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FIB-4 could ID liver risk in primary care
Fibrosis-4 index (FIB-4) scores are strongly associated with severe liver disease outcomes in a primary care population, both in patients with known chronic liver disease and those without known CLD. The result could help identify patients with CLD before their condition becomes severe.
FIB-4 has previously shown utility in predicting the risk of advanced fibrosis in patients with viral hepatitis B and C, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), and alcohol-related liver disease.
“This is really important in primary care because FIB-4 is easy to calculate. Its inputs are accessible, and it is inexpensive, often taking advantage of labs that we’ve ordered anyway. And if we can use it to find advanced fibrosis, it will be critically important because we know that advanced fibrosis is associated with severe liver outcomes – these are going to be patients that we need to make sure are in touch with our hepatology colleagues,” said Andrew Schreiner, MD, during a presentation of the results at the annual meeting of the American Association for the Study of Liver Diseases. Dr. Schreiner is general internist at the Medical University of South Carolina, Charleston.
He also noted that FIB-4 is playing an important role in the assessment of NAFLD and NASH. Many newer algorithms to manage NAFLD in the primary care setting rely on FIB-4, but that application is limited because NAFLD is underdiagnosed according to administrative database studies, which found rates of about 2%-5% despite the fact that estimates put it at having a prevalence of 25%-30% in the U.S. population.
To determine if FIB-4 scores could assist in identifying primary care patients at risk of severe outcomes, including cirrhosis, hepatocellular carcinoma, and liver transplant, the researchers conducted a retrospective analysis of primary care electronic health care data from 20,556 patients between 2007 and 2018 who were seen at their institution. Participants had ALT and AST values less than 500 IU/L, as well as a platelet count within two months preceding or on the day of the liver enzyme tests. They excluded individuals with known chronic or severe liver disease.
65% of patients were female, 45% were Black, and the mean BMI was 29.8 kg/m2. 64% of participants were ranked as low risk (FIB-4 ≤1.3), 29% with undetermined risk (1.3-2.67), and 7% with high risk (>2.67).
The population had more liver risk than expected. “[It is] a distribution that certainly may have more high risk and indeterminant risks than we would have anticipated, but we have seen this in external studies,” said Dr. Schreiner.
Over a mean follow-up period of 8.2 years, 11% were diagnosed with CLD: 2.3% developed NAFLD, 8.2% another CLD, and 0.5% had NAFLD and another CLD. About 4% developed a severe CLD. A severe liver outcome occurred in 2.2% of those who had been classified as FIB-4 low risk, 4.2% classified as indeterminate risk, and 20.8% of those classified as high risk.
“Troublingly,” said Dr. Schreiner, 49% of those who went on to develop a severe liver outcome had no CLD diagnosis before it occurred. “This is a tremendous opportunity to improve diagnosis in this setting.”
After adjustment for race, gender, marital status, smoking history, BMI, and various comorbidities, the researchers found a higher risk of severe liver disease associated with indeterminate FIB-4 risk score (hazard ratio, 1.62; 95% confidence interval, 1.36-1.92) and a high FIB-4 risk score (HR, 6.64; 95% CI, 5.58-7.90), compared with those with a low FIB-4 risk score. The same was true for individual liver diseases, including NAFLD (indeterminate HR, 1.88; 95% CI, 0.99-3.60; high HR, 7.32; 95% CI, 3.44-15.58), other liver diagnosis (indeterminate HR, 2.65; 95% CI, 1.93-3.63; high HR, 11.39; 95% CI, 8.53-15.20), and NAFLD plus another liver disease (intermediate HR, 2.53; 95% CI, 0.79-8.12; high HR, 6.89; 95% CI, 1.82-26.14).
Dr. Schreiner conceded that the study may not be generalizable, since FIB-4 was not designed for use in general populations, and it was conducted at a single center.
During the question-and-answer session after the talk, Dr. Schreiner was asked if the majority of the 49% who had a severe liver outcome without previous liver disease had NAFLD. He said that was the team’s hypothesis, and they are in the process of examining that data, but a significant number appear to be alcohol related. “For us in the primary care setting, it’s just another opportunity to emphasize that we have to do a better job getting exposure histories, and alcohol histories in particular, and finding ways to document those in ways that we can make diagnoses for patients and for our hepatology colleagues,” said Dr. Schreiner.
Comoderator Kathleen Corey, MD, asked Dr. Schreiner if he had any concerns about false positives from FIB-4 screening, and whether that could lead to overtreatment. “We’ve seen other screening tests leading to patient distress and overutilization of resources. How do you think we might be able to mitigate that?” asked Dr. Corey, who is an assistant professor of medicine at Harvard Medical School and director of the Fatty Liver Clinic at Massachusetts General Hospital, both in Boston.
Dr. Schreiner underscored the need for more physician education about FIB-4, both its potential and its pitfalls, since many primary care providers don’t use it or even know about it. “FIB-4 is very popular in the hepatology literature, but in primary care, we don’t talk about it as often. So I think educational efforts about its possible utility, about some of the drawbacks, or some of the things that might lead to inappropriately positive results – like advanced age, for those of us who see patients 60 and older. Those are really important considerations both for the patient and the provider for management of expectations and concerns. I’m worried too about application in our younger cohorts. The explosion of NAFLD in adolescence, and the likelihood that we might get a false negative in maybe a 28-year-old who might have problematic disease, is a concern as well,” said Dr. Schreiner.
Dr. Schreiner has no relevant financial disclosures. Dr. Corey has been on an advisory committee or review panel for Bristol-Myers Squibb, Novo Nordisk, and Gilead. She has consulted for Novo Nordisk and received research support from BMS, Boehringer Ingelheim, Novartis, and Boehringer Ingelheim.
Fibrosis-4 index (FIB-4) scores are strongly associated with severe liver disease outcomes in a primary care population, both in patients with known chronic liver disease and those without known CLD. The result could help identify patients with CLD before their condition becomes severe.
FIB-4 has previously shown utility in predicting the risk of advanced fibrosis in patients with viral hepatitis B and C, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), and alcohol-related liver disease.
“This is really important in primary care because FIB-4 is easy to calculate. Its inputs are accessible, and it is inexpensive, often taking advantage of labs that we’ve ordered anyway. And if we can use it to find advanced fibrosis, it will be critically important because we know that advanced fibrosis is associated with severe liver outcomes – these are going to be patients that we need to make sure are in touch with our hepatology colleagues,” said Andrew Schreiner, MD, during a presentation of the results at the annual meeting of the American Association for the Study of Liver Diseases. Dr. Schreiner is general internist at the Medical University of South Carolina, Charleston.
He also noted that FIB-4 is playing an important role in the assessment of NAFLD and NASH. Many newer algorithms to manage NAFLD in the primary care setting rely on FIB-4, but that application is limited because NAFLD is underdiagnosed according to administrative database studies, which found rates of about 2%-5% despite the fact that estimates put it at having a prevalence of 25%-30% in the U.S. population.
To determine if FIB-4 scores could assist in identifying primary care patients at risk of severe outcomes, including cirrhosis, hepatocellular carcinoma, and liver transplant, the researchers conducted a retrospective analysis of primary care electronic health care data from 20,556 patients between 2007 and 2018 who were seen at their institution. Participants had ALT and AST values less than 500 IU/L, as well as a platelet count within two months preceding or on the day of the liver enzyme tests. They excluded individuals with known chronic or severe liver disease.
65% of patients were female, 45% were Black, and the mean BMI was 29.8 kg/m2. 64% of participants were ranked as low risk (FIB-4 ≤1.3), 29% with undetermined risk (1.3-2.67), and 7% with high risk (>2.67).
The population had more liver risk than expected. “[It is] a distribution that certainly may have more high risk and indeterminant risks than we would have anticipated, but we have seen this in external studies,” said Dr. Schreiner.
Over a mean follow-up period of 8.2 years, 11% were diagnosed with CLD: 2.3% developed NAFLD, 8.2% another CLD, and 0.5% had NAFLD and another CLD. About 4% developed a severe CLD. A severe liver outcome occurred in 2.2% of those who had been classified as FIB-4 low risk, 4.2% classified as indeterminate risk, and 20.8% of those classified as high risk.
“Troublingly,” said Dr. Schreiner, 49% of those who went on to develop a severe liver outcome had no CLD diagnosis before it occurred. “This is a tremendous opportunity to improve diagnosis in this setting.”
After adjustment for race, gender, marital status, smoking history, BMI, and various comorbidities, the researchers found a higher risk of severe liver disease associated with indeterminate FIB-4 risk score (hazard ratio, 1.62; 95% confidence interval, 1.36-1.92) and a high FIB-4 risk score (HR, 6.64; 95% CI, 5.58-7.90), compared with those with a low FIB-4 risk score. The same was true for individual liver diseases, including NAFLD (indeterminate HR, 1.88; 95% CI, 0.99-3.60; high HR, 7.32; 95% CI, 3.44-15.58), other liver diagnosis (indeterminate HR, 2.65; 95% CI, 1.93-3.63; high HR, 11.39; 95% CI, 8.53-15.20), and NAFLD plus another liver disease (intermediate HR, 2.53; 95% CI, 0.79-8.12; high HR, 6.89; 95% CI, 1.82-26.14).
Dr. Schreiner conceded that the study may not be generalizable, since FIB-4 was not designed for use in general populations, and it was conducted at a single center.
During the question-and-answer session after the talk, Dr. Schreiner was asked if the majority of the 49% who had a severe liver outcome without previous liver disease had NAFLD. He said that was the team’s hypothesis, and they are in the process of examining that data, but a significant number appear to be alcohol related. “For us in the primary care setting, it’s just another opportunity to emphasize that we have to do a better job getting exposure histories, and alcohol histories in particular, and finding ways to document those in ways that we can make diagnoses for patients and for our hepatology colleagues,” said Dr. Schreiner.
Comoderator Kathleen Corey, MD, asked Dr. Schreiner if he had any concerns about false positives from FIB-4 screening, and whether that could lead to overtreatment. “We’ve seen other screening tests leading to patient distress and overutilization of resources. How do you think we might be able to mitigate that?” asked Dr. Corey, who is an assistant professor of medicine at Harvard Medical School and director of the Fatty Liver Clinic at Massachusetts General Hospital, both in Boston.
Dr. Schreiner underscored the need for more physician education about FIB-4, both its potential and its pitfalls, since many primary care providers don’t use it or even know about it. “FIB-4 is very popular in the hepatology literature, but in primary care, we don’t talk about it as often. So I think educational efforts about its possible utility, about some of the drawbacks, or some of the things that might lead to inappropriately positive results – like advanced age, for those of us who see patients 60 and older. Those are really important considerations both for the patient and the provider for management of expectations and concerns. I’m worried too about application in our younger cohorts. The explosion of NAFLD in adolescence, and the likelihood that we might get a false negative in maybe a 28-year-old who might have problematic disease, is a concern as well,” said Dr. Schreiner.
Dr. Schreiner has no relevant financial disclosures. Dr. Corey has been on an advisory committee or review panel for Bristol-Myers Squibb, Novo Nordisk, and Gilead. She has consulted for Novo Nordisk and received research support from BMS, Boehringer Ingelheim, Novartis, and Boehringer Ingelheim.
Fibrosis-4 index (FIB-4) scores are strongly associated with severe liver disease outcomes in a primary care population, both in patients with known chronic liver disease and those without known CLD. The result could help identify patients with CLD before their condition becomes severe.
FIB-4 has previously shown utility in predicting the risk of advanced fibrosis in patients with viral hepatitis B and C, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), and alcohol-related liver disease.
“This is really important in primary care because FIB-4 is easy to calculate. Its inputs are accessible, and it is inexpensive, often taking advantage of labs that we’ve ordered anyway. And if we can use it to find advanced fibrosis, it will be critically important because we know that advanced fibrosis is associated with severe liver outcomes – these are going to be patients that we need to make sure are in touch with our hepatology colleagues,” said Andrew Schreiner, MD, during a presentation of the results at the annual meeting of the American Association for the Study of Liver Diseases. Dr. Schreiner is general internist at the Medical University of South Carolina, Charleston.
He also noted that FIB-4 is playing an important role in the assessment of NAFLD and NASH. Many newer algorithms to manage NAFLD in the primary care setting rely on FIB-4, but that application is limited because NAFLD is underdiagnosed according to administrative database studies, which found rates of about 2%-5% despite the fact that estimates put it at having a prevalence of 25%-30% in the U.S. population.
To determine if FIB-4 scores could assist in identifying primary care patients at risk of severe outcomes, including cirrhosis, hepatocellular carcinoma, and liver transplant, the researchers conducted a retrospective analysis of primary care electronic health care data from 20,556 patients between 2007 and 2018 who were seen at their institution. Participants had ALT and AST values less than 500 IU/L, as well as a platelet count within two months preceding or on the day of the liver enzyme tests. They excluded individuals with known chronic or severe liver disease.
65% of patients were female, 45% were Black, and the mean BMI was 29.8 kg/m2. 64% of participants were ranked as low risk (FIB-4 ≤1.3), 29% with undetermined risk (1.3-2.67), and 7% with high risk (>2.67).
The population had more liver risk than expected. “[It is] a distribution that certainly may have more high risk and indeterminant risks than we would have anticipated, but we have seen this in external studies,” said Dr. Schreiner.
Over a mean follow-up period of 8.2 years, 11% were diagnosed with CLD: 2.3% developed NAFLD, 8.2% another CLD, and 0.5% had NAFLD and another CLD. About 4% developed a severe CLD. A severe liver outcome occurred in 2.2% of those who had been classified as FIB-4 low risk, 4.2% classified as indeterminate risk, and 20.8% of those classified as high risk.
“Troublingly,” said Dr. Schreiner, 49% of those who went on to develop a severe liver outcome had no CLD diagnosis before it occurred. “This is a tremendous opportunity to improve diagnosis in this setting.”
After adjustment for race, gender, marital status, smoking history, BMI, and various comorbidities, the researchers found a higher risk of severe liver disease associated with indeterminate FIB-4 risk score (hazard ratio, 1.62; 95% confidence interval, 1.36-1.92) and a high FIB-4 risk score (HR, 6.64; 95% CI, 5.58-7.90), compared with those with a low FIB-4 risk score. The same was true for individual liver diseases, including NAFLD (indeterminate HR, 1.88; 95% CI, 0.99-3.60; high HR, 7.32; 95% CI, 3.44-15.58), other liver diagnosis (indeterminate HR, 2.65; 95% CI, 1.93-3.63; high HR, 11.39; 95% CI, 8.53-15.20), and NAFLD plus another liver disease (intermediate HR, 2.53; 95% CI, 0.79-8.12; high HR, 6.89; 95% CI, 1.82-26.14).
Dr. Schreiner conceded that the study may not be generalizable, since FIB-4 was not designed for use in general populations, and it was conducted at a single center.
During the question-and-answer session after the talk, Dr. Schreiner was asked if the majority of the 49% who had a severe liver outcome without previous liver disease had NAFLD. He said that was the team’s hypothesis, and they are in the process of examining that data, but a significant number appear to be alcohol related. “For us in the primary care setting, it’s just another opportunity to emphasize that we have to do a better job getting exposure histories, and alcohol histories in particular, and finding ways to document those in ways that we can make diagnoses for patients and for our hepatology colleagues,” said Dr. Schreiner.
Comoderator Kathleen Corey, MD, asked Dr. Schreiner if he had any concerns about false positives from FIB-4 screening, and whether that could lead to overtreatment. “We’ve seen other screening tests leading to patient distress and overutilization of resources. How do you think we might be able to mitigate that?” asked Dr. Corey, who is an assistant professor of medicine at Harvard Medical School and director of the Fatty Liver Clinic at Massachusetts General Hospital, both in Boston.
