Early ileocecal resection is associated with better long-term outcomes compared with anti–tumor necrosis factor (TNF) therapy for patients with Crohn’s disease (CD), based on new real-world evidence.

These findings add weight to previously reported data from the LIR!C trial, suggesting that ileocecal resection should be considered a first-line treatment option for CD, reported principal investigator Kristine H. Allin, MD, PhD, of Aalborg University, Copenhagen.

“The LIR!C randomized clinical trial has demonstrated comparable quality of life with ileocecal resection and infliximab as a first-line treatment for limited, nonstricturing ileocecal CD at 1 year of follow-up, and improved outcomes with ileocecal resection on retrospective analysis of long-term follow-up data,” the investigators wrote in Gastroenterology. “However, in the real world, the long-term impact of early ileocecal resection for CD, compared with medical therapy, remains largely unexplored.”

To gather these real-world data, the investigators turned to the Danish National Patient Registry and the Danish National Prescription Registry, which included 1,279 individuals diagnosed with CD between 2003 and 2018 who received anti-TNF therapy or underwent ileocecal resection within 1 year of diagnosis. Within this group, slightly less than half underwent ileocecal resection (45.4%) while the remainder (54.6%) received anti-TNF therapy.

The primary outcome was a composite of one or more events: perianal CD, CD-related surgery, systemic corticosteroid exposure, and CD-related hospitalization. Secondary analyses evaluated the relative risks of these same four events as independent entities.

Multifactor-adjusted Cox proportional hazards regression analysis revealed that patients who underwent ileocecal resection had a 33% lower risk of the composite outcome compared with those who received anti-TNF therapy (adjusted hazard ratio [aHR], 0.67; 95% CI, 0.54-0.83).

In the secondary analyses, which examined risks for each component of the composite outcome, the surgery group had a significantly lower risk of CD-related surgery (aHR, 0.56; 95% CI, 0.39-0.80) and corticosteroid exposure (aHR, 0.71; 95% CI, 0.54-0.92), but not perianal CD or CD-related hospitalization.

After 5 years, half of the patients (49.7%) who underwent ileocecal resection were not receiving any treatment for CD. At the same timepoint, a slightly lower percentage of this group (46.3%) had started immunomodulator therapy, while 16.8% started anti-TNF therapy. Just 1.8% of these patients required a second intestinal resection.

Icahn School of Medicine at Mount Sinai

“To our knowledge, these are the first real-world data in a population-based cohort with long-term follow-up of early ileocecal resection compared with anti-TNF therapy for newly diagnosed ileal and ileocecal CD,” the investigators wrote. “These data suggest that ileocecal resection may have a role as first-line therapy in Crohn’s disease management and challenge the current paradigm of reserving surgery for complicated Crohn’s disease refractory or intolerant to medications.”

Corresponding author Manasi Agrawal, MD, of Icahn School of Medicine at Mount Sinai, New York, suggested that “validation of our findings in external cohorts [is needed], and understanding of factors associated with improved outcomes following ileocecal resection.”

For clinicians and patients choosing between first-line anti-TNF therapy versus ileocecal resection using currently available evidence, Dr. Agrawal suggested that a variety of factors need to be considered, including disease location, extent of terminal ileum involved, presence of complications such as stricture, fistula, comorbid conditions, access to biologics, financial considerations, and patient preferences.

Cleveland Clinic

Benjamin Cohen, MD, staff physician and co-section head and clinical director for inflammatory bowel diseases in the department of gastroenterology, hepatology, and nutrition at Cleveland Clinic, called this “an important study” because it offers the first real-world evidence to support the findings from the LIR!C trial.

Dr. Cohen agreed with Dr. Agrawal that more work is needed to determine which patients benefit most from early ileocecal resection, although he suggested that known risk factors for worse outcomes — such as early age at diagnosis, penetrating features of disease, or perianal disease — may increase strength of surgical candidacy.

Still, based on the “fairly strong” body of data now available, he suggested that all patients should be educated about first-line ileocecal resection, as it is “reasonable” approach.

“It’s always important to present surgery as a treatment option,” Dr. Cohen said in an interview. “We don’t want to think of surgery as a last resort, or a failure, because that really colors it in a negative light, and then that ultimately impacts patients’ quality of life, and their perception of outcomes.”

The study was supported by the Danish National Research Foundation. The investigators disclosed no conflicts of interest. Dr. Cohen disclosed consulting and speaking honoraria from AbbVie.

Early ileocecal resection is associated with better long-term outcomes compared with anti–tumor necrosis factor (TNF) therapy for patients with Crohn’s disease (CD), based on new real-world evidence.

These findings add weight to previously reported data from the LIR!C trial, suggesting that ileocecal resection should be considered a first-line treatment option for CD, reported principal investigator Kristine H. Allin, MD, PhD, of Aalborg University, Copenhagen.

“The LIR!C randomized clinical trial has demonstrated comparable quality of life with ileocecal resection and infliximab as a first-line treatment for limited, nonstricturing ileocecal CD at 1 year of follow-up, and improved outcomes with ileocecal resection on retrospective analysis of long-term follow-up data,” the investigators wrote in Gastroenterology. “However, in the real world, the long-term impact of early ileocecal resection for CD, compared with medical therapy, remains largely unexplored.”

To gather these real-world data, the investigators turned to the Danish National Patient Registry and the Danish National Prescription Registry, which included 1,279 individuals diagnosed with CD between 2003 and 2018 who received anti-TNF therapy or underwent ileocecal resection within 1 year of diagnosis. Within this group, slightly less than half underwent ileocecal resection (45.4%) while the remainder (54.6%) received anti-TNF therapy.

The primary outcome was a composite of one or more events: perianal CD, CD-related surgery, systemic corticosteroid exposure, and CD-related hospitalization. Secondary analyses evaluated the relative risks of these same four events as independent entities.

Multifactor-adjusted Cox proportional hazards regression analysis revealed that patients who underwent ileocecal resection had a 33% lower risk of the composite outcome compared with those who received anti-TNF therapy (adjusted hazard ratio [aHR], 0.67; 95% CI, 0.54-0.83).

In the secondary analyses, which examined risks for each component of the composite outcome, the surgery group had a significantly lower risk of CD-related surgery (aHR, 0.56; 95% CI, 0.39-0.80) and corticosteroid exposure (aHR, 0.71; 95% CI, 0.54-0.92), but not perianal CD or CD-related hospitalization.

After 5 years, half of the patients (49.7%) who underwent ileocecal resection were not receiving any treatment for CD. At the same timepoint, a slightly lower percentage of this group (46.3%) had started immunomodulator therapy, while 16.8% started anti-TNF therapy. Just 1.8% of these patients required a second intestinal resection.

Icahn School of Medicine at Mount Sinai

“To our knowledge, these are the first real-world data in a population-based cohort with long-term follow-up of early ileocecal resection compared with anti-TNF therapy for newly diagnosed ileal and ileocecal CD,” the investigators wrote. “These data suggest that ileocecal resection may have a role as first-line therapy in Crohn’s disease management and challenge the current paradigm of reserving surgery for complicated Crohn’s disease refractory or intolerant to medications.”

Corresponding author Manasi Agrawal, MD, of Icahn School of Medicine at Mount Sinai, New York, suggested that “validation of our findings in external cohorts [is needed], and understanding of factors associated with improved outcomes following ileocecal resection.”

For clinicians and patients choosing between first-line anti-TNF therapy versus ileocecal resection using currently available evidence, Dr. Agrawal suggested that a variety of factors need to be considered, including disease location, extent of terminal ileum involved, presence of complications such as stricture, fistula, comorbid conditions, access to biologics, financial considerations, and patient preferences.

Cleveland Clinic

Benjamin Cohen, MD, staff physician and co-section head and clinical director for inflammatory bowel diseases in the department of gastroenterology, hepatology, and nutrition at Cleveland Clinic, called this “an important study” because it offers the first real-world evidence to support the findings from the LIR!C trial.

Dr. Cohen agreed with Dr. Agrawal that more work is needed to determine which patients benefit most from early ileocecal resection, although he suggested that known risk factors for worse outcomes — such as early age at diagnosis, penetrating features of disease, or perianal disease — may increase strength of surgical candidacy.

Still, based on the “fairly strong” body of data now available, he suggested that all patients should be educated about first-line ileocecal resection, as it is “reasonable” approach.

“It’s always important to present surgery as a treatment option,” Dr. Cohen said in an interview. “We don’t want to think of surgery as a last resort, or a failure, because that really colors it in a negative light, and then that ultimately impacts patients’ quality of life, and their perception of outcomes.”

The study was supported by the Danish National Research Foundation. The investigators disclosed no conflicts of interest. Dr. Cohen disclosed consulting and speaking honoraria from AbbVie.

Early ileocecal resection is associated with better long-term outcomes compared with anti–tumor necrosis factor (TNF) therapy for patients with Crohn’s disease (CD), based on new real-world evidence.

These findings add weight to previously reported data from the LIR!C trial, suggesting that ileocecal resection should be considered a first-line treatment option for CD, reported principal investigator Kristine H. Allin, MD, PhD, of Aalborg University, Copenhagen.

“The LIR!C randomized clinical trial has demonstrated comparable quality of life with ileocecal resection and infliximab as a first-line treatment for limited, nonstricturing ileocecal CD at 1 year of follow-up, and improved outcomes with ileocecal resection on retrospective analysis of long-term follow-up data,” the investigators wrote in Gastroenterology. “However, in the real world, the long-term impact of early ileocecal resection for CD, compared with medical therapy, remains largely unexplored.”

To gather these real-world data, the investigators turned to the Danish National Patient Registry and the Danish National Prescription Registry, which included 1,279 individuals diagnosed with CD between 2003 and 2018 who received anti-TNF therapy or underwent ileocecal resection within 1 year of diagnosis. Within this group, slightly less than half underwent ileocecal resection (45.4%) while the remainder (54.6%) received anti-TNF therapy.

The primary outcome was a composite of one or more events: perianal CD, CD-related surgery, systemic corticosteroid exposure, and CD-related hospitalization. Secondary analyses evaluated the relative risks of these same four events as independent entities.

Multifactor-adjusted Cox proportional hazards regression analysis revealed that patients who underwent ileocecal resection had a 33% lower risk of the composite outcome compared with those who received anti-TNF therapy (adjusted hazard ratio [aHR], 0.67; 95% CI, 0.54-0.83).

In the secondary analyses, which examined risks for each component of the composite outcome, the surgery group had a significantly lower risk of CD-related surgery (aHR, 0.56; 95% CI, 0.39-0.80) and corticosteroid exposure (aHR, 0.71; 95% CI, 0.54-0.92), but not perianal CD or CD-related hospitalization.

After 5 years, half of the patients (49.7%) who underwent ileocecal resection were not receiving any treatment for CD. At the same timepoint, a slightly lower percentage of this group (46.3%) had started immunomodulator therapy, while 16.8% started anti-TNF therapy. Just 1.8% of these patients required a second intestinal resection.

Icahn School of Medicine at Mount Sinai

“To our knowledge, these are the first real-world data in a population-based cohort with long-term follow-up of early ileocecal resection compared with anti-TNF therapy for newly diagnosed ileal and ileocecal CD,” the investigators wrote. “These data suggest that ileocecal resection may have a role as first-line therapy in Crohn’s disease management and challenge the current paradigm of reserving surgery for complicated Crohn’s disease refractory or intolerant to medications.”

Corresponding author Manasi Agrawal, MD, of Icahn School of Medicine at Mount Sinai, New York, suggested that “validation of our findings in external cohorts [is needed], and understanding of factors associated with improved outcomes following ileocecal resection.”

For clinicians and patients choosing between first-line anti-TNF therapy versus ileocecal resection using currently available evidence, Dr. Agrawal suggested that a variety of factors need to be considered, including disease location, extent of terminal ileum involved, presence of complications such as stricture, fistula, comorbid conditions, access to biologics, financial considerations, and patient preferences.

Cleveland Clinic

Benjamin Cohen, MD, staff physician and co-section head and clinical director for inflammatory bowel diseases in the department of gastroenterology, hepatology, and nutrition at Cleveland Clinic, called this “an important study” because it offers the first real-world evidence to support the findings from the LIR!C trial.

Dr. Cohen agreed with Dr. Agrawal that more work is needed to determine which patients benefit most from early ileocecal resection, although he suggested that known risk factors for worse outcomes — such as early age at diagnosis, penetrating features of disease, or perianal disease — may increase strength of surgical candidacy.

Still, based on the “fairly strong” body of data now available, he suggested that all patients should be educated about first-line ileocecal resection, as it is “reasonable” approach.

