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Consider quality of life, comorbidities in hidradenitis suppurativa
LAS VEGAS – , Robert G. Micheletti, MD, said in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.
For patients with HS, “the quality-of-life impact is profound, greater than any other systematically studied dermatologic condition,” said Dr. Micheletti, associate professor of dermatology at the Hospital of the University of Pennsylavnia, and chief of hospital dermatology, and chief of dermatology at Pennsylvania Hospital, Philadelphia.
Two key aspects of quality of life that affect HS patients are sexual health and overall pain, he said. The female-to-male ratio of HS is approximately 3:1, and data show that approximately 40% of female HS patients experience fertility issues and have unaddressed questions about HS and pregnancy, said Dr. Micheletti. Additionally, data from a systematic review showed that 50%-60% of patients with HS reported sexual dysfunction. Impaired sexual function is also associated with both overall impaired quality of life ratings and the presence of mood disorders, he noted.
Pain also has a significant impact on quality of life for HS patients. When these patients present in an emergency department, 70% report severe pain, and approximately 60% receive opioids, said Dr. Micheletti.
Data from a 2021 study showed that HS patients are significantly more likely to receive opioids compared with controls, and also more likely to be diagnosed with opioid use disorder than controls, especially if they are seen by nondermatologists, he noted.
For acute pain, Dr. Micheletti recommended starting with acetaminophen 500 mg every 4 to 6 hours as needed, and topical nonsteroidal anti-inflammatory drugs (NSAIDs). “It still makes sense to do topical care,” said Dr. Micheletti, but he added that he also prescribes medications for anxiety for these patients.
Patients with increased pain severity or refractory disease may benefit from systemic NSAIDs, or intralesional triamcinolone, he noted. Incision and draining of abscesses may provide temporary symptomatic relief, but keep in mind that lesions will recur, he noted.
For the most severe cases, Dr. Micheletti advised adding tramadol as a first-line opioid, or another short-acting opioid for breakthrough pain.
To manage patients with HS who have chronic pain, Dr. Micheletti recommended starting with HS disease–directed therapy, but also screening for pain severity and psychological comorbidities.
His strategies in these cases include nonpharmacological pain management in the form of physical therapy, wound care, and behavioral health. His algorithm for nociceptive pain is NSAIDs with or without acetaminophen; duloxetine or nortriptyline are other options. For neuropathic pain, gabapentin and/or duloxetine are top choices, but pregabalin, venlafaxine, and nortriptyline are on the list as well.
Topical NSAIDs or topical lidocaine may serve as add-ons to systemic therapy in more severe cases, or as first-line therapy for milder chronic pain, Dr. Micheletti noted. Patients who have failed treatment with at least two pharmacologic agents, suffer medically refractory HS with debilitating pain, or use opioids on an ongoing basis should be referred to a pain management specialist, he said.
Don’t forget lifestyle
Although data on the impact of diet on patients with HS are limited, “we know anecdotally that dairy and refined carbohydrates are associated with exacerbations,” said Dr. Micheletti.
In addition, many patients use complementary medicine “and they aren’t always telling us,” he emphasized. Smoking is prevalent among patients with HS, and is a risk factor for the disease in general, and for more severe and refractory disease, he added. Consequently, screening for tobacco smoking is recommended for patients with HS not only because of the impact on disease, but because it is a potentially modifiable cardiovascular risk factor, he explained.
Consider comorbidities
Cardiovascular disease is among several comorbidities associated with HS, said Dr. Micheletti. HS foundations in the United States and Canada recently published evidence-based recommendations for comorbidity screening. The recommendations included screening for 19 specific comorbidities: acne, dissecting cellulitis, pilonidal disease, pyoderma gangrenosum, depression, anxiety, suicide, smoking, substance abuse, polycystic ovary syndrome, obesity, dyslipidemia, diabetes mellitus, metabolic syndrome, hypertension, cardiovascular disease, inflammatory bowel disease, spondyloarthritis, and sexual dysfunction.
Dr. Micheletti highlighted cardiovascular comorbidities, and noted the association between HS and modifiable cardiovascular risk factors: smoking, obesity, diabetes mellitus, and dyslipidemia. “HS is also independently associated with cardiovascular disease leading to myocardial infarction, stroke, cardiovascular-associated death, and all-cause mortality compared to controls,” he said. Studies show an incidence rate ratio of 1.53 for major adverse cardiovascular events in patients with HS compared with controls, with the highest relative risk among those aged 18-29 years, he added.
Medical management
Depending on the patient, medical management of HS may involve antibiotics, hormonal agents, and biologics, said Dr. Micheletti. Some of the most commonly used antibiotic regimens for HS are those recommended in treatment guidelines, including doxycycline and a clindamycin/rifampin combination, he said. However, the use of trimethoprim-sulfamethoxazole or ciprofloxacin has been associated with increased antibiotic resistance and is not supported by available evidence, he noted.
Hormonal therapies may help some women with HS, said Dr. Micheletti. Options include spironolactone, metformin, or estrogen-containing hormonal contraceptives, he said.
When it comes to biologics, only 33% of HS patients meet criteria for their use (Hurley stage II or III, moderate or severe HS), he noted. However, research suggests “a huge gap” in the use of anti-TNF therapy even among patients for whom it is recommended, he said.
Of the TNF-alpha inhibitors, data on adalimumab, which is FDA-approved for HS, are the most recent. Adalimumab “is our gold standard biologic and our gateway biologic, for HS at this time,” Dr. Micheletti said.
However, those who respond to adalimumab “can continue to do better, but they can wax and wane and flare,” he cautioned. Infliximab, while not approved for HS, has been studied in patients with HS and is prescribed by some providers. Although no comparative studies have been done for infliximab versus adalimumab, “anecdotally, response to infliximab tends to be better, and it is the most effective biologic in common use for severe HS,” he noted.
Dr. Micheletti’s top treatment recommendations for using biologics start with considering biosimilars. Most patients on biosimilars do fine, but some patients who previously responded to infliximab will unpredictably lose efficacy or have reactions when switched to a biosimilar, he said.
Patients on biologics also may experience waning efficacy in the wake of an immune response stimulated by foreign antibodies, said Dr. Micheletti. “Anti-drug antibody formation is more likely to occur when treatment is interrupted,” he noted. Minimize the risk of antibody formation by paying attention to adherence issues and dosing frequency, he advised.
If patients fail both adalimumab and infliximab, Dr. Micheletti tells them not to lose hope, and that treatment is a trial-and-error process that may involve more than one therapy. Other biologics in active use for HS include ustekinumab, anakinra, secukinumab, brodalumab, golimumab, and JAK inhibitors, any of which might be effective in any given patient, he said.
Surgical solutions
For HS patients with chronic, recurring inflammation and drainage associated with a sinus tract, surgical deroofing may the best treatment option, Dr. Micheletti said. “Deroofing involves the use of a probe to trace the extent of the subcutaneous tract, followed by incision and removal of the tract ‘roof,’ ’’ he explained. The deroofing procedure involves local anesthesia and has a low morbidity rate, as well as a low recurrence rate and high levels of patient satisfaction, he said.
“The acute role for surgery is to remove active foci of inflammation and relieve pain,” which is achieved more effectively with deroofing, said Dr. Micheletti. By contrast, incision and drainage is associated with an almost 100% recurrence rate, he added.
When planning elective surgery for HS, Dr. Micheletti noted that holding infliximab for less than 4 weeks does not affect postoperative infection rates in patients with rheumatoid arthritis, and a recent randomized, controlled trial showed that adalimumab can be continued safely through HS surgeries.
In fact, “continuing TNF inhibitors through elective surgery does not increase infection risk and results in better disease control,” and dermatologists should work with surgery to balance infection and disease flare concerns in HS patients, he said.
Dr. Micheletti disclosed serving as a consultant or advisor for Adaptimmune and Vertex, and research funding from Amgen and Cabaletta Bio. MedscapeLive and this news organization are owned by the same parent company.
LAS VEGAS – , Robert G. Micheletti, MD, said in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.
For patients with HS, “the quality-of-life impact is profound, greater than any other systematically studied dermatologic condition,” said Dr. Micheletti, associate professor of dermatology at the Hospital of the University of Pennsylavnia, and chief of hospital dermatology, and chief of dermatology at Pennsylvania Hospital, Philadelphia.
Two key aspects of quality of life that affect HS patients are sexual health and overall pain, he said. The female-to-male ratio of HS is approximately 3:1, and data show that approximately 40% of female HS patients experience fertility issues and have unaddressed questions about HS and pregnancy, said Dr. Micheletti. Additionally, data from a systematic review showed that 50%-60% of patients with HS reported sexual dysfunction. Impaired sexual function is also associated with both overall impaired quality of life ratings and the presence of mood disorders, he noted.
Pain also has a significant impact on quality of life for HS patients. When these patients present in an emergency department, 70% report severe pain, and approximately 60% receive opioids, said Dr. Micheletti.
Data from a 2021 study showed that HS patients are significantly more likely to receive opioids compared with controls, and also more likely to be diagnosed with opioid use disorder than controls, especially if they are seen by nondermatologists, he noted.
For acute pain, Dr. Micheletti recommended starting with acetaminophen 500 mg every 4 to 6 hours as needed, and topical nonsteroidal anti-inflammatory drugs (NSAIDs). “It still makes sense to do topical care,” said Dr. Micheletti, but he added that he also prescribes medications for anxiety for these patients.
Patients with increased pain severity or refractory disease may benefit from systemic NSAIDs, or intralesional triamcinolone, he noted. Incision and draining of abscesses may provide temporary symptomatic relief, but keep in mind that lesions will recur, he noted.
For the most severe cases, Dr. Micheletti advised adding tramadol as a first-line opioid, or another short-acting opioid for breakthrough pain.
To manage patients with HS who have chronic pain, Dr. Micheletti recommended starting with HS disease–directed therapy, but also screening for pain severity and psychological comorbidities.
His strategies in these cases include nonpharmacological pain management in the form of physical therapy, wound care, and behavioral health. His algorithm for nociceptive pain is NSAIDs with or without acetaminophen; duloxetine or nortriptyline are other options. For neuropathic pain, gabapentin and/or duloxetine are top choices, but pregabalin, venlafaxine, and nortriptyline are on the list as well.
Topical NSAIDs or topical lidocaine may serve as add-ons to systemic therapy in more severe cases, or as first-line therapy for milder chronic pain, Dr. Micheletti noted. Patients who have failed treatment with at least two pharmacologic agents, suffer medically refractory HS with debilitating pain, or use opioids on an ongoing basis should be referred to a pain management specialist, he said.
Don’t forget lifestyle
Although data on the impact of diet on patients with HS are limited, “we know anecdotally that dairy and refined carbohydrates are associated with exacerbations,” said Dr. Micheletti.
In addition, many patients use complementary medicine “and they aren’t always telling us,” he emphasized. Smoking is prevalent among patients with HS, and is a risk factor for the disease in general, and for more severe and refractory disease, he added. Consequently, screening for tobacco smoking is recommended for patients with HS not only because of the impact on disease, but because it is a potentially modifiable cardiovascular risk factor, he explained.
Consider comorbidities
Cardiovascular disease is among several comorbidities associated with HS, said Dr. Micheletti. HS foundations in the United States and Canada recently published evidence-based recommendations for comorbidity screening. The recommendations included screening for 19 specific comorbidities: acne, dissecting cellulitis, pilonidal disease, pyoderma gangrenosum, depression, anxiety, suicide, smoking, substance abuse, polycystic ovary syndrome, obesity, dyslipidemia, diabetes mellitus, metabolic syndrome, hypertension, cardiovascular disease, inflammatory bowel disease, spondyloarthritis, and sexual dysfunction.
Dr. Micheletti highlighted cardiovascular comorbidities, and noted the association between HS and modifiable cardiovascular risk factors: smoking, obesity, diabetes mellitus, and dyslipidemia. “HS is also independently associated with cardiovascular disease leading to myocardial infarction, stroke, cardiovascular-associated death, and all-cause mortality compared to controls,” he said. Studies show an incidence rate ratio of 1.53 for major adverse cardiovascular events in patients with HS compared with controls, with the highest relative risk among those aged 18-29 years, he added.
Medical management
Depending on the patient, medical management of HS may involve antibiotics, hormonal agents, and biologics, said Dr. Micheletti. Some of the most commonly used antibiotic regimens for HS are those recommended in treatment guidelines, including doxycycline and a clindamycin/rifampin combination, he said. However, the use of trimethoprim-sulfamethoxazole or ciprofloxacin has been associated with increased antibiotic resistance and is not supported by available evidence, he noted.
Hormonal therapies may help some women with HS, said Dr. Micheletti. Options include spironolactone, metformin, or estrogen-containing hormonal contraceptives, he said.
When it comes to biologics, only 33% of HS patients meet criteria for their use (Hurley stage II or III, moderate or severe HS), he noted. However, research suggests “a huge gap” in the use of anti-TNF therapy even among patients for whom it is recommended, he said.
Of the TNF-alpha inhibitors, data on adalimumab, which is FDA-approved for HS, are the most recent. Adalimumab “is our gold standard biologic and our gateway biologic, for HS at this time,” Dr. Micheletti said.
However, those who respond to adalimumab “can continue to do better, but they can wax and wane and flare,” he cautioned. Infliximab, while not approved for HS, has been studied in patients with HS and is prescribed by some providers. Although no comparative studies have been done for infliximab versus adalimumab, “anecdotally, response to infliximab tends to be better, and it is the most effective biologic in common use for severe HS,” he noted.
Dr. Micheletti’s top treatment recommendations for using biologics start with considering biosimilars. Most patients on biosimilars do fine, but some patients who previously responded to infliximab will unpredictably lose efficacy or have reactions when switched to a biosimilar, he said.
Patients on biologics also may experience waning efficacy in the wake of an immune response stimulated by foreign antibodies, said Dr. Micheletti. “Anti-drug antibody formation is more likely to occur when treatment is interrupted,” he noted. Minimize the risk of antibody formation by paying attention to adherence issues and dosing frequency, he advised.
If patients fail both adalimumab and infliximab, Dr. Micheletti tells them not to lose hope, and that treatment is a trial-and-error process that may involve more than one therapy. Other biologics in active use for HS include ustekinumab, anakinra, secukinumab, brodalumab, golimumab, and JAK inhibitors, any of which might be effective in any given patient, he said.
Surgical solutions
For HS patients with chronic, recurring inflammation and drainage associated with a sinus tract, surgical deroofing may the best treatment option, Dr. Micheletti said. “Deroofing involves the use of a probe to trace the extent of the subcutaneous tract, followed by incision and removal of the tract ‘roof,’ ’’ he explained. The deroofing procedure involves local anesthesia and has a low morbidity rate, as well as a low recurrence rate and high levels of patient satisfaction, he said.
“The acute role for surgery is to remove active foci of inflammation and relieve pain,” which is achieved more effectively with deroofing, said Dr. Micheletti. By contrast, incision and drainage is associated with an almost 100% recurrence rate, he added.
When planning elective surgery for HS, Dr. Micheletti noted that holding infliximab for less than 4 weeks does not affect postoperative infection rates in patients with rheumatoid arthritis, and a recent randomized, controlled trial showed that adalimumab can be continued safely through HS surgeries.
In fact, “continuing TNF inhibitors through elective surgery does not increase infection risk and results in better disease control,” and dermatologists should work with surgery to balance infection and disease flare concerns in HS patients, he said.
Dr. Micheletti disclosed serving as a consultant or advisor for Adaptimmune and Vertex, and research funding from Amgen and Cabaletta Bio. MedscapeLive and this news organization are owned by the same parent company.
LAS VEGAS – , Robert G. Micheletti, MD, said in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.
For patients with HS, “the quality-of-life impact is profound, greater than any other systematically studied dermatologic condition,” said Dr. Micheletti, associate professor of dermatology at the Hospital of the University of Pennsylavnia, and chief of hospital dermatology, and chief of dermatology at Pennsylvania Hospital, Philadelphia.
Two key aspects of quality of life that affect HS patients are sexual health and overall pain, he said. The female-to-male ratio of HS is approximately 3:1, and data show that approximately 40% of female HS patients experience fertility issues and have unaddressed questions about HS and pregnancy, said Dr. Micheletti. Additionally, data from a systematic review showed that 50%-60% of patients with HS reported sexual dysfunction. Impaired sexual function is also associated with both overall impaired quality of life ratings and the presence of mood disorders, he noted.
Pain also has a significant impact on quality of life for HS patients. When these patients present in an emergency department, 70% report severe pain, and approximately 60% receive opioids, said Dr. Micheletti.
Data from a 2021 study showed that HS patients are significantly more likely to receive opioids compared with controls, and also more likely to be diagnosed with opioid use disorder than controls, especially if they are seen by nondermatologists, he noted.
For acute pain, Dr. Micheletti recommended starting with acetaminophen 500 mg every 4 to 6 hours as needed, and topical nonsteroidal anti-inflammatory drugs (NSAIDs). “It still makes sense to do topical care,” said Dr. Micheletti, but he added that he also prescribes medications for anxiety for these patients.
Patients with increased pain severity or refractory disease may benefit from systemic NSAIDs, or intralesional triamcinolone, he noted. Incision and draining of abscesses may provide temporary symptomatic relief, but keep in mind that lesions will recur, he noted.
For the most severe cases, Dr. Micheletti advised adding tramadol as a first-line opioid, or another short-acting opioid for breakthrough pain.
To manage patients with HS who have chronic pain, Dr. Micheletti recommended starting with HS disease–directed therapy, but also screening for pain severity and psychological comorbidities.
His strategies in these cases include nonpharmacological pain management in the form of physical therapy, wound care, and behavioral health. His algorithm for nociceptive pain is NSAIDs with or without acetaminophen; duloxetine or nortriptyline are other options. For neuropathic pain, gabapentin and/or duloxetine are top choices, but pregabalin, venlafaxine, and nortriptyline are on the list as well.
Topical NSAIDs or topical lidocaine may serve as add-ons to systemic therapy in more severe cases, or as first-line therapy for milder chronic pain, Dr. Micheletti noted. Patients who have failed treatment with at least two pharmacologic agents, suffer medically refractory HS with debilitating pain, or use opioids on an ongoing basis should be referred to a pain management specialist, he said.
Don’t forget lifestyle
Although data on the impact of diet on patients with HS are limited, “we know anecdotally that dairy and refined carbohydrates are associated with exacerbations,” said Dr. Micheletti.
In addition, many patients use complementary medicine “and they aren’t always telling us,” he emphasized. Smoking is prevalent among patients with HS, and is a risk factor for the disease in general, and for more severe and refractory disease, he added. Consequently, screening for tobacco smoking is recommended for patients with HS not only because of the impact on disease, but because it is a potentially modifiable cardiovascular risk factor, he explained.
Consider comorbidities
Cardiovascular disease is among several comorbidities associated with HS, said Dr. Micheletti. HS foundations in the United States and Canada recently published evidence-based recommendations for comorbidity screening. The recommendations included screening for 19 specific comorbidities: acne, dissecting cellulitis, pilonidal disease, pyoderma gangrenosum, depression, anxiety, suicide, smoking, substance abuse, polycystic ovary syndrome, obesity, dyslipidemia, diabetes mellitus, metabolic syndrome, hypertension, cardiovascular disease, inflammatory bowel disease, spondyloarthritis, and sexual dysfunction.
