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Low-Dose Aspirin Associated With Reduced CRC Risk
TOPLINE:
Low-dose aspirin use is associated with a reduced risk for colorectal cancer (CRC), confirms a large-scale cohort study, which also suggests that the risk reduction is greatest for metastatic disease and in individuals who take the drug for at least 5 years.
METHODOLOGY:
- Researchers used several population-based registries to identify individuals aged ≥ 50 years living in Norway between 2014 and 2018, excluding those with a prior history of invasive cancer or who had lived in Norway for less than 6 months before study commencement.
- Sociodemographic information was obtained, as well as low-dose aspirin prescription data to determine the prescription date, number of dispensed packages, and defined daily dose.
- Follow-up began 6 months after entering the cohort and continued until CRC diagnosis, another cancer diagnosis, death, emigration, or the end of follow-up on December 31, 2018.
- CRC cases were categorized by site as well as by clinical stage.
TAKEAWAY:
- Of 2,186,390 individuals included, 38,577 (1.8%) were diagnosed with CRC after a median follow-up of 10.9 years. Low-dose aspirin was used at least once by 579,196 (26.5%) individuals.
- Low-dose aspirin use was more common among males, older individuals, those with a lower education or lower income, those of Norwegian origin, and individuals using other medications, including those targeting cardiovascular conditions.
- Duration of current aspirin use was also associated with the degree of CRC risk, at HRs of 0.91 for < 3 years, 0.85 for ≥ 3 and < 5 years, and 0.84 for ≥ 5 years.
- It was estimated that aspirin use averted 1073 cases of CRC over the study period.
IN PRACTICE:
“We believe that new randomized controlled trials are urgently needed to confirm the potential protective effect of aspirin against CRC and to identify subgroups in the population who might benefit the most from the use of aspirin,” the authors wrote.
SOURCE:
The research, led by Edoardo Botteri, PhD, Department of Research, Cancer Registry of Norway, National Institute of Public Health, Oslo, Norway, was published online in The American Journal of Gastroenterology.
LIMITATIONS:
This study is limited by its observational nature. Users and nonusers are also “incomparable,” as aspirin is used for the primary prevention of cardiovascular events. Moreover, information was lacking in the registries about “several known risk factors for CRC,” and so the link between aspirin and CRC risk could have been over- or underestimated. Finally, the defined daily dose may not necessarily reflect the dose actually taken by the individual or how often it was taken.
DISCLOSURES:
No relevant financial relationships were declared. The study was funded by the Norwegian Research Council.
A version of this article appeared on Medscape.com.
TOPLINE:
Low-dose aspirin use is associated with a reduced risk for colorectal cancer (CRC), confirms a large-scale cohort study, which also suggests that the risk reduction is greatest for metastatic disease and in individuals who take the drug for at least 5 years.
METHODOLOGY:
- Researchers used several population-based registries to identify individuals aged ≥ 50 years living in Norway between 2014 and 2018, excluding those with a prior history of invasive cancer or who had lived in Norway for less than 6 months before study commencement.
- Sociodemographic information was obtained, as well as low-dose aspirin prescription data to determine the prescription date, number of dispensed packages, and defined daily dose.
- Follow-up began 6 months after entering the cohort and continued until CRC diagnosis, another cancer diagnosis, death, emigration, or the end of follow-up on December 31, 2018.
- CRC cases were categorized by site as well as by clinical stage.
TAKEAWAY:
- Of 2,186,390 individuals included, 38,577 (1.8%) were diagnosed with CRC after a median follow-up of 10.9 years. Low-dose aspirin was used at least once by 579,196 (26.5%) individuals.
- Low-dose aspirin use was more common among males, older individuals, those with a lower education or lower income, those of Norwegian origin, and individuals using other medications, including those targeting cardiovascular conditions.
- Duration of current aspirin use was also associated with the degree of CRC risk, at HRs of 0.91 for < 3 years, 0.85 for ≥ 3 and < 5 years, and 0.84 for ≥ 5 years.
- It was estimated that aspirin use averted 1073 cases of CRC over the study period.
IN PRACTICE:
“We believe that new randomized controlled trials are urgently needed to confirm the potential protective effect of aspirin against CRC and to identify subgroups in the population who might benefit the most from the use of aspirin,” the authors wrote.
SOURCE:
The research, led by Edoardo Botteri, PhD, Department of Research, Cancer Registry of Norway, National Institute of Public Health, Oslo, Norway, was published online in The American Journal of Gastroenterology.
LIMITATIONS:
This study is limited by its observational nature. Users and nonusers are also “incomparable,” as aspirin is used for the primary prevention of cardiovascular events. Moreover, information was lacking in the registries about “several known risk factors for CRC,” and so the link between aspirin and CRC risk could have been over- or underestimated. Finally, the defined daily dose may not necessarily reflect the dose actually taken by the individual or how often it was taken.
DISCLOSURES:
No relevant financial relationships were declared. The study was funded by the Norwegian Research Council.
A version of this article appeared on Medscape.com.
TOPLINE:
Low-dose aspirin use is associated with a reduced risk for colorectal cancer (CRC), confirms a large-scale cohort study, which also suggests that the risk reduction is greatest for metastatic disease and in individuals who take the drug for at least 5 years.
METHODOLOGY:
- Researchers used several population-based registries to identify individuals aged ≥ 50 years living in Norway between 2014 and 2018, excluding those with a prior history of invasive cancer or who had lived in Norway for less than 6 months before study commencement.
- Sociodemographic information was obtained, as well as low-dose aspirin prescription data to determine the prescription date, number of dispensed packages, and defined daily dose.
- Follow-up began 6 months after entering the cohort and continued until CRC diagnosis, another cancer diagnosis, death, emigration, or the end of follow-up on December 31, 2018.
- CRC cases were categorized by site as well as by clinical stage.
TAKEAWAY:
- Of 2,186,390 individuals included, 38,577 (1.8%) were diagnosed with CRC after a median follow-up of 10.9 years. Low-dose aspirin was used at least once by 579,196 (26.5%) individuals.
- Low-dose aspirin use was more common among males, older individuals, those with a lower education or lower income, those of Norwegian origin, and individuals using other medications, including those targeting cardiovascular conditions.
- Duration of current aspirin use was also associated with the degree of CRC risk, at HRs of 0.91 for < 3 years, 0.85 for ≥ 3 and < 5 years, and 0.84 for ≥ 5 years.
- It was estimated that aspirin use averted 1073 cases of CRC over the study period.
IN PRACTICE:
“We believe that new randomized controlled trials are urgently needed to confirm the potential protective effect of aspirin against CRC and to identify subgroups in the population who might benefit the most from the use of aspirin,” the authors wrote.
SOURCE:
The research, led by Edoardo Botteri, PhD, Department of Research, Cancer Registry of Norway, National Institute of Public Health, Oslo, Norway, was published online in The American Journal of Gastroenterology.
LIMITATIONS:
This study is limited by its observational nature. Users and nonusers are also “incomparable,” as aspirin is used for the primary prevention of cardiovascular events. Moreover, information was lacking in the registries about “several known risk factors for CRC,” and so the link between aspirin and CRC risk could have been over- or underestimated. Finally, the defined daily dose may not necessarily reflect the dose actually taken by the individual or how often it was taken.
DISCLOSURES:
No relevant financial relationships were declared. The study was funded by the Norwegian Research Council.
A version of this article appeared on Medscape.com.
Tumor Microbiome Differs in Young- vs Average-Onset CRC
TOPLINE:
and could serve as preventive, diagnostic, and therapeutic targets.
METHODOLOGY:
- The study population was drawn from patients who underwent surgical resection of the primary colorectal tumor at a single center from 2000 to 2020.
- yoCRC was defined as CRC diagnosed before age 50 years, and aoCRC was defined as CRC diagnosed after age 60 years. Patients aged between 50 and 60 years at diagnosis were excluded to ensure two distinct cohorts for meaningful comparison.
- Researchers used various gene sequencing technologies to compare tissue samples from 136 patients with yoCRC against samples from 140 patients with aoCRC.
TAKEAWAY:
- Patients with yoCRC vs those with aoCRC were more likely to have left-sided (72.8% vs 54.3%), rectal (36.7% vs 25%), and stage IV (28% vs 15%) tumors.
- yoCRC and aoCRC tumors had distinct microbial profiles associated with tumor location, sidedness, and stage, and obesity.
- yoCRC tumors had significantly higher microbial alpha diversity and varied beta diversity than aoCRC tumors.
- yoCRC tumors were enriched with Akkermansia and Bacteroides, whereas aoCRC tumors showed greater relative abundances of Bacillus, Staphylococcus, Listeria, Enterococcus, Pseudomonas, Fusobacterium, and Escherichia/Shigella.
- In yoCRC, Fusobacterium and Akkermansia abundance correlated with overall survival.
IN PRACTICE:
“[O]ur findings help to comprehensively define the microbial community that may play a role in young-onset colorectal oncogenesis [and] should encourage the evaluation of environmental and lifestyle risk factors that might contribute to microbial dysbiosis in this patient population,” the authors wrote.
SOURCE:
The study, led by Shimoli V. Barot, MD, Cleveland Clinic, Ohio was published online in eBioMedicine.
LIMITATIONS:
The study had several limitations. It was a single-institution retrospective study with limited diversity in terms of race/ethnicity. Smoking and aspirin use were higher among older participants, whereas the yoCRC group had higher rates of neoadjuvant therapy and metastesectomy. Data on factors affecting the microbiome around the time of specimen collection, such as diet, stress, and antibiotic and probiotic use, were limited and not adjusted for in the analysis.
DISCLOSURES:
The study was funded by the Sondra and Stephen Hardis Chair in Oncology Research. Two coauthors report fees and research funding from industry. Barot and the other coauthors report no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
and could serve as preventive, diagnostic, and therapeutic targets.
METHODOLOGY:
- The study population was drawn from patients who underwent surgical resection of the primary colorectal tumor at a single center from 2000 to 2020.
- yoCRC was defined as CRC diagnosed before age 50 years, and aoCRC was defined as CRC diagnosed after age 60 years. Patients aged between 50 and 60 years at diagnosis were excluded to ensure two distinct cohorts for meaningful comparison.
- Researchers used various gene sequencing technologies to compare tissue samples from 136 patients with yoCRC against samples from 140 patients with aoCRC.
TAKEAWAY:
- Patients with yoCRC vs those with aoCRC were more likely to have left-sided (72.8% vs 54.3%), rectal (36.7% vs 25%), and stage IV (28% vs 15%) tumors.
- yoCRC and aoCRC tumors had distinct microbial profiles associated with tumor location, sidedness, and stage, and obesity.
- yoCRC tumors had significantly higher microbial alpha diversity and varied beta diversity than aoCRC tumors.
- yoCRC tumors were enriched with Akkermansia and Bacteroides, whereas aoCRC tumors showed greater relative abundances of Bacillus, Staphylococcus, Listeria, Enterococcus, Pseudomonas, Fusobacterium, and Escherichia/Shigella.
- In yoCRC, Fusobacterium and Akkermansia abundance correlated with overall survival.
IN PRACTICE:
“[O]ur findings help to comprehensively define the microbial community that may play a role in young-onset colorectal oncogenesis [and] should encourage the evaluation of environmental and lifestyle risk factors that might contribute to microbial dysbiosis in this patient population,” the authors wrote.
SOURCE:
The study, led by Shimoli V. Barot, MD, Cleveland Clinic, Ohio was published online in eBioMedicine.
LIMITATIONS:
The study had several limitations. It was a single-institution retrospective study with limited diversity in terms of race/ethnicity. Smoking and aspirin use were higher among older participants, whereas the yoCRC group had higher rates of neoadjuvant therapy and metastesectomy. Data on factors affecting the microbiome around the time of specimen collection, such as diet, stress, and antibiotic and probiotic use, were limited and not adjusted for in the analysis.
DISCLOSURES:
The study was funded by the Sondra and Stephen Hardis Chair in Oncology Research. Two coauthors report fees and research funding from industry. Barot and the other coauthors report no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
and could serve as preventive, diagnostic, and therapeutic targets.
METHODOLOGY:
- The study population was drawn from patients who underwent surgical resection of the primary colorectal tumor at a single center from 2000 to 2020.
- yoCRC was defined as CRC diagnosed before age 50 years, and aoCRC was defined as CRC diagnosed after age 60 years. Patients aged between 50 and 60 years at diagnosis were excluded to ensure two distinct cohorts for meaningful comparison.
- Researchers used various gene sequencing technologies to compare tissue samples from 136 patients with yoCRC against samples from 140 patients with aoCRC.
TAKEAWAY:
- Patients with yoCRC vs those with aoCRC were more likely to have left-sided (72.8% vs 54.3%), rectal (36.7% vs 25%), and stage IV (28% vs 15%) tumors.
- yoCRC and aoCRC tumors had distinct microbial profiles associated with tumor location, sidedness, and stage, and obesity.
- yoCRC tumors had significantly higher microbial alpha diversity and varied beta diversity than aoCRC tumors.
- yoCRC tumors were enriched with Akkermansia and Bacteroides, whereas aoCRC tumors showed greater relative abundances of Bacillus, Staphylococcus, Listeria, Enterococcus, Pseudomonas, Fusobacterium, and Escherichia/Shigella.
- In yoCRC, Fusobacterium and Akkermansia abundance correlated with overall survival.