“It’s always important to present surgery as a treatment option,” Dr. Cohen said in an interview. “We don’t want to think of surgery as a last resort, or a failure, because that really colors it in a negative light, and then that ultimately impacts patients’ quality of life, and their perception of outcomes.”

The study was supported by the Danish National Research Foundation. The investigators disclosed no conflicts of interest. Dr. Cohen disclosed consulting and speaking honoraria from AbbVie.

ORLANDO — Sleep disorders in people with epilepsy are linked to a significantly higher risk for sudden unexplained death in epilepsy (SUDEP) and all-cause mortality, new research shows.

SUDEP is a major concern for patients with epilepsy, said study investigator Marion Lazaj, MSc, Center for Neuroscience Studies, Queen’s University, Kingston, Ontario, Canada, but she believes that SUDEP risk assessment is overly focused on seizure control.

“We want to push the idea that this mortality risk assessment needs to be widened to include sleep factors, and not just sleep disorders but even sleep disturbances,” said Ms. Lazaj.

She also believes physicians should routinely discuss SUDEP with their patients with epilepsy. Given that the incidence of SUDEP is only about 1%, many clinicians don’t want to unduly frighten their patients, she added.

The findings were presented at the annual meeting of the American Epilepsy Society (AES).

The retrospective study included chart data from 1,506 consecutive patients diagnosed with epilepsy at a single center over 4 years. The mean age of participants was about 37 years but there was a large age range, said Ms. Lazaj.

The cohort was divided into two groups. Group 1 included 1130 patients without a comorbid sleep disorder, and Group 2 had 376 patients with a primary comorbid sleep disorder, mostly obstructive sleep apnea (OSA) but also restless leg syndrome or insomnia.

They gathered demographic information including age, sex, employment status, education, and epilepsy-related data such as epilepsy type, duration, the number of anti-seizure medications and relevant information from hospital and emergency room (ER) records.
 

SUDEP Inventory

Researchers assessed SUDEP risk using the revised SUDEP-7 risk inventory. The first four items on this inventory focus on generalized tonic clonic seizure activity and occurrence while others assess the number of antiseizure medicines, epilepsy duration, and the presence of other developmental delays.

Investigators then stratified patients into high risk (score on the SUDEP-7 of 5 or greater) and low mortality risk (score less than 5).

Results showed a significant association between a high mortality risk and having a comorbid sleep disorder (P = .033). Researchers also looked at all-cause mortality, including drownings and suicides, and found a similar significant association (P = .026). There was also an association between high risk and accidents and trauma (P = .042).

The researchers had access to overnight diagnostic polysomnography data for a smaller group of patients. Here, they found decreased sleep efficiency (P =.0098), increased spontaneous arousal index (P = .034), and prolonged sleep onset latency (P = .0000052) were all significantly associated with high SUDEP risk.

From the polysomnographic data, researchers found high SUDEP risk was significantly associated with a diagnosis of OSA (P = .034).
 

Powerful Study

Commenting on the findings, Gordon F. Buchanan, MD, PhD, Beth L. Tross epilepsy associate professor, Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, said he was “very excited” by the research.

“That this study attempts to look through data in a retrospective way and see if there’s additional risk with having comorbid sleep disorders is really interesting and I think really powerful,” he said.

Sleep disorders “are potentially a really simple thing that we can screen for and test for,” he added. He also noted that additional research is needed to replicate the findings.

Dr. Buchanan acknowledged that the SUDEP-7 inventory is not a particularly good tool and said there is a need for a better means of assessment that includes sleep disorders and other factors like sleep states and circadian rhythm, which he said affect SUDEP risk.

Ms. Lazaj and Dr. Buchanan report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

ORLANDO — Sleep disorders in people with epilepsy are linked to a significantly higher risk for sudden unexplained death in epilepsy (SUDEP) and all-cause mortality, new research shows.

SUDEP is a major concern for patients with epilepsy, said study investigator Marion Lazaj, MSc, Center for Neuroscience Studies, Queen’s University, Kingston, Ontario, Canada, but she believes that SUDEP risk assessment is overly focused on seizure control.

“We want to push the idea that this mortality risk assessment needs to be widened to include sleep factors, and not just sleep disorders but even sleep disturbances,” said Ms. Lazaj.

She also believes physicians should routinely discuss SUDEP with their patients with epilepsy. Given that the incidence of SUDEP is only about 1%, many clinicians don’t want to unduly frighten their patients, she added.

The findings were presented at the annual meeting of the American Epilepsy Society (AES).

The retrospective study included chart data from 1,506 consecutive patients diagnosed with epilepsy at a single center over 4 years. The mean age of participants was about 37 years but there was a large age range, said Ms. Lazaj.

The cohort was divided into two groups. Group 1 included 1130 patients without a comorbid sleep disorder, and Group 2 had 376 patients with a primary comorbid sleep disorder, mostly obstructive sleep apnea (OSA) but also restless leg syndrome or insomnia.

They gathered demographic information including age, sex, employment status, education, and epilepsy-related data such as epilepsy type, duration, the number of anti-seizure medications and relevant information from hospital and emergency room (ER) records.
 

SUDEP Inventory

Researchers assessed SUDEP risk using the revised SUDEP-7 risk inventory. The first four items on this inventory focus on generalized tonic clonic seizure activity and occurrence while others assess the number of antiseizure medicines, epilepsy duration, and the presence of other developmental delays.

Investigators then stratified patients into high risk (score on the SUDEP-7 of 5 or greater) and low mortality risk (score less than 5).

Results showed a significant association between a high mortality risk and having a comorbid sleep disorder (P = .033). Researchers also looked at all-cause mortality, including drownings and suicides, and found a similar significant association (P = .026). There was also an association between high risk and accidents and trauma (P = .042).

The researchers had access to overnight diagnostic polysomnography data for a smaller group of patients. Here, they found decreased sleep efficiency (P =.0098), increased spontaneous arousal index (P = .034), and prolonged sleep onset latency (P = .0000052) were all significantly associated with high SUDEP risk.

From the polysomnographic data, researchers found high SUDEP risk was significantly associated with a diagnosis of OSA (P = .034).
 

Powerful Study

Commenting on the findings, Gordon F. Buchanan, MD, PhD, Beth L. Tross epilepsy associate professor, Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, said he was “very excited” by the research.

“That this study attempts to look through data in a retrospective way and see if there’s additional risk with having comorbid sleep disorders is really interesting and I think really powerful,” he said.

Sleep disorders “are potentially a really simple thing that we can screen for and test for,” he added. He also noted that additional research is needed to replicate the findings.

Dr. Buchanan acknowledged that the SUDEP-7 inventory is not a particularly good tool and said there is a need for a better means of assessment that includes sleep disorders and other factors like sleep states and circadian rhythm, which he said affect SUDEP risk.

Ms. Lazaj and Dr. Buchanan report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

ORLANDO — Sleep disorders in people with epilepsy are linked to a significantly higher risk for sudden unexplained death in epilepsy (SUDEP) and all-cause mortality, new research shows.

SUDEP is a major concern for patients with epilepsy, said study investigator Marion Lazaj, MSc, Center for Neuroscience Studies, Queen’s University, Kingston, Ontario, Canada, but she believes that SUDEP risk assessment is overly focused on seizure control.

“We want to push the idea that this mortality risk assessment needs to be widened to include sleep factors, and not just sleep disorders but even sleep disturbances,” said Ms. Lazaj.

She also believes physicians should routinely discuss SUDEP with their patients with epilepsy. Given that the incidence of SUDEP is only about 1%, many clinicians don’t want to unduly frighten their patients, she added.

The findings were presented at the annual meeting of the American Epilepsy Society (AES).

The retrospective study included chart data from 1,506 consecutive patients diagnosed with epilepsy at a single center over 4 years. The mean age of participants was about 37 years but there was a large age range, said Ms. Lazaj.

The cohort was divided into two groups. Group 1 included 1130 patients without a comorbid sleep disorder, and Group 2 had 376 patients with a primary comorbid sleep disorder, mostly obstructive sleep apnea (OSA) but also restless leg syndrome or insomnia.

They gathered demographic information including age, sex, employment status, education, and epilepsy-related data such as epilepsy type, duration, the number of anti-seizure medications and relevant information from hospital and emergency room (ER) records.
 

SUDEP Inventory

Researchers assessed SUDEP risk using the revised SUDEP-7 risk inventory. The first four items on this inventory focus on generalized tonic clonic seizure activity and occurrence while others assess the number of antiseizure medicines, epilepsy duration, and the presence of other developmental delays.

Investigators then stratified patients into high risk (score on the SUDEP-7 of 5 or greater) and low mortality risk (score less than 5).

Results showed a significant association between a high mortality risk and having a comorbid sleep disorder (P = .033). Researchers also looked at all-cause mortality, including drownings and suicides, and found a similar significant association (P = .026). There was also an association between high risk and accidents and trauma (P = .042).

The researchers had access to overnight diagnostic polysomnography data for a smaller group of patients. Here, they found decreased sleep efficiency (P =.0098), increased spontaneous arousal index (P = .034), and prolonged sleep onset latency (P = .0000052) were all significantly associated with high SUDEP risk.

From the polysomnographic data, researchers found high SUDEP risk was significantly associated with a diagnosis of OSA (P = .034).
 

Powerful Study

Commenting on the findings, Gordon F. Buchanan, MD, PhD, Beth L. Tross epilepsy associate professor, Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, said he was “very excited” by the research.

“That this study attempts to look through data in a retrospective way and see if there’s additional risk with having comorbid sleep disorders is really interesting and I think really powerful,” he said.

Sleep disorders “are potentially a really simple thing that we can screen for and test for,” he added. He also noted that additional research is needed to replicate the findings.

Dr. Buchanan acknowledged that the SUDEP-7 inventory is not a particularly good tool and said there is a need for a better means of assessment that includes sleep disorders and other factors like sleep states and circadian rhythm, which he said affect SUDEP risk.

Ms. Lazaj and Dr. Buchanan report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

TOPLINE: 

Compared with a healthy omnivore diet, a healthy vegan diet led to significant improvement in  low-density lipoprotein cholesterol (LDL-C) as well as fasting insulin and weight loss in a randomized controlled trial of identical twins. 

METHODOLOGY:  

• Researchers randomly assigned 22 pairs of healthy adult identical twins (34 women, mean age 39 years, mean body mass index 25.9) to a healthy vegan or omnivore diet (1 twin per pair) for 8 weeks.
• For the first 4 weeks, diet-specific meals were provided via a meal delivery service. For the final 4 weeks, participants prepared their own diet-appropriate meals/snacks.
• The primary outcome was change in LDL-C; secondary outcomes included changes in body weight and fasting insulin. 

TAKEAWAY:

• After 8 weeks, twins eating a vegan diet showed a significant mean decrease of 13.9 mg/dL in LDL-C compared with twins eating an omnivorous diet.
• The vegan diet also led to a significant mean decrease of 2.9 Times New RomanμIU/mL in fasting insulin and 1.9 kg in body weight after 8 weeks compared with the omnivore diet, although weight loss was observed in both diet groups. 
• The vegan diet group also had a larger but nonsignificant absolute median decrease in fasting HDL-C  triglycerides , vitamin B12, glucose, and trimethylamine N-oxide levels at 8 weeks.

IN PRACTICE: 

“Our results corroborate a previous finding showing that eating a vegan diet can improve cardiovascular health. Clinicians may consider recommending plant-based diets to reduce cardiometabolic risk factors, as well as aligning with environmental benefits,” the researchers concluded. 

SOURCE: 

The study, with first author Matthew J. Landry, PhD, RDN, Stanford Prevention Research Center, Stanford University School of Medicine, California, was published online November 30 in  JAMA Network Open. 

LIMITATIONS: 

The adult twin population was generally healthy and findings may not be generalizable to other populations. The sample size was small, and the duration of intervention was short and there was no follow-up period, which limits insights on stability and sustainability of the diets. 

DISCLOSURES: 

Funding was provided by the Vogt Foundation, and grants from Stanford University and the National Heart, Lung, and Blood Institute. Dr. Landry has no relevant disclosures. One author reported receiving funding from Beyond Meat outside of this study. 

A version of this article appeared on Medscape.com.

TOPLINE: 

Compared with a healthy omnivore diet, a healthy vegan diet led to significant improvement in  low-density lipoprotein cholesterol (LDL-C) as well as fasting insulin and weight loss in a randomized controlled trial of identical twins. 

METHODOLOGY:  

• Researchers randomly assigned 22 pairs of healthy adult identical twins (34 women, mean age 39 years, mean body mass index 25.9) to a healthy vegan or omnivore diet (1 twin per pair) for 8 weeks.
• For the first 4 weeks, diet-specific meals were provided via a meal delivery service. For the final 4 weeks, participants prepared their own diet-appropriate meals/snacks.
• The primary outcome was change in LDL-C; secondary outcomes included changes in body weight and fasting insulin. 