Dr. Micheletti highlighted cardiovascular comorbidities, and noted the association between HS and modifiable cardiovascular risk factors: smoking, obesity, diabetes mellitus, and dyslipidemia. “HS is also independently associated with cardiovascular disease leading to myocardial infarction, stroke, cardiovascular-associated death, and all-cause mortality compared to controls,” he said. Studies show an incidence rate ratio of 1.53 for major adverse cardiovascular events in patients with HS compared with controls, with the highest relative risk among those aged 18-29 years, he added.
Medical management
Depending on the patient, medical management of HS may involve antibiotics, hormonal agents, and biologics, said Dr. Micheletti. Some of the most commonly used antibiotic regimens for HS are those recommended in treatment guidelines, including doxycycline and a clindamycin/rifampin combination, he said. However, the use of trimethoprim-sulfamethoxazole or ciprofloxacin has been associated with increased antibiotic resistance and is not supported by available evidence, he noted.
Hormonal therapies may help some women with HS, said Dr. Micheletti. Options include spironolactone, metformin, or estrogen-containing hormonal contraceptives, he said.
When it comes to biologics, only 33% of HS patients meet criteria for their use (Hurley stage II or III, moderate or severe HS), he noted. However, research suggests “a huge gap” in the use of anti-TNF therapy even among patients for whom it is recommended, he said.
Of the TNF-alpha inhibitors, data on adalimumab, which is FDA-approved for HS, are the most recent. Adalimumab “is our gold standard biologic and our gateway biologic, for HS at this time,” Dr. Micheletti said.
However, those who respond to adalimumab “can continue to do better, but they can wax and wane and flare,” he cautioned. Infliximab, while not approved for HS, has been studied in patients with HS and is prescribed by some providers. Although no comparative studies have been done for infliximab versus adalimumab, “anecdotally, response to infliximab tends to be better, and it is the most effective biologic in common use for severe HS,” he noted.
Dr. Micheletti’s top treatment recommendations for using biologics start with considering biosimilars. Most patients on biosimilars do fine, but some patients who previously responded to infliximab will unpredictably lose efficacy or have reactions when switched to a biosimilar, he said.
Patients on biologics also may experience waning efficacy in the wake of an immune response stimulated by foreign antibodies, said Dr. Micheletti. “Anti-drug antibody formation is more likely to occur when treatment is interrupted,” he noted. Minimize the risk of antibody formation by paying attention to adherence issues and dosing frequency, he advised.
If patients fail both adalimumab and infliximab, Dr. Micheletti tells them not to lose hope, and that treatment is a trial-and-error process that may involve more than one therapy. Other biologics in active use for HS include ustekinumab, anakinra, secukinumab, brodalumab, golimumab, and JAK inhibitors, any of which might be effective in any given patient, he said.
Surgical solutions
For HS patients with chronic, recurring inflammation and drainage associated with a sinus tract, surgical deroofing may the best treatment option, Dr. Micheletti said. “Deroofing involves the use of a probe to trace the extent of the subcutaneous tract, followed by incision and removal of the tract ‘roof,’ ’’ he explained. The deroofing procedure involves local anesthesia and has a low morbidity rate, as well as a low recurrence rate and high levels of patient satisfaction, he said.
“The acute role for surgery is to remove active foci of inflammation and relieve pain,” which is achieved more effectively with deroofing, said Dr. Micheletti. By contrast, incision and drainage is associated with an almost 100% recurrence rate, he added.
When planning elective surgery for HS, Dr. Micheletti noted that holding infliximab for less than 4 weeks does not affect postoperative infection rates in patients with rheumatoid arthritis, and a recent randomized, controlled trial showed that adalimumab can be continued safely through HS surgeries.
In fact, “continuing TNF inhibitors through elective surgery does not increase infection risk and results in better disease control,” and dermatologists should work with surgery to balance infection and disease flare concerns in HS patients, he said.
Dr. Micheletti disclosed serving as a consultant or advisor for Adaptimmune and Vertex, and research funding from Amgen and Cabaletta Bio. MedscapeLive and this news organization are owned by the same parent company.
AT INNOVATIONS IN DERMATOLOGY
Buzzy Lancet long COVID paper under investigation for ‘data errors’
An editorial that accompanied the paper when it was published in January of last year described it as “the first large cohort study with 6-months’ follow-up” of people hospitalized with COVID-19. The article has received plenty of attention since then.
Titled “6-month consequences of COVID-19 in patients discharged from hospital: a cohort study,” the paper has been cited nearly 1,600 times, according to Clarivate’s Web of Science. Altmetric finds references to it in multiple documents from the World Health Organization.
According to the expression of concern, dated November 24, a reader found inconsistencies between the data in the article and a later paper describing the same cohort of patients after a year of follow-up. That discovery sparked an investigation that is still ongoing:
- On Jan 8, 2021, The Lancet published an Article, 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study, by Chaolin Huang and colleagues. 1 On Aug 28, 2021, The Lancet published an Article, 1-year outcomes in hospital survivors with COVID-19: a longitudinal cohort study, by Lixue Huang and colleagues. 2 We received an inquiry from a researcher on data inconsistencies between these two Articles, and we sought an explanation from the corresponding author of the two papers. On Nov 7, 2022, Lancet editors were informed that inconsistencies between the 6-month and the 1-year data were due to “some variables in the dataset used for the 6-month paper were mistakenly disrupted in order”. In view of the extent of these data errors, we now issue an Expression of Concern about the 6-month paper 1 while we investigate further, including further statistical and clinical review of the corrected data. We will update this notice as soon as we have further information.
The corresponding author of both papers, Bin Cao of China’s National Center for Respiratory Medicine and the China-Japan Friendship Hospital in Beijing, has not responded to our request for comment.
A profile of Cao published in Lancet Infectious Diseases last March described him as “a leading researcher in pneumonia and influenza” who “has been instrumental in increasing knowledge about COVID-19.” In addition to the follow-up study of hospitalized COVID patients:
- Cao’s seminal papers during the COVID-19 pandemic include the first report of the clinical characteristics of COVID-19 patients in Wuhan, the description of the risk factors for mortality for adult inpatients, and the results of trials testing the use of antiviral drugs, including lopinavir-ritonavir, to treat COVID-19 in China.
We reached out to The Lancet’s press office and Richard Horton, the journal’s editor-in-chief, and received this statement:
- The Lancet Group treats all communications between editors and authors or readers as confidential. Investigations are continuing, and the Expression of Concern will be updated as soon as we have further information to share. More information about our policies is available here:
This year, The Lancet overtook the New England Journal of Medicine as the medical journal with the highest impact factor, in large part due to the papers it published about COVID-19.
We’ve counted retractions for three of those papers, most notably a paper about the use of the drug hydroxychloroquine that claimed to use medical data from a company called Surgisphere. As Retraction Watch readers may remember, the article was retracted after sleuths questioned if the data were real, and the company would not produce it for review.
This article first appeared on Retraction Watch.
An editorial that accompanied the paper when it was published in January of last year described it as “the first large cohort study with 6-months’ follow-up” of people hospitalized with COVID-19. The article has received plenty of attention since then.
Titled “6-month consequences of COVID-19 in patients discharged from hospital: a cohort study,” the paper has been cited nearly 1,600 times, according to Clarivate’s Web of Science. Altmetric finds references to it in multiple documents from the World Health Organization.
According to the expression of concern, dated November 24, a reader found inconsistencies between the data in the article and a later paper describing the same cohort of patients after a year of follow-up. That discovery sparked an investigation that is still ongoing:
- On Jan 8, 2021, The Lancet published an Article, 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study, by Chaolin Huang and colleagues. 1 On Aug 28, 2021, The Lancet published an Article, 1-year outcomes in hospital survivors with COVID-19: a longitudinal cohort study, by Lixue Huang and colleagues. 2 We received an inquiry from a researcher on data inconsistencies between these two Articles, and we sought an explanation from the corresponding author of the two papers. On Nov 7, 2022, Lancet editors were informed that inconsistencies between the 6-month and the 1-year data were due to “some variables in the dataset used for the 6-month paper were mistakenly disrupted in order”. In view of the extent of these data errors, we now issue an Expression of Concern about the 6-month paper 1 while we investigate further, including further statistical and clinical review of the corrected data. We will update this notice as soon as we have further information.
The corresponding author of both papers, Bin Cao of China’s National Center for Respiratory Medicine and the China-Japan Friendship Hospital in Beijing, has not responded to our request for comment.
A profile of Cao published in Lancet Infectious Diseases last March described him as “a leading researcher in pneumonia and influenza” who “has been instrumental in increasing knowledge about COVID-19.” In addition to the follow-up study of hospitalized COVID patients:
- Cao’s seminal papers during the COVID-19 pandemic include the first report of the clinical characteristics of COVID-19 patients in Wuhan, the description of the risk factors for mortality for adult inpatients, and the results of trials testing the use of antiviral drugs, including lopinavir-ritonavir, to treat COVID-19 in China.
We reached out to The Lancet’s press office and Richard Horton, the journal’s editor-in-chief, and received this statement:
- The Lancet Group treats all communications between editors and authors or readers as confidential. Investigations are continuing, and the Expression of Concern will be updated as soon as we have further information to share. More information about our policies is available here:
This year, The Lancet overtook the New England Journal of Medicine as the medical journal with the highest impact factor, in large part due to the papers it published about COVID-19.
We’ve counted retractions for three of those papers, most notably a paper about the use of the drug hydroxychloroquine that claimed to use medical data from a company called Surgisphere. As Retraction Watch readers may remember, the article was retracted after sleuths questioned if the data were real, and the company would not produce it for review.
This article first appeared on Retraction Watch.
An editorial that accompanied the paper when it was published in January of last year described it as “the first large cohort study with 6-months’ follow-up” of people hospitalized with COVID-19. The article has received plenty of attention since then.
Titled “6-month consequences of COVID-19 in patients discharged from hospital: a cohort study,” the paper has been cited nearly 1,600 times, according to Clarivate’s Web of Science. Altmetric finds references to it in multiple documents from the World Health Organization.
According to the expression of concern, dated November 24, a reader found inconsistencies between the data in the article and a later paper describing the same cohort of patients after a year of follow-up. That discovery sparked an investigation that is still ongoing:
- On Jan 8, 2021, The Lancet published an Article, 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study, by Chaolin Huang and colleagues. 1 On Aug 28, 2021, The Lancet published an Article, 1-year outcomes in hospital survivors with COVID-19: a longitudinal cohort study, by Lixue Huang and colleagues. 2 We received an inquiry from a researcher on data inconsistencies between these two Articles, and we sought an explanation from the corresponding author of the two papers. On Nov 7, 2022, Lancet editors were informed that inconsistencies between the 6-month and the 1-year data were due to “some variables in the dataset used for the 6-month paper were mistakenly disrupted in order”. In view of the extent of these data errors, we now issue an Expression of Concern about the 6-month paper 1 while we investigate further, including further statistical and clinical review of the corrected data. We will update this notice as soon as we have further information.
The corresponding author of both papers, Bin Cao of China’s National Center for Respiratory Medicine and the China-Japan Friendship Hospital in Beijing, has not responded to our request for comment.
A profile of Cao published in Lancet Infectious Diseases last March described him as “a leading researcher in pneumonia and influenza” who “has been instrumental in increasing knowledge about COVID-19.” In addition to the follow-up study of hospitalized COVID patients:
- Cao’s seminal papers during the COVID-19 pandemic include the first report of the clinical characteristics of COVID-19 patients in Wuhan, the description of the risk factors for mortality for adult inpatients, and the results of trials testing the use of antiviral drugs, including lopinavir-ritonavir, to treat COVID-19 in China.
We reached out to The Lancet’s press office and Richard Horton, the journal’s editor-in-chief, and received this statement:
- The Lancet Group treats all communications between editors and authors or readers as confidential. Investigations are continuing, and the Expression of Concern will be updated as soon as we have further information to share. More information about our policies is available here:
This year, The Lancet overtook the New England Journal of Medicine as the medical journal with the highest impact factor, in large part due to the papers it published about COVID-19.
We’ve counted retractions for three of those papers, most notably a paper about the use of the drug hydroxychloroquine that claimed to use medical data from a company called Surgisphere. As Retraction Watch readers may remember, the article was retracted after sleuths questioned if the data were real, and the company would not produce it for review.
This article first appeared on Retraction Watch.
Single chest x-ray could predict 10-year CVD risk
who presented the results of their deep-learning model at the annual meeting of the Radiological Society of North America.
Current American College of Cardiologists and American Heart Association guidelines recommend estimating 10-year risk of major adverse cardiovascular events (MACE) to determine whether a patient should receive statins to help prevent atherosclerotic cardiovascular disease (ASCVD). Statins are recommended for patients with a 10-year risk of 7.5% or higher, the authors noted.
The current ASCVD risk score is determined with nine factors: age, sex, race, systolic blood pressure, hypertension treatment, smoking, type 2 diabetes, and a lipid panel.
Not all data points available in EHR
But not all of those data points may be available through the electronic health record, “which makes novel and easier approaches for population-wide screening desirable,” said lead researcher Jakob Weiss, MD, a radiologist affiliated with the Cardiovascular Imaging Research Center at Massachusetts General Hospital and the AI in medicine program at the Brigham and Women’s Hospital in Boston.
Chest x-ray images, on the other hand, are commonly available. The images carry rich information beyond diagnostic data but have not been used in this type of prediction model because AI models have been lacking, Dr. Weiss said.
The researchers trained a deep-learning model with single chest x-rays only.
They used 147,497 chest x-rays from 40,643 participants in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial, a multicenter, randomized controlled trial designed and sponsored by the National Cancer Institute.
Dr. Weiss acknowledged that the population used to train the model was heavily White and that should be a consideration in validating the model.
They compared their model’s ability to predict 10-year ASCVD risk with the standard ACC/AHA model.
“Based on a single chest radiograph image, deep learning can predict the risk of future cardiovascular events independent of cardiovascular risk factors and with similar performance to the established and guideline-recommended ASCVD risk score,” Dr. Weiss said.
Tested against independent group
They tested the model against an independent group of 11,430 outpatients (average age, 60 years; 42.9% male) who underwent a routine outpatient chest x-ray at Mass General Brigham and were potentially eligible to receive statins.
Of those 11,430 patients, 1,096 (9.6%) had a major adverse cardiac event over the median follow-up of 10.3 years.
There was a significant association of CXR-CVD risk and MACE among patients eligible to receive statins, the researchers found (hazard ratio, 2.03; 95% confidence interval, 1.81-2.30; P < .001), which remained significant after adjusting for cardiovascular risk factors (adjusted HR, 1.63; 95% CI, 1.43-1.86; P < .001).
Some of the variables were missing in the standard model, but in a subgroup of 2,401 patients, all the variables were available.
They calculated ASCVD risk in that subgroup using the standard model and the CXR model and found that the performance was similar (c-statistic, 0.64 vs. 0.65; P = .48) to the ASCVD risk score (aHR, 1.58; 95% CI, 1.20-2.09; P = .001).
Ritu R. Gill MD, MPH, associate professor of radiology at Harvard Medical School in Boston, who was not part of the study, said in an interview that “the predictive algorithm is promising and potentially translatable and could enhance the annual medical checkup in a select population.
“The algorithm was developed using the PLCO cohort with radiographs, which are likely subjects in the lung cancer screening arm,” she said. “This cohort would be at high risk of cardiovascular diseases, as smoking is a known risk factor for atherosclerotic disease, and therefore the results are expected.
“The algorithm needs to be validated in an independent database with inclusion of subjects with younger age groups and adjusted for gender and racial diversity,” Gill said.
David Cho, MD, a cardiologist at the University of California, Los Angeles, who also was not part of the study, said in an interview that “this work is a great example of AI being able to detect clinically relevant outcomes with a widely used and low-cost screening test.
“The volume of data needed to train these models is already out there,” Dr. Cho said. “It just needs to be mined.”
He noted that this tool, if validated in randomized trials, could help determine risk among patients living in places where access to specialized cardiac care is limited.
Dr. Weiss and Dr. Cho disclosed no relevant financial relationships. Dr. Gill has received research support from Cannon Inc and consultant fees from Imbio and WorldCare.
A version of this article first appeared on Medscape.com.
who presented the results of their deep-learning model at the annual meeting of the Radiological Society of North America.
Current American College of Cardiologists and American Heart Association guidelines recommend estimating 10-year risk of major adverse cardiovascular events (MACE) to determine whether a patient should receive statins to help prevent atherosclerotic cardiovascular disease (ASCVD). Statins are recommended for patients with a 10-year risk of 7.5% or higher, the authors noted.
The current ASCVD risk score is determined with nine factors: age, sex, race, systolic blood pressure, hypertension treatment, smoking, type 2 diabetes, and a lipid panel.
Not all data points available in EHR
But not all of those data points may be available through the electronic health record, “which makes novel and easier approaches for population-wide screening desirable,” said lead researcher Jakob Weiss, MD, a radiologist affiliated with the Cardiovascular Imaging Research Center at Massachusetts General Hospital and the AI in medicine program at the Brigham and Women’s Hospital in Boston.
Chest x-ray images, on the other hand, are commonly available. The images carry rich information beyond diagnostic data but have not been used in this type of prediction model because AI models have been lacking, Dr. Weiss said.
The researchers trained a deep-learning model with single chest x-rays only.
They used 147,497 chest x-rays from 40,643 participants in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial, a multicenter, randomized controlled trial designed and sponsored by the National Cancer Institute.
Dr. Weiss acknowledged that the population used to train the model was heavily White and that should be a consideration in validating the model.
They compared their model’s ability to predict 10-year ASCVD risk with the standard ACC/AHA model.
“Based on a single chest radiograph image, deep learning can predict the risk of future cardiovascular events independent of cardiovascular risk factors and with similar performance to the established and guideline-recommended ASCVD risk score,” Dr. Weiss said.
Tested against independent group
They tested the model against an independent group of 11,430 outpatients (average age, 60 years; 42.9% male) who underwent a routine outpatient chest x-ray at Mass General Brigham and were potentially eligible to receive statins.
Of those 11,430 patients, 1,096 (9.6%) had a major adverse cardiac event over the median follow-up of 10.3 years.
There was a significant association of CXR-CVD risk and MACE among patients eligible to receive statins, the researchers found (hazard ratio, 2.03; 95% confidence interval, 1.81-2.30; P < .001), which remained significant after adjusting for cardiovascular risk factors (adjusted HR, 1.63; 95% CI, 1.43-1.86; P < .001).
Some of the variables were missing in the standard model, but in a subgroup of 2,401 patients, all the variables were available.
They calculated ASCVD risk in that subgroup using the standard model and the CXR model and found that the performance was similar (c-statistic, 0.64 vs. 0.65; P = .48) to the ASCVD risk score (aHR, 1.58; 95% CI, 1.20-2.09; P = .001).
Ritu R. Gill MD, MPH, associate professor of radiology at Harvard Medical School in Boston, who was not part of the study, said in an interview that “the predictive algorithm is promising and potentially translatable and could enhance the annual medical checkup in a select population.