IN PRACTICE:
“[O]ur findings help to comprehensively define the microbial community that may play a role in young-onset colorectal oncogenesis [and] should encourage the evaluation of environmental and lifestyle risk factors that might contribute to microbial dysbiosis in this patient population,” the authors wrote.
SOURCE:
The study, led by Shimoli V. Barot, MD, Cleveland Clinic, Ohio was published online in eBioMedicine.
LIMITATIONS:
The study had several limitations. It was a single-institution retrospective study with limited diversity in terms of race/ethnicity. Smoking and aspirin use were higher among older participants, whereas the yoCRC group had higher rates of neoadjuvant therapy and metastesectomy. Data on factors affecting the microbiome around the time of specimen collection, such as diet, stress, and antibiotic and probiotic use, were limited and not adjusted for in the analysis.
DISCLOSURES:
The study was funded by the Sondra and Stephen Hardis Chair in Oncology Research. Two coauthors report fees and research funding from industry. Barot and the other coauthors report no conflicts of interest.
A version of this article appeared on Medscape.com.
FDA Withdraws Melflufen Approval, but EMA Still Allows Its Use
But the European Medicines Agency (EMA) still authorizes the drug’s manufacturer Oncopeptides AB to market the drug, also called Pepaxti, in Europe, Iceland, Lichtenstein, Norway, and the United Kingdom.
Amol Akhade, MBBS, who describes himself as a senior consultant medical and hemato oncologist–bone marrow transplant physician on LinkedIn, raised questions about the inconsistencies between the FDA and EMA’s opinions about these drugs. Dr. Akhad, of Suyog Cancer Clinics in India, posted via the following handle @SuyogCancer on X (Twitter):
“How can one drug and one trial data [have] two diagonally different outcomes from two different drug approval agencies?
Melphalan Flufenamide is finally completely withdrawn by @US_FDA
But approval by @EMA_News stays.
How can be one drug be harmful across one side of Atlantic Ocean and becomes safe and useful on the other side of Atlantic Ocean?
Modern day miracle?”
EMA: Pepaxti’s Benefits Exceed Its Risks
The EMA, which could not be reached for comment regarding why the agency was still allowing patients to use the drug, said the following about Pepaxti on its website:
“The European Medicines Agency decided that Pepaxti’s benefits are greater than its risks and it can be authorised for use in the EU. The Agency noted the unmet medical need for patients with multiple myeloma who no longer improve with the available therapies. Despite some limitations in the studies, the results were considered clinically relevant, with the exception of the subgroup of patients who had an autologous stem cell transplant and whose disease progressed within three years of transplantation.
Regarding safety, although side effects, including severe effects, were seen with treatment involving Pepaxti, these were considered acceptable and manageable,” the agency wrote.
“Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Pepaxti have been included in the summary of product characteristics and the package leaflet.
As for all medicines, data on the use of Pepaxti are continuously monitored. Suspected side effects reported with Pepaxti are carefully evaluated and any necessary action taken to protect patients,” according to the EMA.
The FDA’s final decision, issued on February 23, 2024, follows its warning in 2021 that meflufen plus dexamethasone exposed patients with multiple myeloma to increased risk for death, and its call for withdrawal of the drug in 2022.
“The grounds for withdrawing approval have been met because: (1) the confirmatory study conducted as a condition of accelerated approval did not confirm Pepaxto’s clinical benefit and (2) the available evidence demonstrates that Pepaxto is not shown to be safe or effective under its conditions of use,” Peter Marks, MD, PhD, Director of the FDA Center for Biologics Evaluation and Research, wrote in the final decision document.
Oncopeptides AB: Drug ‘Caters to a Large Unmet Need’
David Augustsson, Director of Corporate Affairs, Oncopeptides AB, explained in an interview why he thinks the EMA and FDA’s actions regarding the drug differ from each other.
“The European Medicines Agency had the opinion that the OCEAN study met its primary endpoint by demonstrating superior progression-free survival and it agreed that the potential detriment of overall survival was limited to patients progressing less than 36 months after an autologous stem cell transplant,” he said.“The FDA was not willing to acknowledge the observed clinically relevant differences across patient subgroups in the OCEAN study as confirmed.”
Mr. Augustsson added that this decision will deprive US patients of access to “a drug we believe caters to a large unmet need among elderly multiple myeloma patients with few treatment options left.”
“While we remain confident that we have science on our side we are of course disappointed in the decision [to remove Pepaxto from the US market],” Oncopeptides AB CEO Sofia Heigis said in a statement. “At the same time this is no change to our plans and we will continue to focus all our attention on the commercialization in Europe, progression of our pipeline and rest of world opportunities.”
FDA 'Took Swift Action' to Ensure Users of Pepaxto Were Informed of Risks
In February 2021, the FDA used the Accelerated Approval Program to enable certain patients with multiple myeloma to be treated with the peptide conjugated alkylating drug melflufen plus dexamethasone. Under the program, Oncopeptides was required to conduct the phase III randomized, controlled OCEAN clinical trial.
OCEAN enrolled 495 patients with relapsed/refractory multiple myeloma who had 2 to 4 lines of prior therapy and who were refractory to lenalidomide in the last line of therapy. Participants in the multinational study received either melflufen plus dexamethasone or pomalidomide plus dexamethasone until disease progression, unacceptable toxicity, or lack of benefit.
In July 2021, the FDA issued an alert that the study results showed increased risk for death in participants treated with melflufen. In October that year, at FDA request, Oncopeptides removed the drug from the US market but continued to provide it to patients already receiving it. In December 2022, the FDA requested that the company withdraw melflufen’s US marketing authorization.
Responding to questions about the timing of the FDA’s most recent decision about Pepaxto and how the decision will affect patient care in the US, the FDA emailed the following statement to this news organization:
“Since the OCEAN trial results for Pepaxto in 2021, the FDA has responded to safety concerns about Pepaxto by issuing a CDER Alert, communicating concerns to Oncopeptides, holding an Oncologic Drugs Advisory Committee meeting in September 2022, and issuing a letter of notice to Oncopeptides in July 2023, proposing to withdraw Pepaxto (NDA 214383). After receiving the notice, Oncopeptides appealed the withdrawal in August 2023. A meeting was held with the Commissioner’s designee, Dr. Peter Marks, Oncopeptides, and others from FDA in October 2023. Dr. Marks reviewed the record and considered the arguments made on appeal and issued a final decision on February 23, 2024. Prior to reaching a decision, the FDA took swift action to ensure those receiving Pepaxto in the post-confirmatory clinical trial were informed of the risks and that no new patients were enrolled in the trial. We also note that it is our understanding that Pepaxto has not been marketed in the U.S. since October 22, 2021.”
“This is the first time FDA has used the amended procedures for withdrawal of accelerated approval that were enacted in 2023, as part of the Food and Drug Omnibus Report Act of 2022 (FDORA),” the agency wrote in a Feb 23 statement. The agency will also remove melflufen from the Approved Drug Products with Therapeutic Equivalence Evaluations, also called the Orange Book.
But the European Medicines Agency (EMA) still authorizes the drug’s manufacturer Oncopeptides AB to market the drug, also called Pepaxti, in Europe, Iceland, Lichtenstein, Norway, and the United Kingdom.
Amol Akhade, MBBS, who describes himself as a senior consultant medical and hemato oncologist–bone marrow transplant physician on LinkedIn, raised questions about the inconsistencies between the FDA and EMA’s opinions about these drugs. Dr. Akhad, of Suyog Cancer Clinics in India, posted via the following handle @SuyogCancer on X (Twitter):
“How can one drug and one trial data [have] two diagonally different outcomes from two different drug approval agencies?
Melphalan Flufenamide is finally completely withdrawn by @US_FDA
But approval by @EMA_News stays.
How can be one drug be harmful across one side of Atlantic Ocean and becomes safe and useful on the other side of Atlantic Ocean?
Modern day miracle?”
EMA: Pepaxti’s Benefits Exceed Its Risks
The EMA, which could not be reached for comment regarding why the agency was still allowing patients to use the drug, said the following about Pepaxti on its website:
“The European Medicines Agency decided that Pepaxti’s benefits are greater than its risks and it can be authorised for use in the EU. The Agency noted the unmet medical need for patients with multiple myeloma who no longer improve with the available therapies. Despite some limitations in the studies, the results were considered clinically relevant, with the exception of the subgroup of patients who had an autologous stem cell transplant and whose disease progressed within three years of transplantation.
Regarding safety, although side effects, including severe effects, were seen with treatment involving Pepaxti, these were considered acceptable and manageable,” the agency wrote.
“Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Pepaxti have been included in the summary of product characteristics and the package leaflet.
As for all medicines, data on the use of Pepaxti are continuously monitored. Suspected side effects reported with Pepaxti are carefully evaluated and any necessary action taken to protect patients,” according to the EMA.
The FDA’s final decision, issued on February 23, 2024, follows its warning in 2021 that meflufen plus dexamethasone exposed patients with multiple myeloma to increased risk for death, and its call for withdrawal of the drug in 2022.
“The grounds for withdrawing approval have been met because: (1) the confirmatory study conducted as a condition of accelerated approval did not confirm Pepaxto’s clinical benefit and (2) the available evidence demonstrates that Pepaxto is not shown to be safe or effective under its conditions of use,” Peter Marks, MD, PhD, Director of the FDA Center for Biologics Evaluation and Research, wrote in the final decision document.
Oncopeptides AB: Drug ‘Caters to a Large Unmet Need’
David Augustsson, Director of Corporate Affairs, Oncopeptides AB, explained in an interview why he thinks the EMA and FDA’s actions regarding the drug differ from each other.
“The European Medicines Agency had the opinion that the OCEAN study met its primary endpoint by demonstrating superior progression-free survival and it agreed that the potential detriment of overall survival was limited to patients progressing less than 36 months after an autologous stem cell transplant,” he said.“The FDA was not willing to acknowledge the observed clinically relevant differences across patient subgroups in the OCEAN study as confirmed.”
Mr. Augustsson added that this decision will deprive US patients of access to “a drug we believe caters to a large unmet need among elderly multiple myeloma patients with few treatment options left.”
“While we remain confident that we have science on our side we are of course disappointed in the decision [to remove Pepaxto from the US market],” Oncopeptides AB CEO Sofia Heigis said in a statement. “At the same time this is no change to our plans and we will continue to focus all our attention on the commercialization in Europe, progression of our pipeline and rest of world opportunities.”
FDA 'Took Swift Action' to Ensure Users of Pepaxto Were Informed of Risks
In February 2021, the FDA used the Accelerated Approval Program to enable certain patients with multiple myeloma to be treated with the peptide conjugated alkylating drug melflufen plus dexamethasone. Under the program, Oncopeptides was required to conduct the phase III randomized, controlled OCEAN clinical trial.
OCEAN enrolled 495 patients with relapsed/refractory multiple myeloma who had 2 to 4 lines of prior therapy and who were refractory to lenalidomide in the last line of therapy. Participants in the multinational study received either melflufen plus dexamethasone or pomalidomide plus dexamethasone until disease progression, unacceptable toxicity, or lack of benefit.
In July 2021, the FDA issued an alert that the study results showed increased risk for death in participants treated with melflufen. In October that year, at FDA request, Oncopeptides removed the drug from the US market but continued to provide it to patients already receiving it. In December 2022, the FDA requested that the company withdraw melflufen’s US marketing authorization.
Responding to questions about the timing of the FDA’s most recent decision about Pepaxto and how the decision will affect patient care in the US, the FDA emailed the following statement to this news organization:
“Since the OCEAN trial results for Pepaxto in 2021, the FDA has responded to safety concerns about Pepaxto by issuing a CDER Alert, communicating concerns to Oncopeptides, holding an Oncologic Drugs Advisory Committee meeting in September 2022, and issuing a letter of notice to Oncopeptides in July 2023, proposing to withdraw Pepaxto (NDA 214383). After receiving the notice, Oncopeptides appealed the withdrawal in August 2023. A meeting was held with the Commissioner’s designee, Dr. Peter Marks, Oncopeptides, and others from FDA in October 2023. Dr. Marks reviewed the record and considered the arguments made on appeal and issued a final decision on February 23, 2024. Prior to reaching a decision, the FDA took swift action to ensure those receiving Pepaxto in the post-confirmatory clinical trial were informed of the risks and that no new patients were enrolled in the trial. We also note that it is our understanding that Pepaxto has not been marketed in the U.S. since October 22, 2021.”
“This is the first time FDA has used the amended procedures for withdrawal of accelerated approval that were enacted in 2023, as part of the Food and Drug Omnibus Report Act of 2022 (FDORA),” the agency wrote in a Feb 23 statement. The agency will also remove melflufen from the Approved Drug Products with Therapeutic Equivalence Evaluations, also called the Orange Book.
But the European Medicines Agency (EMA) still authorizes the drug’s manufacturer Oncopeptides AB to market the drug, also called Pepaxti, in Europe, Iceland, Lichtenstein, Norway, and the United Kingdom.
Amol Akhade, MBBS, who describes himself as a senior consultant medical and hemato oncologist–bone marrow transplant physician on LinkedIn, raised questions about the inconsistencies between the FDA and EMA’s opinions about these drugs. Dr. Akhad, of Suyog Cancer Clinics in India, posted via the following handle @SuyogCancer on X (Twitter):
“How can one drug and one trial data [have] two diagonally different outcomes from two different drug approval agencies?
Melphalan Flufenamide is finally completely withdrawn by @US_FDA
But approval by @EMA_News stays.
How can be one drug be harmful across one side of Atlantic Ocean and becomes safe and useful on the other side of Atlantic Ocean?