TAKEAWAY:

• After 8 weeks, twins eating a vegan diet showed a significant mean decrease of 13.9 mg/dL in LDL-C compared with twins eating an omnivorous diet.
• The vegan diet also led to a significant mean decrease of 2.9 Times New RomanμIU/mL in fasting insulin and 1.9 kg in body weight after 8 weeks compared with the omnivore diet, although weight loss was observed in both diet groups. 
• The vegan diet group also had a larger but nonsignificant absolute median decrease in fasting HDL-C  triglycerides , vitamin B12, glucose, and trimethylamine N-oxide levels at 8 weeks.

IN PRACTICE: 

“Our results corroborate a previous finding showing that eating a vegan diet can improve cardiovascular health. Clinicians may consider recommending plant-based diets to reduce cardiometabolic risk factors, as well as aligning with environmental benefits,” the researchers concluded. 

SOURCE: 

The study, with first author Matthew J. Landry, PhD, RDN, Stanford Prevention Research Center, Stanford University School of Medicine, California, was published online November 30 in  JAMA Network Open. 

LIMITATIONS: 

The adult twin population was generally healthy and findings may not be generalizable to other populations. The sample size was small, and the duration of intervention was short and there was no follow-up period, which limits insights on stability and sustainability of the diets. 

DISCLOSURES: 

Funding was provided by the Vogt Foundation, and grants from Stanford University and the National Heart, Lung, and Blood Institute. Dr. Landry has no relevant disclosures. One author reported receiving funding from Beyond Meat outside of this study. 

A version of this article appeared on Medscape.com.

TOPLINE: 

Compared with a healthy omnivore diet, a healthy vegan diet led to significant improvement in  low-density lipoprotein cholesterol (LDL-C) as well as fasting insulin and weight loss in a randomized controlled trial of identical twins. 

METHODOLOGY:  

• Researchers randomly assigned 22 pairs of healthy adult identical twins (34 women, mean age 39 years, mean body mass index 25.9) to a healthy vegan or omnivore diet (1 twin per pair) for 8 weeks.
• For the first 4 weeks, diet-specific meals were provided via a meal delivery service. For the final 4 weeks, participants prepared their own diet-appropriate meals/snacks.
• The primary outcome was change in LDL-C; secondary outcomes included changes in body weight and fasting insulin. 

TAKEAWAY:

• After 8 weeks, twins eating a vegan diet showed a significant mean decrease of 13.9 mg/dL in LDL-C compared with twins eating an omnivorous diet.
• The vegan diet also led to a significant mean decrease of 2.9 Times New RomanμIU/mL in fasting insulin and 1.9 kg in body weight after 8 weeks compared with the omnivore diet, although weight loss was observed in both diet groups. 
• The vegan diet group also had a larger but nonsignificant absolute median decrease in fasting HDL-C  triglycerides , vitamin B12, glucose, and trimethylamine N-oxide levels at 8 weeks.

IN PRACTICE: 

“Our results corroborate a previous finding showing that eating a vegan diet can improve cardiovascular health. Clinicians may consider recommending plant-based diets to reduce cardiometabolic risk factors, as well as aligning with environmental benefits,” the researchers concluded. 

SOURCE: 

The study, with first author Matthew J. Landry, PhD, RDN, Stanford Prevention Research Center, Stanford University School of Medicine, California, was published online November 30 in  JAMA Network Open. 

LIMITATIONS: 

The adult twin population was generally healthy and findings may not be generalizable to other populations. The sample size was small, and the duration of intervention was short and there was no follow-up period, which limits insights on stability and sustainability of the diets. 

DISCLOSURES: 

Funding was provided by the Vogt Foundation, and grants from Stanford University and the National Heart, Lung, and Blood Institute. Dr. Landry has no relevant disclosures. One author reported receiving funding from Beyond Meat outside of this study. 

A version of this article appeared on Medscape.com.

A new risk model for nonalcoholic fatty liver disease (NAFLD) could offer a simpler and more accurate way of predicting advanced fibrosis in first-degree relatives, according to investigators.

By leveraging basic clinical factors instead of more advanced diagnostic findings, the NAFLD Familial Risk Score is more scalable than existing strategies for identifying advanced fibrosis, reported lead author Rohit Loomba, MD, of the University of California San Diego, La Jolla, and colleagues.

“[G]iven the enormous global burden of NAFLD, it is not possible to perform an imaging-based fibrosis assessment on all individuals with NAFLD,” the investigators wrote in Clinical Gastroenterology and Hepatology. “The ability to identify individuals at risk for advanced fibrosis using routine clinical history taking is a major unmet need in clinical practice.”

To this end, the investigators conducted a prospective, cross-sectional, familial study that comprised 242 consecutive probands and 396 first-degree relatives. All participants underwent liver fibrosis evaluation, most with magnetic resonance elastography.

Dr. Loomba and colleagues first developed the risk model by analyzing data from a derivation cohort of 220 individuals in San Diego, among whom 92 were first-degree relatives of probands without advanced fibrosis and 128 were first-degree relatives of probands with NAFLD and advanced fibrosis.

Their analysis identified the following four risk factors for advanced fibrosis: age of 50 years or more, presence of type 2 diabetes mellitus, obesity, and family history of NAFLD with advanced fibrosis. These variables were used to construct the NAFLD Familial Risk Score, with age and diabetes each accounting for one point, and obesity and family history contributing two points each, for a possible total of six points.

Within the derivation cohort, this scoring system demonstrated an area under the receiver operating characteristic curve (AUROC) of 0.85 (95% CI, 0.76-0.92), suggesting high accuracy for identifying advanced fibrosis.

When applied to a validation cohort of 176 individuals in Finland, the AUROC was higher still, at 0.94 (95% CI, 0.89-0.99). For comparison, in the same group, the FIB-4 index had a significantly lower AUROC of 0.70 (P = .02).

“The NAFLD Familial Risk Score potentially can be used by family members who are aware of the diagnosis of advanced fibrosis in the proband,” the investigators wrote. “Information on how to calculate and interpret the score can be conveyed to first-degree relatives by the proband, or by medical staff to first-degree relatives who accompany the proband to medical appointments. First-degree relatives with a score of four points or more (corresponding to 13% risk of NAFLD with advanced fibrosis) may consider undergoing an imaging-based fibrosis assessment.”

Dr. Loomba and colleagues highlighted the simplicity of their scoring system, which does not require a calculator or any information more complex than a basic clinical history.

“It may be a helpful alternative to FIB-4 for identifying NAFLD with advanced fibrosis among first-degree relatives in clinical practice because it does not require laboratory tests,” they wrote, noting that this, along with the other comparative advantages of the new risk score, “may have implications for surveillance in NAFLD.”

The study was supported by the National Center for Advancing Translational Sciences, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung, and Blood Institute, and others. The investigators disclosed relationships with Aardvark Therapeutics, Altimmune, Anylam/Regeneron, and others.

A new risk model for nonalcoholic fatty liver disease (NAFLD) could offer a simpler and more accurate way of predicting advanced fibrosis in first-degree relatives, according to investigators.

By leveraging basic clinical factors instead of more advanced diagnostic findings, the NAFLD Familial Risk Score is more scalable than existing strategies for identifying advanced fibrosis, reported lead author Rohit Loomba, MD, of the University of California San Diego, La Jolla, and colleagues.

“[G]iven the enormous global burden of NAFLD, it is not possible to perform an imaging-based fibrosis assessment on all individuals with NAFLD,” the investigators wrote in Clinical Gastroenterology and Hepatology. “The ability to identify individuals at risk for advanced fibrosis using routine clinical history taking is a major unmet need in clinical practice.”

To this end, the investigators conducted a prospective, cross-sectional, familial study that comprised 242 consecutive probands and 396 first-degree relatives. All participants underwent liver fibrosis evaluation, most with magnetic resonance elastography.

Dr. Loomba and colleagues first developed the risk model by analyzing data from a derivation cohort of 220 individuals in San Diego, among whom 92 were first-degree relatives of probands without advanced fibrosis and 128 were first-degree relatives of probands with NAFLD and advanced fibrosis.

Their analysis identified the following four risk factors for advanced fibrosis: age of 50 years or more, presence of type 2 diabetes mellitus, obesity, and family history of NAFLD with advanced fibrosis. These variables were used to construct the NAFLD Familial Risk Score, with age and diabetes each accounting for one point, and obesity and family history contributing two points each, for a possible total of six points.

Within the derivation cohort, this scoring system demonstrated an area under the receiver operating characteristic curve (AUROC) of 0.85 (95% CI, 0.76-0.92), suggesting high accuracy for identifying advanced fibrosis.

When applied to a validation cohort of 176 individuals in Finland, the AUROC was higher still, at 0.94 (95% CI, 0.89-0.99). For comparison, in the same group, the FIB-4 index had a significantly lower AUROC of 0.70 (P = .02).

“The NAFLD Familial Risk Score potentially can be used by family members who are aware of the diagnosis of advanced fibrosis in the proband,” the investigators wrote. “Information on how to calculate and interpret the score can be conveyed to first-degree relatives by the proband, or by medical staff to first-degree relatives who accompany the proband to medical appointments. First-degree relatives with a score of four points or more (corresponding to 13% risk of NAFLD with advanced fibrosis) may consider undergoing an imaging-based fibrosis assessment.”

Dr. Loomba and colleagues highlighted the simplicity of their scoring system, which does not require a calculator or any information more complex than a basic clinical history.

“It may be a helpful alternative to FIB-4 for identifying NAFLD with advanced fibrosis among first-degree relatives in clinical practice because it does not require laboratory tests,” they wrote, noting that this, along with the other comparative advantages of the new risk score, “may have implications for surveillance in NAFLD.”

The study was supported by the National Center for Advancing Translational Sciences, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung, and Blood Institute, and others. The investigators disclosed relationships with Aardvark Therapeutics, Altimmune, Anylam/Regeneron, and others.

A new risk model for nonalcoholic fatty liver disease (NAFLD) could offer a simpler and more accurate way of predicting advanced fibrosis in first-degree relatives, according to investigators.

By leveraging basic clinical factors instead of more advanced diagnostic findings, the NAFLD Familial Risk Score is more scalable than existing strategies for identifying advanced fibrosis, reported lead author Rohit Loomba, MD, of the University of California San Diego, La Jolla, and colleagues.

“[G]iven the enormous global burden of NAFLD, it is not possible to perform an imaging-based fibrosis assessment on all individuals with NAFLD,” the investigators wrote in Clinical Gastroenterology and Hepatology. “The ability to identify individuals at risk for advanced fibrosis using routine clinical history taking is a major unmet need in clinical practice.”

To this end, the investigators conducted a prospective, cross-sectional, familial study that comprised 242 consecutive probands and 396 first-degree relatives. All participants underwent liver fibrosis evaluation, most with magnetic resonance elastography.

Dr. Loomba and colleagues first developed the risk model by analyzing data from a derivation cohort of 220 individuals in San Diego, among whom 92 were first-degree relatives of probands without advanced fibrosis and 128 were first-degree relatives of probands with NAFLD and advanced fibrosis.

Their analysis identified the following four risk factors for advanced fibrosis: age of 50 years or more, presence of type 2 diabetes mellitus, obesity, and family history of NAFLD with advanced fibrosis. These variables were used to construct the NAFLD Familial Risk Score, with age and diabetes each accounting for one point, and obesity and family history contributing two points each, for a possible total of six points.

Within the derivation cohort, this scoring system demonstrated an area under the receiver operating characteristic curve (AUROC) of 0.85 (95% CI, 0.76-0.92), suggesting high accuracy for identifying advanced fibrosis.

When applied to a validation cohort of 176 individuals in Finland, the AUROC was higher still, at 0.94 (95% CI, 0.89-0.99). For comparison, in the same group, the FIB-4 index had a significantly lower AUROC of 0.70 (P = .02).

“The NAFLD Familial Risk Score potentially can be used by family members who are aware of the diagnosis of advanced fibrosis in the proband,” the investigators wrote. “Information on how to calculate and interpret the score can be conveyed to first-degree relatives by the proband, or by medical staff to first-degree relatives who accompany the proband to medical appointments. First-degree relatives with a score of four points or more (corresponding to 13% risk of NAFLD with advanced fibrosis) may consider undergoing an imaging-based fibrosis assessment.”

Dr. Loomba and colleagues highlighted the simplicity of their scoring system, which does not require a calculator or any information more complex than a basic clinical history.

“It may be a helpful alternative to FIB-4 for identifying NAFLD with advanced fibrosis among first-degree relatives in clinical practice because it does not require laboratory tests,” they wrote, noting that this, along with the other comparative advantages of the new risk score, “may have implications for surveillance in NAFLD.”