Dr. Schreiner underscored the need for more physician education about FIB-4, both its potential and its pitfalls, since many primary care providers don’t use it or even know about it. “FIB-4 is very popular in the hepatology literature, but in primary care, we don’t talk about it as often. So I think educational efforts about its possible utility, about some of the drawbacks, or some of the things that might lead to inappropriately positive results – like advanced age, for those of us who see patients 60 and older. Those are really important considerations both for the patient and the provider for management of expectations and concerns. I’m worried too about application in our younger cohorts. The explosion of NAFLD in adolescence, and the likelihood that we might get a false negative in maybe a 28-year-old who might have problematic disease, is a concern as well,” said Dr. Schreiner.
Dr. Schreiner has no relevant financial disclosures. Dr. Corey has been on an advisory committee or review panel for Bristol-Myers Squibb, Novo Nordisk, and Gilead. She has consulted for Novo Nordisk and received research support from BMS, Boehringer Ingelheim, Novartis, and Boehringer Ingelheim.
FROM THE LIVER MEETING
Metformin does not improve outcomes in early breast cancer
In the primary analysis, the addition of metformin to standard therapy in moderate/high-risk hormone receptor positive or negative breast cancer did not improve invasive disease–free survival (IDFS), overall survival, or other breast outcomes, explained lead author Pamela J. Goodwin, MD, FRCPC, professor of medicine at the University of Toronto. “Metformin should not be used as breast cancer treatment in this population.”
However, an exploratory analysis suggested that metformin may have a beneficial effect in women with HER2-positive breast cancer, Dr. Goodwin noted.
In this subset, IDFS was improved in patients who received metformin (hazard ratio, 0.64; P = .03), as was overall survival (HR, 0.53; P = .04).
The findings were presented at the San Antonio Breast Cancer Symposium.
“This trial arose from the observation that obesity is associated with poor breast cancer outcomes, and insulin levels are higher in obesity and may be more strongly associated with breast cancer outcomes than obesity,” said Dr. Goodwin.
Metformin was used because of its ability to promote modest weight loss and lower insulin by about 15%-20% in nondiabetic breast cancer survivors. It has also shown anticancer effects in preclinical studies. “In some window of opportunity neoadjuvant studies, it has been shown to reduce Ki67 in breast cancer cells,” she said. “And in preclinical in vitro and in vivo research, it slows growth of breast cancer.”
In addition, emerging evidence from observational studies suggests that the use of metformin to treat diabetes in breast cancer patients may be associated with better outcomes, strengthening the rationale for the study.
The negative results in breast cancer follow recent reports of negative findings in lung cancer, when metformin was found to be ineffective when used alongside chemotherapy in locally advanced lung cancer, as reported by this news organization.
No benefit seen
Metformin was compared to placebo in the phase 3 CCTG MA.32 trial, conducted in 3,649 patients aged 18-74 years with T1-3 N0-3 M0 breast cancer. All patients were treated with standard therapy and were randomized to receive metformin 850 mg twice daily for 5 years or placebo.
In 2016, “futility was declared in ER/PR-negative patients” after a second interim analysis conducted at 29.6 months’ median follow-up, Dr. Goodwin noted. The intervention was stopped in that group, although blinding and follow-up continued.
After that, the study’s primary analysis focused on the 2,533 ER/PR-positive patients (mean age, 52.7 years; mean body mass index, 28.8; approx. 60% postmenopausal).
Just over half of these patients had T2 tumor stage, and most disease was grade 2 or 3.
In addition, 16.5% (of metformin) and 17.4% (of placebo) patients had HER2-positive disease, with the majority (97%) of all HER2 patients receiving trastuzumab.
There was no difference between the two groups in IDFS events, occurring in 18.5% of patients receiving metformin and 18.3% who received placebo, with most (75.6%) events due to breast cancer (HR, 1.01; P = .92).
There were 131 deaths in the metformin arm and 119 in the placebo arm, with most (75.8%) of the deaths related to breast cancer (HR, 1.10; P = .47).
Other breast cancer outcomes had similar results, including distant disease-free survival (HR, 0.99; P = .94) and breast cancer–free interval (HR, 0.98; P = .87), both of which showed no advantage for metformin.
Possible HER2 advantage
However, the exploratory analysis suggested there may be an advantage for patients with HER2-positive disease, but primarily those who had at least one C allele of a prespecified ATM associated rs11212617 SNP. These patients achieved a higher pathologic complete response rate with metformin than that of those without the allele.
There were 620 patients with HER2-positive disease analyzed, with 99.4% receiving chemotherapy and 96.5% receiving trastuzumab. There were 99 IDFS events, and 47 OS events.
In the entire HER2-positive cohort, patients who received metformin had fewer IDFS events (HR, 0.64; P = .026) compared with the placebo arm. Mortality was lower with metformin (HR for overall survival, 0.53; P = .038).
“Subjects with HER2-positive breast cancer, notably those with at least one C allele of the ATM-associated rs11212617 SNP, experienced improved IDFS and overall survival with metformin,” Dr. Goodwin concluded. “However, no P-value ‘spend’ was allocated to this comparison. As a result, it requires replication in a prospective trial focusing on the HER2-positive population.”
More research?
Stephanie Bernik, MD, chief of breast surgery, Mount Sinai West, and associate professor of breast surgery, Icahn School of Medicine at Mount Sinai, New York, was approached by this news organization for an independent comment.
“It has long been known that obesity, which often correlates with diabetes, increases a woman’s risk of breast cancer,” she said.
“This study tried to show that using a medication that helps control insulin levels, even in those without diabetes, might decrease one’s risk of breast cancer,” she said. “Unfortunately, using metformin had no effect on outcomes in this study, even though it has shown promise in other studies. Perhaps more research needs to be carried out to try to pinpoint which mechanisms of action, if any, might be helpful to combat cancer in those with and without diabetes.”
The study was funded by the Canadian Cancer Trials Group, Cancer Therapy Evaluation Program, Breast Cancer Researcher Foundation, Susan G. Komen for the Cure, Canadian Cancer Society, Apotex, Swiss Cancer Research, and the Canadian Breast Cancer Foundation. Dr. Goodwin has no disclosures.
A version of this article first appeared on Medscape.com.
In the primary analysis, the addition of metformin to standard therapy in moderate/high-risk hormone receptor positive or negative breast cancer did not improve invasive disease–free survival (IDFS), overall survival, or other breast outcomes, explained lead author Pamela J. Goodwin, MD, FRCPC, professor of medicine at the University of Toronto. “Metformin should not be used as breast cancer treatment in this population.”
However, an exploratory analysis suggested that metformin may have a beneficial effect in women with HER2-positive breast cancer, Dr. Goodwin noted.
In this subset, IDFS was improved in patients who received metformin (hazard ratio, 0.64; P = .03), as was overall survival (HR, 0.53; P = .04).
The findings were presented at the San Antonio Breast Cancer Symposium.
“This trial arose from the observation that obesity is associated with poor breast cancer outcomes, and insulin levels are higher in obesity and may be more strongly associated with breast cancer outcomes than obesity,” said Dr. Goodwin.
Metformin was used because of its ability to promote modest weight loss and lower insulin by about 15%-20% in nondiabetic breast cancer survivors. It has also shown anticancer effects in preclinical studies. “In some window of opportunity neoadjuvant studies, it has been shown to reduce Ki67 in breast cancer cells,” she said. “And in preclinical in vitro and in vivo research, it slows growth of breast cancer.”
In addition, emerging evidence from observational studies suggests that the use of metformin to treat diabetes in breast cancer patients may be associated with better outcomes, strengthening the rationale for the study.
The negative results in breast cancer follow recent reports of negative findings in lung cancer, when metformin was found to be ineffective when used alongside chemotherapy in locally advanced lung cancer, as reported by this news organization.
No benefit seen
Metformin was compared to placebo in the phase 3 CCTG MA.32 trial, conducted in 3,649 patients aged 18-74 years with T1-3 N0-3 M0 breast cancer. All patients were treated with standard therapy and were randomized to receive metformin 850 mg twice daily for 5 years or placebo.
In 2016, “futility was declared in ER/PR-negative patients” after a second interim analysis conducted at 29.6 months’ median follow-up, Dr. Goodwin noted. The intervention was stopped in that group, although blinding and follow-up continued.
After that, the study’s primary analysis focused on the 2,533 ER/PR-positive patients (mean age, 52.7 years; mean body mass index, 28.8; approx. 60% postmenopausal).
Just over half of these patients had T2 tumor stage, and most disease was grade 2 or 3.
In addition, 16.5% (of metformin) and 17.4% (of placebo) patients had HER2-positive disease, with the majority (97%) of all HER2 patients receiving trastuzumab.
There was no difference between the two groups in IDFS events, occurring in 18.5% of patients receiving metformin and 18.3% who received placebo, with most (75.6%) events due to breast cancer (HR, 1.01; P = .92).
There were 131 deaths in the metformin arm and 119 in the placebo arm, with most (75.8%) of the deaths related to breast cancer (HR, 1.10; P = .47).
Other breast cancer outcomes had similar results, including distant disease-free survival (HR, 0.99; P = .94) and breast cancer–free interval (HR, 0.98; P = .87), both of which showed no advantage for metformin.
Possible HER2 advantage
However, the exploratory analysis suggested there may be an advantage for patients with HER2-positive disease, but primarily those who had at least one C allele of a prespecified ATM associated rs11212617 SNP. These patients achieved a higher pathologic complete response rate with metformin than that of those without the allele.
There were 620 patients with HER2-positive disease analyzed, with 99.4% receiving chemotherapy and 96.5% receiving trastuzumab. There were 99 IDFS events, and 47 OS events.
In the entire HER2-positive cohort, patients who received metformin had fewer IDFS events (HR, 0.64; P = .026) compared with the placebo arm. Mortality was lower with metformin (HR for overall survival, 0.53; P = .038).
“Subjects with HER2-positive breast cancer, notably those with at least one C allele of the ATM-associated rs11212617 SNP, experienced improved IDFS and overall survival with metformin,” Dr. Goodwin concluded. “However, no P-value ‘spend’ was allocated to this comparison. As a result, it requires replication in a prospective trial focusing on the HER2-positive population.”
More research?
Stephanie Bernik, MD, chief of breast surgery, Mount Sinai West, and associate professor of breast surgery, Icahn School of Medicine at Mount Sinai, New York, was approached by this news organization for an independent comment.
“It has long been known that obesity, which often correlates with diabetes, increases a woman’s risk of breast cancer,” she said.
“This study tried to show that using a medication that helps control insulin levels, even in those without diabetes, might decrease one’s risk of breast cancer,” she said. “Unfortunately, using metformin had no effect on outcomes in this study, even though it has shown promise in other studies. Perhaps more research needs to be carried out to try to pinpoint which mechanisms of action, if any, might be helpful to combat cancer in those with and without diabetes.”
The study was funded by the Canadian Cancer Trials Group, Cancer Therapy Evaluation Program, Breast Cancer Researcher Foundation, Susan G. Komen for the Cure, Canadian Cancer Society, Apotex, Swiss Cancer Research, and the Canadian Breast Cancer Foundation. Dr. Goodwin has no disclosures.
A version of this article first appeared on Medscape.com.
In the primary analysis, the addition of metformin to standard therapy in moderate/high-risk hormone receptor positive or negative breast cancer did not improve invasive disease–free survival (IDFS), overall survival, or other breast outcomes, explained lead author Pamela J. Goodwin, MD, FRCPC, professor of medicine at the University of Toronto. “Metformin should not be used as breast cancer treatment in this population.”
However, an exploratory analysis suggested that metformin may have a beneficial effect in women with HER2-positive breast cancer, Dr. Goodwin noted.
In this subset, IDFS was improved in patients who received metformin (hazard ratio, 0.64; P = .03), as was overall survival (HR, 0.53; P = .04).
The findings were presented at the San Antonio Breast Cancer Symposium.
“This trial arose from the observation that obesity is associated with poor breast cancer outcomes, and insulin levels are higher in obesity and may be more strongly associated with breast cancer outcomes than obesity,” said Dr. Goodwin.
Metformin was used because of its ability to promote modest weight loss and lower insulin by about 15%-20% in nondiabetic breast cancer survivors. It has also shown anticancer effects in preclinical studies. “In some window of opportunity neoadjuvant studies, it has been shown to reduce Ki67 in breast cancer cells,” she said. “And in preclinical in vitro and in vivo research, it slows growth of breast cancer.”
In addition, emerging evidence from observational studies suggests that the use of metformin to treat diabetes in breast cancer patients may be associated with better outcomes, strengthening the rationale for the study.
The negative results in breast cancer follow recent reports of negative findings in lung cancer, when metformin was found to be ineffective when used alongside chemotherapy in locally advanced lung cancer, as reported by this news organization.
No benefit seen
Metformin was compared to placebo in the phase 3 CCTG MA.32 trial, conducted in 3,649 patients aged 18-74 years with T1-3 N0-3 M0 breast cancer. All patients were treated with standard therapy and were randomized to receive metformin 850 mg twice daily for 5 years or placebo.
In 2016, “futility was declared in ER/PR-negative patients” after a second interim analysis conducted at 29.6 months’ median follow-up, Dr. Goodwin noted. The intervention was stopped in that group, although blinding and follow-up continued.
After that, the study’s primary analysis focused on the 2,533 ER/PR-positive patients (mean age, 52.7 years; mean body mass index, 28.8; approx. 60% postmenopausal).
Just over half of these patients had T2 tumor stage, and most disease was grade 2 or 3.
In addition, 16.5% (of metformin) and 17.4% (of placebo) patients had HER2-positive disease, with the majority (97%) of all HER2 patients receiving trastuzumab.
There was no difference between the two groups in IDFS events, occurring in 18.5% of patients receiving metformin and 18.3% who received placebo, with most (75.6%) events due to breast cancer (HR, 1.01; P = .92).
There were 131 deaths in the metformin arm and 119 in the placebo arm, with most (75.8%) of the deaths related to breast cancer (HR, 1.10; P = .47).
Other breast cancer outcomes had similar results, including distant disease-free survival (HR, 0.99; P = .94) and breast cancer–free interval (HR, 0.98; P = .87), both of which showed no advantage for metformin.
Possible HER2 advantage
However, the exploratory analysis suggested there may be an advantage for patients with HER2-positive disease, but primarily those who had at least one C allele of a prespecified ATM associated rs11212617 SNP. These patients achieved a higher pathologic complete response rate with metformin than that of those without the allele.
There were 620 patients with HER2-positive disease analyzed, with 99.4% receiving chemotherapy and 96.5% receiving trastuzumab. There were 99 IDFS events, and 47 OS events.
In the entire HER2-positive cohort, patients who received metformin had fewer IDFS events (HR, 0.64; P = .026) compared with the placebo arm. Mortality was lower with metformin (HR for overall survival, 0.53; P = .038).
“Subjects with HER2-positive breast cancer, notably those with at least one C allele of the ATM-associated rs11212617 SNP, experienced improved IDFS and overall survival with metformin,” Dr. Goodwin concluded. “However, no P-value ‘spend’ was allocated to this comparison. As a result, it requires replication in a prospective trial focusing on the HER2-positive population.”
More research?
Stephanie Bernik, MD, chief of breast surgery, Mount Sinai West, and associate professor of breast surgery, Icahn School of Medicine at Mount Sinai, New York, was approached by this news organization for an independent comment.
“It has long been known that obesity, which often correlates with diabetes, increases a woman’s risk of breast cancer,” she said.
“This study tried to show that using a medication that helps control insulin levels, even in those without diabetes, might decrease one’s risk of breast cancer,” she said. “Unfortunately, using metformin had no effect on outcomes in this study, even though it has shown promise in other studies. Perhaps more research needs to be carried out to try to pinpoint which mechanisms of action, if any, might be helpful to combat cancer in those with and without diabetes.”