Modern day miracle?”
EMA: Pepaxti’s Benefits Exceed Its Risks
The EMA, which could not be reached for comment regarding why the agency was still allowing patients to use the drug, said the following about Pepaxti on its website:
“The European Medicines Agency decided that Pepaxti’s benefits are greater than its risks and it can be authorised for use in the EU. The Agency noted the unmet medical need for patients with multiple myeloma who no longer improve with the available therapies. Despite some limitations in the studies, the results were considered clinically relevant, with the exception of the subgroup of patients who had an autologous stem cell transplant and whose disease progressed within three years of transplantation.
Regarding safety, although side effects, including severe effects, were seen with treatment involving Pepaxti, these were considered acceptable and manageable,” the agency wrote.
“Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Pepaxti have been included in the summary of product characteristics and the package leaflet.
As for all medicines, data on the use of Pepaxti are continuously monitored. Suspected side effects reported with Pepaxti are carefully evaluated and any necessary action taken to protect patients,” according to the EMA.
The FDA’s final decision, issued on February 23, 2024, follows its warning in 2021 that meflufen plus dexamethasone exposed patients with multiple myeloma to increased risk for death, and its call for withdrawal of the drug in 2022.
“The grounds for withdrawing approval have been met because: (1) the confirmatory study conducted as a condition of accelerated approval did not confirm Pepaxto’s clinical benefit and (2) the available evidence demonstrates that Pepaxto is not shown to be safe or effective under its conditions of use,” Peter Marks, MD, PhD, Director of the FDA Center for Biologics Evaluation and Research, wrote in the final decision document.
Oncopeptides AB: Drug ‘Caters to a Large Unmet Need’
David Augustsson, Director of Corporate Affairs, Oncopeptides AB, explained in an interview why he thinks the EMA and FDA’s actions regarding the drug differ from each other.
“The European Medicines Agency had the opinion that the OCEAN study met its primary endpoint by demonstrating superior progression-free survival and it agreed that the potential detriment of overall survival was limited to patients progressing less than 36 months after an autologous stem cell transplant,” he said.“The FDA was not willing to acknowledge the observed clinically relevant differences across patient subgroups in the OCEAN study as confirmed.”
Mr. Augustsson added that this decision will deprive US patients of access to “a drug we believe caters to a large unmet need among elderly multiple myeloma patients with few treatment options left.”
“While we remain confident that we have science on our side we are of course disappointed in the decision [to remove Pepaxto from the US market],” Oncopeptides AB CEO Sofia Heigis said in a statement. “At the same time this is no change to our plans and we will continue to focus all our attention on the commercialization in Europe, progression of our pipeline and rest of world opportunities.”
FDA 'Took Swift Action' to Ensure Users of Pepaxto Were Informed of Risks
In February 2021, the FDA used the Accelerated Approval Program to enable certain patients with multiple myeloma to be treated with the peptide conjugated alkylating drug melflufen plus dexamethasone. Under the program, Oncopeptides was required to conduct the phase III randomized, controlled OCEAN clinical trial.
OCEAN enrolled 495 patients with relapsed/refractory multiple myeloma who had 2 to 4 lines of prior therapy and who were refractory to lenalidomide in the last line of therapy. Participants in the multinational study received either melflufen plus dexamethasone or pomalidomide plus dexamethasone until disease progression, unacceptable toxicity, or lack of benefit.
In July 2021, the FDA issued an alert that the study results showed increased risk for death in participants treated with melflufen. In October that year, at FDA request, Oncopeptides removed the drug from the US market but continued to provide it to patients already receiving it. In December 2022, the FDA requested that the company withdraw melflufen’s US marketing authorization.
Responding to questions about the timing of the FDA’s most recent decision about Pepaxto and how the decision will affect patient care in the US, the FDA emailed the following statement to this news organization:
“Since the OCEAN trial results for Pepaxto in 2021, the FDA has responded to safety concerns about Pepaxto by issuing a CDER Alert, communicating concerns to Oncopeptides, holding an Oncologic Drugs Advisory Committee meeting in September 2022, and issuing a letter of notice to Oncopeptides in July 2023, proposing to withdraw Pepaxto (NDA 214383). After receiving the notice, Oncopeptides appealed the withdrawal in August 2023. A meeting was held with the Commissioner’s designee, Dr. Peter Marks, Oncopeptides, and others from FDA in October 2023. Dr. Marks reviewed the record and considered the arguments made on appeal and issued a final decision on February 23, 2024. Prior to reaching a decision, the FDA took swift action to ensure those receiving Pepaxto in the post-confirmatory clinical trial were informed of the risks and that no new patients were enrolled in the trial. We also note that it is our understanding that Pepaxto has not been marketed in the U.S. since October 22, 2021.”
“This is the first time FDA has used the amended procedures for withdrawal of accelerated approval that were enacted in 2023, as part of the Food and Drug Omnibus Report Act of 2022 (FDORA),” the agency wrote in a Feb 23 statement. The agency will also remove melflufen from the Approved Drug Products with Therapeutic Equivalence Evaluations, also called the Orange Book.
What Happens to Surgery Candidates with BHDs and Cancer?
based on data from a new study of nearly 700,000 individuals.
The reason for this association remains unclear, and highlights the need to address existing behavioral health disorders (BHDs), which can be exacerbated after a patient is diagnosed with cancer, wrote Timothy M. Pawlik, MD, of The Ohio State University, Columbus, and colleagues. A cancer diagnosis can cause not only physical stress, but mental, emotional, social, and economic stress that can prompt a new BHD, cause relapse of a previous BHD, or exacerbate a current BHD, the researchers noted.
What is Known About BHDs and Cancer?
Although previous studies have shown a possible association between BHDs and increased cancer risk, as well as reduced compliance with care, the effect of BHDs on outcomes in cancer patients undergoing surgical resection has not been examined, wrote Dr. Pawlik and colleagues.
Previous research has focused on the impact of having a preexisting serious mental illness (SMI) such as schizophrenia and bipolar disorder on cancer care.
A 2023 literature review of 27 studies published in the Journal of Medical Imaging and Radiation Sciences showed that patients with preexisting severe mental illness (such as schizophrenia or bipolar disorder) had greater cancer-related mortality. In that study, the researchers also found that patients with severe mental illness were more likely to have metastatic disease at diagnosis, but less likely to receive optimal treatments, than individuals without SMIs.
Many studies also have focused on patients developing mental health problems (including BHDs) after a cancer diagnosis, but the current study is the first known to examine outcomes in those with BHDs before cancer.
Why Was It Important to Conduct This Study?
“BHDs are a diverse set of mental illnesses that affect an individual’s psychosocial wellbeing, potentially resulting in maladaptive behaviors,” Dr. Pawlik said in an interview. BHDs, which include substance abuse, eating disorders, and sleep disorders, are less common than anxiety/depression, but have an estimated prevalence of 1.3%-3.1% among adults in the United States, he said.
What Does the New Study Add?
In the new review by Dr. Pawlik and colleagues, published in the Journal of the American College of Surgeons (Katayama ES. J Am Coll Surg. 2024 Feb 29. doi: 2024. 10.1097/XCS.0000000000000954), BHDs were defined as substance abuse, eating disorders, or sleep disorders, which had not been the focus of previous studies. The researchers reviewed data from 694,836 adult patients with lung, esophageal, gastric, liver, pancreatic, or colorectal cancer between 2018-2021 using the Medicare Standard Analytic files. A total of 46,719 patients (6.7%) had at least one BHD.
Overall, patients with a BHD were significantly less likely than those without a BHD to undergo surgical resection (20.3% vs. 23.4%). Patients with a BHD also had significantly worse long-term postoperative survival than those without BHDs (median 37.1 months vs. 46.6 months) and significantly higher in-hospital costs ($17,432 vs. 16,159, P less than .001 for all).
Among patients who underwent cancer surgery, the odds of any complication were significantly higher for those with a BHD compared to those with no BHD (odds ratio 1.32), as were the odds of a prolonged length of stay (OR 1.67) and 90-day readmission (OR 1.57).
Dr. Pawlik said he was surprised by several of the findings, including that 1 in 15 Medicare beneficiaries had a BHD diagnosis, “with male sex and minority racial status, as well as higher social vulnerability, being associated with a higher prevalence of BHD.”
Also, the independent association of having a BHD with 30%-50% higher odds of a complication, prolonged length of stay, and 90-day readmission was higher than Dr. Pawlik had anticipated.
Why Do Patients With BHDs Have Fewer Surgeries and Worse Outcomes?
The reasons for this association were likely multifactorial and may reflect the greater burden of medical comorbidity and chronic illness in many patients with BHDs because of maladaptive lifestyles or poor nutrition status, Dr. Pawlik said.
“Patients with BHDs also likely face barriers to accessing care, which was noted particularly among patients with BHDs who lived in socially vulnerable areas,” he said. BHD patients also were more likely to be treated at low-volume rather than high-volume hospitals, “which undoubtedly contributed in part to worse outcomes in this cohort of patients,” he added.
What Can Oncologists Do to Help?
The take-home message for clinicians is that BHDs are linked to worse surgical outcomes and higher health care costs in cancer patients, Dr. Pawlik said in an interview.
“Enhanced accessibility to behavioral healthcare, as well as comprehensive policy reform related to mental health services are needed to improve care of patients with BHDs,” he said. “For example, implementing psychiatry compensation programs may encourage practice in vulnerable areas,” he said.
Other strategies include a following a collaborative care model involving mental health professionals working in tandem with primary care and mid-level practitioners and increasing use and establishment of telehealth systems to improve patient access to BHD services, he said.
What Are the Limitations?
The study by Dr. Pawlik and colleagues was limited by several factors, including the lack of data on younger patients and the full range of BHDs, as well as underreporting of BHDs and the high copays for mental health care, the researchers noted. However, the results suggest that concomitant BHDs are associated with worse cancer outcomes and higher in-hospital costs, and illustrate the need to screen for and target these conditions in cancer patients, the researchers concluded.
What Are the Next Steps for Research?
The current study involved Medicare beneficiaries aged 65 years or older, and more research is needed to investigate the impact of BHDs among younger cancer patients in whom the prevalence may be higher and the impact of BHDs may be different, Dr. Pawlik said in an interview. In addition, the analysis of BHDs as a composite of substance abuse, eating disorders, and sleep disorders (because the numbers were too small to break out data for each disorder, separately) prevented investigation of potential differences and unique challenges faced by distinct subpopulations of BHD patients, he said.
“Future studies should examine the individual impact of substance abuse, eating disorders, and sleep disorders on access to surgery, as well as the potential different impact that each one of these different BHDs may have on postoperative outcomes,” Dr. Pawlik suggested.
The study was supported by The Ohio State University College of Medicine Roessler Summer Research Scholarship. The researchers had no financial conflicts to disclose.
based on data from a new study of nearly 700,000 individuals.
The reason for this association remains unclear, and highlights the need to address existing behavioral health disorders (BHDs), which can be exacerbated after a patient is diagnosed with cancer, wrote Timothy M. Pawlik, MD, of The Ohio State University, Columbus, and colleagues. A cancer diagnosis can cause not only physical stress, but mental, emotional, social, and economic stress that can prompt a new BHD, cause relapse of a previous BHD, or exacerbate a current BHD, the researchers noted.
What is Known About BHDs and Cancer?
Although previous studies have shown a possible association between BHDs and increased cancer risk, as well as reduced compliance with care, the effect of BHDs on outcomes in cancer patients undergoing surgical resection has not been examined, wrote Dr. Pawlik and colleagues.
Previous research has focused on the impact of having a preexisting serious mental illness (SMI) such as schizophrenia and bipolar disorder on cancer care.
A 2023 literature review of 27 studies published in the Journal of Medical Imaging and Radiation Sciences showed that patients with preexisting severe mental illness (such as schizophrenia or bipolar disorder) had greater cancer-related mortality. In that study, the researchers also found that patients with severe mental illness were more likely to have metastatic disease at diagnosis, but less likely to receive optimal treatments, than individuals without SMIs.
Many studies also have focused on patients developing mental health problems (including BHDs) after a cancer diagnosis, but the current study is the first known to examine outcomes in those with BHDs before cancer.
Why Was It Important to Conduct This Study?
“BHDs are a diverse set of mental illnesses that affect an individual’s psychosocial wellbeing, potentially resulting in maladaptive behaviors,” Dr. Pawlik said in an interview. BHDs, which include substance abuse, eating disorders, and sleep disorders, are less common than anxiety/depression, but have an estimated prevalence of 1.3%-3.1% among adults in the United States, he said.
What Does the New Study Add?
In the new review by Dr. Pawlik and colleagues, published in the Journal of the American College of Surgeons (Katayama ES. J Am Coll Surg. 2024 Feb 29. doi: 2024. 10.1097/XCS.0000000000000954), BHDs were defined as substance abuse, eating disorders, or sleep disorders, which had not been the focus of previous studies. The researchers reviewed data from 694,836 adult patients with lung, esophageal, gastric, liver, pancreatic, or colorectal cancer between 2018-2021 using the Medicare Standard Analytic files. A total of 46,719 patients (6.7%) had at least one BHD.
Overall, patients with a BHD were significantly less likely than those without a BHD to undergo surgical resection (20.3% vs. 23.4%). Patients with a BHD also had significantly worse long-term postoperative survival than those without BHDs (median 37.1 months vs. 46.6 months) and significantly higher in-hospital costs ($17,432 vs. 16,159, P less than .001 for all).
