decade (3.75% versus 0.97%).

HBcrAg levels reflect the transcriptional activity of covalently closed circular DNA (cccDNA), the authors noted, while HBsAg can come from cccDNA and HBV-DNA integrated into the host genome. Several novel hepatitis B therapies in development target cccDNA transcription, but it isn’t known if the strategy will result in HBsAg clearance.

In the discussion section, the authors speculated about the possible pathology and treatment implications for several chronic hepatitis B scenarios. For example, the finding that HBcrAg clearance usually precedes HBsAg clearance suggests that reduction of cccDNA transcription is a requirement for curing hepatitis B, the authors speculate, but it also suggests that add-on treatment may need to target HBsAg transcribed from the integrated viral genome for a functional cure.

The researchers noted several study limitations, including that the cohort included only Asians largely with HBV genotypes B or C and that “further validation from Caucasian patients infected with genotypes types A or D is mandatory.”

Tai-Chung Tseng disclosed financial conflicts with Fujirebio, Bristol-Myers Squibb, and Gilead Sciences. The remaining authors had no conflicts of interest. The study received grant support from several institutions, including National Taiwan University Hospital.

Low serum levels of the hepatitis B core-related antigen (HBcrAg) could be an early biomarker of a functional cure of a hepatitis B infection, according to new findings from a retrospective study.

A drop in HBcrAg predicted the seroclearance of hepatitis B surface antigen (HBsAg), the widely accepted measure of optimal liver-related outcomes in patient care and clinical trials, long before HBsAg levels actually fell.

“In a large retrospective cohort study of chronic hepatitis B patients, we found lower levels of HBcrAg were associated with higher probability of clearing HBsAg,” wrote Tai-Chung Tseng and coauthors at National Taiwan University Hospital in Taipei. “Reduction of HBcrAg developed 10 years before decline of HBsAg in patients with high HBsAg levels at baseline.”

Nearly 300 million people worldwide are estimated to be positive for the HBsAg antigen, a marker of active hepatitis B virus (HBV) infection. Chronic HBV puts individuals at greater risk of cirrhosis, hepatocellular carcinoma (HCC), and other liver complications.

Seroclearance of HBsAg is generally regarded as signaling a functional cure, because it is associated with low viral activity and good clinical outcomes. Patients with low HBsAg levels may transition to complete clearance, while those with levels of 1,000 IU/mL or higher rarely achieve clearance either spontaneously or through treatment.

As with HBsAg, higher serum levels of HBcrAg have been linked to a raised risk of adverse events, including increased viral activity and heightened risk of developing hepatitis B e antigen-negative hepatitis, cirrhosis, and HCC. Lower HBcrAg levels are associated with a greater likelihood of HBsAg seroclearance in chronic hepatitis B patients who discontinued antiviral therapy.

In a study published in Gastroenterology, researchers conducted a retrospective Taiwanese cohort study of 2,614 untreated patients with hepatitis B who underwent long-term follow-up at National Taiwan University Hospital. The median age was 38.2 years, and 60.6% were men. At baseline, 14.8% had HBsAg levels of less than 100 IU/mL, and 47.7% had HBcrAg levels less than 10,000 IU/mL. Most (77.5%) were infected with HBV genotype B. From stored serum samples, the researchers quantified levels of HBV DNA, HBsAg, and HBcrAg and evaluated the relationships with spontaneous HBsAg seroclearance.

Over an average follow-up of about 12 years, 465 patients cleared HBsAg, an incidence of 1.43% per year. Researchers stratified patients by levels of viral markers. Compared to those with the highest HBcrAg levels (> 100,000 IU/mL), lower levels of HBcrAg were associated with greater likelihood of HBsAg clearance.

Specifically, intermediate levels (10,000-99,999 IU/mL) were associated with nearly double the chance of HBsAg clearance (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.44-2.65), and the lowest levels (< 10,000 IU/mL) were associated with just over triple the chance of clearance (HR, 3.15; 95% CI, 2.45-4.05). These associations held up with multivariable analyses, and HBV DNA levels were not significantly associated with HBsAg clearance.

“Not surprisingly, HBsAg levels still serve as a better predictor than the other two biomarkers,” the authors wrote. “Notably, the HBsAg levels are more like a short-term predictor” (within 5 years).

For patients with higher HBsAg levels (> 1,000 IU/mL), it took a median of 16 years to achieve HBsAg clearance. A subanalysis of the 1,539 patients with HbsAg levels > 1,000 IU/mL found that only HBcrAg levels below 10,000 IU/mL predicted HBsAg seroclearance versus 100,000 U/mL or higher (adjusted HR, 1.95; 95% CI, 1.16-3.27).

HBsAg levels began to decline later, often between 5 and 9 years before HBsAg seroclearance occurs. However, HBcrAg levels became undetectable 10-14 years before HBsAg seroclearance. Among patients achieving undetectable levels of HBcrAg, the annual HBsAg seroclearance rate was higher in the second decade of follow-up than in the first decade (3.75% versus 0.97%).

HBcrAg levels reflect the transcriptional activity of covalently closed circular DNA (cccDNA), the authors noted, while HBsAg can come from cccDNA and HBV-DNA integrated into the host genome. Several novel hepatitis B therapies in development target cccDNA transcription, but it isn’t known if the strategy will result in HBsAg clearance.