The study was funded by the Canadian Cancer Trials Group, Cancer Therapy Evaluation Program, Breast Cancer Researcher Foundation, Susan G. Komen for the Cure, Canadian Cancer Society, Apotex, Swiss Cancer Research, and the Canadian Breast Cancer Foundation. Dr. Goodwin has no disclosures.
A version of this article first appeared on Medscape.com.
FROM SABCS 2021
Filler complications involving vascular necrosis, vision changes on the rise
analysis showed.
“The ASDS estimates that 1.6 million soft tissue filler procedures were performed in 2019, a 78% increase from 2012,” presenting author Michelle Xiong, a 4th-year student at Brown University, Providence, R.I., said during a virtual abstract session at the annual meeting of the American Society for Dermatologic Surgery. “The popularity of dermal fillers continues to increase. With that, there is increasing concern of possible associated adverse events. Most concerning are those related to vascular occlusion.”
Under the supervision of senior author Kachiu C. Lee, MD, MPH, of Main Line Center for Laser Surgery in Ardmore, Pa., Ms. Xiong and colleagues analyzed the Food and Drug Administration’s Manufacturer and User Facility Device Experience (MAUDE) database of medical device–related adverse event reports, to better understand and characterize dermal filler-related complications. They limited the analysis to adverse events involving injectable fillers from January 2014 to December 2020 and determined the number of complications by type per year and reviewed reports to identify injection site locations. Next, they used the binomial test to compare the proportion of complication categories from 2014 through 2016 and from 2017 through 2020.
In all, 5,994 reports were identified during the 7-year study period. To evaluate trends over time, the researchers estimated the rate of complications per 100 reports each year. While the absolute number of reports increased over time, the rate of adverse events per 100 reports decreased, suggesting an overall improvement in safety.
When the researchers focused on complications involving vascular occlusion, they found that vascular necrosis accounted for 3.5% of all complications, compared with vision changes (1.5% of all complications), and stroke (0.3% of all complications). When comparing the years 2014-2016 with 2017-2020, there was a significant increase in adverse events involving vascular necrosis (0.9%; P = .018) and vision changes (0.94%; P = .001), but no significant difference in the number of reports of stroke (-0.1%; P = .409). “This highlights that serious complications like necrosis and vision changes have increased over time,” Ms. Xiong said.
Overall, the three most common injection sites involving necrosis and vision changes were the cheek, the nose, and the nasolabial fold. The cheek was the most common site associated with stroke. “These findings are similar to those of previous studies, further emphasizing that the nose, nasolabial fold, and cheek are possibly challenging injection sites,” she said.
“In general, as the face is a highly vascular area with many anastomoses, it’s especially important to be aware of facial anatomy when injecting. In addition to awareness of anatomy, injection techniques can influence vascular complications. Unfortunately, the event narratives in the MAUDE database did not go into detail about the procedural technique.”
Ms. Xiong said that as the popularity of dermal fillers continues to grow, “it’s important for providers to understand the possible adverse events, both to better counsel patients and to improve safety management. The proportion of serious complications such as vascular necrosis and vision changes have increased from 2014 to 2020. This highlights an increased need for training to better understand facial anatomy and to emphasize practice techniques to minimize risk.”
Dr. Lee acknowledged certain limitations of the study, including that “submission of adverse events to the MAUDE database are not verified or standardized,” she told this news organization.
“With the ever-increasing popularity of fillers, it is not surprising that the absolute number of complications is rising, but it is also reassuring to see that the overall ratio of complications per hundred reports is down,” said Lawrence J. Green, MD, clinical professor of dermatology at George Washington University, Washington, who was asked to comment on the study. “I would be curious to know what proportion of filler complications are due to non–core practitioners compared to dermatologists and plastic surgeons.”
The researchers reported having no financial disclosures.
Dr. Green disclosed that he is a speaker, consultant, or investigator for numerous pharmaceutical companies.
analysis showed.
“The ASDS estimates that 1.6 million soft tissue filler procedures were performed in 2019, a 78% increase from 2012,” presenting author Michelle Xiong, a 4th-year student at Brown University, Providence, R.I., said during a virtual abstract session at the annual meeting of the American Society for Dermatologic Surgery. “The popularity of dermal fillers continues to increase. With that, there is increasing concern of possible associated adverse events. Most concerning are those related to vascular occlusion.”
Under the supervision of senior author Kachiu C. Lee, MD, MPH, of Main Line Center for Laser Surgery in Ardmore, Pa., Ms. Xiong and colleagues analyzed the Food and Drug Administration’s Manufacturer and User Facility Device Experience (MAUDE) database of medical device–related adverse event reports, to better understand and characterize dermal filler-related complications. They limited the analysis to adverse events involving injectable fillers from January 2014 to December 2020 and determined the number of complications by type per year and reviewed reports to identify injection site locations. Next, they used the binomial test to compare the proportion of complication categories from 2014 through 2016 and from 2017 through 2020.
In all, 5,994 reports were identified during the 7-year study period. To evaluate trends over time, the researchers estimated the rate of complications per 100 reports each year. While the absolute number of reports increased over time, the rate of adverse events per 100 reports decreased, suggesting an overall improvement in safety.
When the researchers focused on complications involving vascular occlusion, they found that vascular necrosis accounted for 3.5% of all complications, compared with vision changes (1.5% of all complications), and stroke (0.3% of all complications). When comparing the years 2014-2016 with 2017-2020, there was a significant increase in adverse events involving vascular necrosis (0.9%; P = .018) and vision changes (0.94%; P = .001), but no significant difference in the number of reports of stroke (-0.1%; P = .409). “This highlights that serious complications like necrosis and vision changes have increased over time,” Ms. Xiong said.
Overall, the three most common injection sites involving necrosis and vision changes were the cheek, the nose, and the nasolabial fold. The cheek was the most common site associated with stroke. “These findings are similar to those of previous studies, further emphasizing that the nose, nasolabial fold, and cheek are possibly challenging injection sites,” she said.
“In general, as the face is a highly vascular area with many anastomoses, it’s especially important to be aware of facial anatomy when injecting. In addition to awareness of anatomy, injection techniques can influence vascular complications. Unfortunately, the event narratives in the MAUDE database did not go into detail about the procedural technique.”
Ms. Xiong said that as the popularity of dermal fillers continues to grow, “it’s important for providers to understand the possible adverse events, both to better counsel patients and to improve safety management. The proportion of serious complications such as vascular necrosis and vision changes have increased from 2014 to 2020. This highlights an increased need for training to better understand facial anatomy and to emphasize practice techniques to minimize risk.”
Dr. Lee acknowledged certain limitations of the study, including that “submission of adverse events to the MAUDE database are not verified or standardized,” she told this news organization.
“With the ever-increasing popularity of fillers, it is not surprising that the absolute number of complications is rising, but it is also reassuring to see that the overall ratio of complications per hundred reports is down,” said Lawrence J. Green, MD, clinical professor of dermatology at George Washington University, Washington, who was asked to comment on the study. “I would be curious to know what proportion of filler complications are due to non–core practitioners compared to dermatologists and plastic surgeons.”
The researchers reported having no financial disclosures.
Dr. Green disclosed that he is a speaker, consultant, or investigator for numerous pharmaceutical companies.
analysis showed.
“The ASDS estimates that 1.6 million soft tissue filler procedures were performed in 2019, a 78% increase from 2012,” presenting author Michelle Xiong, a 4th-year student at Brown University, Providence, R.I., said during a virtual abstract session at the annual meeting of the American Society for Dermatologic Surgery. “The popularity of dermal fillers continues to increase. With that, there is increasing concern of possible associated adverse events. Most concerning are those related to vascular occlusion.”
Under the supervision of senior author Kachiu C. Lee, MD, MPH, of Main Line Center for Laser Surgery in Ardmore, Pa., Ms. Xiong and colleagues analyzed the Food and Drug Administration’s Manufacturer and User Facility Device Experience (MAUDE) database of medical device–related adverse event reports, to better understand and characterize dermal filler-related complications. They limited the analysis to adverse events involving injectable fillers from January 2014 to December 2020 and determined the number of complications by type per year and reviewed reports to identify injection site locations. Next, they used the binomial test to compare the proportion of complication categories from 2014 through 2016 and from 2017 through 2020.
In all, 5,994 reports were identified during the 7-year study period. To evaluate trends over time, the researchers estimated the rate of complications per 100 reports each year. While the absolute number of reports increased over time, the rate of adverse events per 100 reports decreased, suggesting an overall improvement in safety.
When the researchers focused on complications involving vascular occlusion, they found that vascular necrosis accounted for 3.5% of all complications, compared with vision changes (1.5% of all complications), and stroke (0.3% of all complications). When comparing the years 2014-2016 with 2017-2020, there was a significant increase in adverse events involving vascular necrosis (0.9%; P = .018) and vision changes (0.94%; P = .001), but no significant difference in the number of reports of stroke (-0.1%; P = .409). “This highlights that serious complications like necrosis and vision changes have increased over time,” Ms. Xiong said.
Overall, the three most common injection sites involving necrosis and vision changes were the cheek, the nose, and the nasolabial fold. The cheek was the most common site associated with stroke. “These findings are similar to those of previous studies, further emphasizing that the nose, nasolabial fold, and cheek are possibly challenging injection sites,” she said.
“In general, as the face is a highly vascular area with many anastomoses, it’s especially important to be aware of facial anatomy when injecting. In addition to awareness of anatomy, injection techniques can influence vascular complications. Unfortunately, the event narratives in the MAUDE database did not go into detail about the procedural technique.”
Ms. Xiong said that as the popularity of dermal fillers continues to grow, “it’s important for providers to understand the possible adverse events, both to better counsel patients and to improve safety management. The proportion of serious complications such as vascular necrosis and vision changes have increased from 2014 to 2020. This highlights an increased need for training to better understand facial anatomy and to emphasize practice techniques to minimize risk.”
Dr. Lee acknowledged certain limitations of the study, including that “submission of adverse events to the MAUDE database are not verified or standardized,” she told this news organization.
“With the ever-increasing popularity of fillers, it is not surprising that the absolute number of complications is rising, but it is also reassuring to see that the overall ratio of complications per hundred reports is down,” said Lawrence J. Green, MD, clinical professor of dermatology at George Washington University, Washington, who was asked to comment on the study. “I would be curious to know what proportion of filler complications are due to non–core practitioners compared to dermatologists and plastic surgeons.”
The researchers reported having no financial disclosures.
Dr. Green disclosed that he is a speaker, consultant, or investigator for numerous pharmaceutical companies.
FROM ASDS 2021
Updated ACG GERD guideline addresses increased scrutiny of PPI therapy
For the first time since 2013, the American College of Gastroenterology has issued updated evidence-based recommendations and practical guidance on the evaluation and management of gastroesophageal reflux disease (GERD), including pharmacologic, lifestyle, surgical, and endoscopic management.
Over the past 8 years, understanding of the varied presentations of GERD, enhancements in diagnostic testing, and approach to patient management have evolved, and there has been closer scrutiny of proton pump inhibitor (PPI) therapy and its potential side effects, the guideline authors said.
While PPIs remain the “medical treatment of choice” for GERD, multiple studies have raised questions about adverse events, they noted.
“We now know a lot more about PPI adverse events in the sense that we have another 8 years of experience” since the 2013 guideline, first author Philip O. Katz, MD, professor of medicine and director of motility laboratories at Weill Cornell Medicine, New York, added in an interview.
This update emphasizes the importance of making an accurate diagnosis and recommends PPI therapy “when patients really have GERD and being careful to use the lowest effective dose,” Dr. Katz said.
The guideline was published online Nov. 22, 2021, in the American Journal of Gastroenterology.
Benefits outweigh risks
The guideline suggests telling patients that PPIs are the most effective medical treatment for GERD.
Some studies have identified an association between the long-term use of PPIs and the development of several adverse conditions, including intestinal infections, pneumonia, stomach cancer, osteoporosis-related bone fractures, chronic kidney disease, deficiencies of certain vitamins and minerals, heart attacks, strokes, dementia, and early death.
Clinicians should emphasize, however, that these studies have flaws, are not considered definitive, and do not establish a cause-and-effect relationship between PPIs and the adverse conditions.
They should also emphasize to patients that high-quality studies have found that PPIs do not significantly raise the risk of any of these conditions except intestinal infections.
Patients should be told that, for the treatment of GERD, “gastroenterologists generally agree that the well-established benefits of PPIs far outweigh their theoretical risks.”
“Everything in this guideline makes sense,” Scott Gabbard, MD, gastroenterologist and section head, Center for Neurogastroenterology and Motility, Cleveland Clinic, who wasn’t involved in the guideline development, said in an interview.
“A PPI trial for anyone with typical GERD symptoms and having those who respond taper to the lowest effective dose is still the first line for anyone with GERD,” Dr. Gabbard said.
Making the diagnosis
As there is currently no gold standard for the diagnosis of GERD, diagnosis is based on a combination of symptoms, endoscopic evaluation of esophageal mucosa, reflux monitoring, and response to therapeutic intervention, the guideline says.
For patients with classic symptoms of heartburn and regurgitation with no alarm symptoms, the authors recommend an 8-week trial of empiric once-daily PPIs before a meal. If the patient responds, the guideline recommends attempting to discontinue the medication.
The guideline recommends diagnostic endoscopy after PPIs are stopped for 2-4 weeks in patients whose classic symptoms fail to respond adequately to the 8-week empiric PPI trial or in those whose symptoms return when PPIs are discontinued.
For patients with chest pain but no heartburn who have undergone an adequate evaluation to exclude heart disease, the guideline advises objective testing for GERD (endoscopy and/or reflux monitoring).
The use of barium swallow solely as a diagnostic test for GERD is not recommended.
Endoscopy should be the first test for evaluating patients presenting with dysphagia or other alarm symptoms, such as weight loss and gastrointestinal bleeding, as well as for patients with risk factors for Barrett’s esophagus.
For patients in whom the diagnosis of GERD is suspected but unclear and endoscopy fails to show objective evidence of GERD, the guidelines advise reflux monitoring off therapy to establish the diagnosis.
The guideline recommends against reflux monitoring off therapy solely as a diagnostic test for GERD in patients with known endoscopic evidence of Los Angeles grade C or D reflux esophagitis or in patients with long-segment Barrett’s esophagus.
High-resolution manometry solely as a diagnostic test for GERD is also not recommended.
Medical management of GERD
Recommendations for medical management of GERD include weight loss in patients who are overweight or obese, avoidance of meals within 2-3 hours of bedtime, avoidance of tobacco products and “trigger foods,” and elevation of the head of the bed for nighttime symptoms.
Treatment with a PPI is recommended over histamine2-receptor antagonists for healing and maintenance of healing of eosinophilic esophagitis. Taking a PPI 30-60 minutes prior to a meal rather than at bedtime is recommended.
“Use of the lowest effective PPI dose is recommended and logical but must be individualized,” the guideline states.
There is “conceptual rationale” for a trial of switching PPIs for patients who don’t respond to one PPI. However, switching more than once to another PPI “cannot be supported,” the guideline says.
Dr. Gabbard said the advice about switching PPIs in nonresponders is particularly helpful.
“In clinical practice, I see patients who try one PPI, and if it doesn’t work, their doctor puts them on another PPI, then another and another, until they get through five PPIs and gotten nowhere,” he said in an interview.
“This new guideline is very helpful in saying, if a patient has GERD symptoms that do not respond to a PPI, you can do one switch. But, if that doesn’t work, have a low threshold to perform pH testing to determine if the patient truly has reflux or not,” Dr. Gabbard said.
“Some studies have suggested that up to 75% of PPI nonresponders actually don’t have reflux. They have functional heartburn, which is not reflux and is treated without PPIs,” he noted.