Among patients who underwent cancer surgery, the odds of any complication were significantly higher for those with a BHD compared to those with no BHD (odds ratio 1.32), as were the odds of a prolonged length of stay (OR 1.67) and 90-day readmission (OR 1.57).
Dr. Pawlik said he was surprised by several of the findings, including that 1 in 15 Medicare beneficiaries had a BHD diagnosis, “with male sex and minority racial status, as well as higher social vulnerability, being associated with a higher prevalence of BHD.”
Also, the independent association of having a BHD with 30%-50% higher odds of a complication, prolonged length of stay, and 90-day readmission was higher than Dr. Pawlik had anticipated.
Why Do Patients With BHDs Have Fewer Surgeries and Worse Outcomes?
The reasons for this association were likely multifactorial and may reflect the greater burden of medical comorbidity and chronic illness in many patients with BHDs because of maladaptive lifestyles or poor nutrition status, Dr. Pawlik said.
“Patients with BHDs also likely face barriers to accessing care, which was noted particularly among patients with BHDs who lived in socially vulnerable areas,” he said. BHD patients also were more likely to be treated at low-volume rather than high-volume hospitals, “which undoubtedly contributed in part to worse outcomes in this cohort of patients,” he added.
What Can Oncologists Do to Help?
The take-home message for clinicians is that BHDs are linked to worse surgical outcomes and higher health care costs in cancer patients, Dr. Pawlik said in an interview.
“Enhanced accessibility to behavioral healthcare, as well as comprehensive policy reform related to mental health services are needed to improve care of patients with BHDs,” he said. “For example, implementing psychiatry compensation programs may encourage practice in vulnerable areas,” he said.
Other strategies include a following a collaborative care model involving mental health professionals working in tandem with primary care and mid-level practitioners and increasing use and establishment of telehealth systems to improve patient access to BHD services, he said.
What Are the Limitations?
The study by Dr. Pawlik and colleagues was limited by several factors, including the lack of data on younger patients and the full range of BHDs, as well as underreporting of BHDs and the high copays for mental health care, the researchers noted. However, the results suggest that concomitant BHDs are associated with worse cancer outcomes and higher in-hospital costs, and illustrate the need to screen for and target these conditions in cancer patients, the researchers concluded.
What Are the Next Steps for Research?
The current study involved Medicare beneficiaries aged 65 years or older, and more research is needed to investigate the impact of BHDs among younger cancer patients in whom the prevalence may be higher and the impact of BHDs may be different, Dr. Pawlik said in an interview. In addition, the analysis of BHDs as a composite of substance abuse, eating disorders, and sleep disorders (because the numbers were too small to break out data for each disorder, separately) prevented investigation of potential differences and unique challenges faced by distinct subpopulations of BHD patients, he said.
“Future studies should examine the individual impact of substance abuse, eating disorders, and sleep disorders on access to surgery, as well as the potential different impact that each one of these different BHDs may have on postoperative outcomes,” Dr. Pawlik suggested.
The study was supported by The Ohio State University College of Medicine Roessler Summer Research Scholarship. The researchers had no financial conflicts to disclose.
based on data from a new study of nearly 700,000 individuals.
The reason for this association remains unclear, and highlights the need to address existing behavioral health disorders (BHDs), which can be exacerbated after a patient is diagnosed with cancer, wrote Timothy M. Pawlik, MD, of The Ohio State University, Columbus, and colleagues. A cancer diagnosis can cause not only physical stress, but mental, emotional, social, and economic stress that can prompt a new BHD, cause relapse of a previous BHD, or exacerbate a current BHD, the researchers noted.
What is Known About BHDs and Cancer?
Although previous studies have shown a possible association between BHDs and increased cancer risk, as well as reduced compliance with care, the effect of BHDs on outcomes in cancer patients undergoing surgical resection has not been examined, wrote Dr. Pawlik and colleagues.
Previous research has focused on the impact of having a preexisting serious mental illness (SMI) such as schizophrenia and bipolar disorder on cancer care.
A 2023 literature review of 27 studies published in the Journal of Medical Imaging and Radiation Sciences showed that patients with preexisting severe mental illness (such as schizophrenia or bipolar disorder) had greater cancer-related mortality. In that study, the researchers also found that patients with severe mental illness were more likely to have metastatic disease at diagnosis, but less likely to receive optimal treatments, than individuals without SMIs.
Many studies also have focused on patients developing mental health problems (including BHDs) after a cancer diagnosis, but the current study is the first known to examine outcomes in those with BHDs before cancer.
Why Was It Important to Conduct This Study?
“BHDs are a diverse set of mental illnesses that affect an individual’s psychosocial wellbeing, potentially resulting in maladaptive behaviors,” Dr. Pawlik said in an interview. BHDs, which include substance abuse, eating disorders, and sleep disorders, are less common than anxiety/depression, but have an estimated prevalence of 1.3%-3.1% among adults in the United States, he said.
What Does the New Study Add?
In the new review by Dr. Pawlik and colleagues, published in the Journal of the American College of Surgeons (Katayama ES. J Am Coll Surg. 2024 Feb 29. doi: 2024. 10.1097/XCS.0000000000000954), BHDs were defined as substance abuse, eating disorders, or sleep disorders, which had not been the focus of previous studies. The researchers reviewed data from 694,836 adult patients with lung, esophageal, gastric, liver, pancreatic, or colorectal cancer between 2018-2021 using the Medicare Standard Analytic files. A total of 46,719 patients (6.7%) had at least one BHD.
Overall, patients with a BHD were significantly less likely than those without a BHD to undergo surgical resection (20.3% vs. 23.4%). Patients with a BHD also had significantly worse long-term postoperative survival than those without BHDs (median 37.1 months vs. 46.6 months) and significantly higher in-hospital costs ($17,432 vs. 16,159, P less than .001 for all).
Among patients who underwent cancer surgery, the odds of any complication were significantly higher for those with a BHD compared to those with no BHD (odds ratio 1.32), as were the odds of a prolonged length of stay (OR 1.67) and 90-day readmission (OR 1.57).
Dr. Pawlik said he was surprised by several of the findings, including that 1 in 15 Medicare beneficiaries had a BHD diagnosis, “with male sex and minority racial status, as well as higher social vulnerability, being associated with a higher prevalence of BHD.”
Also, the independent association of having a BHD with 30%-50% higher odds of a complication, prolonged length of stay, and 90-day readmission was higher than Dr. Pawlik had anticipated.
Why Do Patients With BHDs Have Fewer Surgeries and Worse Outcomes?
The reasons for this association were likely multifactorial and may reflect the greater burden of medical comorbidity and chronic illness in many patients with BHDs because of maladaptive lifestyles or poor nutrition status, Dr. Pawlik said.
“Patients with BHDs also likely face barriers to accessing care, which was noted particularly among patients with BHDs who lived in socially vulnerable areas,” he said. BHD patients also were more likely to be treated at low-volume rather than high-volume hospitals, “which undoubtedly contributed in part to worse outcomes in this cohort of patients,” he added.
What Can Oncologists Do to Help?
The take-home message for clinicians is that BHDs are linked to worse surgical outcomes and higher health care costs in cancer patients, Dr. Pawlik said in an interview.
“Enhanced accessibility to behavioral healthcare, as well as comprehensive policy reform related to mental health services are needed to improve care of patients with BHDs,” he said. “For example, implementing psychiatry compensation programs may encourage practice in vulnerable areas,” he said.
Other strategies include a following a collaborative care model involving mental health professionals working in tandem with primary care and mid-level practitioners and increasing use and establishment of telehealth systems to improve patient access to BHD services, he said.
What Are the Limitations?
The study by Dr. Pawlik and colleagues was limited by several factors, including the lack of data on younger patients and the full range of BHDs, as well as underreporting of BHDs and the high copays for mental health care, the researchers noted. However, the results suggest that concomitant BHDs are associated with worse cancer outcomes and higher in-hospital costs, and illustrate the need to screen for and target these conditions in cancer patients, the researchers concluded.
What Are the Next Steps for Research?
The current study involved Medicare beneficiaries aged 65 years or older, and more research is needed to investigate the impact of BHDs among younger cancer patients in whom the prevalence may be higher and the impact of BHDs may be different, Dr. Pawlik said in an interview. In addition, the analysis of BHDs as a composite of substance abuse, eating disorders, and sleep disorders (because the numbers were too small to break out data for each disorder, separately) prevented investigation of potential differences and unique challenges faced by distinct subpopulations of BHD patients, he said.
“Future studies should examine the individual impact of substance abuse, eating disorders, and sleep disorders on access to surgery, as well as the potential different impact that each one of these different BHDs may have on postoperative outcomes,” Dr. Pawlik suggested.
The study was supported by The Ohio State University College of Medicine Roessler Summer Research Scholarship. The researchers had no financial conflicts to disclose.
FROM JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
Study: Healthy Plant-Based Diets Do Not Raise Hip Fracture Risk
Long-term adherence to a plant-based diet was not tied to a greater risk of hip fracture and some plant-based regimens may actually reduce the risk, a large cohort study of postmenopausal women in the United States suggested.
Not all plant-centered regimens are healthful, however, and this study factored dietary quality into risk.
Writing in JAMA Network Open, the study authors compared the lowest to highest quintiles of Plant-Based Diet Index scores. They found the most recent intake of a healthy plant-based diet (hPDI) to be associated with a somewhat lower (21%) risk of fracture while the most recent intake of its unhealthy counterpart (uPDI) was linked to a somewhat higher (28%) risk.
“In addition, higher baseline scores in the uPDI were associated with higher risk of hip fracture,” wrote the researchers, led by Mercedes Sotos Prieto, PhD, a nutritional epidemiologist in the Department of Preventive Medicine and Public Health at the Autonomous University of Madrid.
Plant-based diets, characterized by higher consumption of plant foods and lower or no intake of animal foods, have raised concerns about their potential harm to bone health. In a recent meta-analysis, vegetarians, but particularly vegans with no consumption of any animal food, had a higher fracture risk and lower bone mineral density compared with omnivores.
Another study found that compared with meat eaters, fish eaters and vegetarians had a higher risk of hip fractures. These analyses, however, did not assess the quality of the plant-based diets.
“We hypothesized that the differences in the quality of the plant-based diets — whole grains, fruits, and vegetables vs refined carbohydrates or snacks, which are both plant-based but very different, would be important in the association for the risk of hip fracture,” Dr. Sotos Prieto said in an interview.
Study details
Her study drew on data from 70,285 postmenopausal White women who were in the US Nurses’ Health Study from 1984 through 2014; data were analyzed from Jan. 1 to July 31, 2023.
The mean age of the nurses was 54.92 years, and 2038 cases of hip fracture were reported during the study over as long as 30 years of follow-up.
Healthy plant foods included whole grains, fruits, vegetables, nuts, legumes, vegetable oils, and tea or coffee and received positive scores, whereas less healthy plant foods such as fruit juices, sweetened beverages, refined grains, potatoes, sweets, or desserts and animal foods received reversed scores. Dietary and lifestyle information was collected by self-reported questionnaires.
Individuals with higher hPDI scores were leaner, more physically active, less likely to be smokers, and more likely to use vitamin and calcium supplements. Not surprisingly, they also had higher intakes of dietary calcium and healthy plant foods and had lower intake of less healthy plant foods. “It’s plausible that reverse causation may account for the risk associations, as individuals with underlying health conditions that predisposed them to higher fracture risk may have changed their diet,” Dr. Sotos Prieto said. “In addition, baseline diet may reflect diet early on, which could be an important predictor of bone mineral density when there was more active bone turnover.”
Lack of information precluded adjustment for the use of anti-osteoporotic medication.
Neither the hPDI, with a hazard ratio (HR) for highest vs lowest quintile of 0.97 (95% confidence interval, 0.83-1.14) nor the uPDI, with an HR for highest vs lowest quintile of 1.02 (95% CI, 0.87-1.20) for diet adherence over the long term was associated with hip fracture risk.
For recent dietary intake in the highest vs lowest quintiles, however, the hPDI was associated with a 21% lower risk of hip fracture: HR, 0.79 (95% CI, 0.68-0.92; P = .02 for trend). In contrast, the uPDI was associated with a 28% higher risk: HR, 1.28 (95% CI, 1.09-1.51; P = .008 for trend).
Future studies in other populations are needed to confirm the results and enhance their generalizability, Dr. Sotos Prieto said. “Investigating the temporal dynamics of dietary patterns and their effects by examining how recent dietary changes may impact health outcomes over different timeframes is important.” In the meantime, people wishing to follow a plant-based diet should make sure it features high-quality foods.
This work was supported by Instituto de Salud Carlos III, State Secretary of Research, Development and Innovation of Spain, and the European Research Funds and European Social Fund, the Agencia Estatal de Investigación, the National Institutes of Health, and a Ramón y Cajal contract from the Ministry of Science, Innovation, and Universities. A coauthor reported a patent pending. No other disclosures were reported.
Long-term adherence to a plant-based diet was not tied to a greater risk of hip fracture and some plant-based regimens may actually reduce the risk, a large cohort study of postmenopausal women in the United States suggested.
Not all plant-centered regimens are healthful, however, and this study factored dietary quality into risk.
Writing in JAMA Network Open, the study authors compared the lowest to highest quintiles of Plant-Based Diet Index scores. They found the most recent intake of a healthy plant-based diet (hPDI) to be associated with a somewhat lower (21%) risk of fracture while the most recent intake of its unhealthy counterpart (uPDI) was linked to a somewhat higher (28%) risk.