The study was supported by the National Center for Advancing Translational Sciences, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung, and Blood Institute, and others. The investigators disclosed relationships with Aardvark Therapeutics, Altimmune, Anylam/Regeneron, and others.

The US Food and Drug Administration (FDA) has approved iptacopan (Fabhalta, Novartis), the first oral monotherapy for both treatment-naive and pretreated adults with paroxysmal nocturnal hemoglobinuria (PNH).

Iptacopan, a factor B inhibitor, offers “superior hemoglobin improvement in the absence of transfusions” in patients with this rare chronic blood disorder, according to a Novartis press release.

“An efficacious oral treatment with a demonstrated safety profile could be practice-changing for physicians and help relieve burdens experienced by people with PNH,” Vinod Pullarkat, MD, of City of Hope Cancer Center, Duarte, California, said in the company press release.

Previously, the only approved treatments for PNH were injectable C5 complement inhibitors.

The latest approval was based on the randomized, open-label, phase 3 APPLY-PNH trial in 97 adults with PNH and anemia and was supported by safety and efficacy findings from the phase 3, single-arm APPOINT-PNH study in 40 C5 complement inhibitor–naive patients.

APPLY-PNH participants included adults with residual anemia receiving a stable regimen of anti-C5 treatment in the prior 6 months. Patients were randomly assigned to switch to 200 mg of iptacopan (n = 62) given twice daily or to remain on the anti-C5 therapy (n = 35).

The investigators reported greater increases in hemoglobin levels in patients who switched to iptacopan, with sustained increases ≥ 2 g/dL in 82.3% compared with 0% of patients who did not switch. Investigators also observed increases ≥ 12 g/dL in 67.7% of patients who switched vs 0% of those who did not. Almost all patients (95.2%) in the iptacopan group avoided a red blood cell transfusion vs 45.7% among patients who did not switch.

In the APPLY-PNH trial, common adverse reactions with iptacopan vs anti-C5 therapy included headache(19% vs 3%), nasopharyngitis (16% vs 17%), diarrhea (15% vs 6%), abdominal pain (15% vs 3%), bacterial infection(11% vs 11%), nausea (10% vs 3%), and viral infection(10% vs. 31%). Two patients experienced serious adverse events, which included pyelonephritis, urinary tract infection, and COVID-19.

In the APPOINT-PNH trial, the most common adverse events were headache (28%), viral infection (18%), nasopharyngitis (15%), and rash (10%). Serious adverse events, reported in two patients (5%), included COVID-19 and bacterial pneumonia.

“Fabhalta may cause serious infections caused by encapsulated bacteria and is available only through a Risk Evaluation and Mitigation Strategy (REMS) that requires vaccinations for encapsulated bacteria,” Novartis cautioned.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved iptacopan (Fabhalta, Novartis), the first oral monotherapy for both treatment-naive and pretreated adults with paroxysmal nocturnal hemoglobinuria (PNH).

Iptacopan, a factor B inhibitor, offers “superior hemoglobin improvement in the absence of transfusions” in patients with this rare chronic blood disorder, according to a Novartis press release.

“An efficacious oral treatment with a demonstrated safety profile could be practice-changing for physicians and help relieve burdens experienced by people with PNH,” Vinod Pullarkat, MD, of City of Hope Cancer Center, Duarte, California, said in the company press release.

Previously, the only approved treatments for PNH were injectable C5 complement inhibitors.

The latest approval was based on the randomized, open-label, phase 3 APPLY-PNH trial in 97 adults with PNH and anemia and was supported by safety and efficacy findings from the phase 3, single-arm APPOINT-PNH study in 40 C5 complement inhibitor–naive patients.

APPLY-PNH participants included adults with residual anemia receiving a stable regimen of anti-C5 treatment in the prior 6 months. Patients were randomly assigned to switch to 200 mg of iptacopan (n = 62) given twice daily or to remain on the anti-C5 therapy (n = 35).

The investigators reported greater increases in hemoglobin levels in patients who switched to iptacopan, with sustained increases ≥ 2 g/dL in 82.3% compared with 0% of patients who did not switch. Investigators also observed increases ≥ 12 g/dL in 67.7% of patients who switched vs 0% of those who did not. Almost all patients (95.2%) in the iptacopan group avoided a red blood cell transfusion vs 45.7% among patients who did not switch.

In the APPLY-PNH trial, common adverse reactions with iptacopan vs anti-C5 therapy included headache(19% vs 3%), nasopharyngitis (16% vs 17%), diarrhea (15% vs 6%), abdominal pain (15% vs 3%), bacterial infection(11% vs 11%), nausea (10% vs 3%), and viral infection(10% vs. 31%). Two patients experienced serious adverse events, which included pyelonephritis, urinary tract infection, and COVID-19.

In the APPOINT-PNH trial, the most common adverse events were headache (28%), viral infection (18%), nasopharyngitis (15%), and rash (10%). Serious adverse events, reported in two patients (5%), included COVID-19 and bacterial pneumonia.

“Fabhalta may cause serious infections caused by encapsulated bacteria and is available only through a Risk Evaluation and Mitigation Strategy (REMS) that requires vaccinations for encapsulated bacteria,” Novartis cautioned.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved iptacopan (Fabhalta, Novartis), the first oral monotherapy for both treatment-naive and pretreated adults with paroxysmal nocturnal hemoglobinuria (PNH).

Iptacopan, a factor B inhibitor, offers “superior hemoglobin improvement in the absence of transfusions” in patients with this rare chronic blood disorder, according to a Novartis press release.

“An efficacious oral treatment with a demonstrated safety profile could be practice-changing for physicians and help relieve burdens experienced by people with PNH,” Vinod Pullarkat, MD, of City of Hope Cancer Center, Duarte, California, said in the company press release.

Previously, the only approved treatments for PNH were injectable C5 complement inhibitors.

The latest approval was based on the randomized, open-label, phase 3 APPLY-PNH trial in 97 adults with PNH and anemia and was supported by safety and efficacy findings from the phase 3, single-arm APPOINT-PNH study in 40 C5 complement inhibitor–naive patients.

APPLY-PNH participants included adults with residual anemia receiving a stable regimen of anti-C5 treatment in the prior 6 months. Patients were randomly assigned to switch to 200 mg of iptacopan (n = 62) given twice daily or to remain on the anti-C5 therapy (n = 35).

The investigators reported greater increases in hemoglobin levels in patients who switched to iptacopan, with sustained increases ≥ 2 g/dL in 82.3% compared with 0% of patients who did not switch. Investigators also observed increases ≥ 12 g/dL in 67.7% of patients who switched vs 0% of those who did not. Almost all patients (95.2%) in the iptacopan group avoided a red blood cell transfusion vs 45.7% among patients who did not switch.

In the APPLY-PNH trial, common adverse reactions with iptacopan vs anti-C5 therapy included headache(19% vs 3%), nasopharyngitis (16% vs 17%), diarrhea (15% vs 6%), abdominal pain (15% vs 3%), bacterial infection(11% vs 11%), nausea (10% vs 3%), and viral infection(10% vs. 31%). Two patients experienced serious adverse events, which included pyelonephritis, urinary tract infection, and COVID-19.

In the APPOINT-PNH trial, the most common adverse events were headache (28%), viral infection (18%), nasopharyngitis (15%), and rash (10%). Serious adverse events, reported in two patients (5%), included COVID-19 and bacterial pneumonia.

“Fabhalta may cause serious infections caused by encapsulated bacteria and is available only through a Risk Evaluation and Mitigation Strategy (REMS) that requires vaccinations for encapsulated bacteria,” Novartis cautioned.

A version of this article appeared on Medscape.com.

PHILADELPHIA — Promise that the unmet need for more effective pulmonary artery hypertension treatments may soon be met was in strong evidence in research into three strategies presented at this year’s recent American Heart Association scientific sessions; one was based on an ancient Chinese herb epimedium (yin yang huo or horny goat weed) commonly used for treating sexual dysfunction and directly related to the phosphodiesterase inhibitors sildenafil, vardenafil, and tadalafil (sold as Viagra, Levitra, and Cialis). A second studied sotatercept, an investigational, potential first-in-class activin signaling inhibitor biologic, and a third evaluated physically ablating the baroreceptor nerves that stimulate vasoconstriction of the pulmonary artery via catheter-based techniques.

Until as recently as the late 1970s, a pulmonary arterial hypertension diagnosis was a uniformly fatal one.¹ While targeted therapies have since improved prognosis, pulmonary arterial hypertension remains a chronic and progressive disorder of the pulmonary vasculature with significant morbidity and mortality associated with pulmonary and right ventricle remodeling, and leads toward heart failure and death. The complex underlying pathogenesis was divided into six groups by the 6th World Symposium on Pulmonary Hypertension (WSPH) in 2018, and includes as its most common features pulmonary artery endothelial cell dysfunction, pulmonary artery smooth muscle cell proliferation and migration, and dysregulated fibroblast activity leading to dysregulated vasoconstriction, micro and in-situ vascular thrombosis, vascular fibrosis and pathogenic remodeling of pulmonary vessels.¹ The threshold mean arterial pressure (mPAP) for pulmonary arterial hypertension was defined by the 6th [WSPH] at mPAP ≥ 20 mm Hg, twice the upper limit of a normal mPAP of 14.0 ± 3.3 mm Hg as reported by Kovacs et al. in 2018.²

Pathways for current therapies

Current drugs for pulmonary arterial hypertension focus on three signaling pathways, including the endothelin receptor, prostacyclin and nitric oxide pathways, stated Zhi-Cheng Jing, MD, professor of medicine, head of the cardiology department at Peking Union Medical College Hospital, Peking, China. While the phosphodiesterase 5 inhibitors sildenafil and tadalafil, which target the nitric oxide pathway, came into wide use after Food and Drug Administration approval, the need for higher PDE5-selectivity remains, Dr. Jing said. Structurally modified from the active ingredient in epimedium, TPN171H is an investigational PDE5 inhibitor which has shown several favorable features: a greater PDE5 selectivity than both sildenafil and tadalafil in vitro, an ability to decrease right ventricular systolic pressure and alleviate arterial remodeling in animal studies, and safety and tolerability in healthy human subjects.

The current randomized, double-blind, placebo-and active-controlled phase IIa study assessed the hemodynamic impact of a single oral dose of TPN171H in 60 pulmonary arterial hypertension patients (mean age ~34 years, 83.3% female), all with negative vasodilation test results and in WHO class 2 or 3. Only patients aged 18-75 years with group 1 pulmonary arterial hypertension of idiopathic, connective tissue disorder, or repaired congenital heart defects etiology were included. Patients were divided into six groups: placebo, TPN171H at 2.5, 5, and 10 milligrams, and tadalafil at 20 and 40 milligrams.

For the primary endpoint of maximum decrease in pulmonary vascular resistance (PVR), significant reductions vs. placebo were found only for the TPN171H 5-mg group (–41.2% vs. –24.4%; P = .008) and for the 20-mg (–39.8%) and 40-mg (–37.6%) tadalafil groups (both P < .05). What was not seen in the tadalafil groups, but was evident in the TPN171H 5-mg group, was a significant reduction in the secondary endpoint of PVR/SVR (systolic vascular resistance) at 2, 3, and 5 hours (all P < .05). “As we know,” Dr. Jing said in an interview, “the PDE5 inhibitor functions as a vasodilator, having an impact on both pulmonary circulation and systemic circulation. So, to evaluate the  selectivity for pulmonary circulation is crucial when exploring a novel drug for pulmonary arterial hypertension. The change of PVR/SVR ratio from baseline is an indicator for selectivity for pulmonary circulation and implies that TPN171H has good PDE5 selectivity in the pulmonary vasculature,” Dr. Jing said.

TPN171H was well tolerated with no serious adverse effects (vomiting 10% and headache 10% were most common with no discontinuations).
 

TGF-signaling pathway

A meta-analysis of randomized controlled trials of sotatercept, an investigational fusion protein under priority FDA review that modulates the TGF-beta superfamily signaling pathway, looked at PVR, pulmonary arterial pressure (PAP), right arterial pressure (RAP) and N-terminal pro-brain natriuretic peptide (NT-proBNP). A literature search by corresponding author Vamsikalyan Borra, MD, Knapp Medical Center, Weslaco, Texas, and colleagues identified two trials (STELLAR and PULSAR) comprising 429 patients with pulmonary arterial hypertension. The experimental arms (sotatercept) had 237 patients (mean age ~49 years, ~82% female) and the placebo arm had 192 patients (mean age ~47 years, ~80% female).