One area of controversy relates to abrupt PPI discontinuation and potential rebound acid hypersecretion, resulting in increased reflux symptoms. While this has been found in healthy control patients, strong evidence for an increase in symptoms after abrupt PPI withdrawal is lacking.
The guideline makes “no definitive recommendation as to whether weaning or stopping PPIs cold turkey is a better approach, due to a lack of evidence,” Dr. Katz said in an interview.
For patients with GERD without erosive esophagitis or Barrett’s esophagus and whose symptoms resolve with PPI therapy, the guideline says an attempt should be made to discontinue PPI therapy or to switch to on-demand therapy in which a PPI is taken only when symptoms occur and is stopped when they are relieved.
For patients with Los Angeles grade C or D esophagitis, the recommendation is for maintenance PPI therapy indefinitely or antireflux surgery.
Dr. Gabbard said it’s “nice to have in writing from the ACG that patients with erosive esophagitis or Barrett’s esophagus – those who truly need a PPI – should be on indefinite PPI therapy, because the benefit of a PPI far outweighs the theoretical risks.”
The research had no financial support. Dr. Katz has served as consultant for Phathom Pharma and Medtronic, has received research support from Diversatek and royalties from UpToDate, and serves on the Medscape Gastroenterology advisory board. Dr. Gabbard disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
For the first time since 2013, the American College of Gastroenterology has issued updated evidence-based recommendations and practical guidance on the evaluation and management of gastroesophageal reflux disease (GERD), including pharmacologic, lifestyle, surgical, and endoscopic management.
Over the past 8 years, understanding of the varied presentations of GERD, enhancements in diagnostic testing, and approach to patient management have evolved, and there has been closer scrutiny of proton pump inhibitor (PPI) therapy and its potential side effects, the guideline authors said.
While PPIs remain the “medical treatment of choice” for GERD, multiple studies have raised questions about adverse events, they noted.
“We now know a lot more about PPI adverse events in the sense that we have another 8 years of experience” since the 2013 guideline, first author Philip O. Katz, MD, professor of medicine and director of motility laboratories at Weill Cornell Medicine, New York, added in an interview.
This update emphasizes the importance of making an accurate diagnosis and recommends PPI therapy “when patients really have GERD and being careful to use the lowest effective dose,” Dr. Katz said.
The guideline was published online Nov. 22, 2021, in the American Journal of Gastroenterology.
Benefits outweigh risks
The guideline suggests telling patients that PPIs are the most effective medical treatment for GERD.
Some studies have identified an association between the long-term use of PPIs and the development of several adverse conditions, including intestinal infections, pneumonia, stomach cancer, osteoporosis-related bone fractures, chronic kidney disease, deficiencies of certain vitamins and minerals, heart attacks, strokes, dementia, and early death.
Clinicians should emphasize, however, that these studies have flaws, are not considered definitive, and do not establish a cause-and-effect relationship between PPIs and the adverse conditions.
They should also emphasize to patients that high-quality studies have found that PPIs do not significantly raise the risk of any of these conditions except intestinal infections.
Patients should be told that, for the treatment of GERD, “gastroenterologists generally agree that the well-established benefits of PPIs far outweigh their theoretical risks.”
“Everything in this guideline makes sense,” Scott Gabbard, MD, gastroenterologist and section head, Center for Neurogastroenterology and Motility, Cleveland Clinic, who wasn’t involved in the guideline development, said in an interview.
“A PPI trial for anyone with typical GERD symptoms and having those who respond taper to the lowest effective dose is still the first line for anyone with GERD,” Dr. Gabbard said.
Making the diagnosis
As there is currently no gold standard for the diagnosis of GERD, diagnosis is based on a combination of symptoms, endoscopic evaluation of esophageal mucosa, reflux monitoring, and response to therapeutic intervention, the guideline says.
For patients with classic symptoms of heartburn and regurgitation with no alarm symptoms, the authors recommend an 8-week trial of empiric once-daily PPIs before a meal. If the patient responds, the guideline recommends attempting to discontinue the medication.
The guideline recommends diagnostic endoscopy after PPIs are stopped for 2-4 weeks in patients whose classic symptoms fail to respond adequately to the 8-week empiric PPI trial or in those whose symptoms return when PPIs are discontinued.
For patients with chest pain but no heartburn who have undergone an adequate evaluation to exclude heart disease, the guideline advises objective testing for GERD (endoscopy and/or reflux monitoring).
The use of barium swallow solely as a diagnostic test for GERD is not recommended.
Endoscopy should be the first test for evaluating patients presenting with dysphagia or other alarm symptoms, such as weight loss and gastrointestinal bleeding, as well as for patients with risk factors for Barrett’s esophagus.
For patients in whom the diagnosis of GERD is suspected but unclear and endoscopy fails to show objective evidence of GERD, the guidelines advise reflux monitoring off therapy to establish the diagnosis.
The guideline recommends against reflux monitoring off therapy solely as a diagnostic test for GERD in patients with known endoscopic evidence of Los Angeles grade C or D reflux esophagitis or in patients with long-segment Barrett’s esophagus.
High-resolution manometry solely as a diagnostic test for GERD is also not recommended.
Medical management of GERD
Recommendations for medical management of GERD include weight loss in patients who are overweight or obese, avoidance of meals within 2-3 hours of bedtime, avoidance of tobacco products and “trigger foods,” and elevation of the head of the bed for nighttime symptoms.
Treatment with a PPI is recommended over histamine2-receptor antagonists for healing and maintenance of healing of eosinophilic esophagitis. Taking a PPI 30-60 minutes prior to a meal rather than at bedtime is recommended.
“Use of the lowest effective PPI dose is recommended and logical but must be individualized,” the guideline states.
There is “conceptual rationale” for a trial of switching PPIs for patients who don’t respond to one PPI. However, switching more than once to another PPI “cannot be supported,” the guideline says.
Dr. Gabbard said the advice about switching PPIs in nonresponders is particularly helpful.
“In clinical practice, I see patients who try one PPI, and if it doesn’t work, their doctor puts them on another PPI, then another and another, until they get through five PPIs and gotten nowhere,” he said in an interview.
“This new guideline is very helpful in saying, if a patient has GERD symptoms that do not respond to a PPI, you can do one switch. But, if that doesn’t work, have a low threshold to perform pH testing to determine if the patient truly has reflux or not,” Dr. Gabbard said.
“Some studies have suggested that up to 75% of PPI nonresponders actually don’t have reflux. They have functional heartburn, which is not reflux and is treated without PPIs,” he noted.
One area of controversy relates to abrupt PPI discontinuation and potential rebound acid hypersecretion, resulting in increased reflux symptoms. While this has been found in healthy control patients, strong evidence for an increase in symptoms after abrupt PPI withdrawal is lacking.
The guideline makes “no definitive recommendation as to whether weaning or stopping PPIs cold turkey is a better approach, due to a lack of evidence,” Dr. Katz said in an interview.
For patients with GERD without erosive esophagitis or Barrett’s esophagus and whose symptoms resolve with PPI therapy, the guideline says an attempt should be made to discontinue PPI therapy or to switch to on-demand therapy in which a PPI is taken only when symptoms occur and is stopped when they are relieved.
For patients with Los Angeles grade C or D esophagitis, the recommendation is for maintenance PPI therapy indefinitely or antireflux surgery.
Dr. Gabbard said it’s “nice to have in writing from the ACG that patients with erosive esophagitis or Barrett’s esophagus – those who truly need a PPI – should be on indefinite PPI therapy, because the benefit of a PPI far outweighs the theoretical risks.”
The research had no financial support. Dr. Katz has served as consultant for Phathom Pharma and Medtronic, has received research support from Diversatek and royalties from UpToDate, and serves on the Medscape Gastroenterology advisory board. Dr. Gabbard disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
For the first time since 2013, the American College of Gastroenterology has issued updated evidence-based recommendations and practical guidance on the evaluation and management of gastroesophageal reflux disease (GERD), including pharmacologic, lifestyle, surgical, and endoscopic management.
Over the past 8 years, understanding of the varied presentations of GERD, enhancements in diagnostic testing, and approach to patient management have evolved, and there has been closer scrutiny of proton pump inhibitor (PPI) therapy and its potential side effects, the guideline authors said.
While PPIs remain the “medical treatment of choice” for GERD, multiple studies have raised questions about adverse events, they noted.
“We now know a lot more about PPI adverse events in the sense that we have another 8 years of experience” since the 2013 guideline, first author Philip O. Katz, MD, professor of medicine and director of motility laboratories at Weill Cornell Medicine, New York, added in an interview.
This update emphasizes the importance of making an accurate diagnosis and recommends PPI therapy “when patients really have GERD and being careful to use the lowest effective dose,” Dr. Katz said.
The guideline was published online Nov. 22, 2021, in the American Journal of Gastroenterology.
Benefits outweigh risks
The guideline suggests telling patients that PPIs are the most effective medical treatment for GERD.
Some studies have identified an association between the long-term use of PPIs and the development of several adverse conditions, including intestinal infections, pneumonia, stomach cancer, osteoporosis-related bone fractures, chronic kidney disease, deficiencies of certain vitamins and minerals, heart attacks, strokes, dementia, and early death.
Clinicians should emphasize, however, that these studies have flaws, are not considered definitive, and do not establish a cause-and-effect relationship between PPIs and the adverse conditions.
They should also emphasize to patients that high-quality studies have found that PPIs do not significantly raise the risk of any of these conditions except intestinal infections.
Patients should be told that, for the treatment of GERD, “gastroenterologists generally agree that the well-established benefits of PPIs far outweigh their theoretical risks.”
“Everything in this guideline makes sense,” Scott Gabbard, MD, gastroenterologist and section head, Center for Neurogastroenterology and Motility, Cleveland Clinic, who wasn’t involved in the guideline development, said in an interview.
“A PPI trial for anyone with typical GERD symptoms and having those who respond taper to the lowest effective dose is still the first line for anyone with GERD,” Dr. Gabbard said.
Making the diagnosis
As there is currently no gold standard for the diagnosis of GERD, diagnosis is based on a combination of symptoms, endoscopic evaluation of esophageal mucosa, reflux monitoring, and response to therapeutic intervention, the guideline says.
For patients with classic symptoms of heartburn and regurgitation with no alarm symptoms, the authors recommend an 8-week trial of empiric once-daily PPIs before a meal. If the patient responds, the guideline recommends attempting to discontinue the medication.
The guideline recommends diagnostic endoscopy after PPIs are stopped for 2-4 weeks in patients whose classic symptoms fail to respond adequately to the 8-week empiric PPI trial or in those whose symptoms return when PPIs are discontinued.
For patients with chest pain but no heartburn who have undergone an adequate evaluation to exclude heart disease, the guideline advises objective testing for GERD (endoscopy and/or reflux monitoring).
The use of barium swallow solely as a diagnostic test for GERD is not recommended.
Endoscopy should be the first test for evaluating patients presenting with dysphagia or other alarm symptoms, such as weight loss and gastrointestinal bleeding, as well as for patients with risk factors for Barrett’s esophagus.
For patients in whom the diagnosis of GERD is suspected but unclear and endoscopy fails to show objective evidence of GERD, the guidelines advise reflux monitoring off therapy to establish the diagnosis.
The guideline recommends against reflux monitoring off therapy solely as a diagnostic test for GERD in patients with known endoscopic evidence of Los Angeles grade C or D reflux esophagitis or in patients with long-segment Barrett’s esophagus.
High-resolution manometry solely as a diagnostic test for GERD is also not recommended.
Medical management of GERD
Recommendations for medical management of GERD include weight loss in patients who are overweight or obese, avoidance of meals within 2-3 hours of bedtime, avoidance of tobacco products and “trigger foods,” and elevation of the head of the bed for nighttime symptoms.
Treatment with a PPI is recommended over histamine2-receptor antagonists for healing and maintenance of healing of eosinophilic esophagitis. Taking a PPI 30-60 minutes prior to a meal rather than at bedtime is recommended.
“Use of the lowest effective PPI dose is recommended and logical but must be individualized,” the guideline states.
There is “conceptual rationale” for a trial of switching PPIs for patients who don’t respond to one PPI. However, switching more than once to another PPI “cannot be supported,” the guideline says.
Dr. Gabbard said the advice about switching PPIs in nonresponders is particularly helpful.
“In clinical practice, I see patients who try one PPI, and if it doesn’t work, their doctor puts them on another PPI, then another and another, until they get through five PPIs and gotten nowhere,” he said in an interview.
“This new guideline is very helpful in saying, if a patient has GERD symptoms that do not respond to a PPI, you can do one switch. But, if that doesn’t work, have a low threshold to perform pH testing to determine if the patient truly has reflux or not,” Dr. Gabbard said.
“Some studies have suggested that up to 75% of PPI nonresponders actually don’t have reflux. They have functional heartburn, which is not reflux and is treated without PPIs,” he noted.
One area of controversy relates to abrupt PPI discontinuation and potential rebound acid hypersecretion, resulting in increased reflux symptoms. While this has been found in healthy control patients, strong evidence for an increase in symptoms after abrupt PPI withdrawal is lacking.
The guideline makes “no definitive recommendation as to whether weaning or stopping PPIs cold turkey is a better approach, due to a lack of evidence,” Dr. Katz said in an interview.
For patients with GERD without erosive esophagitis or Barrett’s esophagus and whose symptoms resolve with PPI therapy, the guideline says an attempt should be made to discontinue PPI therapy or to switch to on-demand therapy in which a PPI is taken only when symptoms occur and is stopped when they are relieved.
For patients with Los Angeles grade C or D esophagitis, the recommendation is for maintenance PPI therapy indefinitely or antireflux surgery.
Dr. Gabbard said it’s “nice to have in writing from the ACG that patients with erosive esophagitis or Barrett’s esophagus – those who truly need a PPI – should be on indefinite PPI therapy, because the benefit of a PPI far outweighs the theoretical risks.”
The research had no financial support. Dr. Katz has served as consultant for Phathom Pharma and Medtronic, has received research support from Diversatek and royalties from UpToDate, and serves on the Medscape Gastroenterology advisory board. Dr. Gabbard disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE AMERICAN JOURNAL OF GASTROENTEROLOGY
Supreme Court leaves Texas abortion law in place
In a highly anticipated decision, the U.S. Supreme Court ruled Dec. 10 that the controversial Texas abortion law that restricts the procedure to women pregnant for 6 weeks or less may continue to be enforced, but allowed for state and federal courts to hear challenges to whether it violates the Constitution.
As anti-abortion organizations celebrate and abortion rights groups confer on what the decision could mean for women not only in Texas but across the United States, there is another, bigger implication as well.
The Texas law generated a lot of controversy, in part, because it took an unusual approach. In authorizing essentially anyone across the nation to file a lawsuit against a woman in the lone star state who seeks the procedure outside the law, or anyone who assists her -- including healthcare professionals, it opens up the potential for similar legal challenges to other Supreme Court rulings on marriage, guns, and other rights.
The vote was 5-4, with Chief Justice John Roberts joining the liberal members of the court in dissenting.
The ruling allows abortion rights supporters to sue in state court, where a Texas judge on Dec. 9 ruled the law unconstitutional. He stopped short, however, of issuing an injunction against. Abortion rights opponents have vowed to appeal District Judge David Peeples’ ruling.
A timeline on the case
The law took effect on Sept. 1, 2021. The day before, the Supreme Court did not act to put a hold on the law as requested by abortion rights organizations. As a result, many Texas women seeking the procedure after 6 weeks traveled to nearby states. On Oct. 25, the Court agreed to hear a challenge to the law by the Biden Administration.
The Dec. 10 Supreme Court decision to uphold the Texas law contrasts with a general consensus among many legal observers that the justices were receptive to blocking the law, based on questions and issues the judges raised during oral arguments on Nov. 1, 2021.