In the discussion section, the authors speculated about the possible pathology and treatment implications for several chronic hepatitis B scenarios. For example, the finding that HBcrAg clearance usually precedes HBsAg clearance suggests that reduction of cccDNA transcription is a requirement for curing hepatitis B, the authors speculate, but it also suggests that add-on treatment may need to target HBsAg transcribed from the integrated viral genome for a functional cure.

The researchers noted several study limitations, including that the cohort included only Asians largely with HBV genotypes B or C and that “further validation from Caucasian patients infected with genotypes types A or D is mandatory.”

Tai-Chung Tseng disclosed financial conflicts with Fujirebio, Bristol-Myers Squibb, and Gilead Sciences. The remaining authors had no conflicts of interest. The study received grant support from several institutions, including National Taiwan University Hospital.

SAN DIEGO – Clinical characteristics and treatment responses in multiple sclerosis (MS) show unimodal distributions, which suggests that it is a homogeneous condition with lots of variation, rather than a mixture of conditions with different genetic or other causes, according to a new analysis. The work suggests that personalized therapy based on clinical characteristics is likely to be the best approach, rather than precision medicine based on molecular or other subtypes.

Think MS is heterogeneous? Think again

The work drew upon data from 22,000 individuals, 32,000 attacks, 156,000 EDSS scores, 250,000 observation years, and 110,000 treatment years recorded in the Swedish MS registry. The researchers examined distributions in age of onset, severity, and distribution of relapses. Among patients treated with one of 12 disease-modifying therapies, they examined patterns of EDSS progression, appearance of new lesions, and relapses.

“

Karolinska Institutet

Regardless of which clinical characteristic of the MS syndrome that I study, I find a uniform distribution with very few if any outliers. That argues that MS is likely to be a homogeneous condition with some variation, but it’s highly unlikely that MS is a mixture of different conditions masquerading as the same thing,” said Jan Hillert, MD, PhD, who presented the study during a poster session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

“There are big efforts out there trying to decipher the molecular basis of the MS syndrome, thinking that it’s a mixture of different things. And I would argue that our data very strongly argue against that,” said Dr. Hillert, who is a professor of neurology at Karolinska Institutet in Solna, Sweden.

Specific subtypes should produce individual groupings rather than a broad distribution. “If you have a multitude of factors, then this (finding of a broad distribution) is what you have. If you have a small number of strongly acting factors, like if there were genetic subgroups, then you would have a different distribution. So this is in line with the polygenic, complex nature of MS that we have been thinking about for many, many years, and which the genetics also support,” said Dr. Hillert.

The findings suggest that physicians should be emphasizing personalized treatment of MS based on factors like age, weight, disease activity and severity, disability, side effects, and other factors. “Personalized medicine I embrace, but the concept of precision medicine is naive. It’s not founded on any sound scientific evidence,” said Dr. Hillert.
 

An evolving definition

The conclusion is compelling, according to Patricia Coyle, MD, who was asked to comment on the study. “I have not seen this sort of analysis before. I think it doesn’t absolutely prove the case in talking about very small numbers, but it does make a very logical argument. This is not showing any meaningful large subgroups that you can call out,” said Dr. Coyle, who is a professor of neurology and director of the MS Comprehensive Care Center at Stonybrook Neurosciences Institute in New York.

“I think that it’s interesting, because we have routinely said we think this is heterogeneous, because no two patients are alike. But this is speaking against meaningful heterogeneity in MS. When you look at these sorts of statistical results, this is what you’d expect in a normal population, not in a disease where you might say, genetically, or molecularly, you could define significant subsets of individuals,” said Dr. Coyle.

The study isn’t the last word. “You would probably like to see some follow-up data, perhaps in other very large databases to make it more convincing, but I think you’re not hearing as many people talk about MS heterogeneity anymore. We know there’s a focal inflammatory component, we know there’s a neurodegenerative component. Both are present in all MS. People are even arguing that maybe it’s not meaningful to call out progressive and relapsing MS. I don’t agree with that, but I think the concept that there are meaningful subsets of patients is probably incorrect. [The idea that] one set is due to perhaps an infection, another might be molecular mimicry. ... Maybe that’s not the case at all,” said Dr. Coyle.

For example, some companies are looking into whether B cell depletion treatments might be more effective for one set of patients versus another. “The issue is, can you dissect out subsets where hitting B cells is really good and others where it doesn’t seem to matter? That really hasn’t [been successful],” said Dr. Coyle.

Dr. Hillert has served on scientific advisor boards for or received speaker’s fees from Biogen, Bristol Myers Squibb/Celgene, Janssen, Novartis, Teva, Merck KGaA, Sandoz, and Sanofi Genzyme. He has received research support from Biogen, Bristol Myers Squibb/Celgene, Merck, Janssen, Novartis, Roche, and Sanofi-Genzyme. Dr. Coyle has consulted for or received speaker fees from Accordant, Biogen, Bristol Myers Squibb, GlaxoSmithKline, Horizon Therapeutics, LabCorp, Eli Lilly and Company, Mylan, Novartis, Sanofi Genzyme, TG Therapeutics. She has received research support from Actelion, Alkermes, Celgene, CorEvitas, Genentech/Roche, Janssen, MedDay, NINDS, Novartis, and Sanofi Genzyme.
 