“In addition, higher baseline scores in the uPDI were associated with higher risk of hip fracture,” wrote the researchers, led by Mercedes Sotos Prieto, PhD, a nutritional epidemiologist in the Department of Preventive Medicine and Public Health at the Autonomous University of Madrid.
Plant-based diets, characterized by higher consumption of plant foods and lower or no intake of animal foods, have raised concerns about their potential harm to bone health. In a recent meta-analysis, vegetarians, but particularly vegans with no consumption of any animal food, had a higher fracture risk and lower bone mineral density compared with omnivores.
Another study found that compared with meat eaters, fish eaters and vegetarians had a higher risk of hip fractures. These analyses, however, did not assess the quality of the plant-based diets.
“We hypothesized that the differences in the quality of the plant-based diets — whole grains, fruits, and vegetables vs refined carbohydrates or snacks, which are both plant-based but very different, would be important in the association for the risk of hip fracture,” Dr. Sotos Prieto said in an interview.
Study details
Her study drew on data from 70,285 postmenopausal White women who were in the US Nurses’ Health Study from 1984 through 2014; data were analyzed from Jan. 1 to July 31, 2023.
The mean age of the nurses was 54.92 years, and 2038 cases of hip fracture were reported during the study over as long as 30 years of follow-up.
Healthy plant foods included whole grains, fruits, vegetables, nuts, legumes, vegetable oils, and tea or coffee and received positive scores, whereas less healthy plant foods such as fruit juices, sweetened beverages, refined grains, potatoes, sweets, or desserts and animal foods received reversed scores. Dietary and lifestyle information was collected by self-reported questionnaires.
Individuals with higher hPDI scores were leaner, more physically active, less likely to be smokers, and more likely to use vitamin and calcium supplements. Not surprisingly, they also had higher intakes of dietary calcium and healthy plant foods and had lower intake of less healthy plant foods. “It’s plausible that reverse causation may account for the risk associations, as individuals with underlying health conditions that predisposed them to higher fracture risk may have changed their diet,” Dr. Sotos Prieto said. “In addition, baseline diet may reflect diet early on, which could be an important predictor of bone mineral density when there was more active bone turnover.”
Lack of information precluded adjustment for the use of anti-osteoporotic medication.
Neither the hPDI, with a hazard ratio (HR) for highest vs lowest quintile of 0.97 (95% confidence interval, 0.83-1.14) nor the uPDI, with an HR for highest vs lowest quintile of 1.02 (95% CI, 0.87-1.20) for diet adherence over the long term was associated with hip fracture risk.
For recent dietary intake in the highest vs lowest quintiles, however, the hPDI was associated with a 21% lower risk of hip fracture: HR, 0.79 (95% CI, 0.68-0.92; P = .02 for trend). In contrast, the uPDI was associated with a 28% higher risk: HR, 1.28 (95% CI, 1.09-1.51; P = .008 for trend).
Future studies in other populations are needed to confirm the results and enhance their generalizability, Dr. Sotos Prieto said. “Investigating the temporal dynamics of dietary patterns and their effects by examining how recent dietary changes may impact health outcomes over different timeframes is important.” In the meantime, people wishing to follow a plant-based diet should make sure it features high-quality foods.
This work was supported by Instituto de Salud Carlos III, State Secretary of Research, Development and Innovation of Spain, and the European Research Funds and European Social Fund, the Agencia Estatal de Investigación, the National Institutes of Health, and a Ramón y Cajal contract from the Ministry of Science, Innovation, and Universities. A coauthor reported a patent pending. No other disclosures were reported.
Long-term adherence to a plant-based diet was not tied to a greater risk of hip fracture and some plant-based regimens may actually reduce the risk, a large cohort study of postmenopausal women in the United States suggested.
Not all plant-centered regimens are healthful, however, and this study factored dietary quality into risk.
Writing in JAMA Network Open, the study authors compared the lowest to highest quintiles of Plant-Based Diet Index scores. They found the most recent intake of a healthy plant-based diet (hPDI) to be associated with a somewhat lower (21%) risk of fracture while the most recent intake of its unhealthy counterpart (uPDI) was linked to a somewhat higher (28%) risk.
“In addition, higher baseline scores in the uPDI were associated with higher risk of hip fracture,” wrote the researchers, led by Mercedes Sotos Prieto, PhD, a nutritional epidemiologist in the Department of Preventive Medicine and Public Health at the Autonomous University of Madrid.
Plant-based diets, characterized by higher consumption of plant foods and lower or no intake of animal foods, have raised concerns about their potential harm to bone health. In a recent meta-analysis, vegetarians, but particularly vegans with no consumption of any animal food, had a higher fracture risk and lower bone mineral density compared with omnivores.
Another study found that compared with meat eaters, fish eaters and vegetarians had a higher risk of hip fractures. These analyses, however, did not assess the quality of the plant-based diets.
“We hypothesized that the differences in the quality of the plant-based diets — whole grains, fruits, and vegetables vs refined carbohydrates or snacks, which are both plant-based but very different, would be important in the association for the risk of hip fracture,” Dr. Sotos Prieto said in an interview.
Study details
Her study drew on data from 70,285 postmenopausal White women who were in the US Nurses’ Health Study from 1984 through 2014; data were analyzed from Jan. 1 to July 31, 2023.
The mean age of the nurses was 54.92 years, and 2038 cases of hip fracture were reported during the study over as long as 30 years of follow-up.
Healthy plant foods included whole grains, fruits, vegetables, nuts, legumes, vegetable oils, and tea or coffee and received positive scores, whereas less healthy plant foods such as fruit juices, sweetened beverages, refined grains, potatoes, sweets, or desserts and animal foods received reversed scores. Dietary and lifestyle information was collected by self-reported questionnaires.
Individuals with higher hPDI scores were leaner, more physically active, less likely to be smokers, and more likely to use vitamin and calcium supplements. Not surprisingly, they also had higher intakes of dietary calcium and healthy plant foods and had lower intake of less healthy plant foods. “It’s plausible that reverse causation may account for the risk associations, as individuals with underlying health conditions that predisposed them to higher fracture risk may have changed their diet,” Dr. Sotos Prieto said. “In addition, baseline diet may reflect diet early on, which could be an important predictor of bone mineral density when there was more active bone turnover.”
Lack of information precluded adjustment for the use of anti-osteoporotic medication.
Neither the hPDI, with a hazard ratio (HR) for highest vs lowest quintile of 0.97 (95% confidence interval, 0.83-1.14) nor the uPDI, with an HR for highest vs lowest quintile of 1.02 (95% CI, 0.87-1.20) for diet adherence over the long term was associated with hip fracture risk.
For recent dietary intake in the highest vs lowest quintiles, however, the hPDI was associated with a 21% lower risk of hip fracture: HR, 0.79 (95% CI, 0.68-0.92; P = .02 for trend). In contrast, the uPDI was associated with a 28% higher risk: HR, 1.28 (95% CI, 1.09-1.51; P = .008 for trend).
Future studies in other populations are needed to confirm the results and enhance their generalizability, Dr. Sotos Prieto said. “Investigating the temporal dynamics of dietary patterns and their effects by examining how recent dietary changes may impact health outcomes over different timeframes is important.” In the meantime, people wishing to follow a plant-based diet should make sure it features high-quality foods.
This work was supported by Instituto de Salud Carlos III, State Secretary of Research, Development and Innovation of Spain, and the European Research Funds and European Social Fund, the Agencia Estatal de Investigación, the National Institutes of Health, and a Ramón y Cajal contract from the Ministry of Science, Innovation, and Universities. A coauthor reported a patent pending. No other disclosures were reported.
FROM JAMA NETWORK OPEN
SUID and a Cardboard Box
In this February’s issue of the journal Pediatrics there is an interesting paper that explores the demographics and sleep environments of the more than 8000 sudden unexpected infant death (SUID) victims who died in the United States between 2011 and 2020. The authors’ broad conclusion was “Most SUID, regardless of sleep location, had multiple unsafe sleep factors present demonstrating the need for comprehensive sleep counseling for every family at every encounter.”
From the perspective of a former busy primary care physician I shudder when I read a statement this broad because it doesn’t acknowledge the realities of my professional life. A sentence containing “comprehensive” and two “every’s” won’t be taken seriously by most of the practicing pediatricians I know. However, there is an abundance of information generated by these investigators that could help a pediatrician target his advice to the individual families in his practice without having to resort to time-consuming comprehensive counseling, which is likely to sound like just so much chatter to families overwhelmed by the new challenge of raising a child.
For example, nearly 60% of SUID cases were sharing a sleep surface when they died, and surface-sharing infants were more likely to not have a crib in their home. It seems to me that one should start with the simple question, “Do your have a crib in your home ... in all the homes where the baby will sleep?” And, it should be asked in the hospital prior to discharge.
In 1993, our second-born daughter went home from a teaching hospital in a cardboard box. So did all of her nursery mates. It was decorated with a stork motif and had served as her bassinet. Since early in the last century, families in Finland have been offered a similar box filled with baby supplies. Shrinkflation has caused a scale back in its contents, but the box itself has remained as a safe and inexpensive sleep surface for income-challenged families.
Many babies in this country are put to sleep in a variety of places as they are shuttled around to where the inexpensive childcare is available. Offering families as many boxes as they need may avoid the tragedy of their infant smothering on Aunt Louise’s couch or Cousin Martha’s bed littered with pillows. This is particularly important in a family with multiples (twins, triplets, etc.) who are overrepresented in the SUID population. The opening question about crib availability is likely to alert the healthcare provider to a social situation dominated by poverty that may include lower parental education and a higher likelihood of residential insecurity, all of which are associated with surface-sharing.
The authors observe “surface-sharing in and of itself may not be what caregiver education should focus on.” A simple cardboard box, however, is not a sleep surface likely to be shared with an adult.
For the families for whom surface-sharing is a choice and not a necessity, the investigators encourage us to engage families on their motivation for surface-sharing. This is a discussion that clinicians should be initiating, regardless of our concern of SUID prevention, by simply asking “How are you and your baby sleeping?” Is the baby being nursed to sleep? Where? While the authors acknowledge that their raw data did not allow them to make any observations on a relationship between surface-sharing and breastfeeding, my anecdotal observations have found an unfortunate number of mothers who have become human pacifiers for their babies and are co-sleeping. This association can result in a sleep-deprived parent(s) with unhealthy consequences. Although it can be difficult to uncouple breastfeeding from settling, early intervention triggered by asking a simple question can improve the chances of resolution.
Although I may quibble with the wording of authors’ final conclusion, this is an excellent paper worth looking at. SUID while infrequent and for the most part still mysterious is a tragedy that we should be able to prevent.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
In this February’s issue of the journal Pediatrics there is an interesting paper that explores the demographics and sleep environments of the more than 8000 sudden unexpected infant death (SUID) victims who died in the United States between 2011 and 2020. The authors’ broad conclusion was “Most SUID, regardless of sleep location, had multiple unsafe sleep factors present demonstrating the need for comprehensive sleep counseling for every family at every encounter.”
From the perspective of a former busy primary care physician I shudder when I read a statement this broad because it doesn’t acknowledge the realities of my professional life. A sentence containing “comprehensive” and two “every’s” won’t be taken seriously by most of the practicing pediatricians I know. However, there is an abundance of information generated by these investigators that could help a pediatrician target his advice to the individual families in his practice without having to resort to time-consuming comprehensive counseling, which is likely to sound like just so much chatter to families overwhelmed by the new challenge of raising a child.
For example, nearly 60% of SUID cases were sharing a sleep surface when they died, and surface-sharing infants were more likely to not have a crib in their home. It seems to me that one should start with the simple question, “Do your have a crib in your home ... in all the homes where the baby will sleep?” And, it should be asked in the hospital prior to discharge.
In 1993, our second-born daughter went home from a teaching hospital in a cardboard box. So did all of her nursery mates. It was decorated with a stork motif and had served as her bassinet. Since early in the last century, families in Finland have been offered a similar box filled with baby supplies. Shrinkflation has caused a scale back in its contents, but the box itself has remained as a safe and inexpensive sleep surface for income-challenged families.
Many babies in this country are put to sleep in a variety of places as they are shuttled around to where the inexpensive childcare is available. Offering families as many boxes as they need may avoid the tragedy of their infant smothering on Aunt Louise’s couch or Cousin Martha’s bed littered with pillows. This is particularly important in a family with multiples (twins, triplets, etc.) who are overrepresented in the SUID population. The opening question about crib availability is likely to alert the healthcare provider to a social situation dominated by poverty that may include lower parental education and a higher likelihood of residential insecurity, all of which are associated with surface-sharing.
The authors observe “surface-sharing in and of itself may not be what caregiver education should focus on.” A simple cardboard box, however, is not a sleep surface likely to be shared with an adult.
For the families for whom surface-sharing is a choice and not a necessity, the investigators encourage us to engage families on their motivation for surface-sharing. This is a discussion that clinicians should be initiating, regardless of our concern of SUID prevention, by simply asking “How are you and your baby sleeping?” Is the baby being nursed to sleep? Where? While the authors acknowledge that their raw data did not allow them to make any observations on a relationship between surface-sharing and breastfeeding, my anecdotal observations have found an unfortunate number of mothers who have become human pacifiers for their babies and are co-sleeping. This association can result in a sleep-deprived parent(s) with unhealthy consequences. Although it can be difficult to uncouple breastfeeding from settling, early intervention triggered by asking a simple question can improve the chances of resolution.