A separate legal challenge to abortion rights involves a Mississippi law banning the procedure starting at 15 weeks of pregnancy. The Supreme Court justices scheduled oral arguments in that case for Dec. 1, and are expected to issue a ruling in that case in June 2022.
A version of this article first appeared on WebMD.com .
In a highly anticipated decision, the U.S. Supreme Court ruled Dec. 10 that the controversial Texas abortion law that restricts the procedure to women pregnant for 6 weeks or less may continue to be enforced, but allowed for state and federal courts to hear challenges to whether it violates the Constitution.
As anti-abortion organizations celebrate and abortion rights groups confer on what the decision could mean for women not only in Texas but across the United States, there is another, bigger implication as well.
The Texas law generated a lot of controversy, in part, because it took an unusual approach. In authorizing essentially anyone across the nation to file a lawsuit against a woman in the lone star state who seeks the procedure outside the law, or anyone who assists her -- including healthcare professionals, it opens up the potential for similar legal challenges to other Supreme Court rulings on marriage, guns, and other rights.
The vote was 5-4, with Chief Justice John Roberts joining the liberal members of the court in dissenting.
The ruling allows abortion rights supporters to sue in state court, where a Texas judge on Dec. 9 ruled the law unconstitutional. He stopped short, however, of issuing an injunction against. Abortion rights opponents have vowed to appeal District Judge David Peeples’ ruling.
A timeline on the case
The law took effect on Sept. 1, 2021. The day before, the Supreme Court did not act to put a hold on the law as requested by abortion rights organizations. As a result, many Texas women seeking the procedure after 6 weeks traveled to nearby states. On Oct. 25, the Court agreed to hear a challenge to the law by the Biden Administration.
The Dec. 10 Supreme Court decision to uphold the Texas law contrasts with a general consensus among many legal observers that the justices were receptive to blocking the law, based on questions and issues the judges raised during oral arguments on Nov. 1, 2021.
A separate legal challenge to abortion rights involves a Mississippi law banning the procedure starting at 15 weeks of pregnancy. The Supreme Court justices scheduled oral arguments in that case for Dec. 1, and are expected to issue a ruling in that case in June 2022.
A version of this article first appeared on WebMD.com .
In a highly anticipated decision, the U.S. Supreme Court ruled Dec. 10 that the controversial Texas abortion law that restricts the procedure to women pregnant for 6 weeks or less may continue to be enforced, but allowed for state and federal courts to hear challenges to whether it violates the Constitution.
As anti-abortion organizations celebrate and abortion rights groups confer on what the decision could mean for women not only in Texas but across the United States, there is another, bigger implication as well.
The Texas law generated a lot of controversy, in part, because it took an unusual approach. In authorizing essentially anyone across the nation to file a lawsuit against a woman in the lone star state who seeks the procedure outside the law, or anyone who assists her -- including healthcare professionals, it opens up the potential for similar legal challenges to other Supreme Court rulings on marriage, guns, and other rights.
The vote was 5-4, with Chief Justice John Roberts joining the liberal members of the court in dissenting.
The ruling allows abortion rights supporters to sue in state court, where a Texas judge on Dec. 9 ruled the law unconstitutional. He stopped short, however, of issuing an injunction against. Abortion rights opponents have vowed to appeal District Judge David Peeples’ ruling.
A timeline on the case
The law took effect on Sept. 1, 2021. The day before, the Supreme Court did not act to put a hold on the law as requested by abortion rights organizations. As a result, many Texas women seeking the procedure after 6 weeks traveled to nearby states. On Oct. 25, the Court agreed to hear a challenge to the law by the Biden Administration.
The Dec. 10 Supreme Court decision to uphold the Texas law contrasts with a general consensus among many legal observers that the justices were receptive to blocking the law, based on questions and issues the judges raised during oral arguments on Nov. 1, 2021.
A separate legal challenge to abortion rights involves a Mississippi law banning the procedure starting at 15 weeks of pregnancy. The Supreme Court justices scheduled oral arguments in that case for Dec. 1, and are expected to issue a ruling in that case in June 2022.
A version of this article first appeared on WebMD.com .
Omicron may require fourth vaccine dose, Pfizer says
, Pfizer officials said on Dec. 8.
The standard two doses may be less effective against the variant, the company announced earlier in the day, and a booster dose increases neutralizing antibodies.
But the timeline might need to be moved up for a fourth dose. Previously, Pfizer CEO Albert Bourla, PhD, said another dose might be needed about a year after a third shot. Now the company’s scientists believe that a fourth shot, which targets the Omicron variant, could be required sooner.
“With Omicron, we need to wait and see because we have very little information. We may need it faster,” Dr. Bourla said on CNBC’s Squawk Box.
“But for right now, the most important thing is that we have winter in front of us,” he said. “From a healthcare perspective, it is important to understand that we need to be well-protected to go through the winter.”
A third dose should provide protection throughout the winter, Dr. Bourla said. That may buy time until the early spring to develop new shots that target Omicron, which Pfizer could have ready by March, according to Bloomberg News.
As of the afternoon of Dec. 8, 43 people in 19 states had tested positive for the Omicron variant, according to The Associated Press. More than 75% had been vaccinated, and a third had had booster shots. About a third had traveled internationally.
Nearly all of them have had mild symptoms so far, the AP reported, with the most common symptoms being a cough, congestion, and fatigue. One person has been hospitalized, but no deaths have been reported so far.
The CDC is still trying to determine how the Omicron variant may affect the course of the pandemic and whether the strain is more contagious or causes more severe disease.
“What we generally know is the more mutations a variant has, the higher level you need your immunity to be,” Rochelle Walensky, MD, director of the CDC, told the AP.
“We want to make sure we bolster everybody’s immunity,” she said. “And that’s really what motivated the decision to expand our guidance [on boosters for all adults].”
The Omicron variant has been reported in 57 countries so far, World Health Organization officials reported Dec. 8, and they expect that number to continue growing.
“Certain features of Omicron, including its global spread and large number of mutations, suggest it could have a major impact on the course of the pandemic. Exactly what that impact will be is still difficult to know,” Tedros Adhanom Ghebreyesus, PhD, the World Health Organization’s director-general, said during a media briefing.
Several studies suggest that Omicron leads to a rapid increase in transmission, he said, though scientists are still trying to understand whether it can “outcompete Delta.” Data from South Africa also suggests a higher risk of reinfection with Omicron, though it appears to cause milder disease than Delta, he noted.
“Even though we still need answers to some crucial questions, we are not defenseless against Omicron or Delta,” he said. “The steps countries take today, and in the coming days and weeks, will determine how Omicron unfolds.”
A version of this article first appeared on WebMD.com.
, Pfizer officials said on Dec. 8.
The standard two doses may be less effective against the variant, the company announced earlier in the day, and a booster dose increases neutralizing antibodies.
But the timeline might need to be moved up for a fourth dose. Previously, Pfizer CEO Albert Bourla, PhD, said another dose might be needed about a year after a third shot. Now the company’s scientists believe that a fourth shot, which targets the Omicron variant, could be required sooner.
“With Omicron, we need to wait and see because we have very little information. We may need it faster,” Dr. Bourla said on CNBC’s Squawk Box.
“But for right now, the most important thing is that we have winter in front of us,” he said. “From a healthcare perspective, it is important to understand that we need to be well-protected to go through the winter.”
A third dose should provide protection throughout the winter, Dr. Bourla said. That may buy time until the early spring to develop new shots that target Omicron, which Pfizer could have ready by March, according to Bloomberg News.
As of the afternoon of Dec. 8, 43 people in 19 states had tested positive for the Omicron variant, according to The Associated Press. More than 75% had been vaccinated, and a third had had booster shots. About a third had traveled internationally.
Nearly all of them have had mild symptoms so far, the AP reported, with the most common symptoms being a cough, congestion, and fatigue. One person has been hospitalized, but no deaths have been reported so far.
The CDC is still trying to determine how the Omicron variant may affect the course of the pandemic and whether the strain is more contagious or causes more severe disease.
“What we generally know is the more mutations a variant has, the higher level you need your immunity to be,” Rochelle Walensky, MD, director of the CDC, told the AP.
“We want to make sure we bolster everybody’s immunity,” she said. “And that’s really what motivated the decision to expand our guidance [on boosters for all adults].”
The Omicron variant has been reported in 57 countries so far, World Health Organization officials reported Dec. 8, and they expect that number to continue growing.
“Certain features of Omicron, including its global spread and large number of mutations, suggest it could have a major impact on the course of the pandemic. Exactly what that impact will be is still difficult to know,” Tedros Adhanom Ghebreyesus, PhD, the World Health Organization’s director-general, said during a media briefing.
Several studies suggest that Omicron leads to a rapid increase in transmission, he said, though scientists are still trying to understand whether it can “outcompete Delta.” Data from South Africa also suggests a higher risk of reinfection with Omicron, though it appears to cause milder disease than Delta, he noted.
“Even though we still need answers to some crucial questions, we are not defenseless against Omicron or Delta,” he said. “The steps countries take today, and in the coming days and weeks, will determine how Omicron unfolds.”
A version of this article first appeared on WebMD.com.
, Pfizer officials said on Dec. 8.
The standard two doses may be less effective against the variant, the company announced earlier in the day, and a booster dose increases neutralizing antibodies.
But the timeline might need to be moved up for a fourth dose. Previously, Pfizer CEO Albert Bourla, PhD, said another dose might be needed about a year after a third shot. Now the company’s scientists believe that a fourth shot, which targets the Omicron variant, could be required sooner.
“With Omicron, we need to wait and see because we have very little information. We may need it faster,” Dr. Bourla said on CNBC’s Squawk Box.
“But for right now, the most important thing is that we have winter in front of us,” he said. “From a healthcare perspective, it is important to understand that we need to be well-protected to go through the winter.”
A third dose should provide protection throughout the winter, Dr. Bourla said. That may buy time until the early spring to develop new shots that target Omicron, which Pfizer could have ready by March, according to Bloomberg News.
As of the afternoon of Dec. 8, 43 people in 19 states had tested positive for the Omicron variant, according to The Associated Press. More than 75% had been vaccinated, and a third had had booster shots. About a third had traveled internationally.
Nearly all of them have had mild symptoms so far, the AP reported, with the most common symptoms being a cough, congestion, and fatigue. One person has been hospitalized, but no deaths have been reported so far.
The CDC is still trying to determine how the Omicron variant may affect the course of the pandemic and whether the strain is more contagious or causes more severe disease.
“What we generally know is the more mutations a variant has, the higher level you need your immunity to be,” Rochelle Walensky, MD, director of the CDC, told the AP.
“We want to make sure we bolster everybody’s immunity,” she said. “And that’s really what motivated the decision to expand our guidance [on boosters for all adults].”
The Omicron variant has been reported in 57 countries so far, World Health Organization officials reported Dec. 8, and they expect that number to continue growing.
“Certain features of Omicron, including its global spread and large number of mutations, suggest it could have a major impact on the course of the pandemic. Exactly what that impact will be is still difficult to know,” Tedros Adhanom Ghebreyesus, PhD, the World Health Organization’s director-general, said during a media briefing.
Several studies suggest that Omicron leads to a rapid increase in transmission, he said, though scientists are still trying to understand whether it can “outcompete Delta.” Data from South Africa also suggests a higher risk of reinfection with Omicron, though it appears to cause milder disease than Delta, he noted.
“Even though we still need answers to some crucial questions, we are not defenseless against Omicron or Delta,” he said. “The steps countries take today, and in the coming days and weeks, will determine how Omicron unfolds.”
A version of this article first appeared on WebMD.com.
Idiopathic pulmonary fibrosis – a mortality predictor found?
A low lymphocyte-to-monocyte ratio (LMR) is associated with worse survival in newly-diagnosed patients with idiopathic pulmonary fibrosis (IPF), according to a new retrospective, single-center analysis. Patients with both IPF and lung cancer also had a lower LMR than patients with IPF alone.
The study, published online in Respiratory Medicine, was conducted among 77 newly diagnosed patients, 40 end-stage IPF patients, and 17 patients with IPF and lung cancer. All received at least 1 year of antifibrotic therapy (pirfenidone or nintedanib). The researchers collected demographic and clinical data between December 2014 and December 2020.
The disease course of IPF is difficult to predict, with some patients progressing slowly, and others suffer a rapid decline to respiratory failure. Previous studies found that higher levels of monocytes are associated with higher mortality in IPF and other fibrotic lung disease, and both neutrophil-to-lymphocyte ratio (NLR) and LMR have been shown to predict mortality in lung cancer.
A previous study found that IPF patients had a higher NLR and a lower LMR than controls, but that research did not consider the impact of antifibrotic treatment, which may improve outcomes.
There has been accumulating cellular and molecular evidence that leukocyte population abnormalities are associated with IPF outcomes, but that work was more discovery based and relied on tests that aren’t readily available clinically, said Erica L. Herzog, MD, PhD, who was asked to comment on the study. “It’s provided a lot of insight into potential new mechanisms and potential biomarkers, but their clinical utility for patients is limited. So the use of lymphocyte-to-monocyte ratios that can be obtained from a complete blood cell count, which is a test that can be done in any hospital, would really be a game-changer in terms of predictive algorithms for patients with IPF,” said Dr. Herzog, who is a professor of medicine and pathology at Yale University, New Haven, Conn., and director of the Yale ILD Center of Excellence.
In humans, abnormalities in circulating monocytes and lymphocytes have individually been linked worse IPF outcomes. Animal studies have implicated monocyte-derived cells in lung fibrosis, but because animal studies have shown that lymphocyte populations are not required for fibrosis, more work is needed.
“I think what we’re finding is that lymphocytes probably have a regulatory role, and there’s probably a protective population and potentially a pathogenic population. Something about the balance between adaptive immunity, which is reflected by your lymphocytes, and innate immunity, which is reflected by your monocytes. Something about that balance is important for tissue homeostasis, and then when it’s disrupted or perturbed, fibrosis ensues,” said Dr. Herzog.
Study details
The newly diagnosed patients were older (mean age, 70 years) than the end-stage IPF patients (mean age, 60 years) and patients with IPF and lung cancer (mean age, 64 years; P < .0001).
Among newly diagnosed IPF patients, a receiving operating characteristic analysis before antifibrotic treatment determined a cutoff LMR value of less than 4.18, with an area under the curve of 0.67 (P = .025). Values below 4.18 were associated with shorter survival (hazard ratio, 6.88; P = .027).
Patients with LMR less than 4.18 were more likely to be men (89% vs. 67%; P = .036), had a lower percent predicted forced vital capacity (76% vs. 87%; P = .023), and were more likely to die or undergo lung transplant (34% vs. 5%; P = .009).
Mortality results
A Kaplan-Meier curve illustrated a stark difference between patients with LMR of 4.18 or higher, nearly all of whom remained alive out to almost 100 months of follow-up. Around 30% of those with LMR less than 4.18 remained alive while close to 100% of the patients with LMR below this value showed worsened outcomes. “You don’t normally see curves like that,” said Dr. Herzog.
There was no significant difference in blood cell counts and ratios at the time of IPF diagnosis and after 1 year of antifibrotic treatment, which suggests that the risk profile is independent of treatment, according to the study authors.
Among patient subgroups, those with IPF and lung cancer had the lowest mean LMR (2.2), followed by newly diagnosed patients (3.5), and those with end-stage disease (3.6; P < .0001).
The study authors reported financial relationships with various pharmaceutical companies. Dr. Herzog had no relevant financial disclosures.
A low lymphocyte-to-monocyte ratio (LMR) is associated with worse survival in newly-diagnosed patients with idiopathic pulmonary fibrosis (IPF), according to a new retrospective, single-center analysis. Patients with both IPF and lung cancer also had a lower LMR than patients with IPF alone.