A pooled analysis showed significant reductions with sotatercept in PVR (standardization mean difference [SMD] = –1.00, 95% confidence interval [CI] = –1.2, –.79, P < .001), PAP (SMD = –1.34, 95% CI = 1.6, –1.08, P < .001), RAP (SMD = –0.66, 95% CI = –0.93, –0.39, P < .001), and the levels of NT-proBNP (SMD = –0.64, 95% CI = –1.01, –0.27, P < .001) at 24 weeks from baseline. The sotatercept safety profile was favorable, with lower overall incidence of adverse events (84.8% vs. 87.5%) and fewer adverse events leading to death (0.4% vs. 3.1%) compared with placebo. Further investigation is needed, however, according to Dr. Borra, into the higher frequency of reported thrombocytopenia (71.7% vs. 20.8%) with sotatercept. “Our findings,” Dr. Borra said in a poster session, “suggest that sotatercept is an effective treatment option for pulmonary arterial hypertension, with the potential to improve both pulmonary and cardiac function.”
 

Denervation technique

Catheter-based ablation techniques, most commonly using thermal energy, target the afferent and efferent fibers of the baroreceptor reflex in the main pulmonary artery trunk and bifurcation involved in elevated pulmonary artery pressure. Mounica Vorla, MD, Carle Foundation Hospital, Urbana, Illinois, and colleagues conducted an updated systematic review and meta-analysis of the safety and efficacy of pulmonary artery denervation (PADN) for pulmonary arterial hypertension in seven clinical trials with 506 patients with moderate-severe pulmonary arterial hypertension conducted from 2013 to 2022.

Compared with placebo, PADN treatment was associated with a significant reduction in mean pulmonary artery pressure (weighted mean difference [WMD] = –6.9 mm Hg; 95% CI = –9.7, –4.1; P < .01; I2 = 61) and pulmonary vascular resistance (WMD = –3.2; 95% CI = –5.4, –0.9; P = .005). PADN improvements in cardiac output were also statistically significant (WMD = 0.3; 95% CI = 0.07, 0.6; P = .012), with numerical improvement in 6-minute walking distance (WMD = 67.7; 95% CI = –3.73, 139.2; P = .06) in the PADN group. Side effects were less common in the PADN group as compared with the placebo group, Dr. Vorla reported. She concluded, “This updated meta-analysis supports PADN as a safe and efficacious therapy for severe pulmonary arterial hypertension.” The authors noted limitations imposed by the small sample size, large data heterogeneity, and medium-quality literature. Larger randomized, controlled trials with clinical endpoints comparing PADN with optimal medical therapy are needed, they stated.
 

References

1. Shah AJ et al. New Drugs and Therapies in Pulmonary Arterial Hypertension. Int J Mol Sci. 2023 Mar 19;24(6):5850. doi: 10.3390/ijms24065850. PMID: 36982922; PMCID: PMC10058689.

2. Kovacs G et al. Pulmonary Vascular Involvement in Chronic Obstructive Pulmonary Disease. Is There a Pulmonary Vascular Phenotype? Am J Respir Crit Care Med. 2018 Oct 15;198(8):1000-11. doi: 10.1164/rccm.201801-0095PP. PMID: 29746142.

PHILADELPHIA — Promise that the unmet need for more effective pulmonary artery hypertension treatments may soon be met was in strong evidence in research into three strategies presented at this year’s recent American Heart Association scientific sessions; one was based on an ancient Chinese herb epimedium (yin yang huo or horny goat weed) commonly used for treating sexual dysfunction and directly related to the phosphodiesterase inhibitors sildenafil, vardenafil, and tadalafil (sold as Viagra, Levitra, and Cialis). A second studied sotatercept, an investigational, potential first-in-class activin signaling inhibitor biologic, and a third evaluated physically ablating the baroreceptor nerves that stimulate vasoconstriction of the pulmonary artery via catheter-based techniques.

Until as recently as the late 1970s, a pulmonary arterial hypertension diagnosis was a uniformly fatal one.¹ While targeted therapies have since improved prognosis, pulmonary arterial hypertension remains a chronic and progressive disorder of the pulmonary vasculature with significant morbidity and mortality associated with pulmonary and right ventricle remodeling, and leads toward heart failure and death. The complex underlying pathogenesis was divided into six groups by the 6th World Symposium on Pulmonary Hypertension (WSPH) in 2018, and includes as its most common features pulmonary artery endothelial cell dysfunction, pulmonary artery smooth muscle cell proliferation and migration, and dysregulated fibroblast activity leading to dysregulated vasoconstriction, micro and in-situ vascular thrombosis, vascular fibrosis and pathogenic remodeling of pulmonary vessels.¹ The threshold mean arterial pressure (mPAP) for pulmonary arterial hypertension was defined by the 6th [WSPH] at mPAP ≥ 20 mm Hg, twice the upper limit of a normal mPAP of 14.0 ± 3.3 mm Hg as reported by Kovacs et al. in 2018.²

Pathways for current therapies

Current drugs for pulmonary arterial hypertension focus on three signaling pathways, including the endothelin receptor, prostacyclin and nitric oxide pathways, stated Zhi-Cheng Jing, MD, professor of medicine, head of the cardiology department at Peking Union Medical College Hospital, Peking, China. While the phosphodiesterase 5 inhibitors sildenafil and tadalafil, which target the nitric oxide pathway, came into wide use after Food and Drug Administration approval, the need for higher PDE5-selectivity remains, Dr. Jing said. Structurally modified from the active ingredient in epimedium, TPN171H is an investigational PDE5 inhibitor which has shown several favorable features: a greater PDE5 selectivity than both sildenafil and tadalafil in vitro, an ability to decrease right ventricular systolic pressure and alleviate arterial remodeling in animal studies, and safety and tolerability in healthy human subjects.

The current randomized, double-blind, placebo-and active-controlled phase IIa study assessed the hemodynamic impact of a single oral dose of TPN171H in 60 pulmonary arterial hypertension patients (mean age ~34 years, 83.3% female), all with negative vasodilation test results and in WHO class 2 or 3. Only patients aged 18-75 years with group 1 pulmonary arterial hypertension of idiopathic, connective tissue disorder, or repaired congenital heart defects etiology were included. Patients were divided into six groups: placebo, TPN171H at 2.5, 5, and 10 milligrams, and tadalafil at 20 and 40 milligrams.

For the primary endpoint of maximum decrease in pulmonary vascular resistance (PVR), significant reductions vs. placebo were found only for the TPN171H 5-mg group (–41.2% vs. –24.4%; P = .008) and for the 20-mg (–39.8%) and 40-mg (–37.6%) tadalafil groups (both P < .05). What was not seen in the tadalafil groups, but was evident in the TPN171H 5-mg group, was a significant reduction in the secondary endpoint of PVR/SVR (systolic vascular resistance) at 2, 3, and 5 hours (all P < .05). “As we know,” Dr. Jing said in an interview, “the PDE5 inhibitor functions as a vasodilator, having an impact on both pulmonary circulation and systemic circulation. So, to evaluate the  selectivity for pulmonary circulation is crucial when exploring a novel drug for pulmonary arterial hypertension. The change of PVR/SVR ratio from baseline is an indicator for selectivity for pulmonary circulation and implies that TPN171H has good PDE5 selectivity in the pulmonary vasculature,” Dr. Jing said.

TPN171H was well tolerated with no serious adverse effects (vomiting 10% and headache 10% were most common with no discontinuations).
 

TGF-signaling pathway

A meta-analysis of randomized controlled trials of sotatercept, an investigational fusion protein under priority FDA review that modulates the TGF-beta superfamily signaling pathway, looked at PVR, pulmonary arterial pressure (PAP), right arterial pressure (RAP) and N-terminal pro-brain natriuretic peptide (NT-proBNP). A literature search by corresponding author Vamsikalyan Borra, MD, Knapp Medical Center, Weslaco, Texas, and colleagues identified two trials (STELLAR and PULSAR) comprising 429 patients with pulmonary arterial hypertension. The experimental arms (sotatercept) had 237 patients (mean age ~49 years, ~82% female) and the placebo arm had 192 patients (mean age ~47 years, ~80% female).

A pooled analysis showed significant reductions with sotatercept in PVR (standardization mean difference [SMD] = –1.00, 95% confidence interval [CI] = –1.2, –.79, P < .001), PAP (SMD = –1.34, 95% CI = 1.6, –1.08, P < .001), RAP (SMD = –0.66, 95% CI = –0.93, –0.39, P < .001), and the levels of NT-proBNP (SMD = –0.64, 95% CI = –1.01, –0.27, P < .001) at 24 weeks from baseline. The sotatercept safety profile was favorable, with lower overall incidence of adverse events (84.8% vs. 87.5%) and fewer adverse events leading to death (0.4% vs. 3.1%) compared with placebo. Further investigation is needed, however, according to Dr. Borra, into the higher frequency of reported thrombocytopenia (71.7% vs. 20.8%) with sotatercept. “Our findings,” Dr. Borra said in a poster session, “suggest that sotatercept is an effective treatment option for pulmonary arterial hypertension, with the potential to improve both pulmonary and cardiac function.”
 

Denervation technique

Catheter-based ablation techniques, most commonly using thermal energy, target the afferent and efferent fibers of the baroreceptor reflex in the main pulmonary artery trunk and bifurcation involved in elevated pulmonary artery pressure. Mounica Vorla, MD, Carle Foundation Hospital, Urbana, Illinois, and colleagues conducted an updated systematic review and meta-analysis of the safety and efficacy of pulmonary artery denervation (PADN) for pulmonary arterial hypertension in seven clinical trials with 506 patients with moderate-severe pulmonary arterial hypertension conducted from 2013 to 2022.

Compared with placebo, PADN treatment was associated with a significant reduction in mean pulmonary artery pressure (weighted mean difference [WMD] = –6.9 mm Hg; 95% CI = –9.7, –4.1; P < .01; I2 = 61) and pulmonary vascular resistance (WMD = –3.2; 95% CI = –5.4, –0.9; P = .005). PADN improvements in cardiac output were also statistically significant (WMD = 0.3; 95% CI = 0.07, 0.6; P = .012), with numerical improvement in 6-minute walking distance (WMD = 67.7; 95% CI = –3.73, 139.2; P = .06) in the PADN group. Side effects were less common in the PADN group as compared with the placebo group, Dr. Vorla reported. She concluded, “This updated meta-analysis supports PADN as a safe and efficacious therapy for severe pulmonary arterial hypertension.” The authors noted limitations imposed by the small sample size, large data heterogeneity, and medium-quality literature. Larger randomized, controlled trials with clinical endpoints comparing PADN with optimal medical therapy are needed, they stated.
 

References

1. Shah AJ et al. New Drugs and Therapies in Pulmonary Arterial Hypertension. Int J Mol Sci. 2023 Mar 19;24(6):5850. doi: 10.3390/ijms24065850. PMID: 36982922; PMCID: PMC10058689.

2. Kovacs G et al. Pulmonary Vascular Involvement in Chronic Obstructive Pulmonary Disease. Is There a Pulmonary Vascular Phenotype? Am J Respir Crit Care Med. 2018 Oct 15;198(8):1000-11. doi: 10.1164/rccm.201801-0095PP. PMID: 29746142.

PHILADELPHIA — Promise that the unmet need for more effective pulmonary artery hypertension treatments may soon be met was in strong evidence in research into three strategies presented at this year’s recent American Heart Association scientific sessions; one was based on an ancient Chinese herb epimedium (yin yang huo or horny goat weed) commonly used for treating sexual dysfunction and directly related to the phosphodiesterase inhibitors sildenafil, vardenafil, and tadalafil (sold as Viagra, Levitra, and Cialis). A second studied sotatercept, an investigational, potential first-in-class activin signaling inhibitor biologic, and a third evaluated physically ablating the baroreceptor nerves that stimulate vasoconstriction of the pulmonary artery via catheter-based techniques.