Although I may quibble with the wording of authors’ final conclusion, this is an excellent paper worth looking at. SUID while infrequent and for the most part still mysterious is a tragedy that we should be able to prevent.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
In this February’s issue of the journal Pediatrics there is an interesting paper that explores the demographics and sleep environments of the more than 8000 sudden unexpected infant death (SUID) victims who died in the United States between 2011 and 2020. The authors’ broad conclusion was “Most SUID, regardless of sleep location, had multiple unsafe sleep factors present demonstrating the need for comprehensive sleep counseling for every family at every encounter.”
From the perspective of a former busy primary care physician I shudder when I read a statement this broad because it doesn’t acknowledge the realities of my professional life. A sentence containing “comprehensive” and two “every’s” won’t be taken seriously by most of the practicing pediatricians I know. However, there is an abundance of information generated by these investigators that could help a pediatrician target his advice to the individual families in his practice without having to resort to time-consuming comprehensive counseling, which is likely to sound like just so much chatter to families overwhelmed by the new challenge of raising a child.
For example, nearly 60% of SUID cases were sharing a sleep surface when they died, and surface-sharing infants were more likely to not have a crib in their home. It seems to me that one should start with the simple question, “Do your have a crib in your home ... in all the homes where the baby will sleep?” And, it should be asked in the hospital prior to discharge.
In 1993, our second-born daughter went home from a teaching hospital in a cardboard box. So did all of her nursery mates. It was decorated with a stork motif and had served as her bassinet. Since early in the last century, families in Finland have been offered a similar box filled with baby supplies. Shrinkflation has caused a scale back in its contents, but the box itself has remained as a safe and inexpensive sleep surface for income-challenged families.
Many babies in this country are put to sleep in a variety of places as they are shuttled around to where the inexpensive childcare is available. Offering families as many boxes as they need may avoid the tragedy of their infant smothering on Aunt Louise’s couch or Cousin Martha’s bed littered with pillows. This is particularly important in a family with multiples (twins, triplets, etc.) who are overrepresented in the SUID population. The opening question about crib availability is likely to alert the healthcare provider to a social situation dominated by poverty that may include lower parental education and a higher likelihood of residential insecurity, all of which are associated with surface-sharing.
The authors observe “surface-sharing in and of itself may not be what caregiver education should focus on.” A simple cardboard box, however, is not a sleep surface likely to be shared with an adult.
For the families for whom surface-sharing is a choice and not a necessity, the investigators encourage us to engage families on their motivation for surface-sharing. This is a discussion that clinicians should be initiating, regardless of our concern of SUID prevention, by simply asking “How are you and your baby sleeping?” Is the baby being nursed to sleep? Where? While the authors acknowledge that their raw data did not allow them to make any observations on a relationship between surface-sharing and breastfeeding, my anecdotal observations have found an unfortunate number of mothers who have become human pacifiers for their babies and are co-sleeping. This association can result in a sleep-deprived parent(s) with unhealthy consequences. Although it can be difficult to uncouple breastfeeding from settling, early intervention triggered by asking a simple question can improve the chances of resolution.
Although I may quibble with the wording of authors’ final conclusion, this is an excellent paper worth looking at. SUID while infrequent and for the most part still mysterious is a tragedy that we should be able to prevent.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].
National Rapid Genome Testing Program Benefits NICU Care
TOPLINE:
A national study in Israel demonstrates the feasibility and diagnostic benefits of rapid trio genome sequencing in critically ill neonates.
METHODOLOGY:
- Researchers conducted a prospective, multicenter cohort study from October 2021 to December 2022, involving all Israeli medical genetics institutes and neonatal intensive care units.
- A total of 130 critically ill neonates suspected of having a genetic disorder were enrolled, with rapid genome sequencing results expected within 10 days.
TAKEAWAY:
- Rapid trio genome sequencing diagnosed 50% of the neonates with disease-causing variants, including 12 chromosomal and 52 monogenic conditions.
- Another 11% had variants of unknown significance that were suspected to be disease-causing, and 1% had a novel gene suspected of causing disease.
- The mean turnaround time for the rapid reports was 7 days, demonstrating the feasibility of implementing rapid genome sequencing in a national healthcare setting, the researchers said.
- Genomic testing led to a change in clinical management for 22% of the neonates, which shows the clinical utility of this approach to diagnosis, they said.
IN PRACTICE:
Genetic testing may identify patients who are candidates for precision medical treatment and inform family planning, which is “critical for families with a severely affected or deceased child,” the study authors wrote.
SOURCE:
The corresponding author for the study was Daphna Marom, MD, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. It was published online on February 22, 2024, in JAMA Network Open.
LIMITATIONS:
The study’s reliance on voluntary participation may have introduced referral bias, potentially affecting the diagnostic rates. The long-term impact of diagnosis on survival, growth, and development remains to be evaluated. Bioinformatics tools have limitations, as shown by the missed detection of maternal uniparental disomy in one case of a hypotonic infant with Prader-Willi syndrome, the researchers noted. Clinical judgment is still essential, they said.
DISCLOSURES:
The study was sponsored by a collaboration between the Israeli Ministry of Health, Illumina, and the Genomics Center at the Tel Aviv Sourasky Medical Center. Illumina provided reagents, bioinformatics tools, and editorial assistance. Study authors disclosed financial ties to Illumina.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.
TOPLINE:
A national study in Israel demonstrates the feasibility and diagnostic benefits of rapid trio genome sequencing in critically ill neonates.
METHODOLOGY:
- Researchers conducted a prospective, multicenter cohort study from October 2021 to December 2022, involving all Israeli medical genetics institutes and neonatal intensive care units.
- A total of 130 critically ill neonates suspected of having a genetic disorder were enrolled, with rapid genome sequencing results expected within 10 days.
TAKEAWAY:
- Rapid trio genome sequencing diagnosed 50% of the neonates with disease-causing variants, including 12 chromosomal and 52 monogenic conditions.
- Another 11% had variants of unknown significance that were suspected to be disease-causing, and 1% had a novel gene suspected of causing disease.
- The mean turnaround time for the rapid reports was 7 days, demonstrating the feasibility of implementing rapid genome sequencing in a national healthcare setting, the researchers said.
- Genomic testing led to a change in clinical management for 22% of the neonates, which shows the clinical utility of this approach to diagnosis, they said.
IN PRACTICE:
Genetic testing may identify patients who are candidates for precision medical treatment and inform family planning, which is “critical for families with a severely affected or deceased child,” the study authors wrote.
SOURCE:
The corresponding author for the study was Daphna Marom, MD, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. It was published online on February 22, 2024, in JAMA Network Open.
LIMITATIONS:
The study’s reliance on voluntary participation may have introduced referral bias, potentially affecting the diagnostic rates. The long-term impact of diagnosis on survival, growth, and development remains to be evaluated. Bioinformatics tools have limitations, as shown by the missed detection of maternal uniparental disomy in one case of a hypotonic infant with Prader-Willi syndrome, the researchers noted. Clinical judgment is still essential, they said.
DISCLOSURES:
The study was sponsored by a collaboration between the Israeli Ministry of Health, Illumina, and the Genomics Center at the Tel Aviv Sourasky Medical Center. Illumina provided reagents, bioinformatics tools, and editorial assistance. Study authors disclosed financial ties to Illumina.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.
TOPLINE:
A national study in Israel demonstrates the feasibility and diagnostic benefits of rapid trio genome sequencing in critically ill neonates.
METHODOLOGY:
- Researchers conducted a prospective, multicenter cohort study from October 2021 to December 2022, involving all Israeli medical genetics institutes and neonatal intensive care units.
- A total of 130 critically ill neonates suspected of having a genetic disorder were enrolled, with rapid genome sequencing results expected within 10 days.
TAKEAWAY:
- Rapid trio genome sequencing diagnosed 50% of the neonates with disease-causing variants, including 12 chromosomal and 52 monogenic conditions.
- Another 11% had variants of unknown significance that were suspected to be disease-causing, and 1% had a novel gene suspected of causing disease.
- The mean turnaround time for the rapid reports was 7 days, demonstrating the feasibility of implementing rapid genome sequencing in a national healthcare setting, the researchers said.
- Genomic testing led to a change in clinical management for 22% of the neonates, which shows the clinical utility of this approach to diagnosis, they said.
IN PRACTICE:
Genetic testing may identify patients who are candidates for precision medical treatment and inform family planning, which is “critical for families with a severely affected or deceased child,” the study authors wrote.
SOURCE:
The corresponding author for the study was Daphna Marom, MD, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. It was published online on February 22, 2024, in JAMA Network Open.
LIMITATIONS:
The study’s reliance on voluntary participation may have introduced referral bias, potentially affecting the diagnostic rates. The long-term impact of diagnosis on survival, growth, and development remains to be evaluated. Bioinformatics tools have limitations, as shown by the missed detection of maternal uniparental disomy in one case of a hypotonic infant with Prader-Willi syndrome, the researchers noted. Clinical judgment is still essential, they said.
DISCLOSURES:
The study was sponsored by a collaboration between the Israeli Ministry of Health, Illumina, and the Genomics Center at the Tel Aviv Sourasky Medical Center. Illumina provided reagents, bioinformatics tools, and editorial assistance. Study authors disclosed financial ties to Illumina.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.
Dupilumab Earns FDA Priority Review for Add-On COPD Care
The Food and Drug Administration (FDA) has accepted an application for Priority Review for dupilumab as an add-on therapy for adults with uncontrolled chronic obstructive pulmonary disease (COPD), according to a press release from manufacturer Regeneron.
If approved, dupilumab would be the only biologic option for COPD and the first new treatment option in approximately 10 years, according to the company.
Dupilumab works by blocking signaling by the interleukin (IL) 4 and IL-13 pathways, and Regeneron’s development program focuses on a population of COPD patients who also have type 2 inflammation.
The supplemental Biologics License Application was based on data from a pair of clinical trials in the company’s phase 3 COPD clinical research program.
In the studies, known as BOREAS and NOTUS, adults with uncontrolled COPD and type 2 inflammation who were current or former smokers were randomized to 300 mg of subcutaneous dupilumab or placebo once every 2 weeks. Type 2 inflammation was defined as blood eosinophil counts of at least 300 cells per microliter.
All patients received standard-of-care therapy. The primary endpoint of reduced annualized moderate or severe acute COPD exacerbations was 30% and 34% greater in the dupilumab groups in the two studies, respectively, compared with the placebo groups, and the significant differences in improvement persisted at 52 weeks.
Safety data were similar to previous studies of dupilumab for its approved indications. The most common adverse events seen in 5% or more of dupilumab patients compared with placebo patients across the two studies included back pain, COVID-19, diarrhea, headache, and nasopharyngitis.
Priority Review status is granted to applications for approval for therapies that may offer significant improvements, although the therapies are still in clinical development. The target action date for the FDA decision is June 27, 2024, and regulatory submissions for dupilumab for COPD are under consideration in China and Europe in addition to the United States, according to the company.
A version of this article appeared on Medscape.com.
The Food and Drug Administration (FDA) has accepted an application for Priority Review for dupilumab as an add-on therapy for adults with uncontrolled chronic obstructive pulmonary disease (COPD), according to a press release from manufacturer Regeneron.
If approved, dupilumab would be the only biologic option for COPD and the first new treatment option in approximately 10 years, according to the company.
Dupilumab works by blocking signaling by the interleukin (IL) 4 and IL-13 pathways, and Regeneron’s development program focuses on a population of COPD patients who also have type 2 inflammation.
The supplemental Biologics License Application was based on data from a pair of clinical trials in the company’s phase 3 COPD clinical research program.
In the studies, known as BOREAS and NOTUS, adults with uncontrolled COPD and type 2 inflammation who were current or former smokers were randomized to 300 mg of subcutaneous dupilumab or placebo once every 2 weeks. Type 2 inflammation was defined as blood eosinophil counts of at least 300 cells per microliter.
All patients received standard-of-care therapy. The primary endpoint of reduced annualized moderate or severe acute COPD exacerbations was 30% and 34% greater in the dupilumab groups in the two studies, respectively, compared with the placebo groups, and the significant differences in improvement persisted at 52 weeks.
Safety data were similar to previous studies of dupilumab for its approved indications. The most common adverse events seen in 5% or more of dupilumab patients compared with placebo patients across the two studies included back pain, COVID-19, diarrhea, headache, and nasopharyngitis.
Priority Review status is granted to applications for approval for therapies that may offer significant improvements, although the therapies are still in clinical development. The target action date for the FDA decision is June 27, 2024, and regulatory submissions for dupilumab for COPD are under consideration in China and Europe in addition to the United States, according to the company.
A version of this article appeared on Medscape.com.
The Food and Drug Administration (FDA) has accepted an application for Priority Review for dupilumab as an add-on therapy for adults with uncontrolled chronic obstructive pulmonary disease (COPD), according to a press release from manufacturer Regeneron.
If approved, dupilumab would be the only biologic option for COPD and the first new treatment option in approximately 10 years, according to the company.
Dupilumab works by blocking signaling by the interleukin (IL) 4 and IL-13 pathways, and Regeneron’s development program focuses on a population of COPD patients who also have type 2 inflammation.
The supplemental Biologics License Application was based on data from a pair of clinical trials in the company’s phase 3 COPD clinical research program.
In the studies, known as BOREAS and NOTUS, adults with uncontrolled COPD and type 2 inflammation who were current or former smokers were randomized to 300 mg of subcutaneous dupilumab or placebo once every 2 weeks. Type 2 inflammation was defined as blood eosinophil counts of at least 300 cells per microliter.