SAN DIEGO – Clinical characteristics and treatment responses in multiple sclerosis (MS) show unimodal distributions, which suggests that it is a homogeneous condition with lots of variation, rather than a mixture of conditions with different genetic or other causes, according to a new analysis. The work suggests that personalized therapy based on clinical characteristics is likely to be the best approach, rather than precision medicine based on molecular or other subtypes.

Think MS is heterogeneous? Think again

The work drew upon data from 22,000 individuals, 32,000 attacks, 156,000 EDSS scores, 250,000 observation years, and 110,000 treatment years recorded in the Swedish MS registry. The researchers examined distributions in age of onset, severity, and distribution of relapses. Among patients treated with one of 12 disease-modifying therapies, they examined patterns of EDSS progression, appearance of new lesions, and relapses.

“

Karolinska Institutet

Regardless of which clinical characteristic of the MS syndrome that I study, I find a uniform distribution with very few if any outliers. That argues that MS is likely to be a homogeneous condition with some variation, but it’s highly unlikely that MS is a mixture of different conditions masquerading as the same thing,” said Jan Hillert, MD, PhD, who presented the study during a poster session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

“There are big efforts out there trying to decipher the molecular basis of the MS syndrome, thinking that it’s a mixture of different things. And I would argue that our data very strongly argue against that,” said Dr. Hillert, who is a professor of neurology at Karolinska Institutet in Solna, Sweden.

Specific subtypes should produce individual groupings rather than a broad distribution. “If you have a multitude of factors, then this (finding of a broad distribution) is what you have. If you have a small number of strongly acting factors, like if there were genetic subgroups, then you would have a different distribution. So this is in line with the polygenic, complex nature of MS that we have been thinking about for many, many years, and which the genetics also support,” said Dr. Hillert.

The findings suggest that physicians should be emphasizing personalized treatment of MS based on factors like age, weight, disease activity and severity, disability, side effects, and other factors. “Personalized medicine I embrace, but the concept of precision medicine is naive. It’s not founded on any sound scientific evidence,” said Dr. Hillert.
 

An evolving definition

The conclusion is compelling, according to Patricia Coyle, MD, who was asked to comment on the study. “I have not seen this sort of analysis before. I think it doesn’t absolutely prove the case in talking about very small numbers, but it does make a very logical argument. This is not showing any meaningful large subgroups that you can call out,” said Dr. Coyle, who is a professor of neurology and director of the MS Comprehensive Care Center at Stonybrook Neurosciences Institute in New York.

“I think that it’s interesting, because we have routinely said we think this is heterogeneous, because no two patients are alike. But this is speaking against meaningful heterogeneity in MS. When you look at these sorts of statistical results, this is what you’d expect in a normal population, not in a disease where you might say, genetically, or molecularly, you could define significant subsets of individuals,” said Dr. Coyle.

The study isn’t the last word. “You would probably like to see some follow-up data, perhaps in other very large databases to make it more convincing, but I think you’re not hearing as many people talk about MS heterogeneity anymore. We know there’s a focal inflammatory component, we know there’s a neurodegenerative component. Both are present in all MS. People are even arguing that maybe it’s not meaningful to call out progressive and relapsing MS. I don’t agree with that, but I think the concept that there are meaningful subsets of patients is probably incorrect. [The idea that] one set is due to perhaps an infection, another might be molecular mimicry. ... Maybe that’s not the case at all,” said Dr. Coyle.

For example, some companies are looking into whether B cell depletion treatments might be more effective for one set of patients versus another. “The issue is, can you dissect out subsets where hitting B cells is really good and others where it doesn’t seem to matter? That really hasn’t [been successful],” said Dr. Coyle.

Dr. Hillert has served on scientific advisor boards for or received speaker’s fees from Biogen, Bristol Myers Squibb/Celgene, Janssen, Novartis, Teva, Merck KGaA, Sandoz, and Sanofi Genzyme. He has received research support from Biogen, Bristol Myers Squibb/Celgene, Merck, Janssen, Novartis, Roche, and Sanofi-Genzyme. Dr. Coyle has consulted for or received speaker fees from Accordant, Biogen, Bristol Myers Squibb, GlaxoSmithKline, Horizon Therapeutics, LabCorp, Eli Lilly and Company, Mylan, Novartis, Sanofi Genzyme, TG Therapeutics. She has received research support from Actelion, Alkermes, Celgene, CorEvitas, Genentech/Roche, Janssen, MedDay, NINDS, Novartis, and Sanofi Genzyme.
 

SAN DIEGO – Clinical characteristics and treatment responses in multiple sclerosis (MS) show unimodal distributions, which suggests that it is a homogeneous condition with lots of variation, rather than a mixture of conditions with different genetic or other causes, according to a new analysis. The work suggests that personalized therapy based on clinical characteristics is likely to be the best approach, rather than precision medicine based on molecular or other subtypes.

Think MS is heterogeneous? Think again

The work drew upon data from 22,000 individuals, 32,000 attacks, 156,000 EDSS scores, 250,000 observation years, and 110,000 treatment years recorded in the Swedish MS registry. The researchers examined distributions in age of onset, severity, and distribution of relapses. Among patients treated with one of 12 disease-modifying therapies, they examined patterns of EDSS progression, appearance of new lesions, and relapses.