Until as recently as the late 1970s, a pulmonary arterial hypertension diagnosis was a uniformly fatal one.¹ While targeted therapies have since improved prognosis, pulmonary arterial hypertension remains a chronic and progressive disorder of the pulmonary vasculature with significant morbidity and mortality associated with pulmonary and right ventricle remodeling, and leads toward heart failure and death. The complex underlying pathogenesis was divided into six groups by the 6th World Symposium on Pulmonary Hypertension (WSPH) in 2018, and includes as its most common features pulmonary artery endothelial cell dysfunction, pulmonary artery smooth muscle cell proliferation and migration, and dysregulated fibroblast activity leading to dysregulated vasoconstriction, micro and in-situ vascular thrombosis, vascular fibrosis and pathogenic remodeling of pulmonary vessels.¹ The threshold mean arterial pressure (mPAP) for pulmonary arterial hypertension was defined by the 6th [WSPH] at mPAP ≥ 20 mm Hg, twice the upper limit of a normal mPAP of 14.0 ± 3.3 mm Hg as reported by Kovacs et al. in 2018.²

Pathways for current therapies

Current drugs for pulmonary arterial hypertension focus on three signaling pathways, including the endothelin receptor, prostacyclin and nitric oxide pathways, stated Zhi-Cheng Jing, MD, professor of medicine, head of the cardiology department at Peking Union Medical College Hospital, Peking, China. While the phosphodiesterase 5 inhibitors sildenafil and tadalafil, which target the nitric oxide pathway, came into wide use after Food and Drug Administration approval, the need for higher PDE5-selectivity remains, Dr. Jing said. Structurally modified from the active ingredient in epimedium, TPN171H is an investigational PDE5 inhibitor which has shown several favorable features: a greater PDE5 selectivity than both sildenafil and tadalafil in vitro, an ability to decrease right ventricular systolic pressure and alleviate arterial remodeling in animal studies, and safety and tolerability in healthy human subjects.

The current randomized, double-blind, placebo-and active-controlled phase IIa study assessed the hemodynamic impact of a single oral dose of TPN171H in 60 pulmonary arterial hypertension patients (mean age ~34 years, 83.3% female), all with negative vasodilation test results and in WHO class 2 or 3. Only patients aged 18-75 years with group 1 pulmonary arterial hypertension of idiopathic, connective tissue disorder, or repaired congenital heart defects etiology were included. Patients were divided into six groups: placebo, TPN171H at 2.5, 5, and 10 milligrams, and tadalafil at 20 and 40 milligrams.

For the primary endpoint of maximum decrease in pulmonary vascular resistance (PVR), significant reductions vs. placebo were found only for the TPN171H 5-mg group (–41.2% vs. –24.4%; P = .008) and for the 20-mg (–39.8%) and 40-mg (–37.6%) tadalafil groups (both P < .05). What was not seen in the tadalafil groups, but was evident in the TPN171H 5-mg group, was a significant reduction in the secondary endpoint of PVR/SVR (systolic vascular resistance) at 2, 3, and 5 hours (all P < .05). “As we know,” Dr. Jing said in an interview, “the PDE5 inhibitor functions as a vasodilator, having an impact on both pulmonary circulation and systemic circulation. So, to evaluate the  selectivity for pulmonary circulation is crucial when exploring a novel drug for pulmonary arterial hypertension. The change of PVR/SVR ratio from baseline is an indicator for selectivity for pulmonary circulation and implies that TPN171H has good PDE5 selectivity in the pulmonary vasculature,” Dr. Jing said.

TPN171H was well tolerated with no serious adverse effects (vomiting 10% and headache 10% were most common with no discontinuations).
 

TGF-signaling pathway

A meta-analysis of randomized controlled trials of sotatercept, an investigational fusion protein under priority FDA review that modulates the TGF-beta superfamily signaling pathway, looked at PVR, pulmonary arterial pressure (PAP), right arterial pressure (RAP) and N-terminal pro-brain natriuretic peptide (NT-proBNP). A literature search by corresponding author Vamsikalyan Borra, MD, Knapp Medical Center, Weslaco, Texas, and colleagues identified two trials (STELLAR and PULSAR) comprising 429 patients with pulmonary arterial hypertension. The experimental arms (sotatercept) had 237 patients (mean age ~49 years, ~82% female) and the placebo arm had 192 patients (mean age ~47 years, ~80% female).

A pooled analysis showed significant reductions with sotatercept in PVR (standardization mean difference [SMD] = –1.00, 95% confidence interval [CI] = –1.2, –.79, P < .001), PAP (SMD = –1.34, 95% CI = 1.6, –1.08, P < .001), RAP (SMD = –0.66, 95% CI = –0.93, –0.39, P < .001), and the levels of NT-proBNP (SMD = –0.64, 95% CI = –1.01, –0.27, P < .001) at 24 weeks from baseline. The sotatercept safety profile was favorable, with lower overall incidence of adverse events (84.8% vs. 87.5%) and fewer adverse events leading to death (0.4% vs. 3.1%) compared with placebo. Further investigation is needed, however, according to Dr. Borra, into the higher frequency of reported thrombocytopenia (71.7% vs. 20.8%) with sotatercept. “Our findings,” Dr. Borra said in a poster session, “suggest that sotatercept is an effective treatment option for pulmonary arterial hypertension, with the potential to improve both pulmonary and cardiac function.”
 

Denervation technique

Catheter-based ablation techniques, most commonly using thermal energy, target the afferent and efferent fibers of the baroreceptor reflex in the main pulmonary artery trunk and bifurcation involved in elevated pulmonary artery pressure. Mounica Vorla, MD, Carle Foundation Hospital, Urbana, Illinois, and colleagues conducted an updated systematic review and meta-analysis of the safety and efficacy of pulmonary artery denervation (PADN) for pulmonary arterial hypertension in seven clinical trials with 506 patients with moderate-severe pulmonary arterial hypertension conducted from 2013 to 2022.

Compared with placebo, PADN treatment was associated with a significant reduction in mean pulmonary artery pressure (weighted mean difference [WMD] = –6.9 mm Hg; 95% CI = –9.7, –4.1; P < .01; I2 = 61) and pulmonary vascular resistance (WMD = –3.2; 95% CI = –5.4, –0.9; P = .005). PADN improvements in cardiac output were also statistically significant (WMD = 0.3; 95% CI = 0.07, 0.6; P = .012), with numerical improvement in 6-minute walking distance (WMD = 67.7; 95% CI = –3.73, 139.2; P = .06) in the PADN group. Side effects were less common in the PADN group as compared with the placebo group, Dr. Vorla reported. She concluded, “This updated meta-analysis supports PADN as a safe and efficacious therapy for severe pulmonary arterial hypertension.” The authors noted limitations imposed by the small sample size, large data heterogeneity, and medium-quality literature. Larger randomized, controlled trials with clinical endpoints comparing PADN with optimal medical therapy are needed, they stated.
 

References

1. Shah AJ et al. New Drugs and Therapies in Pulmonary Arterial Hypertension. Int J Mol Sci. 2023 Mar 19;24(6):5850. doi: 10.3390/ijms24065850. PMID: 36982922; PMCID: PMC10058689.

2. Kovacs G et al. Pulmonary Vascular Involvement in Chronic Obstructive Pulmonary Disease. Is There a Pulmonary Vascular Phenotype? Am J Respir Crit Care Med. 2018 Oct 15;198(8):1000-11. doi: 10.1164/rccm.201801-0095PP. PMID: 29746142.

I don’t like EMR systems, with all their requirements, click boxes, endless cut & paste abuse, and 20-page notes that say nothing.

But I am a fan of what computers have brought to medical charts.

When I started out in 2000, I had no patients, hence no charts. I had the advantage of being able to start from scratch — there was nothing to convert to digital. So, from the beginning, that’s how I went. Back then, of course, everything came to the office as paper. It had to be scanned in, then named, then placed in the right computer file.

But it was still easier than amassing paper records. At that time I subleased from a doc who’d been in practice for 15 years. His charts were all paper. Charts were neatly filed on shelves, everything was initialed, hole-punched, and put in the right section (which involved pulling out other stuff and putting it back). A few times a year, his staff would comb through the charts in front, and anyone who hadn’t been seen in 2 years would have their chart moved to a storage room in the back. Once a year they’d pull the charts of anyone not seen in 7 years and a company would come in and shred those records.

After 23 years, I still have it all. The whole thing takes up a little over 50 gigabytes on a hard drive, which realistically is nothing these days. Electrons don’t take up much space.

The majority of the charts — those that are more than 7 years old — I’ll probably never need to access, but it still happens sometimes. People call in and say they’ve moved back to Phoenix, or need to see a neurologist again, or need the records for insurance reasons, or whatever. My staff is also spared from moving charts to a storage room, then to shredding. Since they don’t take up any physical space, it’s no effort to keep everything.

And they aren’t just at my office. They’re at home, on my phone, wherever I am. If I get called from an ER, I can pull them up quickly. If I travel, they’re with me. My memory is good, but not that good, and I’d rather be able to look things up than guess.

This, at least to me, is the advantage of computers. Their data storage and retrieval advantages far exceed that of paper. In my opinion EMRs, while well-intentioned, have taken these benefits and twisted them into something cumbersome, geared more to meet nonmedical requirements and billing purposes.

In the process they’ve lost sight of our age-old job of caring for patients.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I don’t like EMR systems, with all their requirements, click boxes, endless cut & paste abuse, and 20-page notes that say nothing.

But I am a fan of what computers have brought to medical charts.

When I started out in 2000, I had no patients, hence no charts. I had the advantage of being able to start from scratch — there was nothing to convert to digital. So, from the beginning, that’s how I went. Back then, of course, everything came to the office as paper. It had to be scanned in, then named, then placed in the right computer file.

But it was still easier than amassing paper records. At that time I subleased from a doc who’d been in practice for 15 years. His charts were all paper. Charts were neatly filed on shelves, everything was initialed, hole-punched, and put in the right section (which involved pulling out other stuff and putting it back). A few times a year, his staff would comb through the charts in front, and anyone who hadn’t been seen in 2 years would have their chart moved to a storage room in the back. Once a year they’d pull the charts of anyone not seen in 7 years and a company would come in and shred those records.

After 23 years, I still have it all. The whole thing takes up a little over 50 gigabytes on a hard drive, which realistically is nothing these days. Electrons don’t take up much space.

The majority of the charts — those that are more than 7 years old — I’ll probably never need to access, but it still happens sometimes. People call in and say they’ve moved back to Phoenix, or need to see a neurologist again, or need the records for insurance reasons, or whatever. My staff is also spared from moving charts to a storage room, then to shredding. Since they don’t take up any physical space, it’s no effort to keep everything.

And they aren’t just at my office. They’re at home, on my phone, wherever I am. If I get called from an ER, I can pull them up quickly. If I travel, they’re with me. My memory is good, but not that good, and I’d rather be able to look things up than guess.

This, at least to me, is the advantage of computers. Their data storage and retrieval advantages far exceed that of paper. In my opinion EMRs, while well-intentioned, have taken these benefits and twisted them into something cumbersome, geared more to meet nonmedical requirements and billing purposes.

In the process they’ve lost sight of our age-old job of caring for patients.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I don’t like EMR systems, with all their requirements, click boxes, endless cut & paste abuse, and 20-page notes that say nothing.

But I am a fan of what computers have brought to medical charts.

When I started out in 2000, I had no patients, hence no charts. I had the advantage of being able to start from scratch — there was nothing to convert to digital. So, from the beginning, that’s how I went. Back then, of course, everything came to the office as paper. It had to be scanned in, then named, then placed in the right computer file.

But it was still easier than amassing paper records. At that time I subleased from a doc who’d been in practice for 15 years. His charts were all paper. Charts were neatly filed on shelves, everything was initialed, hole-punched, and put in the right section (which involved pulling out other stuff and putting it back). A few times a year, his staff would comb through the charts in front, and anyone who hadn’t been seen in 2 years would have their chart moved to a storage room in the back. Once a year they’d pull the charts of anyone not seen in 7 years and a company would come in and shred those records.

After 23 years, I still have it all. The whole thing takes up a little over 50 gigabytes on a hard drive, which realistically is nothing these days. Electrons don’t take up much space.

The majority of the charts — those that are more than 7 years old — I’ll probably never need to access, but it still happens sometimes. People call in and say they’ve moved back to Phoenix, or need to see a neurologist again, or need the records for insurance reasons, or whatever. My staff is also spared from moving charts to a storage room, then to shredding. Since they don’t take up any physical space, it’s no effort to keep everything.

And they aren’t just at my office. They’re at home, on my phone, wherever I am. If I get called from an ER, I can pull them up quickly. If I travel, they’re with me. My memory is good, but not that good, and I’d rather be able to look things up than guess.

This, at least to me, is the advantage of computers. Their data storage and retrieval advantages far exceed that of paper. In my opinion EMRs, while well-intentioned, have taken these benefits and twisted them into something cumbersome, geared more to meet nonmedical requirements and billing purposes.

In the process they’ve lost sight of our age-old job of caring for patients.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Organized labor seems to be experiencing a rebirth of sorts. In October 2022 a strike by railroad workers was averted when a tentative agreement about wages, working conditions, health insurance, and medical leave was hammered out. This past fall, strikes by auto workers that threatened to paralyze the big three manufacturers have now been resolved with agreements that meet many of the workers’ demands. The President even made an appearance on a picket line. Baristas at coffee shops, screenwriters, and actors have all been involved in work actions around the country.