The study, published online in Respiratory Medicine, was conducted among 77 newly diagnosed patients, 40 end-stage IPF patients, and 17 patients with IPF and lung cancer. All received at least 1 year of antifibrotic therapy (pirfenidone or nintedanib). The researchers collected demographic and clinical data between December 2014 and December 2020.
The disease course of IPF is difficult to predict, with some patients progressing slowly, and others suffer a rapid decline to respiratory failure. Previous studies found that higher levels of monocytes are associated with higher mortality in IPF and other fibrotic lung disease, and both neutrophil-to-lymphocyte ratio (NLR) and LMR have been shown to predict mortality in lung cancer.
A previous study found that IPF patients had a higher NLR and a lower LMR than controls, but that research did not consider the impact of antifibrotic treatment, which may improve outcomes.
There has been accumulating cellular and molecular evidence that leukocyte population abnormalities are associated with IPF outcomes, but that work was more discovery based and relied on tests that aren’t readily available clinically, said Erica L. Herzog, MD, PhD, who was asked to comment on the study. “It’s provided a lot of insight into potential new mechanisms and potential biomarkers, but their clinical utility for patients is limited. So the use of lymphocyte-to-monocyte ratios that can be obtained from a complete blood cell count, which is a test that can be done in any hospital, would really be a game-changer in terms of predictive algorithms for patients with IPF,” said Dr. Herzog, who is a professor of medicine and pathology at Yale University, New Haven, Conn., and director of the Yale ILD Center of Excellence.
In humans, abnormalities in circulating monocytes and lymphocytes have individually been linked worse IPF outcomes. Animal studies have implicated monocyte-derived cells in lung fibrosis, but because animal studies have shown that lymphocyte populations are not required for fibrosis, more work is needed.
“I think what we’re finding is that lymphocytes probably have a regulatory role, and there’s probably a protective population and potentially a pathogenic population. Something about the balance between adaptive immunity, which is reflected by your lymphocytes, and innate immunity, which is reflected by your monocytes. Something about that balance is important for tissue homeostasis, and then when it’s disrupted or perturbed, fibrosis ensues,” said Dr. Herzog.
Study details
The newly diagnosed patients were older (mean age, 70 years) than the end-stage IPF patients (mean age, 60 years) and patients with IPF and lung cancer (mean age, 64 years; P < .0001).
Among newly diagnosed IPF patients, a receiving operating characteristic analysis before antifibrotic treatment determined a cutoff LMR value of less than 4.18, with an area under the curve of 0.67 (P = .025). Values below 4.18 were associated with shorter survival (hazard ratio, 6.88; P = .027).
Patients with LMR less than 4.18 were more likely to be men (89% vs. 67%; P = .036), had a lower percent predicted forced vital capacity (76% vs. 87%; P = .023), and were more likely to die or undergo lung transplant (34% vs. 5%; P = .009).
Mortality results
A Kaplan-Meier curve illustrated a stark difference between patients with LMR of 4.18 or higher, nearly all of whom remained alive out to almost 100 months of follow-up. Around 30% of those with LMR less than 4.18 remained alive while close to 100% of the patients with LMR below this value showed worsened outcomes. “You don’t normally see curves like that,” said Dr. Herzog.
There was no significant difference in blood cell counts and ratios at the time of IPF diagnosis and after 1 year of antifibrotic treatment, which suggests that the risk profile is independent of treatment, according to the study authors.
Among patient subgroups, those with IPF and lung cancer had the lowest mean LMR (2.2), followed by newly diagnosed patients (3.5), and those with end-stage disease (3.6; P < .0001).
The study authors reported financial relationships with various pharmaceutical companies. Dr. Herzog had no relevant financial disclosures.
A low lymphocyte-to-monocyte ratio (LMR) is associated with worse survival in newly-diagnosed patients with idiopathic pulmonary fibrosis (IPF), according to a new retrospective, single-center analysis. Patients with both IPF and lung cancer also had a lower LMR than patients with IPF alone.
The study, published online in Respiratory Medicine, was conducted among 77 newly diagnosed patients, 40 end-stage IPF patients, and 17 patients with IPF and lung cancer. All received at least 1 year of antifibrotic therapy (pirfenidone or nintedanib). The researchers collected demographic and clinical data between December 2014 and December 2020.
The disease course of IPF is difficult to predict, with some patients progressing slowly, and others suffer a rapid decline to respiratory failure. Previous studies found that higher levels of monocytes are associated with higher mortality in IPF and other fibrotic lung disease, and both neutrophil-to-lymphocyte ratio (NLR) and LMR have been shown to predict mortality in lung cancer.
A previous study found that IPF patients had a higher NLR and a lower LMR than controls, but that research did not consider the impact of antifibrotic treatment, which may improve outcomes.
There has been accumulating cellular and molecular evidence that leukocyte population abnormalities are associated with IPF outcomes, but that work was more discovery based and relied on tests that aren’t readily available clinically, said Erica L. Herzog, MD, PhD, who was asked to comment on the study. “It’s provided a lot of insight into potential new mechanisms and potential biomarkers, but their clinical utility for patients is limited. So the use of lymphocyte-to-monocyte ratios that can be obtained from a complete blood cell count, which is a test that can be done in any hospital, would really be a game-changer in terms of predictive algorithms for patients with IPF,” said Dr. Herzog, who is a professor of medicine and pathology at Yale University, New Haven, Conn., and director of the Yale ILD Center of Excellence.
In humans, abnormalities in circulating monocytes and lymphocytes have individually been linked worse IPF outcomes. Animal studies have implicated monocyte-derived cells in lung fibrosis, but because animal studies have shown that lymphocyte populations are not required for fibrosis, more work is needed.
“I think what we’re finding is that lymphocytes probably have a regulatory role, and there’s probably a protective population and potentially a pathogenic population. Something about the balance between adaptive immunity, which is reflected by your lymphocytes, and innate immunity, which is reflected by your monocytes. Something about that balance is important for tissue homeostasis, and then when it’s disrupted or perturbed, fibrosis ensues,” said Dr. Herzog.
Study details
The newly diagnosed patients were older (mean age, 70 years) than the end-stage IPF patients (mean age, 60 years) and patients with IPF and lung cancer (mean age, 64 years; P < .0001).
Among newly diagnosed IPF patients, a receiving operating characteristic analysis before antifibrotic treatment determined a cutoff LMR value of less than 4.18, with an area under the curve of 0.67 (P = .025). Values below 4.18 were associated with shorter survival (hazard ratio, 6.88; P = .027).
Patients with LMR less than 4.18 were more likely to be men (89% vs. 67%; P = .036), had a lower percent predicted forced vital capacity (76% vs. 87%; P = .023), and were more likely to die or undergo lung transplant (34% vs. 5%; P = .009).
Mortality results
A Kaplan-Meier curve illustrated a stark difference between patients with LMR of 4.18 or higher, nearly all of whom remained alive out to almost 100 months of follow-up. Around 30% of those with LMR less than 4.18 remained alive while close to 100% of the patients with LMR below this value showed worsened outcomes. “You don’t normally see curves like that,” said Dr. Herzog.
There was no significant difference in blood cell counts and ratios at the time of IPF diagnosis and after 1 year of antifibrotic treatment, which suggests that the risk profile is independent of treatment, according to the study authors.
Among patient subgroups, those with IPF and lung cancer had the lowest mean LMR (2.2), followed by newly diagnosed patients (3.5), and those with end-stage disease (3.6; P < .0001).
The study authors reported financial relationships with various pharmaceutical companies. Dr. Herzog had no relevant financial disclosures.
FROM RESPIRATORY MEDICINE
Decreasing the burden of postacute sequelae of SARS-CoV-2 infection: What we know
On March 11, 2020, the World Health Organization (WHO) declared SARS-CoV-2 a pandemic. As of October 2021, there are over 240 million confirmed COVID-19 cases and over 4 million deaths globally, with the United States having the highest incidence of both cases and deaths (https://covid.cdc.gov/covid-data-tracker/#datatracker-home). As many as 87% of COVID-19 survivors experience persistent symptoms that last beyond the acute phase of illness (Carfi A, et al. JAMA. 2020;324[6]:603-5). In February 2021, the National Institutes of Health (NIH) called for a consensus term to describe this protracted form of COVID-19, and defined it as Post-acute Sequelae of SARS-CoV-2 infection (PASC) (https://www.nih.gov/about-nih/who-we-are/nih-director/statements/nih-launches-new-initiative-study-long-covid).
What are the PASC manifestations?
PASC has a heterogeneous presentation with a broad spectrum of manifestations and can vary from single to multiorgan system involvement. Commonly, PASC involves pulmonary abnormalities (shortness of breath, exercise intolerance, abnormal pulmonary functional test [PFT] and chest imaging), neurocognitive impairments (difficulty concentrating and memory loss), mental health disorders (anxiety, depression, and post-traumatic stress disorder), functional mobility impairments, as well as general and constitutional symptoms (fatigue and muscle weakness) (Groff D, et al. JAMA Netw Open. 2021;4[10]). The most prevalent pulmonary physiologic impairment is reduced diffusion capacity that has been shown to be associated with the severity of acute illness, while the most common radiologic abnormalities on chest CT scan are ground glass opacities. Some studies have shown a temporal improvement in pulmonary physiology and exercise capacity; however, persistent physiological and radiographic abnormalities persist in some patients up to 12 months after discharge (Wu X, et al. Lancet Respir Med. 2021;9:747-54). An abnormal or persistent hyper-inflammatory state, viral-induced autoimmune reaction, and ongoing viral activity have been proposed as possible biological mechanisms for PASC; however, the pathophysiology remains mostly unknown.
Who does PASC affect?
PASC affects patients irrespective of premorbid condition and severity of symptoms in the acute phase. It spans from those who had mild disease not requiring hospitalization to those who had critical illness requiring intensive care unit (ICU) management. COVID-19 ICU survivors seem to have an overlap of PASC and post-intensive care syndrome (PICS), defined by new or worsening physical, cognitive, and/or psychiatric impairments after critical illness. (Biehl M, et al. Cleve Clin J Med. 2020 Aug 5).
Who do we evaluate for PASC?
Given the complexity and chronicity of the associated symptoms and their impact on several major organ systems, a comprehensive and multidisciplinary approach is essential to assist with diagnosis and management of PASC. Listening empathically to patients and acknowledging their symptoms are key factors. Access to ambulatory care, establishment of rapport, effective collaboration and coordination of care among different disciplines, management of comorbidities, continuity of care, access to rehabilitation programs, and reduction of disease burden are some of the principles that guided the creation of dedicated COVID-19 clinics throughout the world. The most common services offered are primary care, pulmonology, cardiology, mental health, neurology, speech and language pathology, physical and occupational therapy, pharmacy, and case management. The involvement of specialties varies depending on the specific patient’s needs (Parker A, et al. The Lancet Respir Med. 2021;S2213-2600[21]00385-4).
The development of diagnostic and care pathways by different specialties ensures standardization of clinical assessment and management while allowing for individualized care. The commonly used tools to assess the respiratory system are the 6-minute walk test, PFT, chest imaging including radiographs and high-resolution CT scan, ventilation perfusion scan, and echocardiography. Some patients exhibit persistent cardiopulmonary symptoms with no evidence of organ injury. These patients have persistent exertional and functional limitation with normal PFT, resting echocardiography, and chest imaging. Cardiopulmonary exercise testing (CPET) and, more specifically, invasive CPET can be used to further investigate the decreased exercise capacity. CPET studies have identified an augmented exercise hyperventilation, and the causes of exercise limitation varied from anemia and reduced oxygen extraction by peripheral muscles to deconditioning, obesity, and lower ventilatory efficiency. A study looking at invasive CPET showed reduced peak exercise aerobic capacity in post COVID-19 patients compared with control participants and was associated with impaired systemic oxygen extraction and an exaggerated hyperventilatory response (Singh, et al. Chest. 2021;S0012-3692[21]03635). A subset of COVID-19 survivors presents with symptoms of autonomic dysfunction such as orthostatic intolerance and postural orthostatic tachycardia. These symptoms have been reported after other viral infections and could be secondary to gastrointestinal fluid loss, prolonged bed rest, and deconditioning of the cardiovascular system. More research is needed to characterize the dysautonomia in patients post–COVID-19.
What is the treatment?
Therapies depend on symptoms and organ involvement. The duration of pulmonary symptoms in long-haulers is not yet known, with cough and exercise intolerance/dyspnea ranking among the most common complaints in these patients. Exercise therapy plays an essential part in the rehabilitation of long-haulers and several studies are underway to assess different exercise and rehabilitation programs. For most patients with normal laboratory, physiologic, and imaging tests, post–COVID-19 clinics are offering physical therapy, occupational therapy, and neuropsychological rehabilitation. While steroids have been shown to improve mortality in hospitalized patients with COVID-19 requiring mechanical ventilation or supplemental oxygen, their role in outpatient COVID-19 infections and for post–COVID-19 lung disease/organizing pneumonia remains unclear. In a UK study of patients admitted to the hospital with COVID-19 disease of varying severity, interstitial abnormalities were noted in ~5% of patients at 6 weeks postdischarge and in 10.8% of patients with persistent respiratory symptoms (Myall, et al. Ann Am Thorac Soc. 2021;18[5]:799). The most common radiological findings (in > 50% of cases) were consistent with organizing pneumonia. Patients with persistent physiological abnormalities and interstitial findings improved with steroids. However, since the trajectory of the disease is unknown, further studies are required to understand the natural history of the disease and assess treatment strategies in patients with persistent inflammatory lung changes. Several studies looking at systemic or inhaled steroids in different phases of COVID-19 infection and varying disease severity are ongoing (ClinicalTrials.gov). Antifibrotics used to treat idiopathic pulmonary fibrosis and progressive fibrotic ILD are also being investigated in COVID-19 lung disease. The rationale for their use is to treat and prevent severe COVID-19 lung injury and prevent lung fibrosis.
The role of vaccinations
Whether patients who were infected with COVID-19, and, more specifically, patients with long-term symptoms post-COVID-19, should get vaccinated is actively being investigated. Vaccinations are protective at preventing infections and severe illness. Studies showed that patients who had COVID-19 infection and got vaccinated had a significantly higher antibody response than previously uninfected vaccine recipients. A review showed that the protective effect of prior SARS-CoV-2 infection on reinfection is high and similar to that of vaccination. However, a recent study of hospitalized patients revealed higher rates of COVID-19 among unvaccinated adults with previous infection compared with vaccinated adults (http://dx.doi.org/10.15585/mmwr.mm7044e1). On the other hand, the impact of vaccine on long-hauler symptoms has raised interest. A UK survey (not peer reviewed) on more than 800 long-haulers reported about 57% with overall improvement in their symptoms, 24% no change, and 19% with worsening symptoms after their first dose of vaccine, suggesting that the chances of experiencing an overall worsening of symptoms after vaccination is small, with more than half experiencing improvement (go.nature.com/3yfqem2). While awaiting longitudinal trials, the main argument to guide vaccination in long-haulers is that COVID-19 vaccinations provide protection from reinfection and appear to have the potential to improve symptoms.
The availability of a patient’s support system, peer support, and patient advocacy groups assist in providing equitable care and are critical in sustaining the recovery of COVID-19 survivors. Providing social, financial, and cultural support is imperative in decreasing the burden of COVID-19. The dedicated post–COVID-19 clinics will not only offer care to COVID-19 survivors, but will also help our understanding of the determinants and course of PASC, and will provide opportunities for research. Long-term longitudinal observational studies and clinical trials are critical to identify those at high risk for PASC, clarify the extent of health consequences attributable to COVID-19, and define best practices for COVID-19 survivors.
Dr. Biehl is Staff Physician, Pulmonary & Critical Care Medicine, Director, Post-ICU Recovery Clinic Respiratory Institute, Cleveland Clinic; Dr.Farha is with Respiratory and Lerner Institutes, Cleveland Clinic.