“

Karolinska Institutet

Regardless of which clinical characteristic of the MS syndrome that I study, I find a uniform distribution with very few if any outliers. That argues that MS is likely to be a homogeneous condition with some variation, but it’s highly unlikely that MS is a mixture of different conditions masquerading as the same thing,” said Jan Hillert, MD, PhD, who presented the study during a poster session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

“There are big efforts out there trying to decipher the molecular basis of the MS syndrome, thinking that it’s a mixture of different things. And I would argue that our data very strongly argue against that,” said Dr. Hillert, who is a professor of neurology at Karolinska Institutet in Solna, Sweden.

Specific subtypes should produce individual groupings rather than a broad distribution. “If you have a multitude of factors, then this (finding of a broad distribution) is what you have. If you have a small number of strongly acting factors, like if there were genetic subgroups, then you would have a different distribution. So this is in line with the polygenic, complex nature of MS that we have been thinking about for many, many years, and which the genetics also support,” said Dr. Hillert.

The findings suggest that physicians should be emphasizing personalized treatment of MS based on factors like age, weight, disease activity and severity, disability, side effects, and other factors. “Personalized medicine I embrace, but the concept of precision medicine is naive. It’s not founded on any sound scientific evidence,” said Dr. Hillert.
 

An evolving definition

The conclusion is compelling, according to Patricia Coyle, MD, who was asked to comment on the study. “I have not seen this sort of analysis before. I think it doesn’t absolutely prove the case in talking about very small numbers, but it does make a very logical argument. This is not showing any meaningful large subgroups that you can call out,” said Dr. Coyle, who is a professor of neurology and director of the MS Comprehensive Care Center at Stonybrook Neurosciences Institute in New York.

“I think that it’s interesting, because we have routinely said we think this is heterogeneous, because no two patients are alike. But this is speaking against meaningful heterogeneity in MS. When you look at these sorts of statistical results, this is what you’d expect in a normal population, not in a disease where you might say, genetically, or molecularly, you could define significant subsets of individuals,” said Dr. Coyle.

The study isn’t the last word. “You would probably like to see some follow-up data, perhaps in other very large databases to make it more convincing, but I think you’re not hearing as many people talk about MS heterogeneity anymore. We know there’s a focal inflammatory component, we know there’s a neurodegenerative component. Both are present in all MS. People are even arguing that maybe it’s not meaningful to call out progressive and relapsing MS. I don’t agree with that, but I think the concept that there are meaningful subsets of patients is probably incorrect. [The idea that] one set is due to perhaps an infection, another might be molecular mimicry. ... Maybe that’s not the case at all,” said Dr. Coyle.

For example, some companies are looking into whether B cell depletion treatments might be more effective for one set of patients versus another. “The issue is, can you dissect out subsets where hitting B cells is really good and others where it doesn’t seem to matter? That really hasn’t [been successful],” said Dr. Coyle.

Dr. Hillert has served on scientific advisor boards for or received speaker’s fees from Biogen, Bristol Myers Squibb/Celgene, Janssen, Novartis, Teva, Merck KGaA, Sandoz, and Sanofi Genzyme. He has received research support from Biogen, Bristol Myers Squibb/Celgene, Merck, Janssen, Novartis, Roche, and Sanofi-Genzyme. Dr. Coyle has consulted for or received speaker fees from Accordant, Biogen, Bristol Myers Squibb, GlaxoSmithKline, Horizon Therapeutics, LabCorp, Eli Lilly and Company, Mylan, Novartis, Sanofi Genzyme, TG Therapeutics. She has received research support from Actelion, Alkermes, Celgene, CorEvitas, Genentech/Roche, Janssen, MedDay, NINDS, Novartis, and Sanofi Genzyme.
 

A blind comparison between a portable, ultra low-field magnetic resonance imaging (MRI) device and a traditional high-field MRI showed that the portable device performed well in detecting periventricular lesions in pateints with multiple sclerosis (MS), suggesting that it could have potential for use in screening high-risk patients.

Although previous studies had shown that the approach could hold up to high-field MRI, the new study was a blind comparison in which raters did not have access to the high-field images.

In addition to portability, the device has potential advantages over high-field MRI, including low cost and no need for high-field physical shielding. It could be used for point-of-care testing, especially in remote or low-resource areas. It does not produce ionizing radiation, and has been used in intensive care units and pediatric facilities.
 

Advantages and limitations

The device isn’t ready for general use in MS. It performed well in periventricular lesions but less well in other areas. Ongoing research could improve its performance, including multiplanar imaging and image analysis.

“I think it still needs some work, but to me if it’s less expensive it will be particularly better for third-world countries and that sort of place, or possibly for use in the field in the United States or in North America. If something is detected, you can then bring the person in for a better scan, but I don’t know how sensitive it is – how much pathology you might miss. But in countries where there are no MRIs, it’s certainly better than nothing,” said Anne Cross, MD, who comoderated the session at the Americas Committee for Treatment and Research in Multiple Sclerosis, where the study was presented.

She also noted that the device is potentially safer than high-field MRI. “I don’t think it would be something insurance companies or patients would want to pay $1,000 for when they could get a better scan somewhere, but it’ll get better,” said Dr. Cross, who is a professor of neurology and chair of neuroimmunology at Washington University in St. Louis.
 

How reliable are low-field images?

In previous work, in which evaluators compared the two scans side by side, the researchers showed in 36 patients that the device performed well, compared with a 64mT scanner. “When we look at tandem evaluations, we can identify dissemination in space in 80%. When a patient has at least one lesion that is larger than 4 millimeters in its largest diameter, we are able to detect it in the ultralow field MRI with 100% sensitivity. The open question here is, what is the diagnostic utility of these scanners when we don’t have any information about the high-field images?” said Serhat Okar, MD, during his presentation of the study. Dr. Okar is a neurologist and postdoctoral researcher at the National Institutes of Health.