“The algorithm was developed using the PLCO cohort with radiographs, which are likely subjects in the lung cancer screening arm,” she said. “This cohort would be at high risk of cardiovascular diseases, as smoking is a known risk factor for atherosclerotic disease, and therefore the results are expected.
“The algorithm needs to be validated in an independent database with inclusion of subjects with younger age groups and adjusted for gender and racial diversity,” Gill said.
David Cho, MD, a cardiologist at the University of California, Los Angeles, who also was not part of the study, said in an interview that “this work is a great example of AI being able to detect clinically relevant outcomes with a widely used and low-cost screening test.
“The volume of data needed to train these models is already out there,” Dr. Cho said. “It just needs to be mined.”
He noted that this tool, if validated in randomized trials, could help determine risk among patients living in places where access to specialized cardiac care is limited.
Dr. Weiss and Dr. Cho disclosed no relevant financial relationships. Dr. Gill has received research support from Cannon Inc and consultant fees from Imbio and WorldCare.
A version of this article first appeared on Medscape.com.
who presented the results of their deep-learning model at the annual meeting of the Radiological Society of North America.
Current American College of Cardiologists and American Heart Association guidelines recommend estimating 10-year risk of major adverse cardiovascular events (MACE) to determine whether a patient should receive statins to help prevent atherosclerotic cardiovascular disease (ASCVD). Statins are recommended for patients with a 10-year risk of 7.5% or higher, the authors noted.
The current ASCVD risk score is determined with nine factors: age, sex, race, systolic blood pressure, hypertension treatment, smoking, type 2 diabetes, and a lipid panel.
Not all data points available in EHR
But not all of those data points may be available through the electronic health record, “which makes novel and easier approaches for population-wide screening desirable,” said lead researcher Jakob Weiss, MD, a radiologist affiliated with the Cardiovascular Imaging Research Center at Massachusetts General Hospital and the AI in medicine program at the Brigham and Women’s Hospital in Boston.
Chest x-ray images, on the other hand, are commonly available. The images carry rich information beyond diagnostic data but have not been used in this type of prediction model because AI models have been lacking, Dr. Weiss said.
The researchers trained a deep-learning model with single chest x-rays only.
They used 147,497 chest x-rays from 40,643 participants in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial, a multicenter, randomized controlled trial designed and sponsored by the National Cancer Institute.
Dr. Weiss acknowledged that the population used to train the model was heavily White and that should be a consideration in validating the model.
They compared their model’s ability to predict 10-year ASCVD risk with the standard ACC/AHA model.
“Based on a single chest radiograph image, deep learning can predict the risk of future cardiovascular events independent of cardiovascular risk factors and with similar performance to the established and guideline-recommended ASCVD risk score,” Dr. Weiss said.
Tested against independent group
They tested the model against an independent group of 11,430 outpatients (average age, 60 years; 42.9% male) who underwent a routine outpatient chest x-ray at Mass General Brigham and were potentially eligible to receive statins.
Of those 11,430 patients, 1,096 (9.6%) had a major adverse cardiac event over the median follow-up of 10.3 years.
There was a significant association of CXR-CVD risk and MACE among patients eligible to receive statins, the researchers found (hazard ratio, 2.03; 95% confidence interval, 1.81-2.30; P < .001), which remained significant after adjusting for cardiovascular risk factors (adjusted HR, 1.63; 95% CI, 1.43-1.86; P < .001).
Some of the variables were missing in the standard model, but in a subgroup of 2,401 patients, all the variables were available.
They calculated ASCVD risk in that subgroup using the standard model and the CXR model and found that the performance was similar (c-statistic, 0.64 vs. 0.65; P = .48) to the ASCVD risk score (aHR, 1.58; 95% CI, 1.20-2.09; P = .001).
Ritu R. Gill MD, MPH, associate professor of radiology at Harvard Medical School in Boston, who was not part of the study, said in an interview that “the predictive algorithm is promising and potentially translatable and could enhance the annual medical checkup in a select population.
“The algorithm was developed using the PLCO cohort with radiographs, which are likely subjects in the lung cancer screening arm,” she said. “This cohort would be at high risk of cardiovascular diseases, as smoking is a known risk factor for atherosclerotic disease, and therefore the results are expected.
“The algorithm needs to be validated in an independent database with inclusion of subjects with younger age groups and adjusted for gender and racial diversity,” Gill said.
David Cho, MD, a cardiologist at the University of California, Los Angeles, who also was not part of the study, said in an interview that “this work is a great example of AI being able to detect clinically relevant outcomes with a widely used and low-cost screening test.
“The volume of data needed to train these models is already out there,” Dr. Cho said. “It just needs to be mined.”
He noted that this tool, if validated in randomized trials, could help determine risk among patients living in places where access to specialized cardiac care is limited.
Dr. Weiss and Dr. Cho disclosed no relevant financial relationships. Dr. Gill has received research support from Cannon Inc and consultant fees from Imbio and WorldCare.
A version of this article first appeared on Medscape.com.
AT RSNA 2022
Covid vax prevents death in children regardless of variant
The vaccine’s effectiveness against infection in the short term has been established, as has the waning effectiveness of the vaccine over time, wrote Juan Manuel Castelli, MD, of the Ministry of Health of Argentina, Buenos Aires, and colleagues, in the British Medical Journal.
However, data on the impact of vaccine effectiveness on mortality in children and adolescents are limited, especially during periods of omicron variant dominance, the researchers said.
In their new study, the researchers reviewed data from 844,460 children and adolescents aged 3-17 years from the National Surveillance System and the Nominalized Federal Vaccination Registry of Argentina, during a time that included a period of omicron dominance.
Argentina began vaccinating adolescents aged 12-17 years against COVID-19 in August 2021 and added children aged 3-11 years in October 2021. Those aged 12-17 years who were considered fully vaccinated received two doses of either Pfizer-BioNTech and/or Moderna vaccines, and fully-vaccinated 3- to 11-year-olds received two doses of Sinopharm vaccine.
The average time from the second vaccine dose to a COVID-19 test was 66 days for those aged 12-17 years and 54 days for 3- to 11-year-olds. The researchers matched COVID-19 cases with uninfected controls, and a total of 139,321 cases were included in the analysis.
Overall, the estimated vaccine effectiveness against COVID-19 was 64.2% during a period of delta dominance (61.2% in children aged 3-11 years and 66.8% in adolescents aged 12-17 years).
During a period of omicron dominance, estimated vaccine effectiveness was 19.9% across all ages (15.9% and 26.0% for younger and older age groups, respectively).
Effectiveness of the vaccine decreased over time, regardless of the dominant variant, but the decline was greater during the omicron dominant period, the researchers noted. During the omicron period, effectiveness in children aged 3-11 years decreased from 37.6% at 15-30 days postvaccination to 2.0% at 60 days or longer after vaccination. In adolescents aged 12-17 years, vaccine effectiveness during the omicron period decreased from 55.8% at 15-30 days postvaccination to 12.4% at 60 days or longer after vaccination.
Despite the waning protection against infection, the vaccine’s effectiveness against death from COVID-19 was 66.9% in children aged 3-11 years and 97.6% in adolescents aged 12-17 during the period of omicron dominance, the researchers noted.
The results are consistent with similar studies showing a decreased vaccine effectiveness against infection but a persistent effectiveness against deaths over time, the researchers wrote in the discussion section of their paper.
“Our results suggest that the primary vaccination schedule is effective in preventing mortality in children and adolescents with COVID-19 regardless of the circulating SARS-CoV-2 variant,” the researchers said.
Study limitations and strengths
The study was limited by several factors including the incomplete data on symptoms and hospital admissions, the possible impact of unmeasured confounding variables, and the observational design that prevents conclusions of causality, the researchers noted. However, the results were strengthened by the large sample size and access to detailed vaccination records, they said.
Both heterologous and homologous mRNA vaccine schedules showed similar effectiveness in preventing short-term infection and mortality from COVID-19 during periods of differing dominant variants, they noted.
The study findings support the vaccination of children against COVID-19 as an important public health measure to prevent mortality in children and adolescents, they concluded.
Data support value of vaccination, outside experts say
“COVID vaccines may not be as effective over time as the gene variants in the SARS-CoV-2 virus change,” Adrienne G. Randolph, MD, a pediatrician at Harvard Medical School and Boston Children’s Hospital, said in an interview. “Therefore, it is essential to assess vaccine effectiveness over time to look at effectiveness against variants and duration of effectiveness.” Dr. Randolph, who was not involved in the study, said she was not surprised by the findings, which she described as consistent with data from the United States. “COVID vaccines are very effective against preventing life-threatening disease, but the effectiveness against less severe illness for COVID vaccines is not as effective against Omicron,” she noted.
The take-home message for clinicians is that it’s important to get children vaccinated against COVID to prevent severe and life-threatening illness, said Dr. Randolph. “Although these cases are uncommon in children, it is not possible to predict which children will be the most severely affected by COVID,” she emphasized.
However, “we need more data on the new COVID booster vaccines in children that are designed to be more effective against Omicron’s newer variants,” Dr. Randolph said in an interview. “We also need more data on COVID vaccine effectiveness in the youngest children, under 5 years of age, and data on vaccinating mothers to prevent COVID in infants,” she said.
Tim Joos, MD, a Seattle-based clinician who practices a combination of internal medicine and pediatrics, agreed that future research should continue to assess how the new COVID boosters are faring against new variants, noting that the current study did not include data from children who received the new bivalent vaccine.
“The methodology of this study uses a test negative case control design which is common for estimating vaccine effectiveness post-release of a vaccine, but is subject to biases,” Dr. Joos explained. “These are not the clean effectiveness numbers of the prospective randomized control trials that we are used to hearing about when a vaccine is first being approved.”
“Nevertheless, the study reinforces the initial manufacturers’ studies that the vaccines are effective at preventing infection in the pediatric population,” Dr. Joos said in an interview. The current study also reinforces the effectiveness of vaccines in preventing “the rare but devastating mortality from COVID-19 in the pediatric population.”
Commenting on other research showing an increasing ratio of COVID deaths among vaccinated individuals compared to total COVID deaths, he noted that this finding is “likely reflecting a denominator effect of rapidly declining COVID deaths overall,” partly from the vaccines and partly from immunity after previous natural infection.
The study received no outside funding. The researchers, Dr. Randolph, and Dr. Joos had no financial conflicts to disclose. Dr. Joos serves on the Editorial Advisory Board of Pediatric News.
The vaccine’s effectiveness against infection in the short term has been established, as has the waning effectiveness of the vaccine over time, wrote Juan Manuel Castelli, MD, of the Ministry of Health of Argentina, Buenos Aires, and colleagues, in the British Medical Journal.
However, data on the impact of vaccine effectiveness on mortality in children and adolescents are limited, especially during periods of omicron variant dominance, the researchers said.
In their new study, the researchers reviewed data from 844,460 children and adolescents aged 3-17 years from the National Surveillance System and the Nominalized Federal Vaccination Registry of Argentina, during a time that included a period of omicron dominance.
Argentina began vaccinating adolescents aged 12-17 years against COVID-19 in August 2021 and added children aged 3-11 years in October 2021. Those aged 12-17 years who were considered fully vaccinated received two doses of either Pfizer-BioNTech and/or Moderna vaccines, and fully-vaccinated 3- to 11-year-olds received two doses of Sinopharm vaccine.
The average time from the second vaccine dose to a COVID-19 test was 66 days for those aged 12-17 years and 54 days for 3- to 11-year-olds. The researchers matched COVID-19 cases with uninfected controls, and a total of 139,321 cases were included in the analysis.
Overall, the estimated vaccine effectiveness against COVID-19 was 64.2% during a period of delta dominance (61.2% in children aged 3-11 years and 66.8% in adolescents aged 12-17 years).
During a period of omicron dominance, estimated vaccine effectiveness was 19.9% across all ages (15.9% and 26.0% for younger and older age groups, respectively).
Effectiveness of the vaccine decreased over time, regardless of the dominant variant, but the decline was greater during the omicron dominant period, the researchers noted. During the omicron period, effectiveness in children aged 3-11 years decreased from 37.6% at 15-30 days postvaccination to 2.0% at 60 days or longer after vaccination. In adolescents aged 12-17 years, vaccine effectiveness during the omicron period decreased from 55.8% at 15-30 days postvaccination to 12.4% at 60 days or longer after vaccination.
Despite the waning protection against infection, the vaccine’s effectiveness against death from COVID-19 was 66.9% in children aged 3-11 years and 97.6% in adolescents aged 12-17 during the period of omicron dominance, the researchers noted.
The results are consistent with similar studies showing a decreased vaccine effectiveness against infection but a persistent effectiveness against deaths over time, the researchers wrote in the discussion section of their paper.
“Our results suggest that the primary vaccination schedule is effective in preventing mortality in children and adolescents with COVID-19 regardless of the circulating SARS-CoV-2 variant,” the researchers said.
Study limitations and strengths
The study was limited by several factors including the incomplete data on symptoms and hospital admissions, the possible impact of unmeasured confounding variables, and the observational design that prevents conclusions of causality, the researchers noted. However, the results were strengthened by the large sample size and access to detailed vaccination records, they said.
Both heterologous and homologous mRNA vaccine schedules showed similar effectiveness in preventing short-term infection and mortality from COVID-19 during periods of differing dominant variants, they noted.
The study findings support the vaccination of children against COVID-19 as an important public health measure to prevent mortality in children and adolescents, they concluded.
Data support value of vaccination, outside experts say
“COVID vaccines may not be as effective over time as the gene variants in the SARS-CoV-2 virus change,” Adrienne G. Randolph, MD, a pediatrician at Harvard Medical School and Boston Children’s Hospital, said in an interview. “Therefore, it is essential to assess vaccine effectiveness over time to look at effectiveness against variants and duration of effectiveness.” Dr. Randolph, who was not involved in the study, said she was not surprised by the findings, which she described as consistent with data from the United States. “COVID vaccines are very effective against preventing life-threatening disease, but the effectiveness against less severe illness for COVID vaccines is not as effective against Omicron,” she noted.
The take-home message for clinicians is that it’s important to get children vaccinated against COVID to prevent severe and life-threatening illness, said Dr. Randolph. “Although these cases are uncommon in children, it is not possible to predict which children will be the most severely affected by COVID,” she emphasized.
However, “we need more data on the new COVID booster vaccines in children that are designed to be more effective against Omicron’s newer variants,” Dr. Randolph said in an interview. “We also need more data on COVID vaccine effectiveness in the youngest children, under 5 years of age, and data on vaccinating mothers to prevent COVID in infants,” she said.
Tim Joos, MD, a Seattle-based clinician who practices a combination of internal medicine and pediatrics, agreed that future research should continue to assess how the new COVID boosters are faring against new variants, noting that the current study did not include data from children who received the new bivalent vaccine.
“The methodology of this study uses a test negative case control design which is common for estimating vaccine effectiveness post-release of a vaccine, but is subject to biases,” Dr. Joos explained. “These are not the clean effectiveness numbers of the prospective randomized control trials that we are used to hearing about when a vaccine is first being approved.”
“Nevertheless, the study reinforces the initial manufacturers’ studies that the vaccines are effective at preventing infection in the pediatric population,” Dr. Joos said in an interview. The current study also reinforces the effectiveness of vaccines in preventing “the rare but devastating mortality from COVID-19 in the pediatric population.”
Commenting on other research showing an increasing ratio of COVID deaths among vaccinated individuals compared to total COVID deaths, he noted that this finding is “likely reflecting a denominator effect of rapidly declining COVID deaths overall,” partly from the vaccines and partly from immunity after previous natural infection.
The study received no outside funding. The researchers, Dr. Randolph, and Dr. Joos had no financial conflicts to disclose. Dr. Joos serves on the Editorial Advisory Board of Pediatric News.
The vaccine’s effectiveness against infection in the short term has been established, as has the waning effectiveness of the vaccine over time, wrote Juan Manuel Castelli, MD, of the Ministry of Health of Argentina, Buenos Aires, and colleagues, in the British Medical Journal.
However, data on the impact of vaccine effectiveness on mortality in children and adolescents are limited, especially during periods of omicron variant dominance, the researchers said.
In their new study, the researchers reviewed data from 844,460 children and adolescents aged 3-17 years from the National Surveillance System and the Nominalized Federal Vaccination Registry of Argentina, during a time that included a period of omicron dominance.
Argentina began vaccinating adolescents aged 12-17 years against COVID-19 in August 2021 and added children aged 3-11 years in October 2021. Those aged 12-17 years who were considered fully vaccinated received two doses of either Pfizer-BioNTech and/or Moderna vaccines, and fully-vaccinated 3- to 11-year-olds received two doses of Sinopharm vaccine.
The average time from the second vaccine dose to a COVID-19 test was 66 days for those aged 12-17 years and 54 days for 3- to 11-year-olds. The researchers matched COVID-19 cases with uninfected controls, and a total of 139,321 cases were included in the analysis.
Overall, the estimated vaccine effectiveness against COVID-19 was 64.2% during a period of delta dominance (61.2% in children aged 3-11 years and 66.8% in adolescents aged 12-17 years).
During a period of omicron dominance, estimated vaccine effectiveness was 19.9% across all ages (15.9% and 26.0% for younger and older age groups, respectively).
Effectiveness of the vaccine decreased over time, regardless of the dominant variant, but the decline was greater during the omicron dominant period, the researchers noted. During the omicron period, effectiveness in children aged 3-11 years decreased from 37.6% at 15-30 days postvaccination to 2.0% at 60 days or longer after vaccination. In adolescents aged 12-17 years, vaccine effectiveness during the omicron period decreased from 55.8% at 15-30 days postvaccination to 12.4% at 60 days or longer after vaccination.
Despite the waning protection against infection, the vaccine’s effectiveness against death from COVID-19 was 66.9% in children aged 3-11 years and 97.6% in adolescents aged 12-17 during the period of omicron dominance, the researchers noted.
The results are consistent with similar studies showing a decreased vaccine effectiveness against infection but a persistent effectiveness against deaths over time, the researchers wrote in the discussion section of their paper.
“Our results suggest that the primary vaccination schedule is effective in preventing mortality in children and adolescents with COVID-19 regardless of the circulating SARS-CoV-2 variant,” the researchers said.
Study limitations and strengths
The study was limited by several factors including the incomplete data on symptoms and hospital admissions, the possible impact of unmeasured confounding variables, and the observational design that prevents conclusions of causality, the researchers noted. However, the results were strengthened by the large sample size and access to detailed vaccination records, they said.
Both heterologous and homologous mRNA vaccine schedules showed similar effectiveness in preventing short-term infection and mortality from COVID-19 during periods of differing dominant variants, they noted.
The study findings support the vaccination of children against COVID-19 as an important public health measure to prevent mortality in children and adolescents, they concluded.