On March 11, 2020, the World Health Organization (WHO) declared SARS-CoV-2 a pandemic. As of October 2021, there are over 240 million confirmed COVID-19 cases and over 4 million deaths globally, with the United States having the highest incidence of both cases and deaths (https://covid.cdc.gov/covid-data-tracker/#datatracker-home). As many as 87% of COVID-19 survivors experience persistent symptoms that last beyond the acute phase of illness (Carfi A, et al. JAMA. 2020;324[6]:603-5). In February 2021, the National Institutes of Health (NIH) called for a consensus term to describe this protracted form of COVID-19, and defined it as Post-acute Sequelae of SARS-CoV-2 infection (PASC) (https://www.nih.gov/about-nih/who-we-are/nih-director/statements/nih-launches-new-initiative-study-long-covid).
What are the PASC manifestations?
PASC has a heterogeneous presentation with a broad spectrum of manifestations and can vary from single to multiorgan system involvement. Commonly, PASC involves pulmonary abnormalities (shortness of breath, exercise intolerance, abnormal pulmonary functional test [PFT] and chest imaging), neurocognitive impairments (difficulty concentrating and memory loss), mental health disorders (anxiety, depression, and post-traumatic stress disorder), functional mobility impairments, as well as general and constitutional symptoms (fatigue and muscle weakness) (Groff D, et al. JAMA Netw Open. 2021;4[10]). The most prevalent pulmonary physiologic impairment is reduced diffusion capacity that has been shown to be associated with the severity of acute illness, while the most common radiologic abnormalities on chest CT scan are ground glass opacities. Some studies have shown a temporal improvement in pulmonary physiology and exercise capacity; however, persistent physiological and radiographic abnormalities persist in some patients up to 12 months after discharge (Wu X, et al. Lancet Respir Med. 2021;9:747-54). An abnormal or persistent hyper-inflammatory state, viral-induced autoimmune reaction, and ongoing viral activity have been proposed as possible biological mechanisms for PASC; however, the pathophysiology remains mostly unknown.
Who does PASC affect?
PASC affects patients irrespective of premorbid condition and severity of symptoms in the acute phase. It spans from those who had mild disease not requiring hospitalization to those who had critical illness requiring intensive care unit (ICU) management. COVID-19 ICU survivors seem to have an overlap of PASC and post-intensive care syndrome (PICS), defined by new or worsening physical, cognitive, and/or psychiatric impairments after critical illness. (Biehl M, et al. Cleve Clin J Med. 2020 Aug 5).
Who do we evaluate for PASC?
Given the complexity and chronicity of the associated symptoms and their impact on several major organ systems, a comprehensive and multidisciplinary approach is essential to assist with diagnosis and management of PASC. Listening empathically to patients and acknowledging their symptoms are key factors. Access to ambulatory care, establishment of rapport, effective collaboration and coordination of care among different disciplines, management of comorbidities, continuity of care, access to rehabilitation programs, and reduction of disease burden are some of the principles that guided the creation of dedicated COVID-19 clinics throughout the world. The most common services offered are primary care, pulmonology, cardiology, mental health, neurology, speech and language pathology, physical and occupational therapy, pharmacy, and case management. The involvement of specialties varies depending on the specific patient’s needs (Parker A, et al. The Lancet Respir Med. 2021;S2213-2600[21]00385-4).
The development of diagnostic and care pathways by different specialties ensures standardization of clinical assessment and management while allowing for individualized care. The commonly used tools to assess the respiratory system are the 6-minute walk test, PFT, chest imaging including radiographs and high-resolution CT scan, ventilation perfusion scan, and echocardiography. Some patients exhibit persistent cardiopulmonary symptoms with no evidence of organ injury. These patients have persistent exertional and functional limitation with normal PFT, resting echocardiography, and chest imaging. Cardiopulmonary exercise testing (CPET) and, more specifically, invasive CPET can be used to further investigate the decreased exercise capacity. CPET studies have identified an augmented exercise hyperventilation, and the causes of exercise limitation varied from anemia and reduced oxygen extraction by peripheral muscles to deconditioning, obesity, and lower ventilatory efficiency. A study looking at invasive CPET showed reduced peak exercise aerobic capacity in post COVID-19 patients compared with control participants and was associated with impaired systemic oxygen extraction and an exaggerated hyperventilatory response (Singh, et al. Chest. 2021;S0012-3692[21]03635). A subset of COVID-19 survivors presents with symptoms of autonomic dysfunction such as orthostatic intolerance and postural orthostatic tachycardia. These symptoms have been reported after other viral infections and could be secondary to gastrointestinal fluid loss, prolonged bed rest, and deconditioning of the cardiovascular system. More research is needed to characterize the dysautonomia in patients post–COVID-19.
What is the treatment?
Therapies depend on symptoms and organ involvement. The duration of pulmonary symptoms in long-haulers is not yet known, with cough and exercise intolerance/dyspnea ranking among the most common complaints in these patients. Exercise therapy plays an essential part in the rehabilitation of long-haulers and several studies are underway to assess different exercise and rehabilitation programs. For most patients with normal laboratory, physiologic, and imaging tests, post–COVID-19 clinics are offering physical therapy, occupational therapy, and neuropsychological rehabilitation. While steroids have been shown to improve mortality in hospitalized patients with COVID-19 requiring mechanical ventilation or supplemental oxygen, their role in outpatient COVID-19 infections and for post–COVID-19 lung disease/organizing pneumonia remains unclear. In a UK study of patients admitted to the hospital with COVID-19 disease of varying severity, interstitial abnormalities were noted in ~5% of patients at 6 weeks postdischarge and in 10.8% of patients with persistent respiratory symptoms (Myall, et al. Ann Am Thorac Soc. 2021;18[5]:799). The most common radiological findings (in > 50% of cases) were consistent with organizing pneumonia. Patients with persistent physiological abnormalities and interstitial findings improved with steroids. However, since the trajectory of the disease is unknown, further studies are required to understand the natural history of the disease and assess treatment strategies in patients with persistent inflammatory lung changes. Several studies looking at systemic or inhaled steroids in different phases of COVID-19 infection and varying disease severity are ongoing (ClinicalTrials.gov). Antifibrotics used to treat idiopathic pulmonary fibrosis and progressive fibrotic ILD are also being investigated in COVID-19 lung disease. The rationale for their use is to treat and prevent severe COVID-19 lung injury and prevent lung fibrosis.
The role of vaccinations
Whether patients who were infected with COVID-19, and, more specifically, patients with long-term symptoms post-COVID-19, should get vaccinated is actively being investigated. Vaccinations are protective at preventing infections and severe illness. Studies showed that patients who had COVID-19 infection and got vaccinated had a significantly higher antibody response than previously uninfected vaccine recipients. A review showed that the protective effect of prior SARS-CoV-2 infection on reinfection is high and similar to that of vaccination. However, a recent study of hospitalized patients revealed higher rates of COVID-19 among unvaccinated adults with previous infection compared with vaccinated adults (http://dx.doi.org/10.15585/mmwr.mm7044e1). On the other hand, the impact of vaccine on long-hauler symptoms has raised interest. A UK survey (not peer reviewed) on more than 800 long-haulers reported about 57% with overall improvement in their symptoms, 24% no change, and 19% with worsening symptoms after their first dose of vaccine, suggesting that the chances of experiencing an overall worsening of symptoms after vaccination is small, with more than half experiencing improvement (go.nature.com/3yfqem2). While awaiting longitudinal trials, the main argument to guide vaccination in long-haulers is that COVID-19 vaccinations provide protection from reinfection and appear to have the potential to improve symptoms.
The availability of a patient’s support system, peer support, and patient advocacy groups assist in providing equitable care and are critical in sustaining the recovery of COVID-19 survivors. Providing social, financial, and cultural support is imperative in decreasing the burden of COVID-19. The dedicated post–COVID-19 clinics will not only offer care to COVID-19 survivors, but will also help our understanding of the determinants and course of PASC, and will provide opportunities for research. Long-term longitudinal observational studies and clinical trials are critical to identify those at high risk for PASC, clarify the extent of health consequences attributable to COVID-19, and define best practices for COVID-19 survivors.
Dr. Biehl is Staff Physician, Pulmonary & Critical Care Medicine, Director, Post-ICU Recovery Clinic Respiratory Institute, Cleveland Clinic; Dr.Farha is with Respiratory and Lerner Institutes, Cleveland Clinic.
On March 11, 2020, the World Health Organization (WHO) declared SARS-CoV-2 a pandemic. As of October 2021, there are over 240 million confirmed COVID-19 cases and over 4 million deaths globally, with the United States having the highest incidence of both cases and deaths (https://covid.cdc.gov/covid-data-tracker/#datatracker-home). As many as 87% of COVID-19 survivors experience persistent symptoms that last beyond the acute phase of illness (Carfi A, et al. JAMA. 2020;324[6]:603-5). In February 2021, the National Institutes of Health (NIH) called for a consensus term to describe this protracted form of COVID-19, and defined it as Post-acute Sequelae of SARS-CoV-2 infection (PASC) (https://www.nih.gov/about-nih/who-we-are/nih-director/statements/nih-launches-new-initiative-study-long-covid).
What are the PASC manifestations?
PASC has a heterogeneous presentation with a broad spectrum of manifestations and can vary from single to multiorgan system involvement. Commonly, PASC involves pulmonary abnormalities (shortness of breath, exercise intolerance, abnormal pulmonary functional test [PFT] and chest imaging), neurocognitive impairments (difficulty concentrating and memory loss), mental health disorders (anxiety, depression, and post-traumatic stress disorder), functional mobility impairments, as well as general and constitutional symptoms (fatigue and muscle weakness) (Groff D, et al. JAMA Netw Open. 2021;4[10]). The most prevalent pulmonary physiologic impairment is reduced diffusion capacity that has been shown to be associated with the severity of acute illness, while the most common radiologic abnormalities on chest CT scan are ground glass opacities. Some studies have shown a temporal improvement in pulmonary physiology and exercise capacity; however, persistent physiological and radiographic abnormalities persist in some patients up to 12 months after discharge (Wu X, et al. Lancet Respir Med. 2021;9:747-54). An abnormal or persistent hyper-inflammatory state, viral-induced autoimmune reaction, and ongoing viral activity have been proposed as possible biological mechanisms for PASC; however, the pathophysiology remains mostly unknown.
Who does PASC affect?
PASC affects patients irrespective of premorbid condition and severity of symptoms in the acute phase. It spans from those who had mild disease not requiring hospitalization to those who had critical illness requiring intensive care unit (ICU) management. COVID-19 ICU survivors seem to have an overlap of PASC and post-intensive care syndrome (PICS), defined by new or worsening physical, cognitive, and/or psychiatric impairments after critical illness. (Biehl M, et al. Cleve Clin J Med. 2020 Aug 5).
Who do we evaluate for PASC?
Given the complexity and chronicity of the associated symptoms and their impact on several major organ systems, a comprehensive and multidisciplinary approach is essential to assist with diagnosis and management of PASC. Listening empathically to patients and acknowledging their symptoms are key factors. Access to ambulatory care, establishment of rapport, effective collaboration and coordination of care among different disciplines, management of comorbidities, continuity of care, access to rehabilitation programs, and reduction of disease burden are some of the principles that guided the creation of dedicated COVID-19 clinics throughout the world. The most common services offered are primary care, pulmonology, cardiology, mental health, neurology, speech and language pathology, physical and occupational therapy, pharmacy, and case management. The involvement of specialties varies depending on the specific patient’s needs (Parker A, et al. The Lancet Respir Med. 2021;S2213-2600[21]00385-4).
The development of diagnostic and care pathways by different specialties ensures standardization of clinical assessment and management while allowing for individualized care. The commonly used tools to assess the respiratory system are the 6-minute walk test, PFT, chest imaging including radiographs and high-resolution CT scan, ventilation perfusion scan, and echocardiography. Some patients exhibit persistent cardiopulmonary symptoms with no evidence of organ injury. These patients have persistent exertional and functional limitation with normal PFT, resting echocardiography, and chest imaging. Cardiopulmonary exercise testing (CPET) and, more specifically, invasive CPET can be used to further investigate the decreased exercise capacity. CPET studies have identified an augmented exercise hyperventilation, and the causes of exercise limitation varied from anemia and reduced oxygen extraction by peripheral muscles to deconditioning, obesity, and lower ventilatory efficiency. A study looking at invasive CPET showed reduced peak exercise aerobic capacity in post COVID-19 patients compared with control participants and was associated with impaired systemic oxygen extraction and an exaggerated hyperventilatory response (Singh, et al. Chest. 2021;S0012-3692[21]03635). A subset of COVID-19 survivors presents with symptoms of autonomic dysfunction such as orthostatic intolerance and postural orthostatic tachycardia. These symptoms have been reported after other viral infections and could be secondary to gastrointestinal fluid loss, prolonged bed rest, and deconditioning of the cardiovascular system. More research is needed to characterize the dysautonomia in patients post–COVID-19.
What is the treatment?
Therapies depend on symptoms and organ involvement. The duration of pulmonary symptoms in long-haulers is not yet known, with cough and exercise intolerance/dyspnea ranking among the most common complaints in these patients. Exercise therapy plays an essential part in the rehabilitation of long-haulers and several studies are underway to assess different exercise and rehabilitation programs. For most patients with normal laboratory, physiologic, and imaging tests, post–COVID-19 clinics are offering physical therapy, occupational therapy, and neuropsychological rehabilitation. While steroids have been shown to improve mortality in hospitalized patients with COVID-19 requiring mechanical ventilation or supplemental oxygen, their role in outpatient COVID-19 infections and for post–COVID-19 lung disease/organizing pneumonia remains unclear. In a UK study of patients admitted to the hospital with COVID-19 disease of varying severity, interstitial abnormalities were noted in ~5% of patients at 6 weeks postdischarge and in 10.8% of patients with persistent respiratory symptoms (Myall, et al. Ann Am Thorac Soc. 2021;18[5]:799). The most common radiological findings (in > 50% of cases) were consistent with organizing pneumonia. Patients with persistent physiological abnormalities and interstitial findings improved with steroids. However, since the trajectory of the disease is unknown, further studies are required to understand the natural history of the disease and assess treatment strategies in patients with persistent inflammatory lung changes. Several studies looking at systemic or inhaled steroids in different phases of COVID-19 infection and varying disease severity are ongoing (ClinicalTrials.gov). Antifibrotics used to treat idiopathic pulmonary fibrosis and progressive fibrotic ILD are also being investigated in COVID-19 lung disease. The rationale for their use is to treat and prevent severe COVID-19 lung injury and prevent lung fibrosis.
The role of vaccinations
Whether patients who were infected with COVID-19, and, more specifically, patients with long-term symptoms post-COVID-19, should get vaccinated is actively being investigated. Vaccinations are protective at preventing infections and severe illness. Studies showed that patients who had COVID-19 infection and got vaccinated had a significantly higher antibody response than previously uninfected vaccine recipients. A review showed that the protective effect of prior SARS-CoV-2 infection on reinfection is high and similar to that of vaccination. However, a recent study of hospitalized patients revealed higher rates of COVID-19 among unvaccinated adults with previous infection compared with vaccinated adults (http://dx.doi.org/10.15585/mmwr.mm7044e1). On the other hand, the impact of vaccine on long-hauler symptoms has raised interest. A UK survey (not peer reviewed) on more than 800 long-haulers reported about 57% with overall improvement in their symptoms, 24% no change, and 19% with worsening symptoms after their first dose of vaccine, suggesting that the chances of experiencing an overall worsening of symptoms after vaccination is small, with more than half experiencing improvement (go.nature.com/3yfqem2). While awaiting longitudinal trials, the main argument to guide vaccination in long-haulers is that COVID-19 vaccinations provide protection from reinfection and appear to have the potential to improve symptoms.