All patients received standard-of-care therapy. The primary endpoint of reduced annualized moderate or severe acute COPD exacerbations was 30% and 34% greater in the dupilumab groups in the two studies, respectively, compared with the placebo groups, and the significant differences in improvement persisted at 52 weeks.
Safety data were similar to previous studies of dupilumab for its approved indications. The most common adverse events seen in 5% or more of dupilumab patients compared with placebo patients across the two studies included back pain, COVID-19, diarrhea, headache, and nasopharyngitis.
Priority Review status is granted to applications for approval for therapies that may offer significant improvements, although the therapies are still in clinical development. The target action date for the FDA decision is June 27, 2024, and regulatory submissions for dupilumab for COPD are under consideration in China and Europe in addition to the United States, according to the company.
A version of this article appeared on Medscape.com.
FDA Clears Medical Grade Over-the-Counter Pulse Oximeter
The MightySat Medical, an over-the-counter medical fingertip pulse oximeter, has received clearance from the US Food and Drug Administration (FDA) for use without a prescription, according to a press release from manufacturer Masimo.
The device is the first medical fingertip pulse oximeter available directly to consumers without a prescription that includes the same technology used by many hospitals, according to the company.
According to the FDA, home pulse oximeters are currently generally of two classes: hospital-grade prescription devices which have been vetted for accuracy through clinical trials, and over-the-counter devices which are sold direct to consumers but often estimate oxygen saturation. FDA communication on pulse oximeter accuracy states "OTC oximeters that are sold as either general wellness or sporting/aviation products are not intended for medical purposes, so they do not undergo FDA review."
Pulse oximeter use is important for patients diagnosed with breathing problems or lung diseases such as asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, lung cancer, flu, pneumonia, or COVID-19 to collect accurate data on arterial blood oxygen saturation that they can share with their healthcare providers, according to the company. Patients with cardiac conditions, including pulmonary hypertension and heart failure may also benefit from pulse oximeter monitoring.
However, challenges of pulse oximeter use include measuring accuracy when patients are moving, measuring patients with poor circulation, and measuring patients with cool, thick, or darker skin. The MightySat Medical is designed to provide reliable measures of oxygen saturation and pulse rate across all patient groups, the manufacturers wrote in the press release.
Asked for additional comment, Diego J. Maselli, MD, FCCP, Professor and Chief in the division of Pulmonary Diseases and Critical Care at UT Health at San Antonio, noted, "Over the past decades, there has been an increased interest in home monitoring of medical conditions, particulrly with the development of more portable and accessible technology."
"This was heightended by the COVID-19 pandemic where telemedicine was frequently required as a means of delivering care," Dr. Maselli continued. "One of the important characteristics to monitor was the oxgen saturation in patients that had an active COVID-19 infection as it would dictate management and was part of the protocol for monitoring the clinical course of infection. Because of this need, many companies developed portable pulse oximeters for home use. This resulted in widespread use of pulse oximeters at home and other places outside clinic or hospital."
Other over-the-counter pulse oximeters that are not cleared by the FDA may create confusion among patients about the accuracy of their measurements, according to the company.
Dr. Maselli also commented that pulse oximeters' value can vary. "Unfortunately, these devices vary in quality and reliability and patients may not be fully aware of this. Most recently, the FDA approved a hospital-grade pulse oximeter that requires no prescription. This device may provide a more accurate reading in a wide range of clinical situations outside the healthcare setting. Patients should be aware that there are different grades of pulse oximeter before selecting one for home use. In addition, patients should work closely with their providers to better select the monitoring modaility that best fits their clinical situation," he said.
MightySat Medical is indicated for individuals aged 18 years and older who are well or poorly perfused under no motion conditions and is not intended as a diagnostic or screening tool for lung disease, according to the release. Treatment decisions based on data from the device should be made only in consultation with a healthcare provider, the company said. Dr. Maselli serves as a member of the CHEST Physician editorial board.
The FDA’s website offers further guidance related to at-home pulse oximeter use, with recommendations and limitations, as well as information on initiatives to ensure accurate and equitable pulse oximetry for all patients.
A version of this article appeared on Medscape.com.
The MightySat Medical, an over-the-counter medical fingertip pulse oximeter, has received clearance from the US Food and Drug Administration (FDA) for use without a prescription, according to a press release from manufacturer Masimo.
The device is the first medical fingertip pulse oximeter available directly to consumers without a prescription that includes the same technology used by many hospitals, according to the company.
According to the FDA, home pulse oximeters are currently generally of two classes: hospital-grade prescription devices which have been vetted for accuracy through clinical trials, and over-the-counter devices which are sold direct to consumers but often estimate oxygen saturation. FDA communication on pulse oximeter accuracy states "OTC oximeters that are sold as either general wellness or sporting/aviation products are not intended for medical purposes, so they do not undergo FDA review."
Pulse oximeter use is important for patients diagnosed with breathing problems or lung diseases such as asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, lung cancer, flu, pneumonia, or COVID-19 to collect accurate data on arterial blood oxygen saturation that they can share with their healthcare providers, according to the company. Patients with cardiac conditions, including pulmonary hypertension and heart failure may also benefit from pulse oximeter monitoring.
However, challenges of pulse oximeter use include measuring accuracy when patients are moving, measuring patients with poor circulation, and measuring patients with cool, thick, or darker skin. The MightySat Medical is designed to provide reliable measures of oxygen saturation and pulse rate across all patient groups, the manufacturers wrote in the press release.
Asked for additional comment, Diego J. Maselli, MD, FCCP, Professor and Chief in the division of Pulmonary Diseases and Critical Care at UT Health at San Antonio, noted, "Over the past decades, there has been an increased interest in home monitoring of medical conditions, particulrly with the development of more portable and accessible technology."
"This was heightended by the COVID-19 pandemic where telemedicine was frequently required as a means of delivering care," Dr. Maselli continued. "One of the important characteristics to monitor was the oxgen saturation in patients that had an active COVID-19 infection as it would dictate management and was part of the protocol for monitoring the clinical course of infection. Because of this need, many companies developed portable pulse oximeters for home use. This resulted in widespread use of pulse oximeters at home and other places outside clinic or hospital."
Other over-the-counter pulse oximeters that are not cleared by the FDA may create confusion among patients about the accuracy of their measurements, according to the company.
Dr. Maselli also commented that pulse oximeters' value can vary. "Unfortunately, these devices vary in quality and reliability and patients may not be fully aware of this. Most recently, the FDA approved a hospital-grade pulse oximeter that requires no prescription. This device may provide a more accurate reading in a wide range of clinical situations outside the healthcare setting. Patients should be aware that there are different grades of pulse oximeter before selecting one for home use. In addition, patients should work closely with their providers to better select the monitoring modaility that best fits their clinical situation," he said.
MightySat Medical is indicated for individuals aged 18 years and older who are well or poorly perfused under no motion conditions and is not intended as a diagnostic or screening tool for lung disease, according to the release. Treatment decisions based on data from the device should be made only in consultation with a healthcare provider, the company said. Dr. Maselli serves as a member of the CHEST Physician editorial board.
The FDA’s website offers further guidance related to at-home pulse oximeter use, with recommendations and limitations, as well as information on initiatives to ensure accurate and equitable pulse oximetry for all patients.
A version of this article appeared on Medscape.com.
The MightySat Medical, an over-the-counter medical fingertip pulse oximeter, has received clearance from the US Food and Drug Administration (FDA) for use without a prescription, according to a press release from manufacturer Masimo.
The device is the first medical fingertip pulse oximeter available directly to consumers without a prescription that includes the same technology used by many hospitals, according to the company.
According to the FDA, home pulse oximeters are currently generally of two classes: hospital-grade prescription devices which have been vetted for accuracy through clinical trials, and over-the-counter devices which are sold direct to consumers but often estimate oxygen saturation. FDA communication on pulse oximeter accuracy states "OTC oximeters that are sold as either general wellness or sporting/aviation products are not intended for medical purposes, so they do not undergo FDA review."
Pulse oximeter use is important for patients diagnosed with breathing problems or lung diseases such as asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, lung cancer, flu, pneumonia, or COVID-19 to collect accurate data on arterial blood oxygen saturation that they can share with their healthcare providers, according to the company. Patients with cardiac conditions, including pulmonary hypertension and heart failure may also benefit from pulse oximeter monitoring.
However, challenges of pulse oximeter use include measuring accuracy when patients are moving, measuring patients with poor circulation, and measuring patients with cool, thick, or darker skin. The MightySat Medical is designed to provide reliable measures of oxygen saturation and pulse rate across all patient groups, the manufacturers wrote in the press release.
Asked for additional comment, Diego J. Maselli, MD, FCCP, Professor and Chief in the division of Pulmonary Diseases and Critical Care at UT Health at San Antonio, noted, "Over the past decades, there has been an increased interest in home monitoring of medical conditions, particulrly with the development of more portable and accessible technology."
"This was heightended by the COVID-19 pandemic where telemedicine was frequently required as a means of delivering care," Dr. Maselli continued. "One of the important characteristics to monitor was the oxgen saturation in patients that had an active COVID-19 infection as it would dictate management and was part of the protocol for monitoring the clinical course of infection. Because of this need, many companies developed portable pulse oximeters for home use. This resulted in widespread use of pulse oximeters at home and other places outside clinic or hospital."
Other over-the-counter pulse oximeters that are not cleared by the FDA may create confusion among patients about the accuracy of their measurements, according to the company.
Dr. Maselli also commented that pulse oximeters' value can vary. "Unfortunately, these devices vary in quality and reliability and patients may not be fully aware of this. Most recently, the FDA approved a hospital-grade pulse oximeter that requires no prescription. This device may provide a more accurate reading in a wide range of clinical situations outside the healthcare setting. Patients should be aware that there are different grades of pulse oximeter before selecting one for home use. In addition, patients should work closely with their providers to better select the monitoring modaility that best fits their clinical situation," he said.
MightySat Medical is indicated for individuals aged 18 years and older who are well or poorly perfused under no motion conditions and is not intended as a diagnostic or screening tool for lung disease, according to the release. Treatment decisions based on data from the device should be made only in consultation with a healthcare provider, the company said. Dr. Maselli serves as a member of the CHEST Physician editorial board.
The FDA’s website offers further guidance related to at-home pulse oximeter use, with recommendations and limitations, as well as information on initiatives to ensure accurate and equitable pulse oximetry for all patients.
A version of this article appeared on Medscape.com.
Florida’s Stance on Measles Upends Expert Guidance
Amid an ongoing measles outbreak in Florida possibly sparked by vaccine hesitancy, the state’s surgeon general Joseph Ladapo, MD, is contradicting public health guidance of encouraging quarantine of unvaccinated children.
Rather than requesting that parents keep children unvaccinated against measles home from school or to get their children vaccinated, both critical tools in containing an outbreak, Dr. Ladapo has advised parents to do whatever they think is best. Pediatricians and infectious disease specialists fear a free-for-all will fuel the spread of the highly infectious virus, including in their own clinics.
The outbreak has been traced to an elementary school in Weston and has so far sickened at least eight children, one of whom is younger than 5 years. According to the Centers for Disease Control and Prevention, roughly 91% of the 230,000-odd kindergarteners in Florida had received the requisite doses of the MMR vaccine, which also protects against mumps and rubella, for the 2022-2023 school year, below the 95% vaccination level which public health authorities believes confers herd immunity against measles. An estimated 4.5% of kindergarteners in the state have received an exemption for the vaccine, which prevents measles in 97% of the people who get the shots, for a lifetime. The first dose is given around age 13 months and the second when people are age 4 or 5 years and soon to enter school.
“If you’re vaccinated you have a very slim chance of getting the virus,” said Rana Alissa, MD, a pediatrician at University of Florida Health in Jacksonville.
An unvaccinated child has no protection against measles, and could spread it to others merely by sneezing or touching a surface. In a school setting, infection could spread to a teacher who cannot receive the measles vaccine due to a weakened immune system, or the unvaccinated child could spread the virus at a pediatric clinic or hospital when seeking care for measles unless the clinic staff takes rigorous steps to separate the child from other children. Some children at the clinic won’t be able to get the measles vaccine either because of immunodeficiency or perhaps having had a bone marrow transplant.
Assuming the unvaccinated child is healthy, the measles infection will run its course, and the child will then be immune to the disease, Dr. Alissa said. But meanwhile, the child could pose a significant risk to others.
“We’re not worried about the unvaccinated kids who are very healthy. We’re worried about the adults who did not get vaccinated and who are very sick,” said Dr. Alissa, vice president of the Florida chapter of the American Academy of Pediatrics (AAP). “We’re worried about the little kids who are less than 13 months old. We’re worried about the kids with immunodeficiency disorders.” The Florida chapter of the AAP encourages parents to get their children vaccinated against measles amid the ongoing outbreak.
“I wish our surgeon general was on the same page as us,” Dr. Alissa added, noting that she thinks misplaced vaccine hesitancy has caused some parents to forego a safe and effective vaccine for their children.
Never Too Late to Vaxx
Measles symptoms appear 10-14 days after exposure and can include sore throat, cough, runny nose, inflamed eyes, fever, and blotchy skin rashes. According to the Centers for Disease Control and Prevention (CDC), 20% of people who are unvaccinated against measles will be hospitalized for the virus if they contract it.
Given the incubation period for the virus, clinicians and public health officials recommend unvaccinated children isolate for 21 days after being exposed to measles at school. The advice applies to any unvaccinated child, whether because their parent opted against the vaccine or because they cannot safely receive the immunization.