Data support value of vaccination, outside experts say
“COVID vaccines may not be as effective over time as the gene variants in the SARS-CoV-2 virus change,” Adrienne G. Randolph, MD, a pediatrician at Harvard Medical School and Boston Children’s Hospital, said in an interview. “Therefore, it is essential to assess vaccine effectiveness over time to look at effectiveness against variants and duration of effectiveness.” Dr. Randolph, who was not involved in the study, said she was not surprised by the findings, which she described as consistent with data from the United States. “COVID vaccines are very effective against preventing life-threatening disease, but the effectiveness against less severe illness for COVID vaccines is not as effective against Omicron,” she noted.
The take-home message for clinicians is that it’s important to get children vaccinated against COVID to prevent severe and life-threatening illness, said Dr. Randolph. “Although these cases are uncommon in children, it is not possible to predict which children will be the most severely affected by COVID,” she emphasized.
However, “we need more data on the new COVID booster vaccines in children that are designed to be more effective against Omicron’s newer variants,” Dr. Randolph said in an interview. “We also need more data on COVID vaccine effectiveness in the youngest children, under 5 years of age, and data on vaccinating mothers to prevent COVID in infants,” she said.
Tim Joos, MD, a Seattle-based clinician who practices a combination of internal medicine and pediatrics, agreed that future research should continue to assess how the new COVID boosters are faring against new variants, noting that the current study did not include data from children who received the new bivalent vaccine.
“The methodology of this study uses a test negative case control design which is common for estimating vaccine effectiveness post-release of a vaccine, but is subject to biases,” Dr. Joos explained. “These are not the clean effectiveness numbers of the prospective randomized control trials that we are used to hearing about when a vaccine is first being approved.”
“Nevertheless, the study reinforces the initial manufacturers’ studies that the vaccines are effective at preventing infection in the pediatric population,” Dr. Joos said in an interview. The current study also reinforces the effectiveness of vaccines in preventing “the rare but devastating mortality from COVID-19 in the pediatric population.”
Commenting on other research showing an increasing ratio of COVID deaths among vaccinated individuals compared to total COVID deaths, he noted that this finding is “likely reflecting a denominator effect of rapidly declining COVID deaths overall,” partly from the vaccines and partly from immunity after previous natural infection.
The study received no outside funding. The researchers, Dr. Randolph, and Dr. Joos had no financial conflicts to disclose. Dr. Joos serves on the Editorial Advisory Board of Pediatric News.
FROM THE BMJ
Gestational hypertension-diabetes combo signals CVD risk
Women who develop transient hypertensive disorders during their pregnancy are at risk for developing subsequent cardiovascular disease (CVD), particularly if this experienced at the same time as gestational diabetes.
In a large population-based study, the adjusted hazard ratios for developing CVD following a gestational hypertensive disorder (GHTD) alone were 1.90 (95% confidence interval, 1.151-2.25) within 5 years and 1.41 (95% CI, 1.12-1.76) after 5 years or more.
When gestational diabetes was added into the mix, however, the risk for CVD after 5 years more than doubled (aHR, 2.43; 95% CI, 1.60-3.67). Risk in the earlier postpartum period was also raised by the combination, but this was not significant (aHR, 1.42; 95% CI, 0.78-2.58).
Having gestational diabetes by itself did not seem to increase the risk for later CVD in the analysis, despite being linked to higher heart disease risk in other studies.
“These are women coming out of a pregnancy – young women of reproductive age – so this is not a group that typically has cardiovascular events,” said Ravi Retnakaran, MD, in an interview, an investigator in the new study, which is published in JAMA Network Open.
“If they are somebody who has both disorders concurrently in their pregnancy, they may be at even greater risk than a woman with one or the other disorder,” added Dr. Retnakaran, who is professor of medicine at the University of Toronto and an endocrinologist at the Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, also in Toronto. “In other words, amongst already high-risk patients. This is identifying a subset at maybe an even higher risk.”
It doesn’t mean that there is a huge absolute risk, Dr. Retnakaran said, but it is showing that there is a heightened risk such that women and their clinicians need to be aware of and potentially the need for greater preventative care in the future.
“It is allowing you to identify future lifetime risk of cardiovascular disease,” he said.
Study rationale and design
GHTD is “a forerunner of hypertension,” and gestational diabetes is “a precursor of diabetes” – each associated with a high risk of developing CVD in the years after pregnancy, the investigators said. While studies have looked at their individual contributions to future CVD risk, not many had looked to see what risks having both may confer in the postpregnancy years.
For the analysis, data on 886,295 women with GHTD (43,861), gestational diabetes (54,061), both (4,975), or neither (783,398) were obtained from several Canadian administrative health databases.
The mean age was around 30 years across the groups, with those with both conditions or gestational diabetes alone more likely to be older than those with GTHD alone or neither condition (32 vs. 29 years, respectively, P < .001).
After a total follow-up period of 12 years, 1,999 CVD events were recorded, most of them (1,162) 5 years after the pregnancy.
Pregnancy is a stress test for the heart
“We know that what we call adverse pregnancy outcomes – things like gestational hypertension, and gestational diabetes, and preeclampsia – are on the rise globally,” Natalie A. Bello, MD, director of hypertension research at the Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, commented in an interview.
“People who are younger and of childbearing age who are going into pregnancy now are less healthy than they perhaps were in the past,” Dr. Bello suggested, with more hypertension, more obesity, and people being less physically active. “We think that’s translating into some of the pregnancy complications.”
That’s concerning for a number of reasons, said Dr. Bello, who is also the cochair of the American College of Cardiology’s Cardio-Obstetrics Workgroup, and the biggest one perhaps is the stress that these may conditions may be placing on the heart.
“We know that when individuals have an adverse pregnancy outcome like gestational hypertension, or gestational diabetes, their risk for heart disease is increased in the future compared to someone who has an uncomplicated pregnancy,” she said. “So, we sort of say pregnancy is like a stress test for your heart.”
Dr. Bello added that “these situations, these adverse pregnancy outcomes are an indicator for us as physicians, but also they should be for patients as well, to sort of make sure they’re talking to their doctor about their risk factors and modifying them whenever possible.”
The population studied came from quite a racially, ethnically, and economically diverse area of Canada, Dr. Bello pointed out, although because of the nature of an administrative database there wasn’t information on individual level risk factors.
“We don’t know things like smoking, or if individuals were obese when they were pregnant. So, there are some limitations that should be noted,” she said.
Also, the results don’t mean that isolated gestational diabetes “isn’t something we need to be concerned about,” Dr. Bello observed, adding that the study may have been underpowered to look at this association. “It may just be that it will take a longer time for individuals who have gestational diabetes who don’t make lifestyle changes to develop diabetes, and then develop heart disease.”
The main message is that the women who have a co-occurrence of gestational hypertension and gestational diabetes are at particularly high risk of cardiovascular disease in the future,” said Dr. Retnakaran.
“The way to look at it from a patient standpoint is that we are all on different tracks in terms of our cardiometabolic destiny,” and that these data give “some understanding of what kind of tracks they are on for future risk,” Dr. Retnakaran said.
“A history of either gestational hypertension, and/or gestational diabetes should be really a warning sign for physicians and for patients that they have a higher risk of heart disease,” said Dr. Bello.
She added that this is a signal “that we need to do things to modify their risk, because we know that about 80% of heart disease is modifiable and preventable with proper risk factor management.”
The study was funded by the Ontario Ministry of Health and Long-Term Care. Dr. Retnakaran has received grants and personal fees from Novo Nordisk and Merck, grants from Boehringer Ingelheim, and personal fees from Eli Lily Takeda, and Sanofi. Dr. Bello had no conflicts of interest to disclose.
Women who develop transient hypertensive disorders during their pregnancy are at risk for developing subsequent cardiovascular disease (CVD), particularly if this experienced at the same time as gestational diabetes.
In a large population-based study, the adjusted hazard ratios for developing CVD following a gestational hypertensive disorder (GHTD) alone were 1.90 (95% confidence interval, 1.151-2.25) within 5 years and 1.41 (95% CI, 1.12-1.76) after 5 years or more.
When gestational diabetes was added into the mix, however, the risk for CVD after 5 years more than doubled (aHR, 2.43; 95% CI, 1.60-3.67). Risk in the earlier postpartum period was also raised by the combination, but this was not significant (aHR, 1.42; 95% CI, 0.78-2.58).
Having gestational diabetes by itself did not seem to increase the risk for later CVD in the analysis, despite being linked to higher heart disease risk in other studies.
“These are women coming out of a pregnancy – young women of reproductive age – so this is not a group that typically has cardiovascular events,” said Ravi Retnakaran, MD, in an interview, an investigator in the new study, which is published in JAMA Network Open.
“If they are somebody who has both disorders concurrently in their pregnancy, they may be at even greater risk than a woman with one or the other disorder,” added Dr. Retnakaran, who is professor of medicine at the University of Toronto and an endocrinologist at the Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, also in Toronto. “In other words, amongst already high-risk patients. This is identifying a subset at maybe an even higher risk.”
It doesn’t mean that there is a huge absolute risk, Dr. Retnakaran said, but it is showing that there is a heightened risk such that women and their clinicians need to be aware of and potentially the need for greater preventative care in the future.
“It is allowing you to identify future lifetime risk of cardiovascular disease,” he said.
Study rationale and design
GHTD is “a forerunner of hypertension,” and gestational diabetes is “a precursor of diabetes” – each associated with a high risk of developing CVD in the years after pregnancy, the investigators said. While studies have looked at their individual contributions to future CVD risk, not many had looked to see what risks having both may confer in the postpregnancy years.
For the analysis, data on 886,295 women with GHTD (43,861), gestational diabetes (54,061), both (4,975), or neither (783,398) were obtained from several Canadian administrative health databases.
The mean age was around 30 years across the groups, with those with both conditions or gestational diabetes alone more likely to be older than those with GTHD alone or neither condition (32 vs. 29 years, respectively, P < .001).
After a total follow-up period of 12 years, 1,999 CVD events were recorded, most of them (1,162) 5 years after the pregnancy.
Pregnancy is a stress test for the heart
“We know that what we call adverse pregnancy outcomes – things like gestational hypertension, and gestational diabetes, and preeclampsia – are on the rise globally,” Natalie A. Bello, MD, director of hypertension research at the Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, commented in an interview.
“People who are younger and of childbearing age who are going into pregnancy now are less healthy than they perhaps were in the past,” Dr. Bello suggested, with more hypertension, more obesity, and people being less physically active. “We think that’s translating into some of the pregnancy complications.”
That’s concerning for a number of reasons, said Dr. Bello, who is also the cochair of the American College of Cardiology’s Cardio-Obstetrics Workgroup, and the biggest one perhaps is the stress that these may conditions may be placing on the heart.
“We know that when individuals have an adverse pregnancy outcome like gestational hypertension, or gestational diabetes, their risk for heart disease is increased in the future compared to someone who has an uncomplicated pregnancy,” she said. “So, we sort of say pregnancy is like a stress test for your heart.”
Dr. Bello added that “these situations, these adverse pregnancy outcomes are an indicator for us as physicians, but also they should be for patients as well, to sort of make sure they’re talking to their doctor about their risk factors and modifying them whenever possible.”
The population studied came from quite a racially, ethnically, and economically diverse area of Canada, Dr. Bello pointed out, although because of the nature of an administrative database there wasn’t information on individual level risk factors.
“We don’t know things like smoking, or if individuals were obese when they were pregnant. So, there are some limitations that should be noted,” she said.
Also, the results don’t mean that isolated gestational diabetes “isn’t something we need to be concerned about,” Dr. Bello observed, adding that the study may have been underpowered to look at this association. “It may just be that it will take a longer time for individuals who have gestational diabetes who don’t make lifestyle changes to develop diabetes, and then develop heart disease.”
The main message is that the women who have a co-occurrence of gestational hypertension and gestational diabetes are at particularly high risk of cardiovascular disease in the future,” said Dr. Retnakaran.
“The way to look at it from a patient standpoint is that we are all on different tracks in terms of our cardiometabolic destiny,” and that these data give “some understanding of what kind of tracks they are on for future risk,” Dr. Retnakaran said.
“A history of either gestational hypertension, and/or gestational diabetes should be really a warning sign for physicians and for patients that they have a higher risk of heart disease,” said Dr. Bello.
She added that this is a signal “that we need to do things to modify their risk, because we know that about 80% of heart disease is modifiable and preventable with proper risk factor management.”
The study was funded by the Ontario Ministry of Health and Long-Term Care. Dr. Retnakaran has received grants and personal fees from Novo Nordisk and Merck, grants from Boehringer Ingelheim, and personal fees from Eli Lily Takeda, and Sanofi. Dr. Bello had no conflicts of interest to disclose.
Women who develop transient hypertensive disorders during their pregnancy are at risk for developing subsequent cardiovascular disease (CVD), particularly if this experienced at the same time as gestational diabetes.
In a large population-based study, the adjusted hazard ratios for developing CVD following a gestational hypertensive disorder (GHTD) alone were 1.90 (95% confidence interval, 1.151-2.25) within 5 years and 1.41 (95% CI, 1.12-1.76) after 5 years or more.
When gestational diabetes was added into the mix, however, the risk for CVD after 5 years more than doubled (aHR, 2.43; 95% CI, 1.60-3.67). Risk in the earlier postpartum period was also raised by the combination, but this was not significant (aHR, 1.42; 95% CI, 0.78-2.58).
Having gestational diabetes by itself did not seem to increase the risk for later CVD in the analysis, despite being linked to higher heart disease risk in other studies.
“These are women coming out of a pregnancy – young women of reproductive age – so this is not a group that typically has cardiovascular events,” said Ravi Retnakaran, MD, in an interview, an investigator in the new study, which is published in JAMA Network Open.
“If they are somebody who has both disorders concurrently in their pregnancy, they may be at even greater risk than a woman with one or the other disorder,” added Dr. Retnakaran, who is professor of medicine at the University of Toronto and an endocrinologist at the Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, also in Toronto. “In other words, amongst already high-risk patients. This is identifying a subset at maybe an even higher risk.”
It doesn’t mean that there is a huge absolute risk, Dr. Retnakaran said, but it is showing that there is a heightened risk such that women and their clinicians need to be aware of and potentially the need for greater preventative care in the future.
“It is allowing you to identify future lifetime risk of cardiovascular disease,” he said.
Study rationale and design
GHTD is “a forerunner of hypertension,” and gestational diabetes is “a precursor of diabetes” – each associated with a high risk of developing CVD in the years after pregnancy, the investigators said. While studies have looked at their individual contributions to future CVD risk, not many had looked to see what risks having both may confer in the postpregnancy years.
For the analysis, data on 886,295 women with GHTD (43,861), gestational diabetes (54,061), both (4,975), or neither (783,398) were obtained from several Canadian administrative health databases.
The mean age was around 30 years across the groups, with those with both conditions or gestational diabetes alone more likely to be older than those with GTHD alone or neither condition (32 vs. 29 years, respectively, P < .001).
After a total follow-up period of 12 years, 1,999 CVD events were recorded, most of them (1,162) 5 years after the pregnancy.
Pregnancy is a stress test for the heart
“We know that what we call adverse pregnancy outcomes – things like gestational hypertension, and gestational diabetes, and preeclampsia – are on the rise globally,” Natalie A. Bello, MD, director of hypertension research at the Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, commented in an interview.
“People who are younger and of childbearing age who are going into pregnancy now are less healthy than they perhaps were in the past,” Dr. Bello suggested, with more hypertension, more obesity, and people being less physically active. “We think that’s translating into some of the pregnancy complications.”
That’s concerning for a number of reasons, said Dr. Bello, who is also the cochair of the American College of Cardiology’s Cardio-Obstetrics Workgroup, and the biggest one perhaps is the stress that these may conditions may be placing on the heart.
“We know that when individuals have an adverse pregnancy outcome like gestational hypertension, or gestational diabetes, their risk for heart disease is increased in the future compared to someone who has an uncomplicated pregnancy,” she said. “So, we sort of say pregnancy is like a stress test for your heart.”
Dr. Bello added that “these situations, these adverse pregnancy outcomes are an indicator for us as physicians, but also they should be for patients as well, to sort of make sure they’re talking to their doctor about their risk factors and modifying them whenever possible.”
The population studied came from quite a racially, ethnically, and economically diverse area of Canada, Dr. Bello pointed out, although because of the nature of an administrative database there wasn’t information on individual level risk factors.
“We don’t know things like smoking, or if individuals were obese when they were pregnant. So, there are some limitations that should be noted,” she said.
Also, the results don’t mean that isolated gestational diabetes “isn’t something we need to be concerned about,” Dr. Bello observed, adding that the study may have been underpowered to look at this association. “It may just be that it will take a longer time for individuals who have gestational diabetes who don’t make lifestyle changes to develop diabetes, and then develop heart disease.”
The main message is that the women who have a co-occurrence of gestational hypertension and gestational diabetes are at particularly high risk of cardiovascular disease in the future,” said Dr. Retnakaran.
“The way to look at it from a patient standpoint is that we are all on different tracks in terms of our cardiometabolic destiny,” and that these data give “some understanding of what kind of tracks they are on for future risk,” Dr. Retnakaran said.
“A history of either gestational hypertension, and/or gestational diabetes should be really a warning sign for physicians and for patients that they have a higher risk of heart disease,” said Dr. Bello.
She added that this is a signal “that we need to do things to modify their risk, because we know that about 80% of heart disease is modifiable and preventable with proper risk factor management.”
The study was funded by the Ontario Ministry of Health and Long-Term Care. Dr. Retnakaran has received grants and personal fees from Novo Nordisk and Merck, grants from Boehringer Ingelheim, and personal fees from Eli Lily Takeda, and Sanofi. Dr. Bello had no conflicts of interest to disclose.
FROM JAMA NETWORK OPEN
Higher potency of fentanyl affects addiction treatment, screening
As fentanyl-related overdose deaths continue to increase, clinicians should take note of important differences that set the drug apart from the other drugs of misuse – and the troubling reality that fentanyl now contaminates most of them.
“It would be fair to tell patients, if you’re buying any illicit drugs – pills, powder, liquid, whatever it is, you’ve got to assume it’s either contaminated with or replaced by fentanyl,” said Edwin Salsitz, MD, an associate clinical professor at the Icahn School of Medicine at Mount Sinai, New York, during a presentation on the subject at the 21st Annual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
In many if not most cases, he noted, patients become addicted to fentanyl unknowingly. They assume they are ingesting oxycodone, cocaine, or another drug, and have no realization that they are even exposed to fentanyl until they test positive for it – or overdose.
Meanwhile, the high potency of fentanyl can overcome the opioid blockade of addiction treatment therapies – methadone and buprenorphine – that take away the high that users get from less potent drugs such as heroin.
“Fentanyl is overcoming this blockade that methadone and buprenorphine used to provide,” Dr. Salsitz said. “With fentanyl having such a higher potency, patients are saying ‘no, I still feel the fentanyl effects,’ and they continue feeling it even with 200 milligrams of methadone or 24 milligrams of buprenorphine.”
‘Wooden chest syndrome’
Among the lesser-known dangers of fentanyl is the possibility that some overdose deaths may occur as the result of a syndrome previously reported as a rare complication following the medical use of fentanyl in critically ill patients – fentanyl-induced chest-wall rigidity, or “wooden chest syndrome,” Dr. Salsitz explained.
In such cases, the muscles of respiration become rigid and paralyzed, causing suffocation within a matter of minutes – too soon to benefit from the overdose rescue medication naloxone.