National Institutes of Health

To answer that question, the researchers asked two raters to examine scans from the low-field MRI, but only an independent party evaluator had access to both scans.

The study included 55 MS patients who were seen for either clinical or research purposes. The average age was 41 years, and 43 patients were female. Two neuroradiologists served as scan raters. Rater 1 had 17 years of experience, and rater 2 had 9 years of experience. They each conducted assessments for periventricular, juxtacortical, infratentorial, deep white matter, and deep gray matter lesions, as well as dissemination in space. They marked the scan and filled out an online form with number of observed lesions and whether they observed dissemination in space, with responses checked against a high-field image by an independent neuroradiologist for true positive and false positive findings.

There was significant discordance between raters for observation of dissemination in space, with rater 1 reporting 81% positivity and reader 2, 49%. False positive analyses revealed a difference in their approaches: Rater 1 was more conservative in marking lesions, which led to fewer true positive and fewer false positive findings. Both raters had good performance in the periventricular lesions with similar, low rates of false positives.

Other areas were a different story. Both raters found a greater number of true positive and false positive areas in the juxtacortical, deep white matter, and deep gray matter areas.

The study was funded by Hyperfine. Dr. Okar and Dr. Cross have no relevant financial disclosures.

A blind comparison between a portable, ultra low-field magnetic resonance imaging (MRI) device and a traditional high-field MRI showed that the portable device performed well in detecting periventricular lesions in pateints with multiple sclerosis (MS), suggesting that it could have potential for use in screening high-risk patients.

Although previous studies had shown that the approach could hold up to high-field MRI, the new study was a blind comparison in which raters did not have access to the high-field images.

In addition to portability, the device has potential advantages over high-field MRI, including low cost and no need for high-field physical shielding. It could be used for point-of-care testing, especially in remote or low-resource areas. It does not produce ionizing radiation, and has been used in intensive care units and pediatric facilities.
 

Advantages and limitations

The device isn’t ready for general use in MS. It performed well in periventricular lesions but less well in other areas. Ongoing research could improve its performance, including multiplanar imaging and image analysis.

“I think it still needs some work, but to me if it’s less expensive it will be particularly better for third-world countries and that sort of place, or possibly for use in the field in the United States or in North America. If something is detected, you can then bring the person in for a better scan, but I don’t know how sensitive it is – how much pathology you might miss. But in countries where there are no MRIs, it’s certainly better than nothing,” said Anne Cross, MD, who comoderated the session at the Americas Committee for Treatment and Research in Multiple Sclerosis, where the study was presented.

She also noted that the device is potentially safer than high-field MRI. “I don’t think it would be something insurance companies or patients would want to pay $1,000 for when they could get a better scan somewhere, but it’ll get better,” said Dr. Cross, who is a professor of neurology and chair of neuroimmunology at Washington University in St. Louis.
 

How reliable are low-field images?

In previous work, in which evaluators compared the two scans side by side, the researchers showed in 36 patients that the device performed well, compared with a 64mT scanner. “When we look at tandem evaluations, we can identify dissemination in space in 80%. When a patient has at least one lesion that is larger than 4 millimeters in its largest diameter, we are able to detect it in the ultralow field MRI with 100% sensitivity. The open question here is, what is the diagnostic utility of these scanners when we don’t have any information about the high-field images?” said Serhat Okar, MD, during his presentation of the study. Dr. Okar is a neurologist and postdoctoral researcher at the National Institutes of Health.

National Institutes of Health

To answer that question, the researchers asked two raters to examine scans from the low-field MRI, but only an independent party evaluator had access to both scans.

The study included 55 MS patients who were seen for either clinical or research purposes. The average age was 41 years, and 43 patients were female. Two neuroradiologists served as scan raters. Rater 1 had 17 years of experience, and rater 2 had 9 years of experience. They each conducted assessments for periventricular, juxtacortical, infratentorial, deep white matter, and deep gray matter lesions, as well as dissemination in space. They marked the scan and filled out an online form with number of observed lesions and whether they observed dissemination in space, with responses checked against a high-field image by an independent neuroradiologist for true positive and false positive findings.

There was significant discordance between raters for observation of dissemination in space, with rater 1 reporting 81% positivity and reader 2, 49%. False positive analyses revealed a difference in their approaches: Rater 1 was more conservative in marking lesions, which led to fewer true positive and fewer false positive findings. Both raters had good performance in the periventricular lesions with similar, low rates of false positives.

Other areas were a different story. Both raters found a greater number of true positive and false positive areas in the juxtacortical, deep white matter, and deep gray matter areas.

The study was funded by Hyperfine. Dr. Okar and Dr. Cross have no relevant financial disclosures.

A blind comparison between a portable, ultra low-field magnetic resonance imaging (MRI) device and a traditional high-field MRI showed that the portable device performed well in detecting periventricular lesions in pateints with multiple sclerosis (MS), suggesting that it could have potential for use in screening high-risk patients.

Although previous studies had shown that the approach could hold up to high-field MRI, the new study was a blind comparison in which raters did not have access to the high-field images.