This is the guidance that Surgeon General Ladapo is flouting.
“We have a public health system. They’re awesome. They’re the experts. Let’s use them,” Dr. Alissa noted. “Their recommendation is to keep the unvaccinated kids at home for 21 days when you have an outbreak.”
“We’re not calling him doctor anymore,” said Andrew Pavia, MD, chief of the Division of Pediatric Infectious Diseases at the University of Utah in Salt Lake City.
“Getting your kids immunized before they enter school is so critical,” added Dr. Pavia, because the 21-day quarantine period is onerous for children and parents alike.
In a February 26 statement, Marcus Plescia, MD, MPH, chief medical officer of the Association of State and Territorial Health Officials, said “well-established public health practice recommends that unvaccinated persons exposed to measles stay home for at least 21 days to prevent further growth of the outbreak. While this is undoubtedly disruptive to the persons impacted, imagine how much more disruptive it would be if measles takes hold again in the United States, spreading widely, and impacting children and communities across the entire nation.”
During an outbreak, it’s still possible to give a measles vaccine to a child who has not yet received the shots, Dr. Pavia stressed. But time is of the essence: Vaccination should occur within 72 hours of the first known measles case in a school.
“It’s not perfect, they may still get measles, but it will greatly decrease the severity,” Dr. Pavia said.
If some children won’t get vaccinated during an outbreak, their parents may call a pediatrician or hospital staff for help as measles symptoms take hold. Clinicians should advise everyone in the home who is older than 2 years to begin wearing N95 masks and gloves, Dr. Alissa said. And when the child comes into the clinic he or she should be examined in a separate room, ideally one with negative air pressure and frequent filtration, Dr. Alissa added. If not, any private room will do if nobody else uses the room for at least 2 hours afterward.
“Measles is phenomenally transmissible,” Dr. Pavia said. A person with the virus can infect 12 to 18 others who are not protected against the pathogen.
Someone with a severe reaction to measles could get an injection of intramuscular immunoglobulin, Dr. Pavia said, although this tends to be uncomfortable and expensive.
“The vaccine works. We almost got rid of measles,” Dr. Alissa said, although parents who choose to send their unvaccinated children to school can do so if they choose to.
“The fear of every pediatrician is to have a child die from this,” she said. “People who are sick, please stay at home.”
Dr. Pavia reported an advisory relationship with Sanofi Pasteur regarding an RSV vaccine. Dr. Alissa reported no relevant financial conflicts of interest.
A version of this article appeared on Medscape.com.
Amid an ongoing measles outbreak in Florida possibly sparked by vaccine hesitancy, the state’s surgeon general Joseph Ladapo, MD, is contradicting public health guidance of encouraging quarantine of unvaccinated children.
Rather than requesting that parents keep children unvaccinated against measles home from school or to get their children vaccinated, both critical tools in containing an outbreak, Dr. Ladapo has advised parents to do whatever they think is best. Pediatricians and infectious disease specialists fear a free-for-all will fuel the spread of the highly infectious virus, including in their own clinics.
The outbreak has been traced to an elementary school in Weston and has so far sickened at least eight children, one of whom is younger than 5 years. According to the Centers for Disease Control and Prevention, roughly 91% of the 230,000-odd kindergarteners in Florida had received the requisite doses of the MMR vaccine, which also protects against mumps and rubella, for the 2022-2023 school year, below the 95% vaccination level which public health authorities believes confers herd immunity against measles. An estimated 4.5% of kindergarteners in the state have received an exemption for the vaccine, which prevents measles in 97% of the people who get the shots, for a lifetime. The first dose is given around age 13 months and the second when people are age 4 or 5 years and soon to enter school.
“If you’re vaccinated you have a very slim chance of getting the virus,” said Rana Alissa, MD, a pediatrician at University of Florida Health in Jacksonville.
An unvaccinated child has no protection against measles, and could spread it to others merely by sneezing or touching a surface. In a school setting, infection could spread to a teacher who cannot receive the measles vaccine due to a weakened immune system, or the unvaccinated child could spread the virus at a pediatric clinic or hospital when seeking care for measles unless the clinic staff takes rigorous steps to separate the child from other children. Some children at the clinic won’t be able to get the measles vaccine either because of immunodeficiency or perhaps having had a bone marrow transplant.
Assuming the unvaccinated child is healthy, the measles infection will run its course, and the child will then be immune to the disease, Dr. Alissa said. But meanwhile, the child could pose a significant risk to others.
“We’re not worried about the unvaccinated kids who are very healthy. We’re worried about the adults who did not get vaccinated and who are very sick,” said Dr. Alissa, vice president of the Florida chapter of the American Academy of Pediatrics (AAP). “We’re worried about the little kids who are less than 13 months old. We’re worried about the kids with immunodeficiency disorders.” The Florida chapter of the AAP encourages parents to get their children vaccinated against measles amid the ongoing outbreak.
“I wish our surgeon general was on the same page as us,” Dr. Alissa added, noting that she thinks misplaced vaccine hesitancy has caused some parents to forego a safe and effective vaccine for their children.
Never Too Late to Vaxx
Measles symptoms appear 10-14 days after exposure and can include sore throat, cough, runny nose, inflamed eyes, fever, and blotchy skin rashes. According to the Centers for Disease Control and Prevention (CDC), 20% of people who are unvaccinated against measles will be hospitalized for the virus if they contract it.
Given the incubation period for the virus, clinicians and public health officials recommend unvaccinated children isolate for 21 days after being exposed to measles at school. The advice applies to any unvaccinated child, whether because their parent opted against the vaccine or because they cannot safely receive the immunization.
This is the guidance that Surgeon General Ladapo is flouting.
“We have a public health system. They’re awesome. They’re the experts. Let’s use them,” Dr. Alissa noted. “Their recommendation is to keep the unvaccinated kids at home for 21 days when you have an outbreak.”
“We’re not calling him doctor anymore,” said Andrew Pavia, MD, chief of the Division of Pediatric Infectious Diseases at the University of Utah in Salt Lake City.
“Getting your kids immunized before they enter school is so critical,” added Dr. Pavia, because the 21-day quarantine period is onerous for children and parents alike.
In a February 26 statement, Marcus Plescia, MD, MPH, chief medical officer of the Association of State and Territorial Health Officials, said “well-established public health practice recommends that unvaccinated persons exposed to measles stay home for at least 21 days to prevent further growth of the outbreak. While this is undoubtedly disruptive to the persons impacted, imagine how much more disruptive it would be if measles takes hold again in the United States, spreading widely, and impacting children and communities across the entire nation.”
During an outbreak, it’s still possible to give a measles vaccine to a child who has not yet received the shots, Dr. Pavia stressed. But time is of the essence: Vaccination should occur within 72 hours of the first known measles case in a school.
“It’s not perfect, they may still get measles, but it will greatly decrease the severity,” Dr. Pavia said.
If some children won’t get vaccinated during an outbreak, their parents may call a pediatrician or hospital staff for help as measles symptoms take hold. Clinicians should advise everyone in the home who is older than 2 years to begin wearing N95 masks and gloves, Dr. Alissa said. And when the child comes into the clinic he or she should be examined in a separate room, ideally one with negative air pressure and frequent filtration, Dr. Alissa added. If not, any private room will do if nobody else uses the room for at least 2 hours afterward.
“Measles is phenomenally transmissible,” Dr. Pavia said. A person with the virus can infect 12 to 18 others who are not protected against the pathogen.
Someone with a severe reaction to measles could get an injection of intramuscular immunoglobulin, Dr. Pavia said, although this tends to be uncomfortable and expensive.
“The vaccine works. We almost got rid of measles,” Dr. Alissa said, although parents who choose to send their unvaccinated children to school can do so if they choose to.
“The fear of every pediatrician is to have a child die from this,” she said. “People who are sick, please stay at home.”
Dr. Pavia reported an advisory relationship with Sanofi Pasteur regarding an RSV vaccine. Dr. Alissa reported no relevant financial conflicts of interest.
A version of this article appeared on Medscape.com.
Amid an ongoing measles outbreak in Florida possibly sparked by vaccine hesitancy, the state’s surgeon general Joseph Ladapo, MD, is contradicting public health guidance of encouraging quarantine of unvaccinated children.
Rather than requesting that parents keep children unvaccinated against measles home from school or to get their children vaccinated, both critical tools in containing an outbreak, Dr. Ladapo has advised parents to do whatever they think is best. Pediatricians and infectious disease specialists fear a free-for-all will fuel the spread of the highly infectious virus, including in their own clinics.
The outbreak has been traced to an elementary school in Weston and has so far sickened at least eight children, one of whom is younger than 5 years. According to the Centers for Disease Control and Prevention, roughly 91% of the 230,000-odd kindergarteners in Florida had received the requisite doses of the MMR vaccine, which also protects against mumps and rubella, for the 2022-2023 school year, below the 95% vaccination level which public health authorities believes confers herd immunity against measles. An estimated 4.5% of kindergarteners in the state have received an exemption for the vaccine, which prevents measles in 97% of the people who get the shots, for a lifetime. The first dose is given around age 13 months and the second when people are age 4 or 5 years and soon to enter school.
“If you’re vaccinated you have a very slim chance of getting the virus,” said Rana Alissa, MD, a pediatrician at University of Florida Health in Jacksonville.
An unvaccinated child has no protection against measles, and could spread it to others merely by sneezing or touching a surface. In a school setting, infection could spread to a teacher who cannot receive the measles vaccine due to a weakened immune system, or the unvaccinated child could spread the virus at a pediatric clinic or hospital when seeking care for measles unless the clinic staff takes rigorous steps to separate the child from other children. Some children at the clinic won’t be able to get the measles vaccine either because of immunodeficiency or perhaps having had a bone marrow transplant.
Assuming the unvaccinated child is healthy, the measles infection will run its course, and the child will then be immune to the disease, Dr. Alissa said. But meanwhile, the child could pose a significant risk to others.
“We’re not worried about the unvaccinated kids who are very healthy. We’re worried about the adults who did not get vaccinated and who are very sick,” said Dr. Alissa, vice president of the Florida chapter of the American Academy of Pediatrics (AAP). “We’re worried about the little kids who are less than 13 months old. We’re worried about the kids with immunodeficiency disorders.” The Florida chapter of the AAP encourages parents to get their children vaccinated against measles amid the ongoing outbreak.
“I wish our surgeon general was on the same page as us,” Dr. Alissa added, noting that she thinks misplaced vaccine hesitancy has caused some parents to forego a safe and effective vaccine for their children.
Never Too Late to Vaxx
Measles symptoms appear 10-14 days after exposure and can include sore throat, cough, runny nose, inflamed eyes, fever, and blotchy skin rashes. According to the Centers for Disease Control and Prevention (CDC), 20% of people who are unvaccinated against measles will be hospitalized for the virus if they contract it.
Given the incubation period for the virus, clinicians and public health officials recommend unvaccinated children isolate for 21 days after being exposed to measles at school. The advice applies to any unvaccinated child, whether because their parent opted against the vaccine or because they cannot safely receive the immunization.
This is the guidance that Surgeon General Ladapo is flouting.
“We have a public health system. They’re awesome. They’re the experts. Let’s use them,” Dr. Alissa noted. “Their recommendation is to keep the unvaccinated kids at home for 21 days when you have an outbreak.”
“We’re not calling him doctor anymore,” said Andrew Pavia, MD, chief of the Division of Pediatric Infectious Diseases at the University of Utah in Salt Lake City.
“Getting your kids immunized before they enter school is so critical,” added Dr. Pavia, because the 21-day quarantine period is onerous for children and parents alike.
In a February 26 statement, Marcus Plescia, MD, MPH, chief medical officer of the Association of State and Territorial Health Officials, said “well-established public health practice recommends that unvaccinated persons exposed to measles stay home for at least 21 days to prevent further growth of the outbreak. While this is undoubtedly disruptive to the persons impacted, imagine how much more disruptive it would be if measles takes hold again in the United States, spreading widely, and impacting children and communities across the entire nation.”
During an outbreak, it’s still possible to give a measles vaccine to a child who has not yet received the shots, Dr. Pavia stressed. But time is of the essence: Vaccination should occur within 72 hours of the first known measles case in a school.
“It’s not perfect, they may still get measles, but it will greatly decrease the severity,” Dr. Pavia said.
If some children won’t get vaccinated during an outbreak, their parents may call a pediatrician or hospital staff for help as measles symptoms take hold. Clinicians should advise everyone in the home who is older than 2 years to begin wearing N95 masks and gloves, Dr. Alissa said. And when the child comes into the clinic he or she should be examined in a separate room, ideally one with negative air pressure and frequent filtration, Dr. Alissa added. If not, any private room will do if nobody else uses the room for at least 2 hours afterward.
“Measles is phenomenally transmissible,” Dr. Pavia said. A person with the virus can infect 12 to 18 others who are not protected against the pathogen.
Someone with a severe reaction to measles could get an injection of intramuscular immunoglobulin, Dr. Pavia said, although this tends to be uncomfortable and expensive.
“The vaccine works. We almost got rid of measles,” Dr. Alissa said, although parents who choose to send their unvaccinated children to school can do so if they choose to.
“The fear of every pediatrician is to have a child die from this,” she said. “People who are sick, please stay at home.”
Dr. Pavia reported an advisory relationship with Sanofi Pasteur regarding an RSV vaccine. Dr. Alissa reported no relevant financial conflicts of interest.
A version of this article appeared on Medscape.com.