In one recent study published in Clinical Toxicology , nearly half of fentanyl overdose deaths were found to have occurred even before the body had a chance to produce norfentanyl, a metabolite of fentanyl that takes only about 2-3 minutes to appear in the system, suggesting the deaths occurred rapidly.
In the study of 48 fentanyl deaths, no appreciable concentrations of norfentanyl could be detected in 20 of the 48 overdose deaths (42%), and concentrations were less than 1 ng/mL in 25 cases (52%).
“The lack of any measurable norfentanyl in half of our cases suggests a very rapid death, consistent with acute chest rigidity,” the authors reported.
“In several cases fentanyl concentrations were strikingly high (22 ng/mL and 20 ng/mL) with no norfentanyl detected,” they said.
Dr. Salsitz noted that the syndrome is not well known among the addiction treatment community.
“This is different than the usual respiratory opioid overdose where there’s a gradual decrease in the breathing rate and a gradual decrease in how much air is going in and out of the lungs,” Dr. Salsitz explained.
“With those cases, some may survive for an hour or longer, allowing time for someone to administer naloxone or to get the patient to the emergency room,” he said. “But with this, breathing stops and people can die within minutes.
“I think that this is one of the reasons that fentanyl deaths keep going up despite more and more naloxone availability out there,” he said.
Clearance may take longer
In toxicology testing for fentanyl, clinicians should also note the important difference between fentanyl and other opioids – that fentanyl, because of its high lipophilicity, may be detected in urine toxicology testing up to 3 weeks after last use. This is much longer than the 2- to 4-day clearance observed with other opioids, possibly causing patients to continue to test positive for the drug weeks after cessation.
This effect was observed in one recent study of 12 opioid use disorder patients in a residential treatment program who had previously been exposed to daily fentanyl.
The study showed the mean amount of time of fentanyl clearance was 2 weeks, with a range of 4-26 days after last use.
The authors pointed out that the findings “might explain recent reports of difficulty in buprenorphine inductions for persons who use fentanyl, and point to a need to better understand the pharmacokinetics of fentanyl in the context of opioid withdrawal in persons who regularly use fentanyl.”
Though the study was small, Dr. Salsitz said “that’s not a stumbling block to the important finding that, with regular use of fentanyl, the drug may stay in the urine for a long time.”
Dr. Salsitz noted that similar observations have been made at his center, with clinicians logically assuming that patients were still somehow getting fentanyl.
“When we initially found this in patients, we thought that they were using on the unit, perhaps that they brought in the fentanyl, because otherwise how could it stay in the urine that long,” he noted. “But fentanyl appears to be more lipophilic and gets into the fat; it’s then excreted very slowly and then stays in the urine.”
Dr. Salsitz said most practitioners think of fentanyl as a short-acting drug, so “it’s important to realize that people may continue to test positive and it should be thought of as a long-acting opioid.”
Opiate screening tests don’t work
Dr. Salsitz warned of another misconception in fentanyl testing – the common mistake of assuming that fentanyl should show up in a test for opiates – when in fact fentanyl is not, technically, an opiate.
“The word opiate only refers to morphine, codeine, heroin and sometimes hydrocodone,” he explained. “Other opioids are classified as semisynthetic, such as oxycodone, or synthetics, such as fentanyl and methadone, buprenorphine.”
“In order to detect the synthetics, you must have a separate strip for each one of those drugs. They will not show up positive on a screen for opiates,” he noted.
The belief that fentanyl and other synthetic and semisynthetic opioids will show positive on an opiate screen is a common misconception, he said. “The misunderstanding in toxicology interpretation is a problem for many practitioners, [but] it’s essential to understand because otherwise false assumptions about the patient will be considered.”
Another important testing misreading can occur with the antidepressant drug trazodone, which Dr. Salsitz cautioned may falsely test as positive for fentanyl on immunoassays.
“Trazodone is very commonly used in addiction treatment centers, but it can give a false positive on the fentanyl immunoassay and we’ve had a number of those cases,” he said.
Dr. Salsitz had no disclosures to report.
The Psychopharmacology Update was sponsored by Medscape Live. Medscape Live and this news organization are owned by the same parent company.
As fentanyl-related overdose deaths continue to increase, clinicians should take note of important differences that set the drug apart from the other drugs of misuse – and the troubling reality that fentanyl now contaminates most of them.
“It would be fair to tell patients, if you’re buying any illicit drugs – pills, powder, liquid, whatever it is, you’ve got to assume it’s either contaminated with or replaced by fentanyl,” said Edwin Salsitz, MD, an associate clinical professor at the Icahn School of Medicine at Mount Sinai, New York, during a presentation on the subject at the 21st Annual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
In many if not most cases, he noted, patients become addicted to fentanyl unknowingly. They assume they are ingesting oxycodone, cocaine, or another drug, and have no realization that they are even exposed to fentanyl until they test positive for it – or overdose.
Meanwhile, the high potency of fentanyl can overcome the opioid blockade of addiction treatment therapies – methadone and buprenorphine – that take away the high that users get from less potent drugs such as heroin.
“Fentanyl is overcoming this blockade that methadone and buprenorphine used to provide,” Dr. Salsitz said. “With fentanyl having such a higher potency, patients are saying ‘no, I still feel the fentanyl effects,’ and they continue feeling it even with 200 milligrams of methadone or 24 milligrams of buprenorphine.”
‘Wooden chest syndrome’
Among the lesser-known dangers of fentanyl is the possibility that some overdose deaths may occur as the result of a syndrome previously reported as a rare complication following the medical use of fentanyl in critically ill patients – fentanyl-induced chest-wall rigidity, or “wooden chest syndrome,” Dr. Salsitz explained.
In such cases, the muscles of respiration become rigid and paralyzed, causing suffocation within a matter of minutes – too soon to benefit from the overdose rescue medication naloxone.
In one recent study published in Clinical Toxicology , nearly half of fentanyl overdose deaths were found to have occurred even before the body had a chance to produce norfentanyl, a metabolite of fentanyl that takes only about 2-3 minutes to appear in the system, suggesting the deaths occurred rapidly.
In the study of 48 fentanyl deaths, no appreciable concentrations of norfentanyl could be detected in 20 of the 48 overdose deaths (42%), and concentrations were less than 1 ng/mL in 25 cases (52%).
“The lack of any measurable norfentanyl in half of our cases suggests a very rapid death, consistent with acute chest rigidity,” the authors reported.
“In several cases fentanyl concentrations were strikingly high (22 ng/mL and 20 ng/mL) with no norfentanyl detected,” they said.
Dr. Salsitz noted that the syndrome is not well known among the addiction treatment community.
“This is different than the usual respiratory opioid overdose where there’s a gradual decrease in the breathing rate and a gradual decrease in how much air is going in and out of the lungs,” Dr. Salsitz explained.
“With those cases, some may survive for an hour or longer, allowing time for someone to administer naloxone or to get the patient to the emergency room,” he said. “But with this, breathing stops and people can die within minutes.
“I think that this is one of the reasons that fentanyl deaths keep going up despite more and more naloxone availability out there,” he said.
Clearance may take longer
In toxicology testing for fentanyl, clinicians should also note the important difference between fentanyl and other opioids – that fentanyl, because of its high lipophilicity, may be detected in urine toxicology testing up to 3 weeks after last use. This is much longer than the 2- to 4-day clearance observed with other opioids, possibly causing patients to continue to test positive for the drug weeks after cessation.
This effect was observed in one recent study of 12 opioid use disorder patients in a residential treatment program who had previously been exposed to daily fentanyl.
The study showed the mean amount of time of fentanyl clearance was 2 weeks, with a range of 4-26 days after last use.
The authors pointed out that the findings “might explain recent reports of difficulty in buprenorphine inductions for persons who use fentanyl, and point to a need to better understand the pharmacokinetics of fentanyl in the context of opioid withdrawal in persons who regularly use fentanyl.”
Though the study was small, Dr. Salsitz said “that’s not a stumbling block to the important finding that, with regular use of fentanyl, the drug may stay in the urine for a long time.”
Dr. Salsitz noted that similar observations have been made at his center, with clinicians logically assuming that patients were still somehow getting fentanyl.
“When we initially found this in patients, we thought that they were using on the unit, perhaps that they brought in the fentanyl, because otherwise how could it stay in the urine that long,” he noted. “But fentanyl appears to be more lipophilic and gets into the fat; it’s then excreted very slowly and then stays in the urine.”
Dr. Salsitz said most practitioners think of fentanyl as a short-acting drug, so “it’s important to realize that people may continue to test positive and it should be thought of as a long-acting opioid.”
Opiate screening tests don’t work
Dr. Salsitz warned of another misconception in fentanyl testing – the common mistake of assuming that fentanyl should show up in a test for opiates – when in fact fentanyl is not, technically, an opiate.
“The word opiate only refers to morphine, codeine, heroin and sometimes hydrocodone,” he explained. “Other opioids are classified as semisynthetic, such as oxycodone, or synthetics, such as fentanyl and methadone, buprenorphine.”
“In order to detect the synthetics, you must have a separate strip for each one of those drugs. They will not show up positive on a screen for opiates,” he noted.
The belief that fentanyl and other synthetic and semisynthetic opioids will show positive on an opiate screen is a common misconception, he said. “The misunderstanding in toxicology interpretation is a problem for many practitioners, [but] it’s essential to understand because otherwise false assumptions about the patient will be considered.”
Another important testing misreading can occur with the antidepressant drug trazodone, which Dr. Salsitz cautioned may falsely test as positive for fentanyl on immunoassays.
“Trazodone is very commonly used in addiction treatment centers, but it can give a false positive on the fentanyl immunoassay and we’ve had a number of those cases,” he said.
Dr. Salsitz had no disclosures to report.
The Psychopharmacology Update was sponsored by Medscape Live. Medscape Live and this news organization are owned by the same parent company.
As fentanyl-related overdose deaths continue to increase, clinicians should take note of important differences that set the drug apart from the other drugs of misuse – and the troubling reality that fentanyl now contaminates most of them.
“It would be fair to tell patients, if you’re buying any illicit drugs – pills, powder, liquid, whatever it is, you’ve got to assume it’s either contaminated with or replaced by fentanyl,” said Edwin Salsitz, MD, an associate clinical professor at the Icahn School of Medicine at Mount Sinai, New York, during a presentation on the subject at the 21st Annual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
In many if not most cases, he noted, patients become addicted to fentanyl unknowingly. They assume they are ingesting oxycodone, cocaine, or another drug, and have no realization that they are even exposed to fentanyl until they test positive for it – or overdose.
Meanwhile, the high potency of fentanyl can overcome the opioid blockade of addiction treatment therapies – methadone and buprenorphine – that take away the high that users get from less potent drugs such as heroin.
“Fentanyl is overcoming this blockade that methadone and buprenorphine used to provide,” Dr. Salsitz said. “With fentanyl having such a higher potency, patients are saying ‘no, I still feel the fentanyl effects,’ and they continue feeling it even with 200 milligrams of methadone or 24 milligrams of buprenorphine.”
‘Wooden chest syndrome’
Among the lesser-known dangers of fentanyl is the possibility that some overdose deaths may occur as the result of a syndrome previously reported as a rare complication following the medical use of fentanyl in critically ill patients – fentanyl-induced chest-wall rigidity, or “wooden chest syndrome,” Dr. Salsitz explained.
In such cases, the muscles of respiration become rigid and paralyzed, causing suffocation within a matter of minutes – too soon to benefit from the overdose rescue medication naloxone.
In one recent study published in Clinical Toxicology , nearly half of fentanyl overdose deaths were found to have occurred even before the body had a chance to produce norfentanyl, a metabolite of fentanyl that takes only about 2-3 minutes to appear in the system, suggesting the deaths occurred rapidly.
In the study of 48 fentanyl deaths, no appreciable concentrations of norfentanyl could be detected in 20 of the 48 overdose deaths (42%), and concentrations were less than 1 ng/mL in 25 cases (52%).
“The lack of any measurable norfentanyl in half of our cases suggests a very rapid death, consistent with acute chest rigidity,” the authors reported.
“In several cases fentanyl concentrations were strikingly high (22 ng/mL and 20 ng/mL) with no norfentanyl detected,” they said.
Dr. Salsitz noted that the syndrome is not well known among the addiction treatment community.
“This is different than the usual respiratory opioid overdose where there’s a gradual decrease in the breathing rate and a gradual decrease in how much air is going in and out of the lungs,” Dr. Salsitz explained.
“With those cases, some may survive for an hour or longer, allowing time for someone to administer naloxone or to get the patient to the emergency room,” he said. “But with this, breathing stops and people can die within minutes.
“I think that this is one of the reasons that fentanyl deaths keep going up despite more and more naloxone availability out there,” he said.
Clearance may take longer
In toxicology testing for fentanyl, clinicians should also note the important difference between fentanyl and other opioids – that fentanyl, because of its high lipophilicity, may be detected in urine toxicology testing up to 3 weeks after last use. This is much longer than the 2- to 4-day clearance observed with other opioids, possibly causing patients to continue to test positive for the drug weeks after cessation.
This effect was observed in one recent study of 12 opioid use disorder patients in a residential treatment program who had previously been exposed to daily fentanyl.
The study showed the mean amount of time of fentanyl clearance was 2 weeks, with a range of 4-26 days after last use.
The authors pointed out that the findings “might explain recent reports of difficulty in buprenorphine inductions for persons who use fentanyl, and point to a need to better understand the pharmacokinetics of fentanyl in the context of opioid withdrawal in persons who regularly use fentanyl.”
Though the study was small, Dr. Salsitz said “that’s not a stumbling block to the important finding that, with regular use of fentanyl, the drug may stay in the urine for a long time.”
Dr. Salsitz noted that similar observations have been made at his center, with clinicians logically assuming that patients were still somehow getting fentanyl.
“When we initially found this in patients, we thought that they were using on the unit, perhaps that they brought in the fentanyl, because otherwise how could it stay in the urine that long,” he noted. “But fentanyl appears to be more lipophilic and gets into the fat; it’s then excreted very slowly and then stays in the urine.”
Dr. Salsitz said most practitioners think of fentanyl as a short-acting drug, so “it’s important to realize that people may continue to test positive and it should be thought of as a long-acting opioid.”
Opiate screening tests don’t work
Dr. Salsitz warned of another misconception in fentanyl testing – the common mistake of assuming that fentanyl should show up in a test for opiates – when in fact fentanyl is not, technically, an opiate.
“The word opiate only refers to morphine, codeine, heroin and sometimes hydrocodone,” he explained. “Other opioids are classified as semisynthetic, such as oxycodone, or synthetics, such as fentanyl and methadone, buprenorphine.”
“In order to detect the synthetics, you must have a separate strip for each one of those drugs. They will not show up positive on a screen for opiates,” he noted.
The belief that fentanyl and other synthetic and semisynthetic opioids will show positive on an opiate screen is a common misconception, he said. “The misunderstanding in toxicology interpretation is a problem for many practitioners, [but] it’s essential to understand because otherwise false assumptions about the patient will be considered.”
Another important testing misreading can occur with the antidepressant drug trazodone, which Dr. Salsitz cautioned may falsely test as positive for fentanyl on immunoassays.
“Trazodone is very commonly used in addiction treatment centers, but it can give a false positive on the fentanyl immunoassay and we’ve had a number of those cases,” he said.
Dr. Salsitz had no disclosures to report.
The Psychopharmacology Update was sponsored by Medscape Live. Medscape Live and this news organization are owned by the same parent company.
FROM PSYCHOPHARMACOLOGY UPDATE
Lung cancer screening pushes 20-year survival rate to 80%
CHICAGO – , findings from a 20-year international study indicate.
Claudia Henschke, MD, PhD, professor of radiology and director of the Early Lung and Cardiac Action Program at the Icahn School of Medicine at Mount Sinai, New York, presented research results at the annual meeting of the Radiological Society of North America.
The researchers studied lung-cancer–specific survival (LCS) of 87,416 participants enrolled in an international, prospective study named the International Early Lung Cancer Action Program.
Lung cancer is the leading cause of cancer death. The American Lung Association states the average 5-year survival rate is 18.6%. Only 16% of the cancers are caught early and more than half of people with lung cancer die within a year of diagnosis.
Participants’ 20-year survival rate 80%
Results of this large international study showed the overall 20-year survival rate for the 1,285 screening participants diagnosed with early-stage cancer was 80% (95% confidence interval, 77%-83%). Among the 1,285 diagnosed, 83% had stage 1 cancer, Dr. Henschke said.
Lung cancer survival (LCS) was 100% for the 139 participants with nonsolid nodule consistency and for the 155 participants with part-solid consistency. LCS was 73% (95% CI, 69%-77%) for the 991 with solid consistency, and for clinical stage IA participants LCS was 86% (95% CI, 83%-89%), regardless of consistency.
For participants with pathologic stage IA lung cancer 10 mm or less in average diameter, the 20-year survival rate with identification and resection was 92% (95% CI, 87%-96%).
No lung cancer deaths were identified in the part-solid and nonsolid cancers, the researchers report.
These results show the 10-year findings from 2006 published in the New England Journal of Medicine, which also showed 80% survival rates with low-dose CT, have persisted, she said.
At the time of the 2006 paper, 95% of Americans diagnosed with lung cancer died from it, Dr. Henschke said.
Dr. Henschke notes that by the time symptoms appear, lung cancer is often advanced, so the best tool for detecting early-stage lung cancer is enrolling in an annual screening program.
When cancer is small enough and can be surgically removed, patients can be effectively cured long-term, she said.
“In the future, perhaps blood markers will allow us to detect it in the first half of the life cycle of lung cancer instead of CT at the beginning of the second half of the life cycle,” Dr. Henschke said.
“The study raises the power of prospective data collection in the context of clinical care as recommended by the Institute of Medicine long ago,” she said.
Findings “very promising”
Ernest Hawk, MD, MPH, head of the division of cancer prevention and population sciences at the University of Texas MD Anderson Cancer, Houston, told this news organization the findings look “very promising.” Dr. Hawk was not involved in the study.
“This was one of the earliest studies to evaluate low-dose CT scanning. Their report that the initial benefits seem to be holding up over a longer period of observation is great,” he said.
“This bolsters the data that lung cancer screening is beneficial over a longer period of observation,” he said, noting that most of the randomized controlled trials have been shorter.
Lung cancer screening is now recommended for high-risk individuals – those with at least a 20-pack-year history of tobacco use who are between 50 and 80 years old.
So far, screening is still limited to people at high risk, Dr. Hawk said, though there’s discussion about whether benefit would extend to people exposed to asbestos, for instance, or secondhand smoke.
“The biggest challenge right now is getting the screening to those who actually meet the criteria,” Dr. Hawk said.
Medscape reported earlier this month that less than 6% of high-risk smokers have the recommended annual lung cancer screening, according to a new report from the American Lung Association.
Dr. Henschke is on the Advisory Board for LungLifeAI and is on the board for the Early Diagnosis and Treatment Research Foundation. Dr. Hawk reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CHICAGO – , findings from a 20-year international study indicate.