In addition to portability, the device has potential advantages over high-field MRI, including low cost and no need for high-field physical shielding. It could be used for point-of-care testing, especially in remote or low-resource areas. It does not produce ionizing radiation, and has been used in intensive care units and pediatric facilities.
 

Advantages and limitations

The device isn’t ready for general use in MS. It performed well in periventricular lesions but less well in other areas. Ongoing research could improve its performance, including multiplanar imaging and image analysis.

“I think it still needs some work, but to me if it’s less expensive it will be particularly better for third-world countries and that sort of place, or possibly for use in the field in the United States or in North America. If something is detected, you can then bring the person in for a better scan, but I don’t know how sensitive it is – how much pathology you might miss. But in countries where there are no MRIs, it’s certainly better than nothing,” said Anne Cross, MD, who comoderated the session at the Americas Committee for Treatment and Research in Multiple Sclerosis, where the study was presented.

She also noted that the device is potentially safer than high-field MRI. “I don’t think it would be something insurance companies or patients would want to pay $1,000 for when they could get a better scan somewhere, but it’ll get better,” said Dr. Cross, who is a professor of neurology and chair of neuroimmunology at Washington University in St. Louis.
 

How reliable are low-field images?

In previous work, in which evaluators compared the two scans side by side, the researchers showed in 36 patients that the device performed well, compared with a 64mT scanner. “When we look at tandem evaluations, we can identify dissemination in space in 80%. When a patient has at least one lesion that is larger than 4 millimeters in its largest diameter, we are able to detect it in the ultralow field MRI with 100% sensitivity. The open question here is, what is the diagnostic utility of these scanners when we don’t have any information about the high-field images?” said Serhat Okar, MD, during his presentation of the study. Dr. Okar is a neurologist and postdoctoral researcher at the National Institutes of Health.

National Institutes of Health

To answer that question, the researchers asked two raters to examine scans from the low-field MRI, but only an independent party evaluator had access to both scans.

The study included 55 MS patients who were seen for either clinical or research purposes. The average age was 41 years, and 43 patients were female. Two neuroradiologists served as scan raters. Rater 1 had 17 years of experience, and rater 2 had 9 years of experience. They each conducted assessments for periventricular, juxtacortical, infratentorial, deep white matter, and deep gray matter lesions, as well as dissemination in space. They marked the scan and filled out an online form with number of observed lesions and whether they observed dissemination in space, with responses checked against a high-field image by an independent neuroradiologist for true positive and false positive findings.

There was significant discordance between raters for observation of dissemination in space, with rater 1 reporting 81% positivity and reader 2, 49%. False positive analyses revealed a difference in their approaches: Rater 1 was more conservative in marking lesions, which led to fewer true positive and fewer false positive findings. Both raters had good performance in the periventricular lesions with similar, low rates of false positives.

Other areas were a different story. Both raters found a greater number of true positive and false positive areas in the juxtacortical, deep white matter, and deep gray matter areas.

The study was funded by Hyperfine. Dr. Okar and Dr. Cross have no relevant financial disclosures.

A digital tool to measure walking has the potential to improve measurement of disability among patients with multiple sclerosis (MS).

“When you measure disability, what you really want to know is how things are changing in the patient’s life and not your perception of how they’re changing,” said Mark Gudesblatt, MD, who presented a study comparing the technique, called quantitative gait analysis, to other measures at a poster session during the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).

South Shore Neurologic Associates

The device, called Protokinetics, has been used in clinical studies for Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, stroke, Friederich’s ataxia, and other conditions. The device is a digitized carpet that senses weight change and pressure as the individual walks.

“We can actually measure performance, and the performance is not just how fast you walk 25 feet. We’re measuring things that underlie how you walk: step length, step length variability, velocity, weight shift, how much time you spend on one leg. So it’s like listening to a symphony. We’re not measuring just the trumpets or the violins, we’re measuring everything,” said Dr. Gudesblatt, who is medical director of the Comprehensive MS Center at South Shore Neurologic Associates, Patchogue, N.Y.

Commonly used measures include the Expanded Disability Status Scale (EDSS), the 25-foot time walk (25’TW), and the Timed Up and Go (TUG).

Those measures are useful but don’t really measure up to clinical need, Dr. Gudesblatt said. “What you want is no evidence of disease activity, whether that’s multiple dimensions of thinking or multiple dimensions of walking, or changes on an MRI that are not the radiologist’s impression. Patients always say: ‘Doc, I’m worse.’ And we say: ‘Well, your exam is unchanged, your MRI has not changed. But they are worse for reasons – either their perception or their performance. So you can measure this very granularly, and you can relate it to their fear of falling, their balance confidence. This ups the game,” said Dr. Gudesblatt.

“And here’s where it gets even more interesting. You can use this for signatures of disease,” he added. The data can, for example, suggest that instead of Parkinson’s disease, a patient may have a Parkinson’s variant. “What we’re doing is showing how the 25-foot timed walk and Timed Up and Go are very traditional, conservative measures. They’re equivalent to the Pony Express. They’re good, but not where you want to be.”
 

Technology provides more sensitive, but more complex data

Digital tools to measure a variety of functions, including gait, cognition, and upper limb function are becoming increasingly common in MS, according to Catherine Larochelle, MD, PhD, who was asked for comment. “They are easily providing measures that are likely more sensitive and diverse and probably more meaningful about the daily functional status of a person than our usual EDSS,” said Dr. Larochelle, who is an associate professor at Université de Montréal.