While the health care industry has been relatively immune to threatened work stoppages, there are a growing number of hospitals and clinics where nurses and physicians are exploring the possibility of organizing to give themselves a stronger voice in how health care is being delivered. The realities that come when you transition from owner to employee are finally beginning to sink in for physicians, whether they are specialists or primary care providers.

One of the most significant efforts toward unionization recently occurred in Minnesota and Wisconsin. About 400 physicians and 150 physician’s assistants and nurse practitioners employed at Allina Health System voted to unionize and join the Doctors Council.

In an interview with Jacobin, a publication that offers a socialist perspective, three of the providers involved in the process that led to the vote shared their observations. The physicians claim that the first steps toward unionization came after multiple efforts to work with the Allina’s administration were rebuffed. As primary care physicians, their initial demands focused on getting help with hiring staffing and getting support with paperwork and administrative obligations.

The organizers complained that while Medicare hoped to bolster primary care by paying the providers more, the funds went to the companies, who then distributed them in a way that often did little to help the overworked providers. In addition to achieving a more equitable distribution of the monies, one of the organizers sees unionization as a way to provide a layer of protection when providers feel they must speak out about situations which clearly put quality of care at risk.

The organizers say the idea of unionization has been particularly appealing to the younger providers who are feeling threatened by burnout. When these new physicians look to their older coworkers for advice, they often find that the seasoned employees are as stressed as they are. Realizing that things aren’t going to improve with time, acting now to strengthen their voices sounds appealing.

With the vote for unionization behind them, the organizers are now ready to formulate a prioritized list of demands. Those of you who are regular readers of Letters from Maine know that I have been urging primary care physicians to find their voices. Unfortunately, unionization seems to be becoming a more common fall-back strategy when other avenues have failed to reach a sympathetic ear in the corporate boardrooms.

As more unions form, it will be interesting to see how the organizers structure their demands and job actions. While walkouts and strikes can certainly be effective in gaining attention, that attention can carry a risk of counter productivity sometimes by alienating patients, who should become allies.

Since an unsustainable burden of paperwork and administrative demands seems to be at the top of everyone’s priority list, it might make sense to adopt this message as a scaffolding on which to built a work action. Instead of walking off the job or marching on a picket line, why not stay in the hospital and continue to see patients but only for part of the work day. The remainder of the day would be spent doing all the clerical work that has become so onerous.

Providers would agree to see patients in the mornings, saving up the clerical work and administrative obligations for the afternoon. The definition of “morning” could vary depending on local conditions.

The important message to the public and the patients would be that the providers were not abandoning them by walking out. The patients’ access to face-to-face care was being limited not because the doctors didn’t want to see them but because the providers were being forced to accept other responsibilities by the administration. The physicians would always be on site in case of a crisis, but until reasonable demands for support from the company were met, a certain portion of the providers’ day would be spent doing things not directly related to face-to-face patient care. This burden of meaningless work is the reality as it stands already. Why not organize it in a way that makes it startlingly visible to the patients and the public.

There would be no video clips of physicians walking the picket lines carrying signs. Any images released to the media would be of empty waiting rooms while providers sat hunched over their computers or talking on the phone to insurance companies.

The strategy needs a catchy phrase like “a paperwork-in” but I’m still struggling with a name. Let me know if you have a better one or even a better strategy.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

Organized labor seems to be experiencing a rebirth of sorts. In October 2022 a strike by railroad workers was averted when a tentative agreement about wages, working conditions, health insurance, and medical leave was hammered out. This past fall, strikes by auto workers that threatened to paralyze the big three manufacturers have now been resolved with agreements that meet many of the workers’ demands. The President even made an appearance on a picket line. Baristas at coffee shops, screenwriters, and actors have all been involved in work actions around the country.

While the health care industry has been relatively immune to threatened work stoppages, there are a growing number of hospitals and clinics where nurses and physicians are exploring the possibility of organizing to give themselves a stronger voice in how health care is being delivered. The realities that come when you transition from owner to employee are finally beginning to sink in for physicians, whether they are specialists or primary care providers.

One of the most significant efforts toward unionization recently occurred in Minnesota and Wisconsin. About 400 physicians and 150 physician’s assistants and nurse practitioners employed at Allina Health System voted to unionize and join the Doctors Council.

In an interview with Jacobin, a publication that offers a socialist perspective, three of the providers involved in the process that led to the vote shared their observations. The physicians claim that the first steps toward unionization came after multiple efforts to work with the Allina’s administration were rebuffed. As primary care physicians, their initial demands focused on getting help with hiring staffing and getting support with paperwork and administrative obligations.

The organizers complained that while Medicare hoped to bolster primary care by paying the providers more, the funds went to the companies, who then distributed them in a way that often did little to help the overworked providers. In addition to achieving a more equitable distribution of the monies, one of the organizers sees unionization as a way to provide a layer of protection when providers feel they must speak out about situations which clearly put quality of care at risk.

The organizers say the idea of unionization has been particularly appealing to the younger providers who are feeling threatened by burnout. When these new physicians look to their older coworkers for advice, they often find that the seasoned employees are as stressed as they are. Realizing that things aren’t going to improve with time, acting now to strengthen their voices sounds appealing.

With the vote for unionization behind them, the organizers are now ready to formulate a prioritized list of demands. Those of you who are regular readers of Letters from Maine know that I have been urging primary care physicians to find their voices. Unfortunately, unionization seems to be becoming a more common fall-back strategy when other avenues have failed to reach a sympathetic ear in the corporate boardrooms.

As more unions form, it will be interesting to see how the organizers structure their demands and job actions. While walkouts and strikes can certainly be effective in gaining attention, that attention can carry a risk of counter productivity sometimes by alienating patients, who should become allies.

Since an unsustainable burden of paperwork and administrative demands seems to be at the top of everyone’s priority list, it might make sense to adopt this message as a scaffolding on which to built a work action. Instead of walking off the job or marching on a picket line, why not stay in the hospital and continue to see patients but only for part of the work day. The remainder of the day would be spent doing all the clerical work that has become so onerous.

Providers would agree to see patients in the mornings, saving up the clerical work and administrative obligations for the afternoon. The definition of “morning” could vary depending on local conditions.

The important message to the public and the patients would be that the providers were not abandoning them by walking out. The patients’ access to face-to-face care was being limited not because the doctors didn’t want to see them but because the providers were being forced to accept other responsibilities by the administration. The physicians would always be on site in case of a crisis, but until reasonable demands for support from the company were met, a certain portion of the providers’ day would be spent doing things not directly related to face-to-face patient care. This burden of meaningless work is the reality as it stands already. Why not organize it in a way that makes it startlingly visible to the patients and the public.

There would be no video clips of physicians walking the picket lines carrying signs. Any images released to the media would be of empty waiting rooms while providers sat hunched over their computers or talking on the phone to insurance companies.

The strategy needs a catchy phrase like “a paperwork-in” but I’m still struggling with a name. Let me know if you have a better one or even a better strategy.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

Organized labor seems to be experiencing a rebirth of sorts. In October 2022 a strike by railroad workers was averted when a tentative agreement about wages, working conditions, health insurance, and medical leave was hammered out. This past fall, strikes by auto workers that threatened to paralyze the big three manufacturers have now been resolved with agreements that meet many of the workers’ demands. The President even made an appearance on a picket line. Baristas at coffee shops, screenwriters, and actors have all been involved in work actions around the country.

While the health care industry has been relatively immune to threatened work stoppages, there are a growing number of hospitals and clinics where nurses and physicians are exploring the possibility of organizing to give themselves a stronger voice in how health care is being delivered. The realities that come when you transition from owner to employee are finally beginning to sink in for physicians, whether they are specialists or primary care providers.

One of the most significant efforts toward unionization recently occurred in Minnesota and Wisconsin. About 400 physicians and 150 physician’s assistants and nurse practitioners employed at Allina Health System voted to unionize and join the Doctors Council.

In an interview with Jacobin, a publication that offers a socialist perspective, three of the providers involved in the process that led to the vote shared their observations. The physicians claim that the first steps toward unionization came after multiple efforts to work with the Allina’s administration were rebuffed. As primary care physicians, their initial demands focused on getting help with hiring staffing and getting support with paperwork and administrative obligations.

The organizers complained that while Medicare hoped to bolster primary care by paying the providers more, the funds went to the companies, who then distributed them in a way that often did little to help the overworked providers. In addition to achieving a more equitable distribution of the monies, one of the organizers sees unionization as a way to provide a layer of protection when providers feel they must speak out about situations which clearly put quality of care at risk.

The organizers say the idea of unionization has been particularly appealing to the younger providers who are feeling threatened by burnout. When these new physicians look to their older coworkers for advice, they often find that the seasoned employees are as stressed as they are. Realizing that things aren’t going to improve with time, acting now to strengthen their voices sounds appealing.

With the vote for unionization behind them, the organizers are now ready to formulate a prioritized list of demands. Those of you who are regular readers of Letters from Maine know that I have been urging primary care physicians to find their voices. Unfortunately, unionization seems to be becoming a more common fall-back strategy when other avenues have failed to reach a sympathetic ear in the corporate boardrooms.

As more unions form, it will be interesting to see how the organizers structure their demands and job actions. While walkouts and strikes can certainly be effective in gaining attention, that attention can carry a risk of counter productivity sometimes by alienating patients, who should become allies.

Since an unsustainable burden of paperwork and administrative demands seems to be at the top of everyone’s priority list, it might make sense to adopt this message as a scaffolding on which to built a work action. Instead of walking off the job or marching on a picket line, why not stay in the hospital and continue to see patients but only for part of the work day. The remainder of the day would be spent doing all the clerical work that has become so onerous.

Providers would agree to see patients in the mornings, saving up the clerical work and administrative obligations for the afternoon. The definition of “morning” could vary depending on local conditions.

The important message to the public and the patients would be that the providers were not abandoning them by walking out. The patients’ access to face-to-face care was being limited not because the doctors didn’t want to see them but because the providers were being forced to accept other responsibilities by the administration. The physicians would always be on site in case of a crisis, but until reasonable demands for support from the company were met, a certain portion of the providers’ day would be spent doing things not directly related to face-to-face patient care. This burden of meaningless work is the reality as it stands already. Why not organize it in a way that makes it startlingly visible to the patients and the public.

There would be no video clips of physicians walking the picket lines carrying signs. Any images released to the media would be of empty waiting rooms while providers sat hunched over their computers or talking on the phone to insurance companies.

The strategy needs a catchy phrase like “a paperwork-in” but I’m still struggling with a name. Let me know if you have a better one or even a better strategy.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

In a letter dated Nov. 30, 2023, the Food and Drug Administration informed isotretinoin manufacturers that they have 6 months to make five changes to existing iPLEDGE Risk Evaluation and Mitigation Strategy (REMS) requirements for the acne drug isotretinoin.

The development follows a March 2023 joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee about iPLEDGE REMS requirements, which included feedback from patients and dermatologists and recommendations for changes to the REMS program, aimed at minimizing the burden of the program on patients, pharmacies, and prescribers while continuing to maintain safe use of the highly teratogenic drug for patients.

The five changes include the following:

• Remove the requirement that pregnancy tests must be performed in a specially certified (i.e., Clinical Laboratory Improvement Amendments [CLIA]) laboratory. In the opinion of John S. Barbieri, MD, MBA, director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, this change “may make it easier to perform pregnancy tests in a clinic setting without needing to send the patient to a separate lab,” he said in an interview.
• Allow prescribers the option of using home pregnancy testing for their patients during and after isotretinoin treatment. Prescribers who rely on the patient to perform a home pregnancy test need to take steps to minimize patients falsifying the results of these tests. According to Dr. Barbieri, this means that two pregnancy tests prior to starting isotretinoin must be done in a lab or office setting. “However, all the pregnancy tests on therapy can be either in a medical setting or using a home pregnancy test,” he told this news organization. “This option facilitates the use of telemedicine so that patients would not need to come in; they can just share a pregnancy test with their name and date with their dermatologist.”
• Remove the waiting period requirement — also known as the “19-day lockout” — for patients if they do not obtain isotretinoin within the first 7-day prescription window. According to Dr. Barbieri, this change helps to ensure that patients can begin isotretinoin in a timely manner. “Insurance and pharmacy delays that are no fault of the patient can commonly cause missed initial window periods,” he said. “Allowing for immediate repeat of a pregnancy test to start a new window period, rather than requiring the patient to wait 19 more days, can ensure patient safety and pregnancy prevention without negatively impacting access.”
• Revise the pregnancy registry requirement to remove the objective to document the pregnancy and fetal outcomes for each pregnancy.
• Revise the requirement for prescribers to document patient counseling in patients who cannot become pregnant from monthly to only at enrollment. Dr. Barbieri characterized this change as “major” and said that it could eliminate the need for monthly visits for persons of non–childbearing potential. “This could substantially reduce logistical burdens for patients and reduce wait times to see a dermatologist,” he said.