Claudia Henschke, MD, PhD, professor of radiology and director of the Early Lung and Cardiac Action Program at the Icahn School of Medicine at Mount Sinai, New York, presented research results at the annual meeting of the Radiological Society of North America.
The researchers studied lung-cancer–specific survival (LCS) of 87,416 participants enrolled in an international, prospective study named the International Early Lung Cancer Action Program.
Lung cancer is the leading cause of cancer death. The American Lung Association states the average 5-year survival rate is 18.6%. Only 16% of the cancers are caught early and more than half of people with lung cancer die within a year of diagnosis.
Participants’ 20-year survival rate 80%
Results of this large international study showed the overall 20-year survival rate for the 1,285 screening participants diagnosed with early-stage cancer was 80% (95% confidence interval, 77%-83%). Among the 1,285 diagnosed, 83% had stage 1 cancer, Dr. Henschke said.
Lung cancer survival (LCS) was 100% for the 139 participants with nonsolid nodule consistency and for the 155 participants with part-solid consistency. LCS was 73% (95% CI, 69%-77%) for the 991 with solid consistency, and for clinical stage IA participants LCS was 86% (95% CI, 83%-89%), regardless of consistency.
For participants with pathologic stage IA lung cancer 10 mm or less in average diameter, the 20-year survival rate with identification and resection was 92% (95% CI, 87%-96%).
No lung cancer deaths were identified in the part-solid and nonsolid cancers, the researchers report.
These results show the 10-year findings from 2006 published in the New England Journal of Medicine, which also showed 80% survival rates with low-dose CT, have persisted, she said.
At the time of the 2006 paper, 95% of Americans diagnosed with lung cancer died from it, Dr. Henschke said.
Dr. Henschke notes that by the time symptoms appear, lung cancer is often advanced, so the best tool for detecting early-stage lung cancer is enrolling in an annual screening program.
When cancer is small enough and can be surgically removed, patients can be effectively cured long-term, she said.
“In the future, perhaps blood markers will allow us to detect it in the first half of the life cycle of lung cancer instead of CT at the beginning of the second half of the life cycle,” Dr. Henschke said.
“The study raises the power of prospective data collection in the context of clinical care as recommended by the Institute of Medicine long ago,” she said.
Findings “very promising”
Ernest Hawk, MD, MPH, head of the division of cancer prevention and population sciences at the University of Texas MD Anderson Cancer, Houston, told this news organization the findings look “very promising.” Dr. Hawk was not involved in the study.
“This was one of the earliest studies to evaluate low-dose CT scanning. Their report that the initial benefits seem to be holding up over a longer period of observation is great,” he said.
“This bolsters the data that lung cancer screening is beneficial over a longer period of observation,” he said, noting that most of the randomized controlled trials have been shorter.
Lung cancer screening is now recommended for high-risk individuals – those with at least a 20-pack-year history of tobacco use who are between 50 and 80 years old.
So far, screening is still limited to people at high risk, Dr. Hawk said, though there’s discussion about whether benefit would extend to people exposed to asbestos, for instance, or secondhand smoke.
“The biggest challenge right now is getting the screening to those who actually meet the criteria,” Dr. Hawk said.
Medscape reported earlier this month that less than 6% of high-risk smokers have the recommended annual lung cancer screening, according to a new report from the American Lung Association.
Dr. Henschke is on the Advisory Board for LungLifeAI and is on the board for the Early Diagnosis and Treatment Research Foundation. Dr. Hawk reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CHICAGO – , findings from a 20-year international study indicate.
Claudia Henschke, MD, PhD, professor of radiology and director of the Early Lung and Cardiac Action Program at the Icahn School of Medicine at Mount Sinai, New York, presented research results at the annual meeting of the Radiological Society of North America.
The researchers studied lung-cancer–specific survival (LCS) of 87,416 participants enrolled in an international, prospective study named the International Early Lung Cancer Action Program.
Lung cancer is the leading cause of cancer death. The American Lung Association states the average 5-year survival rate is 18.6%. Only 16% of the cancers are caught early and more than half of people with lung cancer die within a year of diagnosis.
Participants’ 20-year survival rate 80%
Results of this large international study showed the overall 20-year survival rate for the 1,285 screening participants diagnosed with early-stage cancer was 80% (95% confidence interval, 77%-83%). Among the 1,285 diagnosed, 83% had stage 1 cancer, Dr. Henschke said.
Lung cancer survival (LCS) was 100% for the 139 participants with nonsolid nodule consistency and for the 155 participants with part-solid consistency. LCS was 73% (95% CI, 69%-77%) for the 991 with solid consistency, and for clinical stage IA participants LCS was 86% (95% CI, 83%-89%), regardless of consistency.
For participants with pathologic stage IA lung cancer 10 mm or less in average diameter, the 20-year survival rate with identification and resection was 92% (95% CI, 87%-96%).
No lung cancer deaths were identified in the part-solid and nonsolid cancers, the researchers report.
These results show the 10-year findings from 2006 published in the New England Journal of Medicine, which also showed 80% survival rates with low-dose CT, have persisted, she said.
At the time of the 2006 paper, 95% of Americans diagnosed with lung cancer died from it, Dr. Henschke said.
Dr. Henschke notes that by the time symptoms appear, lung cancer is often advanced, so the best tool for detecting early-stage lung cancer is enrolling in an annual screening program.
When cancer is small enough and can be surgically removed, patients can be effectively cured long-term, she said.
“In the future, perhaps blood markers will allow us to detect it in the first half of the life cycle of lung cancer instead of CT at the beginning of the second half of the life cycle,” Dr. Henschke said.
“The study raises the power of prospective data collection in the context of clinical care as recommended by the Institute of Medicine long ago,” she said.
Findings “very promising”
Ernest Hawk, MD, MPH, head of the division of cancer prevention and population sciences at the University of Texas MD Anderson Cancer, Houston, told this news organization the findings look “very promising.” Dr. Hawk was not involved in the study.
“This was one of the earliest studies to evaluate low-dose CT scanning. Their report that the initial benefits seem to be holding up over a longer period of observation is great,” he said.
“This bolsters the data that lung cancer screening is beneficial over a longer period of observation,” he said, noting that most of the randomized controlled trials have been shorter.
Lung cancer screening is now recommended for high-risk individuals – those with at least a 20-pack-year history of tobacco use who are between 50 and 80 years old.
So far, screening is still limited to people at high risk, Dr. Hawk said, though there’s discussion about whether benefit would extend to people exposed to asbestos, for instance, or secondhand smoke.
“The biggest challenge right now is getting the screening to those who actually meet the criteria,” Dr. Hawk said.
Medscape reported earlier this month that less than 6% of high-risk smokers have the recommended annual lung cancer screening, according to a new report from the American Lung Association.
Dr. Henschke is on the Advisory Board for LungLifeAI and is on the board for the Early Diagnosis and Treatment Research Foundation. Dr. Hawk reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT RSNA 2022
The TikTok trend that triggered a diabetes drug shortage
Weight loss advice is everywhere you look on social media, but one trend sweeping TikTok has led to shortages of an important diabetes drug.
Ozempic, a weekly injection that helps boost insulin sensitivity in people with type 2 diabetes, also suppresses appetite, which leads to weight loss. Stories of celebrities using the drug off-label to lose a few pounds have led to an explosion of interest. And now people with diabetes – people whose lives could be saved by the drug – are having trouble finding it.
Kim Kardashian and Elon Musk
In the spring, Kim Kardashian pulled off a dramatic weight loss to fit into Marilyn Monroe’s dress for the Met Gala. Soon rumors began to circulate that she’d used Ozempic to do it. Just this week, new Twitter owner Elon Musk tweeted about his own use of Ozempic and its sibling drug, Wegovy.
Variety dubbed Ozempic “the worst kept secret in Hollywood – especially given that its most enthusiastic users are not prediabetic and do not require the drug.” The rich and famous are spending $1,200 to $1,500 a month to get access.
As so often happens, high-profile use sparked a trend. Videos on TikTok hashtagged #ozempic have amassed more than 275 million views, and #ozempicweightloss has more than 110 million.
This raises concerns about who, exactly, is watching these videos, and what message they’re receiving.
“Forty-two percent of Americans have obesity, and even more have overweight. That’s affecting our younger people and our adolescents,” says Caroline Apovian, MD, codirector of the Center for Weight Management and Wellness at the Brigham and Women’s Hospital in Boston. “They’re looking at TikTok and other social media outlets for help.”
A new study shows how damaging this can be: Researchers analyzed 1,000 videos with nutrition, food, and weight-related hashtags, with over 1 billion views combined. They found that nearly all included messages glorifying weight loss and thinness.
At last, an effective weight-loss drug
Ozempic is Danish drug company Novo Nordisk’s brand name for semaglutide, which works by mimicking a naturally occurring hormone known as GLP-1. It travels to your brain and helps you feel full on less food. That leads to weight loss. In one 68-week study, semaglutide helped people lose an average of 15% of their body weight. But it’s not a miracle drug: You still have to change your eating habits and stay physically active.
The FDA approved Ozempic to treat people with type 2 diabetes in 2017. Four years later, Novo Nordisk received the green light for a higher-dose version meant specifically for people with obesity. Wegovy is approved for use only if you have a BMI of at least 27 with one or more weight-related ailments, or a BMI of 30 or more with none.
“These drugs are dominating my practice, because they’re so effective,” says Amanda Velazquez, MD, director of obesity medicine at Cedars-Sinai Medical Center in Los Angeles. The drug is considered safe, “so the majority of patients are good candidates.”
More demand than supply
As word spread about how well Ozempic and Wegovy worked, social media posts helped drive even more people to seek out the drugs. Now demand is outpacing the supply – according to the FDA, starter doses of Ozempic will have limited availability through January.
“In Hollywood, people are losing 10 pounds, getting it for $1,500 a month, and depleting stores for people who have such severe obesity that they have congestive heart failure and diabetes,” Dr. Apovian says. “These are people who are going to die, and you’re taking it away just for cosmetic weight loss. That is deplorable.”
In addition to huge demand, Wegovy also had a disruption in its supply chain. Right now, it isn’t available at all in lower doses, which is helping to spike off-label demand for Ozempic. Novo Nordisk expects to have these problems sorted out by the end of the year, with distribution following soon after.
The price of access
With a list price of $1,350 a month, Wegovy costs as much as many mortgages. And Medicaid, Medicare, and many insurance companies don’t cover it. Although obesity is a disease, the insurance industry treats weight loss as more of a vanity issue – so even if you could find the drug, you might not be able to afford it.
“We’re seeing that roughly half the prescriptions we write aren’t being covered,” Dr. Apovian says. “And for the half that are covered, we have to do prior authorization, which takes days, and it’s laborious.” In some instances, she says, insurance companies withdraw authorization after 3 months if they don’t see enough weight coming off.
It’s not like you can take Wegovy for 3 months, lose some weight, and expect it to stay off, either. The medication requires a real commitment, potentially for life. That’s because once the semaglutide leaves your system, your appetite returns. In one study, people regained two-thirds of the weight they’d lost within a year of stopping.
Many see a double standard in the insurance companies’ refusal to cover a drug that could prevent serious illness or death.
“They’re saying it’s not cost-effective to give the 42% of Americans who have a BMI over 30 Wegovy. Did they say this when statins came out?” Dr. Apovian says. “Why are they doing this with antiobesity agents? It’s the culture. The culture isn’t ready to adopt obesity as the disease that it is.”
Unpleasant side effects
Let’s assume you’re one of the lucky ones – your insurance covers Wegovy, and you can actually find some. You might discover that using it is no walk in the park. Common side effects include gastrointestinal issues like nausea, vomiting, and diarrhea.
“The way we counteract that is to start very slowly at a low dose of these medications,” Dr. Apovian says. “We only go up when the patient doesn’t have nausea or it gets better.”
Elise Davenport was excited to try Wegovy. “I did my online research. I’m the type who’s interested in early adoption, tech gadgets and stuff,” says the 40-year-old technical writer. “I wanted to try it because I’d tried so many other things that failed, or hadn’t worked long-term.”
With a BMI over 30, Ms. Davenport qualified for the drug. She signed up for an online program that guaranteed insurance coverage and started taking it in October 2021. At first, the side effects were mild, just a touch of nausea and diarrhea. And the results were impressive. She found it easy to feel satisfied with smaller portions and lost her cravings for sugar and highly processed foods. The weight fell off, roughly 5 pounds a week.
It turns out, that’s too much, too fast. Dr. Apovian and Dr. Velazquez say their patients lose more like 2 pounds each week, with careful monitoring.
By early December, Ms. Davenport’s side effects were ramping up. Because of shortages in lower dosages, the online program wasn’t able to adjust hers right away. She felt nauseated all the time, bad enough that brushing her teeth made her vomit and she had to force herself to eat. Some weeks, she managed less than 500 calories a day. Her sleep patterns became erratic. And then her depression, which medication had kept under control for years, spiraled.
“I remember sitting on the floor of my bathroom crying, thinking I’d rather carry the extra weight,” she says. “I used to take a lot of enjoyment from food, and I had none of that anymore. It was such a joyless experience at that point.”
Eventually, her dosage was reduced and the symptoms let up, but her primary care doctor encouraged her to stop. By the time she did, in March, she’d lost 55 pounds. So far, she’s gained back about 10.
More than just weight loss
Even though Ms. Davenport’s experience wasn’t a good one, with better monitoring, she’d be willing to try again. For one thing, seeing how easy it was to eat less with medical help helped to undo years of shame.
“Our culture treats obesity like a moral failing. I realized I’d been made to feel that way by doctors and programs – that I wasn’t doing enough,” she says. “This drug made me realize there are legit physiological things going on in my body, things that are often excluded from the conversation.”
Dr. Apovian and Dr. Velazquez say their patients regularly discover similar things.
“Obesity is not a disease of willpower. Medications are not the easy way out,” Dr. Velazquez says. “This is a chronic, relapsing medical condition, and because of that, we should treat it how we treat diabetes, high blood pressure, all these other conditions. We’d never hold back medication for individuals coming in with high blood pressure, tell them to work on willpower and withhold drugs they’d qualify for.”
A version of this article first appeared on WebMD.com.
Weight loss advice is everywhere you look on social media, but one trend sweeping TikTok has led to shortages of an important diabetes drug.
Ozempic, a weekly injection that helps boost insulin sensitivity in people with type 2 diabetes, also suppresses appetite, which leads to weight loss. Stories of celebrities using the drug off-label to lose a few pounds have led to an explosion of interest. And now people with diabetes – people whose lives could be saved by the drug – are having trouble finding it.
Kim Kardashian and Elon Musk
In the spring, Kim Kardashian pulled off a dramatic weight loss to fit into Marilyn Monroe’s dress for the Met Gala. Soon rumors began to circulate that she’d used Ozempic to do it. Just this week, new Twitter owner Elon Musk tweeted about his own use of Ozempic and its sibling drug, Wegovy.
Variety dubbed Ozempic “the worst kept secret in Hollywood – especially given that its most enthusiastic users are not prediabetic and do not require the drug.” The rich and famous are spending $1,200 to $1,500 a month to get access.
As so often happens, high-profile use sparked a trend. Videos on TikTok hashtagged #ozempic have amassed more than 275 million views, and #ozempicweightloss has more than 110 million.
This raises concerns about who, exactly, is watching these videos, and what message they’re receiving.
“Forty-two percent of Americans have obesity, and even more have overweight. That’s affecting our younger people and our adolescents,” says Caroline Apovian, MD, codirector of the Center for Weight Management and Wellness at the Brigham and Women’s Hospital in Boston. “They’re looking at TikTok and other social media outlets for help.”
A new study shows how damaging this can be: Researchers analyzed 1,000 videos with nutrition, food, and weight-related hashtags, with over 1 billion views combined. They found that nearly all included messages glorifying weight loss and thinness.
At last, an effective weight-loss drug
Ozempic is Danish drug company Novo Nordisk’s brand name for semaglutide, which works by mimicking a naturally occurring hormone known as GLP-1. It travels to your brain and helps you feel full on less food. That leads to weight loss. In one 68-week study, semaglutide helped people lose an average of 15% of their body weight. But it’s not a miracle drug: You still have to change your eating habits and stay physically active.
The FDA approved Ozempic to treat people with type 2 diabetes in 2017. Four years later, Novo Nordisk received the green light for a higher-dose version meant specifically for people with obesity. Wegovy is approved for use only if you have a BMI of at least 27 with one or more weight-related ailments, or a BMI of 30 or more with none.
“These drugs are dominating my practice, because they’re so effective,” says Amanda Velazquez, MD, director of obesity medicine at Cedars-Sinai Medical Center in Los Angeles. The drug is considered safe, “so the majority of patients are good candidates.”
More demand than supply
As word spread about how well Ozempic and Wegovy worked, social media posts helped drive even more people to seek out the drugs. Now demand is outpacing the supply – according to the FDA, starter doses of Ozempic will have limited availability through January.
“In Hollywood, people are losing 10 pounds, getting it for $1,500 a month, and depleting stores for people who have such severe obesity that they have congestive heart failure and diabetes,” Dr. Apovian says. “These are people who are going to die, and you’re taking it away just for cosmetic weight loss. That is deplorable.”
In addition to huge demand, Wegovy also had a disruption in its supply chain. Right now, it isn’t available at all in lower doses, which is helping to spike off-label demand for Ozempic. Novo Nordisk expects to have these problems sorted out by the end of the year, with distribution following soon after.
The price of access
With a list price of $1,350 a month, Wegovy costs as much as many mortgages. And Medicaid, Medicare, and many insurance companies don’t cover it. Although obesity is a disease, the insurance industry treats weight loss as more of a vanity issue – so even if you could find the drug, you might not be able to afford it.
“We’re seeing that roughly half the prescriptions we write aren’t being covered,” Dr. Apovian says. “And for the half that are covered, we have to do prior authorization, which takes days, and it’s laborious.” In some instances, she says, insurance companies withdraw authorization after 3 months if they don’t see enough weight coming off.
It’s not like you can take Wegovy for 3 months, lose some weight, and expect it to stay off, either. The medication requires a real commitment, potentially for life. That’s because once the semaglutide leaves your system, your appetite returns. In one study, people regained two-thirds of the weight they’d lost within a year of stopping.
Many see a double standard in the insurance companies’ refusal to cover a drug that could prevent serious illness or death.
“They’re saying it’s not cost-effective to give the 42% of Americans who have a BMI over 30 Wegovy. Did they say this when statins came out?” Dr. Apovian says. “Why are they doing this with antiobesity agents? It’s the culture. The culture isn’t ready to adopt obesity as the disease that it is.”
Unpleasant side effects
Let’s assume you’re one of the lucky ones – your insurance covers Wegovy, and you can actually find some. You might discover that using it is no walk in the park. Common side effects include gastrointestinal issues like nausea, vomiting, and diarrhea.
“The way we counteract that is to start very slowly at a low dose of these medications,” Dr. Apovian says. “We only go up when the patient doesn’t have nausea or it gets better.”
Elise Davenport was excited to try Wegovy. “I did my online research. I’m the type who’s interested in early adoption, tech gadgets and stuff,” says the 40-year-old technical writer. “I wanted to try it because I’d tried so many other things that failed, or hadn’t worked long-term.”