The availability of a patient’s support system, peer support, and patient advocacy groups assist in providing equitable care and are critical in sustaining the recovery of COVID-19 survivors. Providing social, financial, and cultural support is imperative in decreasing the burden of COVID-19. The dedicated post–COVID-19 clinics will not only offer care to COVID-19 survivors, but will also help our understanding of the determinants and course of PASC, and will provide opportunities for research. Long-term longitudinal observational studies and clinical trials are critical to identify those at high risk for PASC, clarify the extent of health consequences attributable to COVID-19, and define best practices for COVID-19 survivors.
Dr. Biehl is Staff Physician, Pulmonary & Critical Care Medicine, Director, Post-ICU Recovery Clinic Respiratory Institute, Cleveland Clinic; Dr.Farha is with Respiratory and Lerner Institutes, Cleveland Clinic.
Final rule update – November 2021
The 2,414 page final rule for the CMS Physician Fee Schedule (PFS) was published on November 2, 2021, and contains a number of changes that are important for pulmonary/critical care/ sleep providers. As is typical, the rule does bring some good news, as well as decisions that are seemingly contrary to logic and precedence. Most of the changes will be effective on January 1, 2022, although some will become effective when the inpatient evaluation and management (E/M) changes take effect in 2023. For more information, please see 2021-23972.pdf (federalregister.gov).
The first change to be noted is a decrease in the conversion factor from $34.89 to $33.59. This is due primarily to the expiration of the 3.75% increase that was mandated by the Consolidated Appropriations Act of 2021. On a positive note, CMS did institute a plan to update clinical labor prices over the next 4 years, which will result in an increase in reimbursement for practice expense costs. CMS predicts that the combined impact of these two changes will result in no change in reimbursement for pulmonary or critical care medicine. Unfortunately, CMS did not publish data for sleep medicine.
There will be substantial changes in critical care services beginning next year. The CPT® definition of critical care will continue to be recognized by CMS, and the list of bundled services remains the same. Providers may now report critical care services with E/M visits done on the same day. The E/M visit must precede the critical care service, and it must be documented that the patient did not require critical care services at that time. The critical care visit must also be billed with a –25 modifier. This also applies to multiple practitioners in the same group of the same specialty. Critical care services provided concurrently by multiple practitioners of different specialties may now be billed by each individual practitioner if the services are medically necessary. There was a concern that CMS would not allow billing of critical care services during a surgical global period, but this will be allowed if the critical care services are unrelated to the general surgical procedure performed. There will be a new modifier developed to allow CMS to track this care. If critical care management is transferred from the surgeon to an intensivist, then the latter will append modifier –55 (postoperative management only), as well as the new modifier. Finally, and most importantly, CMS now recognizes the benefit of team-based care and will allow split (or shared) billing of critical care services. Physicians and qualified nonphysician providers (NPP) add their times to determine the level of critical care services. The provider who is responsible for more than half of the critical care time should be the billing provider.
Pulmonary rehabilitation CPT codes 94625 and 94626 were accepted by CMS but the RVU values recommended by the RUC were not. CPT code 94625 received a finalized work RVU of 0.36 and code 94626 received 0.56. On a more positive note, patients hospitalized with COVID-19 who are having persistent symptoms, including respiratory dysfunction, for at least 4 weeks after hospitalization would now qualify for pulmonary rehab services. The current pulmonary rehabilitation HCPCS code G0424 is replaced by the two new CPT codes and should no longer be used after December 31, 2021.
These are but a few of the changes in the final rule that may impact one’s practice. Additional changes may be found in the final rule link 2021-23972.pdf (federalregister.gov) and in future CHEST Physician editions.
The 2,414 page final rule for the CMS Physician Fee Schedule (PFS) was published on November 2, 2021, and contains a number of changes that are important for pulmonary/critical care/ sleep providers. As is typical, the rule does bring some good news, as well as decisions that are seemingly contrary to logic and precedence. Most of the changes will be effective on January 1, 2022, although some will become effective when the inpatient evaluation and management (E/M) changes take effect in 2023. For more information, please see 2021-23972.pdf (federalregister.gov).
The first change to be noted is a decrease in the conversion factor from $34.89 to $33.59. This is due primarily to the expiration of the 3.75% increase that was mandated by the Consolidated Appropriations Act of 2021. On a positive note, CMS did institute a plan to update clinical labor prices over the next 4 years, which will result in an increase in reimbursement for practice expense costs. CMS predicts that the combined impact of these two changes will result in no change in reimbursement for pulmonary or critical care medicine. Unfortunately, CMS did not publish data for sleep medicine.
There will be substantial changes in critical care services beginning next year. The CPT® definition of critical care will continue to be recognized by CMS, and the list of bundled services remains the same. Providers may now report critical care services with E/M visits done on the same day. The E/M visit must precede the critical care service, and it must be documented that the patient did not require critical care services at that time. The critical care visit must also be billed with a –25 modifier. This also applies to multiple practitioners in the same group of the same specialty. Critical care services provided concurrently by multiple practitioners of different specialties may now be billed by each individual practitioner if the services are medically necessary. There was a concern that CMS would not allow billing of critical care services during a surgical global period, but this will be allowed if the critical care services are unrelated to the general surgical procedure performed. There will be a new modifier developed to allow CMS to track this care. If critical care management is transferred from the surgeon to an intensivist, then the latter will append modifier –55 (postoperative management only), as well as the new modifier. Finally, and most importantly, CMS now recognizes the benefit of team-based care and will allow split (or shared) billing of critical care services. Physicians and qualified nonphysician providers (NPP) add their times to determine the level of critical care services. The provider who is responsible for more than half of the critical care time should be the billing provider.
Pulmonary rehabilitation CPT codes 94625 and 94626 were accepted by CMS but the RVU values recommended by the RUC were not. CPT code 94625 received a finalized work RVU of 0.36 and code 94626 received 0.56. On a more positive note, patients hospitalized with COVID-19 who are having persistent symptoms, including respiratory dysfunction, for at least 4 weeks after hospitalization would now qualify for pulmonary rehab services. The current pulmonary rehabilitation HCPCS code G0424 is replaced by the two new CPT codes and should no longer be used after December 31, 2021.
These are but a few of the changes in the final rule that may impact one’s practice. Additional changes may be found in the final rule link 2021-23972.pdf (federalregister.gov) and in future CHEST Physician editions.
The 2,414 page final rule for the CMS Physician Fee Schedule (PFS) was published on November 2, 2021, and contains a number of changes that are important for pulmonary/critical care/ sleep providers. As is typical, the rule does bring some good news, as well as decisions that are seemingly contrary to logic and precedence. Most of the changes will be effective on January 1, 2022, although some will become effective when the inpatient evaluation and management (E/M) changes take effect in 2023. For more information, please see 2021-23972.pdf (federalregister.gov).
The first change to be noted is a decrease in the conversion factor from $34.89 to $33.59. This is due primarily to the expiration of the 3.75% increase that was mandated by the Consolidated Appropriations Act of 2021. On a positive note, CMS did institute a plan to update clinical labor prices over the next 4 years, which will result in an increase in reimbursement for practice expense costs. CMS predicts that the combined impact of these two changes will result in no change in reimbursement for pulmonary or critical care medicine. Unfortunately, CMS did not publish data for sleep medicine.
There will be substantial changes in critical care services beginning next year. The CPT® definition of critical care will continue to be recognized by CMS, and the list of bundled services remains the same. Providers may now report critical care services with E/M visits done on the same day. The E/M visit must precede the critical care service, and it must be documented that the patient did not require critical care services at that time. The critical care visit must also be billed with a –25 modifier. This also applies to multiple practitioners in the same group of the same specialty. Critical care services provided concurrently by multiple practitioners of different specialties may now be billed by each individual practitioner if the services are medically necessary. There was a concern that CMS would not allow billing of critical care services during a surgical global period, but this will be allowed if the critical care services are unrelated to the general surgical procedure performed. There will be a new modifier developed to allow CMS to track this care. If critical care management is transferred from the surgeon to an intensivist, then the latter will append modifier –55 (postoperative management only), as well as the new modifier. Finally, and most importantly, CMS now recognizes the benefit of team-based care and will allow split (or shared) billing of critical care services. Physicians and qualified nonphysician providers (NPP) add their times to determine the level of critical care services. The provider who is responsible for more than half of the critical care time should be the billing provider.
Pulmonary rehabilitation CPT codes 94625 and 94626 were accepted by CMS but the RVU values recommended by the RUC were not. CPT code 94625 received a finalized work RVU of 0.36 and code 94626 received 0.56. On a more positive note, patients hospitalized with COVID-19 who are having persistent symptoms, including respiratory dysfunction, for at least 4 weeks after hospitalization would now qualify for pulmonary rehab services. The current pulmonary rehabilitation HCPCS code G0424 is replaced by the two new CPT codes and should no longer be used after December 31, 2021.
These are but a few of the changes in the final rule that may impact one’s practice. Additional changes may be found in the final rule link 2021-23972.pdf (federalregister.gov) and in future CHEST Physician editions.
CHEST SEEK™ Education enhances learning with interactive discussions
If you’ve ever wondered about the content creation process that goes into exam study material, SEEK is offering you an insider perspective.
Recently added to the SEEK Library, CHEST SEEK™ Peer Review Discussions are behind-the-scenes recordings of the deliberations and debates between SEEK Editorial Board members as they review their draft questions. Each video showcases CHEST authors reviewing and finessing a case-based chest medicine question to prepare for its inclusion in printed SEEK books and the electronic library.
With an opportunity to glean invaluable knowledge from distinguished practitioners in the pulmonary, critical care, and sleep medicine fields, SEEK Peer Review Discussions can be used to help supplement board exam study, advance one’s clinical knowledge, and learn from the peer review process for their own professional development.
“The opportunity to observe how much critical review there is from a scientific content standpoint – and also from a test creation standpoint – is really interesting,” said CHEST SEEK Sleep Editor and President-Elect David Schulman, MD, MPH, FCCP.
“Many of us on SEEK have written for some of the standardized exams that readers will take,” he said. “Somebody can learn how writers come up with wrong answers and think, ‘‘If I can see how this test is constructed, I may have a better chance of doing well on it.’”
SEEK Peer Review Discussions not only offer a more engaging form of education but also provide an opportunity to watch leaders in the field test, challenge, and collaborate with one another.
“The audience gets to see that these big names you see on the page – authors, coauthors, and editors – are just normal people like anybody else,” Dr. Schulman said. “They joke around a little bit, and they push each other a little bit. I think getting to see under the hood of CHEST and seeing what leadership is like is a really valuable experience.”
Through these discussions, CHEST SEEK learners discover the intensity and rigorousness of the conversations with a window into CHEST leaders’ discourse.
The collection of SEEK Peer Review Discussions is part of the new, enhanced CHEST SEEK subscription option, SEEK Library Plus. Available for subscription viewing now are three question videos from the SEEK Pulmonary Medicine Editorial Board and three question videos from the SEEK Sleep Medicine Editorial Board.
Subscribers to SEEK Library Plus also gain access to SEEK Session videos from CHEST Board Review 2021, a print export study pack plus a compilation of favorite questions from SEEK’s 30-year history.
For a sneak peek of the peer review videos and to subscribe to SEEK Library Plus, visit seeklibrary.chestnet.org.
If you’ve ever wondered about the content creation process that goes into exam study material, SEEK is offering you an insider perspective.
Recently added to the SEEK Library, CHEST SEEK™ Peer Review Discussions are behind-the-scenes recordings of the deliberations and debates between SEEK Editorial Board members as they review their draft questions. Each video showcases CHEST authors reviewing and finessing a case-based chest medicine question to prepare for its inclusion in printed SEEK books and the electronic library.
With an opportunity to glean invaluable knowledge from distinguished practitioners in the pulmonary, critical care, and sleep medicine fields, SEEK Peer Review Discussions can be used to help supplement board exam study, advance one’s clinical knowledge, and learn from the peer review process for their own professional development.
“The opportunity to observe how much critical review there is from a scientific content standpoint – and also from a test creation standpoint – is really interesting,” said CHEST SEEK Sleep Editor and President-Elect David Schulman, MD, MPH, FCCP.
“Many of us on SEEK have written for some of the standardized exams that readers will take,” he said. “Somebody can learn how writers come up with wrong answers and think, ‘‘If I can see how this test is constructed, I may have a better chance of doing well on it.’”
SEEK Peer Review Discussions not only offer a more engaging form of education but also provide an opportunity to watch leaders in the field test, challenge, and collaborate with one another.
“The audience gets to see that these big names you see on the page – authors, coauthors, and editors – are just normal people like anybody else,” Dr. Schulman said. “They joke around a little bit, and they push each other a little bit. I think getting to see under the hood of CHEST and seeing what leadership is like is a really valuable experience.”
Through these discussions, CHEST SEEK learners discover the intensity and rigorousness of the conversations with a window into CHEST leaders’ discourse.
The collection of SEEK Peer Review Discussions is part of the new, enhanced CHEST SEEK subscription option, SEEK Library Plus. Available for subscription viewing now are three question videos from the SEEK Pulmonary Medicine Editorial Board and three question videos from the SEEK Sleep Medicine Editorial Board.
Subscribers to SEEK Library Plus also gain access to SEEK Session videos from CHEST Board Review 2021, a print export study pack plus a compilation of favorite questions from SEEK’s 30-year history.
For a sneak peek of the peer review videos and to subscribe to SEEK Library Plus, visit seeklibrary.chestnet.org.
If you’ve ever wondered about the content creation process that goes into exam study material, SEEK is offering you an insider perspective.
Recently added to the SEEK Library, CHEST SEEK™ Peer Review Discussions are behind-the-scenes recordings of the deliberations and debates between SEEK Editorial Board members as they review their draft questions. Each video showcases CHEST authors reviewing and finessing a case-based chest medicine question to prepare for its inclusion in printed SEEK books and the electronic library.
With an opportunity to glean invaluable knowledge from distinguished practitioners in the pulmonary, critical care, and sleep medicine fields, SEEK Peer Review Discussions can be used to help supplement board exam study, advance one’s clinical knowledge, and learn from the peer review process for their own professional development.
“The opportunity to observe how much critical review there is from a scientific content standpoint – and also from a test creation standpoint – is really interesting,” said CHEST SEEK Sleep Editor and President-Elect David Schulman, MD, MPH, FCCP.
“Many of us on SEEK have written for some of the standardized exams that readers will take,” he said. “Somebody can learn how writers come up with wrong answers and think, ‘‘If I can see how this test is constructed, I may have a better chance of doing well on it.’”
SEEK Peer Review Discussions not only offer a more engaging form of education but also provide an opportunity to watch leaders in the field test, challenge, and collaborate with one another.
“The audience gets to see that these big names you see on the page – authors, coauthors, and editors – are just normal people like anybody else,” Dr. Schulman said. “They joke around a little bit, and they push each other a little bit. I think getting to see under the hood of CHEST and seeing what leadership is like is a really valuable experience.”
Through these discussions, CHEST SEEK learners discover the intensity and rigorousness of the conversations with a window into CHEST leaders’ discourse.
The collection of SEEK Peer Review Discussions is part of the new, enhanced CHEST SEEK subscription option, SEEK Library Plus. Available for subscription viewing now are three question videos from the SEEK Pulmonary Medicine Editorial Board and three question videos from the SEEK Sleep Medicine Editorial Board.
Subscribers to SEEK Library Plus also gain access to SEEK Session videos from CHEST Board Review 2021, a print export study pack plus a compilation of favorite questions from SEEK’s 30-year history.
For a sneak peek of the peer review videos and to subscribe to SEEK Library Plus, visit seeklibrary.chestnet.org.