The next step is to determine how best to use the complex data that such devices generate. “Lots of research is being done to better understand how to use the rich but complex data obtained with these tools to provide useful information to people with MS and their clinical team, to help guide shared clinical decisions, and likely accelerate and improve outcomes in clinical trials. So this is a very exciting new era in terms of clinical neurological assessment,” said Dr. Larochelle.
 

Granular gait analysis

Dr. Gudesblatt and colleagues analyzed retrospective data from 105 people with MS (69% female; average age, 53.7 years). Participants underwent all tests on the same day. The digital gait analysis captured velocity, double support, cadence, functional ambulation profile, gait variability index, and walk ratio over three trials conducted at preferred walking speed (PWS) and during dual task walking.

There were statistically significant relationships (P ≤ .01) between TUG and 25’TW (R² = 0.62). There were also significant relationships between 25’TW and digital parameters measured at PWS: velocity (R² = 0.63); double support (R² = 0.74); cadence (R² = 0.56); and gait variability index (R² = 0.54). During dual task walking, there were relationships between 25’TW and velocity (R² = 0.53); double support (R² = 0.30); cadence (R² = 0.43); and gait variability index (R² = 0.46).

TUG values were significantly associated with gait parameters during PWS: velocity (R² = 0.71); double support (R² = 0.75); cadence (R² = 0.43); gait variability index (R² = 0.45); and walk ratio (R² = 0.06). During dual task walking, TUG values were significantly associated with velocity (R² = 0.55), double support (R^{2 =} 0.21), cadence (R² = 0.45), and gait variability index (R² = 0.39).

“With the availability multiple effective disease modifying therapies and the future potential of restorative or reparative treatments, more granular, validated standardized outcome measures are urgently needed,” said Dr. Gudesblatt. Analysis of gait cycle can provide clinically useful information not adequately captured by the current, more traditional approaches of measuring outcomes in MS.

Dr. Gudesblatt and Dr. Larochelle have no relevant financial disclosures.

A digital tool to measure walking has the potential to improve measurement of disability among patients with multiple sclerosis (MS).

“When you measure disability, what you really want to know is how things are changing in the patient’s life and not your perception of how they’re changing,” said Mark Gudesblatt, MD, who presented a study comparing the technique, called quantitative gait analysis, to other measures at a poster session during the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).

South Shore Neurologic Associates

The device, called Protokinetics, has been used in clinical studies for Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, stroke, Friederich’s ataxia, and other conditions. The device is a digitized carpet that senses weight change and pressure as the individual walks.

“We can actually measure performance, and the performance is not just how fast you walk 25 feet. We’re measuring things that underlie how you walk: step length, step length variability, velocity, weight shift, how much time you spend on one leg. So it’s like listening to a symphony. We’re not measuring just the trumpets or the violins, we’re measuring everything,” said Dr. Gudesblatt, who is medical director of the Comprehensive MS Center at South Shore Neurologic Associates, Patchogue, N.Y.

Commonly used measures include the Expanded Disability Status Scale (EDSS), the 25-foot time walk (25’TW), and the Timed Up and Go (TUG).

Those measures are useful but don’t really measure up to clinical need, Dr. Gudesblatt said. “What you want is no evidence of disease activity, whether that’s multiple dimensions of thinking or multiple dimensions of walking, or changes on an MRI that are not the radiologist’s impression. Patients always say: ‘Doc, I’m worse.’ And we say: ‘Well, your exam is unchanged, your MRI has not changed. But they are worse for reasons – either their perception or their performance. So you can measure this very granularly, and you can relate it to their fear of falling, their balance confidence. This ups the game,” said Dr. Gudesblatt.

“And here’s where it gets even more interesting. You can use this for signatures of disease,” he added. The data can, for example, suggest that instead of Parkinson’s disease, a patient may have a Parkinson’s variant. “What we’re doing is showing how the 25-foot timed walk and Timed Up and Go are very traditional, conservative measures. They’re equivalent to the Pony Express. They’re good, but not where you want to be.”
 

Technology provides more sensitive, but more complex data

Digital tools to measure a variety of functions, including gait, cognition, and upper limb function are becoming increasingly common in MS, according to Catherine Larochelle, MD, PhD, who was asked for comment. “They are easily providing measures that are likely more sensitive and diverse and probably more meaningful about the daily functional status of a person than our usual EDSS,” said Dr. Larochelle, who is an associate professor at Université de Montréal.

The next step is to determine how best to use the complex data that such devices generate. “Lots of research is being done to better understand how to use the rich but complex data obtained with these tools to provide useful information to people with MS and their clinical team, to help guide shared clinical decisions, and likely accelerate and improve outcomes in clinical trials. So this is a very exciting new era in terms of clinical neurological assessment,” said Dr. Larochelle.
 

Granular gait analysis

Dr. Gudesblatt and colleagues analyzed retrospective data from 105 people with MS (69% female; average age, 53.7 years). Participants underwent all tests on the same day. The digital gait analysis captured velocity, double support, cadence, functional ambulation profile, gait variability index, and walk ratio over three trials conducted at preferred walking speed (PWS) and during dual task walking.

There were statistically significant relationships (P ≤ .01) between TUG and 25’TW (R² = 0.62). There were also significant relationships between 25’TW and digital parameters measured at PWS: velocity (R² = 0.63); double support (R² = 0.74); cadence (R² = 0.56); and gait variability index (R² = 0.54). During dual task walking, there were relationships between 25’TW and velocity (R² = 0.53); double support (R² = 0.30); cadence (R² = 0.43); and gait variability index (R² = 0.46).