With a BMI over 30, Ms. Davenport qualified for the drug. She signed up for an online program that guaranteed insurance coverage and started taking it in October 2021. At first, the side effects were mild, just a touch of nausea and diarrhea. And the results were impressive. She found it easy to feel satisfied with smaller portions and lost her cravings for sugar and highly processed foods. The weight fell off, roughly 5 pounds a week.
It turns out, that’s too much, too fast. Dr. Apovian and Dr. Velazquez say their patients lose more like 2 pounds each week, with careful monitoring.
By early December, Ms. Davenport’s side effects were ramping up. Because of shortages in lower dosages, the online program wasn’t able to adjust hers right away. She felt nauseated all the time, bad enough that brushing her teeth made her vomit and she had to force herself to eat. Some weeks, she managed less than 500 calories a day. Her sleep patterns became erratic. And then her depression, which medication had kept under control for years, spiraled.
“I remember sitting on the floor of my bathroom crying, thinking I’d rather carry the extra weight,” she says. “I used to take a lot of enjoyment from food, and I had none of that anymore. It was such a joyless experience at that point.”
Eventually, her dosage was reduced and the symptoms let up, but her primary care doctor encouraged her to stop. By the time she did, in March, she’d lost 55 pounds. So far, she’s gained back about 10.
More than just weight loss
Even though Ms. Davenport’s experience wasn’t a good one, with better monitoring, she’d be willing to try again. For one thing, seeing how easy it was to eat less with medical help helped to undo years of shame.
“Our culture treats obesity like a moral failing. I realized I’d been made to feel that way by doctors and programs – that I wasn’t doing enough,” she says. “This drug made me realize there are legit physiological things going on in my body, things that are often excluded from the conversation.”
Dr. Apovian and Dr. Velazquez say their patients regularly discover similar things.
“Obesity is not a disease of willpower. Medications are not the easy way out,” Dr. Velazquez says. “This is a chronic, relapsing medical condition, and because of that, we should treat it how we treat diabetes, high blood pressure, all these other conditions. We’d never hold back medication for individuals coming in with high blood pressure, tell them to work on willpower and withhold drugs they’d qualify for.”
A version of this article first appeared on WebMD.com.
Weight loss advice is everywhere you look on social media, but one trend sweeping TikTok has led to shortages of an important diabetes drug.
Ozempic, a weekly injection that helps boost insulin sensitivity in people with type 2 diabetes, also suppresses appetite, which leads to weight loss. Stories of celebrities using the drug off-label to lose a few pounds have led to an explosion of interest. And now people with diabetes – people whose lives could be saved by the drug – are having trouble finding it.
Kim Kardashian and Elon Musk
In the spring, Kim Kardashian pulled off a dramatic weight loss to fit into Marilyn Monroe’s dress for the Met Gala. Soon rumors began to circulate that she’d used Ozempic to do it. Just this week, new Twitter owner Elon Musk tweeted about his own use of Ozempic and its sibling drug, Wegovy.
Variety dubbed Ozempic “the worst kept secret in Hollywood – especially given that its most enthusiastic users are not prediabetic and do not require the drug.” The rich and famous are spending $1,200 to $1,500 a month to get access.
As so often happens, high-profile use sparked a trend. Videos on TikTok hashtagged #ozempic have amassed more than 275 million views, and #ozempicweightloss has more than 110 million.
This raises concerns about who, exactly, is watching these videos, and what message they’re receiving.
“Forty-two percent of Americans have obesity, and even more have overweight. That’s affecting our younger people and our adolescents,” says Caroline Apovian, MD, codirector of the Center for Weight Management and Wellness at the Brigham and Women’s Hospital in Boston. “They’re looking at TikTok and other social media outlets for help.”
A new study shows how damaging this can be: Researchers analyzed 1,000 videos with nutrition, food, and weight-related hashtags, with over 1 billion views combined. They found that nearly all included messages glorifying weight loss and thinness.
At last, an effective weight-loss drug
Ozempic is Danish drug company Novo Nordisk’s brand name for semaglutide, which works by mimicking a naturally occurring hormone known as GLP-1. It travels to your brain and helps you feel full on less food. That leads to weight loss. In one 68-week study, semaglutide helped people lose an average of 15% of their body weight. But it’s not a miracle drug: You still have to change your eating habits and stay physically active.
The FDA approved Ozempic to treat people with type 2 diabetes in 2017. Four years later, Novo Nordisk received the green light for a higher-dose version meant specifically for people with obesity. Wegovy is approved for use only if you have a BMI of at least 27 with one or more weight-related ailments, or a BMI of 30 or more with none.
“These drugs are dominating my practice, because they’re so effective,” says Amanda Velazquez, MD, director of obesity medicine at Cedars-Sinai Medical Center in Los Angeles. The drug is considered safe, “so the majority of patients are good candidates.”
More demand than supply
As word spread about how well Ozempic and Wegovy worked, social media posts helped drive even more people to seek out the drugs. Now demand is outpacing the supply – according to the FDA, starter doses of Ozempic will have limited availability through January.
“In Hollywood, people are losing 10 pounds, getting it for $1,500 a month, and depleting stores for people who have such severe obesity that they have congestive heart failure and diabetes,” Dr. Apovian says. “These are people who are going to die, and you’re taking it away just for cosmetic weight loss. That is deplorable.”
In addition to huge demand, Wegovy also had a disruption in its supply chain. Right now, it isn’t available at all in lower doses, which is helping to spike off-label demand for Ozempic. Novo Nordisk expects to have these problems sorted out by the end of the year, with distribution following soon after.
The price of access
With a list price of $1,350 a month, Wegovy costs as much as many mortgages. And Medicaid, Medicare, and many insurance companies don’t cover it. Although obesity is a disease, the insurance industry treats weight loss as more of a vanity issue – so even if you could find the drug, you might not be able to afford it.
“We’re seeing that roughly half the prescriptions we write aren’t being covered,” Dr. Apovian says. “And for the half that are covered, we have to do prior authorization, which takes days, and it’s laborious.” In some instances, she says, insurance companies withdraw authorization after 3 months if they don’t see enough weight coming off.
It’s not like you can take Wegovy for 3 months, lose some weight, and expect it to stay off, either. The medication requires a real commitment, potentially for life. That’s because once the semaglutide leaves your system, your appetite returns. In one study, people regained two-thirds of the weight they’d lost within a year of stopping.
Many see a double standard in the insurance companies’ refusal to cover a drug that could prevent serious illness or death.
“They’re saying it’s not cost-effective to give the 42% of Americans who have a BMI over 30 Wegovy. Did they say this when statins came out?” Dr. Apovian says. “Why are they doing this with antiobesity agents? It’s the culture. The culture isn’t ready to adopt obesity as the disease that it is.”
Unpleasant side effects
Let’s assume you’re one of the lucky ones – your insurance covers Wegovy, and you can actually find some. You might discover that using it is no walk in the park. Common side effects include gastrointestinal issues like nausea, vomiting, and diarrhea.
“The way we counteract that is to start very slowly at a low dose of these medications,” Dr. Apovian says. “We only go up when the patient doesn’t have nausea or it gets better.”
Elise Davenport was excited to try Wegovy. “I did my online research. I’m the type who’s interested in early adoption, tech gadgets and stuff,” says the 40-year-old technical writer. “I wanted to try it because I’d tried so many other things that failed, or hadn’t worked long-term.”
With a BMI over 30, Ms. Davenport qualified for the drug. She signed up for an online program that guaranteed insurance coverage and started taking it in October 2021. At first, the side effects were mild, just a touch of nausea and diarrhea. And the results were impressive. She found it easy to feel satisfied with smaller portions and lost her cravings for sugar and highly processed foods. The weight fell off, roughly 5 pounds a week.
It turns out, that’s too much, too fast. Dr. Apovian and Dr. Velazquez say their patients lose more like 2 pounds each week, with careful monitoring.
By early December, Ms. Davenport’s side effects were ramping up. Because of shortages in lower dosages, the online program wasn’t able to adjust hers right away. She felt nauseated all the time, bad enough that brushing her teeth made her vomit and she had to force herself to eat. Some weeks, she managed less than 500 calories a day. Her sleep patterns became erratic. And then her depression, which medication had kept under control for years, spiraled.
“I remember sitting on the floor of my bathroom crying, thinking I’d rather carry the extra weight,” she says. “I used to take a lot of enjoyment from food, and I had none of that anymore. It was such a joyless experience at that point.”
Eventually, her dosage was reduced and the symptoms let up, but her primary care doctor encouraged her to stop. By the time she did, in March, she’d lost 55 pounds. So far, she’s gained back about 10.
More than just weight loss
Even though Ms. Davenport’s experience wasn’t a good one, with better monitoring, she’d be willing to try again. For one thing, seeing how easy it was to eat less with medical help helped to undo years of shame.
“Our culture treats obesity like a moral failing. I realized I’d been made to feel that way by doctors and programs – that I wasn’t doing enough,” she says. “This drug made me realize there are legit physiological things going on in my body, things that are often excluded from the conversation.”
Dr. Apovian and Dr. Velazquez say their patients regularly discover similar things.
“Obesity is not a disease of willpower. Medications are not the easy way out,” Dr. Velazquez says. “This is a chronic, relapsing medical condition, and because of that, we should treat it how we treat diabetes, high blood pressure, all these other conditions. We’d never hold back medication for individuals coming in with high blood pressure, tell them to work on willpower and withhold drugs they’d qualify for.”
A version of this article first appeared on WebMD.com.
Both potatoes and beans reduced insulin resistance, weight in controlled study
Low energy–density diets that are based either on potatoes or beans similarly reduced insulin resistance in adults with poor blood glucose control, according to a controlled feeding study in 36 individuals.
Potatoes have gotten a bad rap for their high glycemic index, but they have little fat and a low energy density, wrote the study investigators. In fact, “cooling of gelatinized potatoes generates appreciable levels of slowly digested starch (resistant starch type 3) and substantially lowers the blood glucose response that potatoes elicit.”
“There is a view that potatoes are a less healthy plant food, but there is very little empirical data from randomized trials to support this view,” senior investigator John P. Kirwan, PhD, said in an interview.
Dry beans and peas (known as pulses) also contain resistant starch that improves insulin sensitivity and glucose tolerance, and multiple studies support pulses as part of a low-glycemic diet to improve glucose control in adults, the researchers explained, but because the density of food often guides how much people eat, they hypothesized that potatoes could substitute for beans and provide similar glucose control benefits.
In a study published in the Journal of Medicinal Food, the researchers randomized 36 adults aged 18-60 years with insulin resistance to 8 weeks of a low energy–density diet (1 kcal/g) high in either potatoes or beans. The baseline body mass index ranged from 25 to 40 kg/m2. Insulin resistance was defined using the homeostatic model assessment of insulin resistance (HOMA-IR) with a score greater than 2.
The controlled diet consisted of 50%-55% carbohydrates, 30%-35% fats, and 15%-20% protein. Each meal in the potato group included a side of potatoes, and each meal in the bean group included a side of beans.
The primary outcome was the mean change in blood glucose concentration; the researchers also assessed weight loss.
A total of 14 individuals in the potato group and 17 in the bean group completed the study; but data from the 18 individuals in each group were included in an intent-to-treat analysis.
Among study completers, HOMA-IR in the bean group showed an average decrease of 1.4 from baseline (P = .02 ); a similar decrease of 1.3 occurred in the potato group (P < .05) with no significant difference between the two diets.
Overall compliance with both diets was roughly 88%. Body weight reductions were similar in both groups and significantly reduced from baseline over the study period, with average reductions in intent-to-treat analysis of 5.82 kg in the potato group and 4.0 kg in the bean group. BMI also was significantly reduced from baseline in both potato and bean groups (2.04 kg/m2 and 1.35 kg/m2, respectively). Although baseline differences were not significant, “BMI at baseline was higher and the reduction in response to the treatment was significantly greater in the potato diet compared with the bean diet,” the researchers noted. The effect on blood glucose response was not significantly different between the two groups or from baseline, they said.
The findings were limited by several factors including the small size, relatively short study period, and controlled nature of the study diet, the researchers noted. “The addition of a typical Western diet would have enhanced our understanding of the effect of low energy–dense diets on metabolic outcomes,” they noted in their discussion.
However, both diets led to a reduction in body weight, and the low energy density of both potato and bean diets promoted weight loss without affecting appetite or requiring calorie restriction, the researchers explained. Therefore, “this weight loss if sustained over time could have a substantial impact on body weight,” they said.
“We hypothesized that there would be equivalence between the potato and bean diet and this hypothesis proved to be correct,” said Dr. Kirwan, of the Pennington Biomedical Research Center, Baton Rouge, La., in an interview.
The take-home message for clinicians is that, though small, the study was very well-controlled, Dr. Kirwan emphasized. “Clinicians ought to consider the health benefits of the potato when it is cooked and served appropriately.”
Looking ahead, larger randomized controlled trials with additional control arms, longer time of at least 12 weeks, and different patient populations are needed, Dr. Kirwan added.
Findings mitigate food myths
The debate continues about whether there are foods that are “good” or “evil;” or foods that one “should not eat” or “should eat,” said Amy Rothberg, MD, associate professor of internal medicine and of nutritional sciences at the University of Michigan, Ann Arbor, in an interview.
“This study dispels the myth that incorporating a small portion of potato into the diet (although these are not potatoes that are fried, or are topped with cheese, bacon, sour cream, etc.) results in deleterious metabolic outcomes when compared to a diet that is comprised of beans (pulses) as part of a low energy–dense diet,” she explained.
“The diet in both groups was of low energy density, which has been shown to result in fewer calories consumed, weight loss, and improvement in insulin resistance,” so the similarity in results was not so surprising, said Dr. Rothberg.
For the clinical takeaway, Dr. Rothberg agreed with the study authors: “Clinicians may counsel their patients that they can still consume a small potato (with the caveat above regarding cooking methods and toppings) as part of a balanced meal so long as they are keeping their overall calories low and not exceeding their metabolic requirements based on body weight/BMI,” she said.
As for additional research, studies with a longer time frame and a larger and more diverse study population are needed, including populations with common insulin resistance comorbidities such as type 2 diabetes, fatty liver disease, and cardiovascular disease, Dr. Rothberg noted.
Consumer considerations, with caveats
The key message for consumers is that, “based on this very small study of short duration, consuming a small portion of potato as part of an overall balanced, low-energy diet did not produce adverse effects on glucose or insulin when compared to a diet of pulses known to have favorable effects on glucose and insulin,” Dr. Rothberg told this news organization. However, “consumers should note that, although the results from this small study are encouraging, it would be premature to extrapolate the findings from this study to other populations,” she said. Also, keep in mind that the study was supported in part by the Alliance for Potato Research, although the authors stated that none of the funders (Alliance for Potato Research and Education and the National Institutes of Health) had any role in the design, analysis, or writing of the article, she added.
The study was supported in part by the Alliance for Potato Research and Education and the National Institutes of Health, which funds the Louisiana Clinical and Translational Science Center. The researchers and Dr. Rothberg had no financial conflicts to disclose.
Low energy–density diets that are based either on potatoes or beans similarly reduced insulin resistance in adults with poor blood glucose control, according to a controlled feeding study in 36 individuals.
Potatoes have gotten a bad rap for their high glycemic index, but they have little fat and a low energy density, wrote the study investigators. In fact, “cooling of gelatinized potatoes generates appreciable levels of slowly digested starch (resistant starch type 3) and substantially lowers the blood glucose response that potatoes elicit.”
“There is a view that potatoes are a less healthy plant food, but there is very little empirical data from randomized trials to support this view,” senior investigator John P. Kirwan, PhD, said in an interview.
Dry beans and peas (known as pulses) also contain resistant starch that improves insulin sensitivity and glucose tolerance, and multiple studies support pulses as part of a low-glycemic diet to improve glucose control in adults, the researchers explained, but because the density of food often guides how much people eat, they hypothesized that potatoes could substitute for beans and provide similar glucose control benefits.
In a study published in the Journal of Medicinal Food, the researchers randomized 36 adults aged 18-60 years with insulin resistance to 8 weeks of a low energy–density diet (1 kcal/g) high in either potatoes or beans. The baseline body mass index ranged from 25 to 40 kg/m2. Insulin resistance was defined using the homeostatic model assessment of insulin resistance (HOMA-IR) with a score greater than 2.
The controlled diet consisted of 50%-55% carbohydrates, 30%-35% fats, and 15%-20% protein. Each meal in the potato group included a side of potatoes, and each meal in the bean group included a side of beans.
The primary outcome was the mean change in blood glucose concentration; the researchers also assessed weight loss.
A total of 14 individuals in the potato group and 17 in the bean group completed the study; but data from the 18 individuals in each group were included in an intent-to-treat analysis.
Among study completers, HOMA-IR in the bean group showed an average decrease of 1.4 from baseline (P = .02 ); a similar decrease of 1.3 occurred in the potato group (P < .05) with no significant difference between the two diets.
Overall compliance with both diets was roughly 88%. Body weight reductions were similar in both groups and significantly reduced from baseline over the study period, with average reductions in intent-to-treat analysis of 5.82 kg in the potato group and 4.0 kg in the bean group. BMI also was significantly reduced from baseline in both potato and bean groups (2.04 kg/m2 and 1.35 kg/m2, respectively). Although baseline differences were not significant, “BMI at baseline was higher and the reduction in response to the treatment was significantly greater in the potato diet compared with the bean diet,” the researchers noted. The effect on blood glucose response was not significantly different between the two groups or from baseline, they said.
The findings were limited by several factors including the small size, relatively short study period, and controlled nature of the study diet, the researchers noted. “The addition of a typical Western diet would have enhanced our understanding of the effect of low energy–dense diets on metabolic outcomes,” they noted in their discussion.
However, both diets led to a reduction in body weight, and the low energy density of both potato and bean diets promoted weight loss without affecting appetite or requiring calorie restriction, the researchers explained. Therefore, “this weight loss if sustained over time could have a substantial impact on body weight,” they said.
“We hypothesized that there would be equivalence between the potato and bean diet and this hypothesis proved to be correct,” said Dr. Kirwan, of the Pennington Biomedical Research Center, Baton Rouge, La., in an interview.
The take-home message for clinicians is that, though small, the study was very well-controlled, Dr. Kirwan emphasized. “Clinicians ought to consider the health benefits of the potato when it is cooked and served appropriately.”
Looking ahead, larger randomized controlled trials with additional control arms, longer time of at least 12 weeks, and different patient populations are needed, Dr. Kirwan added.
Findings mitigate food myths
The debate continues about whether there are foods that are “good” or “evil;” or foods that one “should not eat” or “should eat,” said Amy Rothberg, MD, associate professor of internal medicine and of nutritional sciences at the University of Michigan, Ann Arbor, in an interview.
“This study dispels the myth that incorporating a small portion of potato into the diet (although these are not potatoes that are fried, or are topped with cheese, bacon, sour cream, etc.) results in deleterious metabolic outcomes when compared to a diet that is comprised of beans (pulses) as part of a low energy–dense diet,” she explained.