Future changes to iPLEDGE that Dr. Barbieri would like to see include allowing for home pregnancy tests prior to starting therapy — particularly the test after the 30-day window period. “In addition, it would be good to be able to reduce the 30-day waiting period prior to therapy to something shorter,” such as 14 days, which would still “reliably exclude pregnancy, particularly for those on stable long-acting reversible contraception,” he said. There are also opportunities to improve the iPLEDGE website functionality and to ensure that the website is accessible to patients with limited English proficiency, he added.

He also recommended greater transparency by the Isotretinoin Products Manufacturers Group and inclusion of input from diverse stakeholders such as dermatologists, patients, and pharmacists.

Dr. Barbieri reported personal fees from Dexcel Pharma.

In a letter dated Nov. 30, 2023, the Food and Drug Administration informed isotretinoin manufacturers that they have 6 months to make five changes to existing iPLEDGE Risk Evaluation and Mitigation Strategy (REMS) requirements for the acne drug isotretinoin.

The development follows a March 2023 joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee about iPLEDGE REMS requirements, which included feedback from patients and dermatologists and recommendations for changes to the REMS program, aimed at minimizing the burden of the program on patients, pharmacies, and prescribers while continuing to maintain safe use of the highly teratogenic drug for patients.

The five changes include the following:

• Remove the requirement that pregnancy tests must be performed in a specially certified (i.e., Clinical Laboratory Improvement Amendments [CLIA]) laboratory. In the opinion of John S. Barbieri, MD, MBA, director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, this change “may make it easier to perform pregnancy tests in a clinic setting without needing to send the patient to a separate lab,” he said in an interview.
• Allow prescribers the option of using home pregnancy testing for their patients during and after isotretinoin treatment. Prescribers who rely on the patient to perform a home pregnancy test need to take steps to minimize patients falsifying the results of these tests. According to Dr. Barbieri, this means that two pregnancy tests prior to starting isotretinoin must be done in a lab or office setting. “However, all the pregnancy tests on therapy can be either in a medical setting or using a home pregnancy test,” he told this news organization. “This option facilitates the use of telemedicine so that patients would not need to come in; they can just share a pregnancy test with their name and date with their dermatologist.”
• Remove the waiting period requirement — also known as the “19-day lockout” — for patients if they do not obtain isotretinoin within the first 7-day prescription window. According to Dr. Barbieri, this change helps to ensure that patients can begin isotretinoin in a timely manner. “Insurance and pharmacy delays that are no fault of the patient can commonly cause missed initial window periods,” he said. “Allowing for immediate repeat of a pregnancy test to start a new window period, rather than requiring the patient to wait 19 more days, can ensure patient safety and pregnancy prevention without negatively impacting access.”
• Revise the pregnancy registry requirement to remove the objective to document the pregnancy and fetal outcomes for each pregnancy.
• Revise the requirement for prescribers to document patient counseling in patients who cannot become pregnant from monthly to only at enrollment. Dr. Barbieri characterized this change as “major” and said that it could eliminate the need for monthly visits for persons of non–childbearing potential. “This could substantially reduce logistical burdens for patients and reduce wait times to see a dermatologist,” he said.

Future changes to iPLEDGE that Dr. Barbieri would like to see include allowing for home pregnancy tests prior to starting therapy — particularly the test after the 30-day window period. “In addition, it would be good to be able to reduce the 30-day waiting period prior to therapy to something shorter,” such as 14 days, which would still “reliably exclude pregnancy, particularly for those on stable long-acting reversible contraception,” he said. There are also opportunities to improve the iPLEDGE website functionality and to ensure that the website is accessible to patients with limited English proficiency, he added.

He also recommended greater transparency by the Isotretinoin Products Manufacturers Group and inclusion of input from diverse stakeholders such as dermatologists, patients, and pharmacists.

Dr. Barbieri reported personal fees from Dexcel Pharma.

In a letter dated Nov. 30, 2023, the Food and Drug Administration informed isotretinoin manufacturers that they have 6 months to make five changes to existing iPLEDGE Risk Evaluation and Mitigation Strategy (REMS) requirements for the acne drug isotretinoin.

The development follows a March 2023 joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee about iPLEDGE REMS requirements, which included feedback from patients and dermatologists and recommendations for changes to the REMS program, aimed at minimizing the burden of the program on patients, pharmacies, and prescribers while continuing to maintain safe use of the highly teratogenic drug for patients.

The five changes include the following:

• Remove the requirement that pregnancy tests must be performed in a specially certified (i.e., Clinical Laboratory Improvement Amendments [CLIA]) laboratory. In the opinion of John S. Barbieri, MD, MBA, director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, this change “may make it easier to perform pregnancy tests in a clinic setting without needing to send the patient to a separate lab,” he said in an interview.
• Allow prescribers the option of using home pregnancy testing for their patients during and after isotretinoin treatment. Prescribers who rely on the patient to perform a home pregnancy test need to take steps to minimize patients falsifying the results of these tests. According to Dr. Barbieri, this means that two pregnancy tests prior to starting isotretinoin must be done in a lab or office setting. “However, all the pregnancy tests on therapy can be either in a medical setting or using a home pregnancy test,” he told this news organization. “This option facilitates the use of telemedicine so that patients would not need to come in; they can just share a pregnancy test with their name and date with their dermatologist.”
• Remove the waiting period requirement — also known as the “19-day lockout” — for patients if they do not obtain isotretinoin within the first 7-day prescription window. According to Dr. Barbieri, this change helps to ensure that patients can begin isotretinoin in a timely manner. “Insurance and pharmacy delays that are no fault of the patient can commonly cause missed initial window periods,” he said. “Allowing for immediate repeat of a pregnancy test to start a new window period, rather than requiring the patient to wait 19 more days, can ensure patient safety and pregnancy prevention without negatively impacting access.”
• Revise the pregnancy registry requirement to remove the objective to document the pregnancy and fetal outcomes for each pregnancy.
• Revise the requirement for prescribers to document patient counseling in patients who cannot become pregnant from monthly to only at enrollment. Dr. Barbieri characterized this change as “major” and said that it could eliminate the need for monthly visits for persons of non–childbearing potential. “This could substantially reduce logistical burdens for patients and reduce wait times to see a dermatologist,” he said.

Future changes to iPLEDGE that Dr. Barbieri would like to see include allowing for home pregnancy tests prior to starting therapy — particularly the test after the 30-day window period. “In addition, it would be good to be able to reduce the 30-day waiting period prior to therapy to something shorter,” such as 14 days, which would still “reliably exclude pregnancy, particularly for those on stable long-acting reversible contraception,” he said. There are also opportunities to improve the iPLEDGE website functionality and to ensure that the website is accessible to patients with limited English proficiency, he added.

He also recommended greater transparency by the Isotretinoin Products Manufacturers Group and inclusion of input from diverse stakeholders such as dermatologists, patients, and pharmacists.

Dr. Barbieri reported personal fees from Dexcel Pharma.

This transcript has been edited for clarity.

Much of my research focuses on what is known as clinical decision support — prompts and messages to providers to help them make good decisions for their patients. I know that these things can be annoying, which is exactly why I study them — to figure out which ones actually help.

When I got started on this about 10 years ago, we were learning a lot about how best to message providers about their patients. My team had developed a simple alert for acute kidney injury (AKI). We knew that providers often missed the diagnosis, so maybe letting them know would improve patient outcomes.

As we tested the alert, we got feedback, and I have kept an email from an ICU doctor from those early days. It read:

Dear Dr. Wilson: Thank you for the automated alert informing me that my patient had AKI. Regrettably, the alert fired about an hour after the patient had died. I feel that the information is less than actionable at this time.

Our early system had neglected to add a conditional flag ensuring that the patient was still alive at the time it sent the alert message. A small oversight, but one that had very large implications. Future studies would show that “false positive” alerts like this seriously degrade physician confidence in the system. And why wouldn’t they?

Knowing whether a patient is alive or dead seems like it should be trivial. But, as it turns out, in our modern balkanized health care system, it can be quite difficult. Not knowing the vital status of a patient can have major consequences.

Health systems send messages to their patients all the time: reminders of appointments, reminders for preventive care, reminders for vaccinations, and so on.

But what if the patient being reminded has died? It’s a waste of resources, of course, but more than that, it can be painful for their families and reflects poorly on the health care system. Of all the people who should know whether someone is alive or dead, shouldn’t their doctor be at the top of the list?

A new study in JAMA Internal Medicine quantifies this very phenomenon.

Researchers examined 11,658 primary care patients in their health system who met the criteria of being “seriously ill” and followed them for 2 years. During that period of time, 25% were recorded as deceased in the electronic health record. But 30.8% had died. That left 676 patients who had died, but were not known to have died, left in the system.

Courtesy Dr. F. Perry Wilson

Courtesy Dr. F. Perry Wilson

Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Connecticut. He has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com .

This transcript has been edited for clarity.

Much of my research focuses on what is known as clinical decision support — prompts and messages to providers to help them make good decisions for their patients. I know that these things can be annoying, which is exactly why I study them — to figure out which ones actually help.

When I got started on this about 10 years ago, we were learning a lot about how best to message providers about their patients. My team had developed a simple alert for acute kidney injury (AKI). We knew that providers often missed the diagnosis, so maybe letting them know would improve patient outcomes.

As we tested the alert, we got feedback, and I have kept an email from an ICU doctor from those early days. It read:

Dear Dr. Wilson: Thank you for the automated alert informing me that my patient had AKI. Regrettably, the alert fired about an hour after the patient had died. I feel that the information is less than actionable at this time.

Our early system had neglected to add a conditional flag ensuring that the patient was still alive at the time it sent the alert message. A small oversight, but one that had very large implications. Future studies would show that “false positive” alerts like this seriously degrade physician confidence in the system. And why wouldn’t they?

Knowing whether a patient is alive or dead seems like it should be trivial. But, as it turns out, in our modern balkanized health care system, it can be quite difficult. Not knowing the vital status of a patient can have major consequences.

Health systems send messages to their patients all the time: reminders of appointments, reminders for preventive care, reminders for vaccinations, and so on.

But what if the patient being reminded has died? It’s a waste of resources, of course, but more than that, it can be painful for their families and reflects poorly on the health care system. Of all the people who should know whether someone is alive or dead, shouldn’t their doctor be at the top of the list?

A new study in JAMA Internal Medicine quantifies this very phenomenon.

Researchers examined 11,658 primary care patients in their health system who met the criteria of being “seriously ill” and followed them for 2 years. During that period of time, 25% were recorded as deceased in the electronic health record. But 30.8% had died. That left 676 patients who had died, but were not known to have died, left in the system.

Courtesy Dr. F. Perry Wilson

Courtesy Dr. F. Perry Wilson

Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Connecticut. He has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com .

This transcript has been edited for clarity.

Much of my research focuses on what is known as clinical decision support — prompts and messages to providers to help them make good decisions for their patients. I know that these things can be annoying, which is exactly why I study them — to figure out which ones actually help.

When I got started on this about 10 years ago, we were learning a lot about how best to message providers about their patients. My team had developed a simple alert for acute kidney injury (AKI). We knew that providers often missed the diagnosis, so maybe letting them know would improve patient outcomes.

As we tested the alert, we got feedback, and I have kept an email from an ICU doctor from those early days. It read:

Dear Dr. Wilson: Thank you for the automated alert informing me that my patient had AKI. Regrettably, the alert fired about an hour after the patient had died. I feel that the information is less than actionable at this time.

Our early system had neglected to add a conditional flag ensuring that the patient was still alive at the time it sent the alert message. A small oversight, but one that had very large implications. Future studies would show that “false positive” alerts like this seriously degrade physician confidence in the system. And why wouldn’t they?

Knowing whether a patient is alive or dead seems like it should be trivial. But, as it turns out, in our modern balkanized health care system, it can be quite difficult. Not knowing the vital status of a patient can have major consequences.

Health systems send messages to their patients all the time: reminders of appointments, reminders for preventive care, reminders for vaccinations, and so on.

But what if the patient being reminded has died? It’s a waste of resources, of course, but more than that, it can be painful for their families and reflects poorly on the health care system. Of all the people who should know whether someone is alive or dead, shouldn’t their doctor be at the top of the list?

A new study in JAMA Internal Medicine quantifies this very phenomenon.

Researchers examined 11,658 primary care patients in their health system who met the criteria of being “seriously ill” and followed them for 2 years. During that period of time, 25% were recorded as deceased in the electronic health record. But 30.8% had died. That left 676 patients who had died, but were not known to have died, left in the system.

Courtesy Dr. F. Perry Wilson

Courtesy Dr. F. Perry Wilson

Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Connecticut. He has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com .