TUG values were significantly associated with gait parameters during PWS: velocity (R² = 0.71); double support (R² = 0.75); cadence (R² = 0.43); gait variability index (R² = 0.45); and walk ratio (R² = 0.06). During dual task walking, TUG values were significantly associated with velocity (R² = 0.55), double support (R^{2 =} 0.21), cadence (R² = 0.45), and gait variability index (R² = 0.39).

“With the availability multiple effective disease modifying therapies and the future potential of restorative or reparative treatments, more granular, validated standardized outcome measures are urgently needed,” said Dr. Gudesblatt. Analysis of gait cycle can provide clinically useful information not adequately captured by the current, more traditional approaches of measuring outcomes in MS.

Dr. Gudesblatt and Dr. Larochelle have no relevant financial disclosures.

A digital tool to measure walking has the potential to improve measurement of disability among patients with multiple sclerosis (MS).

“When you measure disability, what you really want to know is how things are changing in the patient’s life and not your perception of how they’re changing,” said Mark Gudesblatt, MD, who presented a study comparing the technique, called quantitative gait analysis, to other measures at a poster session during the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).

South Shore Neurologic Associates

The device, called Protokinetics, has been used in clinical studies for Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, stroke, Friederich’s ataxia, and other conditions. The device is a digitized carpet that senses weight change and pressure as the individual walks.

“We can actually measure performance, and the performance is not just how fast you walk 25 feet. We’re measuring things that underlie how you walk: step length, step length variability, velocity, weight shift, how much time you spend on one leg. So it’s like listening to a symphony. We’re not measuring just the trumpets or the violins, we’re measuring everything,” said Dr. Gudesblatt, who is medical director of the Comprehensive MS Center at South Shore Neurologic Associates, Patchogue, N.Y.

Commonly used measures include the Expanded Disability Status Scale (EDSS), the 25-foot time walk (25’TW), and the Timed Up and Go (TUG).

Those measures are useful but don’t really measure up to clinical need, Dr. Gudesblatt said. “What you want is no evidence of disease activity, whether that’s multiple dimensions of thinking or multiple dimensions of walking, or changes on an MRI that are not the radiologist’s impression. Patients always say: ‘Doc, I’m worse.’ And we say: ‘Well, your exam is unchanged, your MRI has not changed. But they are worse for reasons – either their perception or their performance. So you can measure this very granularly, and you can relate it to their fear of falling, their balance confidence. This ups the game,” said Dr. Gudesblatt.

“And here’s where it gets even more interesting. You can use this for signatures of disease,” he added. The data can, for example, suggest that instead of Parkinson’s disease, a patient may have a Parkinson’s variant. “What we’re doing is showing how the 25-foot timed walk and Timed Up and Go are very traditional, conservative measures. They’re equivalent to the Pony Express. They’re good, but not where you want to be.”
 

Technology provides more sensitive, but more complex data

Digital tools to measure a variety of functions, including gait, cognition, and upper limb function are becoming increasingly common in MS, according to Catherine Larochelle, MD, PhD, who was asked for comment. “They are easily providing measures that are likely more sensitive and diverse and probably more meaningful about the daily functional status of a person than our usual EDSS,” said Dr. Larochelle, who is an associate professor at Université de Montréal.

The next step is to determine how best to use the complex data that such devices generate. “Lots of research is being done to better understand how to use the rich but complex data obtained with these tools to provide useful information to people with MS and their clinical team, to help guide shared clinical decisions, and likely accelerate and improve outcomes in clinical trials. So this is a very exciting new era in terms of clinical neurological assessment,” said Dr. Larochelle.
 

Granular gait analysis

Dr. Gudesblatt and colleagues analyzed retrospective data from 105 people with MS (69% female; average age, 53.7 years). Participants underwent all tests on the same day. The digital gait analysis captured velocity, double support, cadence, functional ambulation profile, gait variability index, and walk ratio over three trials conducted at preferred walking speed (PWS) and during dual task walking.

There were statistically significant relationships (P ≤ .01) between TUG and 25’TW (R² = 0.62). There were also significant relationships between 25’TW and digital parameters measured at PWS: velocity (R² = 0.63); double support (R² = 0.74); cadence (R² = 0.56); and gait variability index (R² = 0.54). During dual task walking, there were relationships between 25’TW and velocity (R² = 0.53); double support (R² = 0.30); cadence (R² = 0.43); and gait variability index (R² = 0.46).

TUG values were significantly associated with gait parameters during PWS: velocity (R² = 0.71); double support (R² = 0.75); cadence (R² = 0.43); gait variability index (R² = 0.45); and walk ratio (R² = 0.06). During dual task walking, TUG values were significantly associated with velocity (R² = 0.55), double support (R^{2 =} 0.21), cadence (R² = 0.45), and gait variability index (R² = 0.39).

“With the availability multiple effective disease modifying therapies and the future potential of restorative or reparative treatments, more granular, validated standardized outcome measures are urgently needed,” said Dr. Gudesblatt. Analysis of gait cycle can provide clinically useful information not adequately captured by the current, more traditional approaches of measuring outcomes in MS.

Dr. Gudesblatt and Dr. Larochelle have no relevant financial disclosures.