“The diet in both groups was of low energy density, which has been shown to result in fewer calories consumed, weight loss, and improvement in insulin resistance,” so the similarity in results was not so surprising, said Dr. Rothberg.
For the clinical takeaway, Dr. Rothberg agreed with the study authors: “Clinicians may counsel their patients that they can still consume a small potato (with the caveat above regarding cooking methods and toppings) as part of a balanced meal so long as they are keeping their overall calories low and not exceeding their metabolic requirements based on body weight/BMI,” she said.
As for additional research, studies with a longer time frame and a larger and more diverse study population are needed, including populations with common insulin resistance comorbidities such as type 2 diabetes, fatty liver disease, and cardiovascular disease, Dr. Rothberg noted.
Consumer considerations, with caveats
The key message for consumers is that, “based on this very small study of short duration, consuming a small portion of potato as part of an overall balanced, low-energy diet did not produce adverse effects on glucose or insulin when compared to a diet of pulses known to have favorable effects on glucose and insulin,” Dr. Rothberg told this news organization. However, “consumers should note that, although the results from this small study are encouraging, it would be premature to extrapolate the findings from this study to other populations,” she said. Also, keep in mind that the study was supported in part by the Alliance for Potato Research, although the authors stated that none of the funders (Alliance for Potato Research and Education and the National Institutes of Health) had any role in the design, analysis, or writing of the article, she added.
The study was supported in part by the Alliance for Potato Research and Education and the National Institutes of Health, which funds the Louisiana Clinical and Translational Science Center. The researchers and Dr. Rothberg had no financial conflicts to disclose.
Low energy–density diets that are based either on potatoes or beans similarly reduced insulin resistance in adults with poor blood glucose control, according to a controlled feeding study in 36 individuals.
Potatoes have gotten a bad rap for their high glycemic index, but they have little fat and a low energy density, wrote the study investigators. In fact, “cooling of gelatinized potatoes generates appreciable levels of slowly digested starch (resistant starch type 3) and substantially lowers the blood glucose response that potatoes elicit.”
“There is a view that potatoes are a less healthy plant food, but there is very little empirical data from randomized trials to support this view,” senior investigator John P. Kirwan, PhD, said in an interview.
Dry beans and peas (known as pulses) also contain resistant starch that improves insulin sensitivity and glucose tolerance, and multiple studies support pulses as part of a low-glycemic diet to improve glucose control in adults, the researchers explained, but because the density of food often guides how much people eat, they hypothesized that potatoes could substitute for beans and provide similar glucose control benefits.
In a study published in the Journal of Medicinal Food, the researchers randomized 36 adults aged 18-60 years with insulin resistance to 8 weeks of a low energy–density diet (1 kcal/g) high in either potatoes or beans. The baseline body mass index ranged from 25 to 40 kg/m2. Insulin resistance was defined using the homeostatic model assessment of insulin resistance (HOMA-IR) with a score greater than 2.
The controlled diet consisted of 50%-55% carbohydrates, 30%-35% fats, and 15%-20% protein. Each meal in the potato group included a side of potatoes, and each meal in the bean group included a side of beans.
The primary outcome was the mean change in blood glucose concentration; the researchers also assessed weight loss.
A total of 14 individuals in the potato group and 17 in the bean group completed the study; but data from the 18 individuals in each group were included in an intent-to-treat analysis.
Among study completers, HOMA-IR in the bean group showed an average decrease of 1.4 from baseline (P = .02 ); a similar decrease of 1.3 occurred in the potato group (P < .05) with no significant difference between the two diets.
Overall compliance with both diets was roughly 88%. Body weight reductions were similar in both groups and significantly reduced from baseline over the study period, with average reductions in intent-to-treat analysis of 5.82 kg in the potato group and 4.0 kg in the bean group. BMI also was significantly reduced from baseline in both potato and bean groups (2.04 kg/m2 and 1.35 kg/m2, respectively). Although baseline differences were not significant, “BMI at baseline was higher and the reduction in response to the treatment was significantly greater in the potato diet compared with the bean diet,” the researchers noted. The effect on blood glucose response was not significantly different between the two groups or from baseline, they said.
The findings were limited by several factors including the small size, relatively short study period, and controlled nature of the study diet, the researchers noted. “The addition of a typical Western diet would have enhanced our understanding of the effect of low energy–dense diets on metabolic outcomes,” they noted in their discussion.
However, both diets led to a reduction in body weight, and the low energy density of both potato and bean diets promoted weight loss without affecting appetite or requiring calorie restriction, the researchers explained. Therefore, “this weight loss if sustained over time could have a substantial impact on body weight,” they said.
“We hypothesized that there would be equivalence between the potato and bean diet and this hypothesis proved to be correct,” said Dr. Kirwan, of the Pennington Biomedical Research Center, Baton Rouge, La., in an interview.
The take-home message for clinicians is that, though small, the study was very well-controlled, Dr. Kirwan emphasized. “Clinicians ought to consider the health benefits of the potato when it is cooked and served appropriately.”
Looking ahead, larger randomized controlled trials with additional control arms, longer time of at least 12 weeks, and different patient populations are needed, Dr. Kirwan added.
Findings mitigate food myths
The debate continues about whether there are foods that are “good” or “evil;” or foods that one “should not eat” or “should eat,” said Amy Rothberg, MD, associate professor of internal medicine and of nutritional sciences at the University of Michigan, Ann Arbor, in an interview.
“This study dispels the myth that incorporating a small portion of potato into the diet (although these are not potatoes that are fried, or are topped with cheese, bacon, sour cream, etc.) results in deleterious metabolic outcomes when compared to a diet that is comprised of beans (pulses) as part of a low energy–dense diet,” she explained.
“The diet in both groups was of low energy density, which has been shown to result in fewer calories consumed, weight loss, and improvement in insulin resistance,” so the similarity in results was not so surprising, said Dr. Rothberg.
For the clinical takeaway, Dr. Rothberg agreed with the study authors: “Clinicians may counsel their patients that they can still consume a small potato (with the caveat above regarding cooking methods and toppings) as part of a balanced meal so long as they are keeping their overall calories low and not exceeding their metabolic requirements based on body weight/BMI,” she said.
As for additional research, studies with a longer time frame and a larger and more diverse study population are needed, including populations with common insulin resistance comorbidities such as type 2 diabetes, fatty liver disease, and cardiovascular disease, Dr. Rothberg noted.
Consumer considerations, with caveats
The key message for consumers is that, “based on this very small study of short duration, consuming a small portion of potato as part of an overall balanced, low-energy diet did not produce adverse effects on glucose or insulin when compared to a diet of pulses known to have favorable effects on glucose and insulin,” Dr. Rothberg told this news organization. However, “consumers should note that, although the results from this small study are encouraging, it would be premature to extrapolate the findings from this study to other populations,” she said. Also, keep in mind that the study was supported in part by the Alliance for Potato Research, although the authors stated that none of the funders (Alliance for Potato Research and Education and the National Institutes of Health) had any role in the design, analysis, or writing of the article, she added.
The study was supported in part by the Alliance for Potato Research and Education and the National Institutes of Health, which funds the Louisiana Clinical and Translational Science Center. The researchers and Dr. Rothberg had no financial conflicts to disclose.
FROM THE JOURNAL OF MEDICINAL FOOD
New framework for MS diagnosis and treatment proposed
The goal is to eventually move away from the current system, which classifies MS based on disease progression into distinct relapsing-remitting, secondary progressive, and primary progressive subtypes.
Members of the International Advisory Committee on Clinical Trials in Multiple Sclerosis, which developed the framework, note the new framework is based on underlying biology of disease and acknowledges the different trajectories of individual patients. “The categorization of patients into distinct subtypes or stages is artificial,” said framework coauthor Jeffrey Cohen, MD, director of experimental therapeutics, Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic. “The rationale for the new framework was recent studies demonstrating that the biologic processes that underlie relapses and progression are present to varying degrees throughout the disease course, representing a continuum.”
The proposal was published online in The Lancet Neurology.
A more responsive system
Since the current MS classification, dubbed the Lublin-Reingold descriptors, was introduced, there have been calls for a different system that is more responsive to biological changes inherent in MS. The committee, which is jointly sponsored by the European Committee for Treatment and Research in Multiple Sclerosis and the U.S. National Multiple Sclerosis Society, responded by clarifying clinical course descriptions published in 1996 and 2013. The proposed framework grew out of that process.
“One of the main points is the concept that patients don’t evolve into secondary progressive MS,” Dr. Cohen said. “The processes that underlie progression and the findings of proxy measures of progression are present from the earliest stages of the disease.”
In its report, the committee reviews current data on the pathophysiology of injury and compensatory mechanisms in MS, presenting findings that suggest disease progression is caused not by a single disease mechanism, but from a combination of several processes that vary from patient to patient.
Current research studies highlighted in the report include those focused on mechanisms of injury, such as acute and chronic inflammation, myelin loss, nerve fiber and neuron loss, and mitochondrial dysfunction. How the body responds to that injury is likely to determine how MS evolves in each patient, the committee wrote.
Studies point to a range of factors that influence how MS manifests and progresses, including patients’ age at onset, biological sex, genes, race, ethnicity, comorbid health conditions, health behaviors, therapies, and social and environmental exposures.
Potential for better treatments
Any new framework for classifying the disease in the future would enable the development and approval of more biologically based treatment approaches, Dr. Cohen said. “One anticipated advantage of the new framework is that treatments should be evaluated based on their efficacy on biologic processes, not in artificial categories of patients.”
Dr. Cohen and other committee members acknowledged that developing the framework is just a first step in what would likely be a long and complicated process. “This proposal is among many initiatives that the committee has supported over the years as part of its overarching aim to constantly improve, update, and enhance clinical trial design and inform clinical care delivery for people living with MS and their health care teams,” committee chair Ruth Ann Marrie, MD, PhD, director of the Multiple Sclerosis Clinic at the University of Manitoba Health Sciences Center, Winnipeg, said in a press release.
Commenting on the proposal, Tony Reder, MD, professor of neurology at the University of Chicago Medicine, said the paper offers a “good framework for all trialists attempting to go beyond the usual markers.”
The time is right for reclassifying MS
The authors “have good reasons to propose the need for a new mechanism-driven framework to define MS progression,” wrote Takashi Yamamura, MD, PhD, director and chief of the Neuroimmunology Section and director of Multiple Sclerosis Center, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan, in an accompanying commentary.
Adopting biologically based definitions of MS progression will be challenging to implement, the authors admitted. The current subtype classification is woven into clinical care and research models and is the basis for regulatory approval of new therapeutics. Replacing it will take time and require external validation in the clinic and the lab.
“Although the goal is distant and many obstacles might arise (such as reaching a consensus between physicians, academia, and stakeholders), the time seems right to launch initiatives to reframe the classification of MS subtypes,” Dr. Yamamura added.
The study was supported by the German Research Foundation and the Intramural Research Program of NINDS. Dr. Cohen reported personal compensation for consulting for Biogen, Convelo, EMD Serono, Gossamer Bio, Mylan, and PSI. Dr. Yamamura has received support from AMED-CREST, Novartis, and Chiome Bioscience, and speaker honoraria from Novartis, Biogen, Chugai, Alexion, Mitsubishi-Tanabe, and Takeda.
A version of this article first appeared on Medscape.com.
The goal is to eventually move away from the current system, which classifies MS based on disease progression into distinct relapsing-remitting, secondary progressive, and primary progressive subtypes.
Members of the International Advisory Committee on Clinical Trials in Multiple Sclerosis, which developed the framework, note the new framework is based on underlying biology of disease and acknowledges the different trajectories of individual patients. “The categorization of patients into distinct subtypes or stages is artificial,” said framework coauthor Jeffrey Cohen, MD, director of experimental therapeutics, Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic. “The rationale for the new framework was recent studies demonstrating that the biologic processes that underlie relapses and progression are present to varying degrees throughout the disease course, representing a continuum.”
The proposal was published online in The Lancet Neurology.
A more responsive system
Since the current MS classification, dubbed the Lublin-Reingold descriptors, was introduced, there have been calls for a different system that is more responsive to biological changes inherent in MS. The committee, which is jointly sponsored by the European Committee for Treatment and Research in Multiple Sclerosis and the U.S. National Multiple Sclerosis Society, responded by clarifying clinical course descriptions published in 1996 and 2013. The proposed framework grew out of that process.
“One of the main points is the concept that patients don’t evolve into secondary progressive MS,” Dr. Cohen said. “The processes that underlie progression and the findings of proxy measures of progression are present from the earliest stages of the disease.”
In its report, the committee reviews current data on the pathophysiology of injury and compensatory mechanisms in MS, presenting findings that suggest disease progression is caused not by a single disease mechanism, but from a combination of several processes that vary from patient to patient.
Current research studies highlighted in the report include those focused on mechanisms of injury, such as acute and chronic inflammation, myelin loss, nerve fiber and neuron loss, and mitochondrial dysfunction. How the body responds to that injury is likely to determine how MS evolves in each patient, the committee wrote.
Studies point to a range of factors that influence how MS manifests and progresses, including patients’ age at onset, biological sex, genes, race, ethnicity, comorbid health conditions, health behaviors, therapies, and social and environmental exposures.
Potential for better treatments
Any new framework for classifying the disease in the future would enable the development and approval of more biologically based treatment approaches, Dr. Cohen said. “One anticipated advantage of the new framework is that treatments should be evaluated based on their efficacy on biologic processes, not in artificial categories of patients.”
Dr. Cohen and other committee members acknowledged that developing the framework is just a first step in what would likely be a long and complicated process. “This proposal is among many initiatives that the committee has supported over the years as part of its overarching aim to constantly improve, update, and enhance clinical trial design and inform clinical care delivery for people living with MS and their health care teams,” committee chair Ruth Ann Marrie, MD, PhD, director of the Multiple Sclerosis Clinic at the University of Manitoba Health Sciences Center, Winnipeg, said in a press release.
Commenting on the proposal, Tony Reder, MD, professor of neurology at the University of Chicago Medicine, said the paper offers a “good framework for all trialists attempting to go beyond the usual markers.”
The time is right for reclassifying MS
The authors “have good reasons to propose the need for a new mechanism-driven framework to define MS progression,” wrote Takashi Yamamura, MD, PhD, director and chief of the Neuroimmunology Section and director of Multiple Sclerosis Center, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan, in an accompanying commentary.
Adopting biologically based definitions of MS progression will be challenging to implement, the authors admitted. The current subtype classification is woven into clinical care and research models and is the basis for regulatory approval of new therapeutics. Replacing it will take time and require external validation in the clinic and the lab.
“Although the goal is distant and many obstacles might arise (such as reaching a consensus between physicians, academia, and stakeholders), the time seems right to launch initiatives to reframe the classification of MS subtypes,” Dr. Yamamura added.
The study was supported by the German Research Foundation and the Intramural Research Program of NINDS. Dr. Cohen reported personal compensation for consulting for Biogen, Convelo, EMD Serono, Gossamer Bio, Mylan, and PSI. Dr. Yamamura has received support from AMED-CREST, Novartis, and Chiome Bioscience, and speaker honoraria from Novartis, Biogen, Chugai, Alexion, Mitsubishi-Tanabe, and Takeda.
A version of this article first appeared on Medscape.com.
The goal is to eventually move away from the current system, which classifies MS based on disease progression into distinct relapsing-remitting, secondary progressive, and primary progressive subtypes.
Members of the International Advisory Committee on Clinical Trials in Multiple Sclerosis, which developed the framework, note the new framework is based on underlying biology of disease and acknowledges the different trajectories of individual patients. “The categorization of patients into distinct subtypes or stages is artificial,” said framework coauthor Jeffrey Cohen, MD, director of experimental therapeutics, Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic. “The rationale for the new framework was recent studies demonstrating that the biologic processes that underlie relapses and progression are present to varying degrees throughout the disease course, representing a continuum.”
The proposal was published online in The Lancet Neurology.
A more responsive system
Since the current MS classification, dubbed the Lublin-Reingold descriptors, was introduced, there have been calls for a different system that is more responsive to biological changes inherent in MS. The committee, which is jointly sponsored by the European Committee for Treatment and Research in Multiple Sclerosis and the U.S. National Multiple Sclerosis Society, responded by clarifying clinical course descriptions published in 1996 and 2013. The proposed framework grew out of that process.
“One of the main points is the concept that patients don’t evolve into secondary progressive MS,” Dr. Cohen said. “The processes that underlie progression and the findings of proxy measures of progression are present from the earliest stages of the disease.”
In its report, the committee reviews current data on the pathophysiology of injury and compensatory mechanisms in MS, presenting findings that suggest disease progression is caused not by a single disease mechanism, but from a combination of several processes that vary from patient to patient.
Current research studies highlighted in the report include those focused on mechanisms of injury, such as acute and chronic inflammation, myelin loss, nerve fiber and neuron loss, and mitochondrial dysfunction. How the body responds to that injury is likely to determine how MS evolves in each patient, the committee wrote.
Studies point to a range of factors that influence how MS manifests and progresses, including patients’ age at onset, biological sex, genes, race, ethnicity, comorbid health conditions, health behaviors, therapies, and social and environmental exposures.
Potential for better treatments
Any new framework for classifying the disease in the future would enable the development and approval of more biologically based treatment approaches, Dr. Cohen said. “One anticipated advantage of the new framework is that treatments should be evaluated based on their efficacy on biologic processes, not in artificial categories of patients.”
Dr. Cohen and other committee members acknowledged that developing the framework is just a first step in what would likely be a long and complicated process. “This proposal is among many initiatives that the committee has supported over the years as part of its overarching aim to constantly improve, update, and enhance clinical trial design and inform clinical care delivery for people living with MS and their health care teams,” committee chair Ruth Ann Marrie, MD, PhD, director of the Multiple Sclerosis Clinic at the University of Manitoba Health Sciences Center, Winnipeg, said in a press release.
Commenting on the proposal, Tony Reder, MD, professor of neurology at the University of Chicago Medicine, said the paper offers a “good framework for all trialists attempting to go beyond the usual markers.”
The time is right for reclassifying MS
The authors “have good reasons to propose the need for a new mechanism-driven framework to define MS progression,” wrote Takashi Yamamura, MD, PhD, director and chief of the Neuroimmunology Section and director of Multiple Sclerosis Center, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan, in an accompanying commentary.
Adopting biologically based definitions of MS progression will be challenging to implement, the authors admitted. The current subtype classification is woven into clinical care and research models and is the basis for regulatory approval of new therapeutics. Replacing it will take time and require external validation in the clinic and the lab.
“Although the goal is distant and many obstacles might arise (such as reaching a consensus between physicians, academia, and stakeholders), the time seems right to launch initiatives to reframe the classification of MS subtypes,” Dr. Yamamura added.
The study was supported by the German Research Foundation and the Intramural Research Program of NINDS. Dr. Cohen reported personal compensation for consulting for Biogen, Convelo, EMD Serono, Gossamer Bio, Mylan, and PSI. Dr. Yamamura has received support from AMED-CREST, Novartis, and Chiome Bioscience, and speaker honoraria from Novartis, Biogen, Chugai, Alexion, Mitsubishi-Tanabe, and Takeda.
A version of this article first appeared on Medscape.com.
FROM THE LANCET NEUROLOGY