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FDA Approves Tarlatamab for Extensive-Stage Small Cell Lung Cancer
Tarlatamab is a first-in-class bispecific T-cell engager (BiTE) that binds delta-like ligand 3 on the surface of cells, including tumor cells, and CD3 expressed on the surface of T cells. It causes T-cell activation, release of inflammatory cytokines, and lysis of DLL3-expressing cells, according to labeling.
Approval was based on data from 99 patients in the DeLLphi-301 trial with relapsed/refractory extensive-stage SCLC who had progressed after platinum-based chemotherapy. Patients with symptomatic brain metastases, interstitial lung disease, noninfectious pneumonitis, and active immunodeficiency were excluded.
The overall response rate was 40%, and median duration of response 9.7 months. The overall response rate was 52% in 27 patients with platinum-resistant SCLC and 31% in 42 with platinum-sensitive disease.
Continued approval may depend on verification of clinical benefit in a confirmatory trial.
Labeling includes a box warning of serious or life-threatening cytokine release syndrome and neurologic toxicity, including immune effector cell–associated neurotoxicity syndrome.
The most common adverse events, occurring in 20% or more of patients, were cytokine release syndrome, fatigue, pyrexia, dysgeusia, decreased appetite, musculoskeletal pain, constipation, anemia, and nausea.
The most common grade 3 or 4 laboratory abnormalities included decreased lymphocytes, decreased sodium, increased uric acid, decreased total neutrophils, decreased hemoglobin, increased activated partial thromboplastin time, and decreased potassium.
The starting dose is 1 mg given intravenously over 1 hour on the first day of the first cycle followed by 10 mg on day 8 and day 15 of the first cycle, then every 2 weeks until disease progression or unacceptable toxicity.
M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: [email protected]
A version of this article appeared on Medscape.com.
Tarlatamab is a first-in-class bispecific T-cell engager (BiTE) that binds delta-like ligand 3 on the surface of cells, including tumor cells, and CD3 expressed on the surface of T cells. It causes T-cell activation, release of inflammatory cytokines, and lysis of DLL3-expressing cells, according to labeling.
Approval was based on data from 99 patients in the DeLLphi-301 trial with relapsed/refractory extensive-stage SCLC who had progressed after platinum-based chemotherapy. Patients with symptomatic brain metastases, interstitial lung disease, noninfectious pneumonitis, and active immunodeficiency were excluded.
The overall response rate was 40%, and median duration of response 9.7 months. The overall response rate was 52% in 27 patients with platinum-resistant SCLC and 31% in 42 with platinum-sensitive disease.
Continued approval may depend on verification of clinical benefit in a confirmatory trial.
Labeling includes a box warning of serious or life-threatening cytokine release syndrome and neurologic toxicity, including immune effector cell–associated neurotoxicity syndrome.
The most common adverse events, occurring in 20% or more of patients, were cytokine release syndrome, fatigue, pyrexia, dysgeusia, decreased appetite, musculoskeletal pain, constipation, anemia, and nausea.
The most common grade 3 or 4 laboratory abnormalities included decreased lymphocytes, decreased sodium, increased uric acid, decreased total neutrophils, decreased hemoglobin, increased activated partial thromboplastin time, and decreased potassium.
The starting dose is 1 mg given intravenously over 1 hour on the first day of the first cycle followed by 10 mg on day 8 and day 15 of the first cycle, then every 2 weeks until disease progression or unacceptable toxicity.
M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: [email protected]
A version of this article appeared on Medscape.com.
Tarlatamab is a first-in-class bispecific T-cell engager (BiTE) that binds delta-like ligand 3 on the surface of cells, including tumor cells, and CD3 expressed on the surface of T cells. It causes T-cell activation, release of inflammatory cytokines, and lysis of DLL3-expressing cells, according to labeling.
Approval was based on data from 99 patients in the DeLLphi-301 trial with relapsed/refractory extensive-stage SCLC who had progressed after platinum-based chemotherapy. Patients with symptomatic brain metastases, interstitial lung disease, noninfectious pneumonitis, and active immunodeficiency were excluded.
The overall response rate was 40%, and median duration of response 9.7 months. The overall response rate was 52% in 27 patients with platinum-resistant SCLC and 31% in 42 with platinum-sensitive disease.
Continued approval may depend on verification of clinical benefit in a confirmatory trial.
Labeling includes a box warning of serious or life-threatening cytokine release syndrome and neurologic toxicity, including immune effector cell–associated neurotoxicity syndrome.
The most common adverse events, occurring in 20% or more of patients, were cytokine release syndrome, fatigue, pyrexia, dysgeusia, decreased appetite, musculoskeletal pain, constipation, anemia, and nausea.
The most common grade 3 or 4 laboratory abnormalities included decreased lymphocytes, decreased sodium, increased uric acid, decreased total neutrophils, decreased hemoglobin, increased activated partial thromboplastin time, and decreased potassium.
The starting dose is 1 mg given intravenously over 1 hour on the first day of the first cycle followed by 10 mg on day 8 and day 15 of the first cycle, then every 2 weeks until disease progression or unacceptable toxicity.
M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: [email protected]
A version of this article appeared on Medscape.com.
Aquagenic Wrinkling Among Skin-Related Signs of Cystic Fibrosis
TOPLINE:
METHODOLOGY:
- Patients with CF, caused by a mutation in the CF Transmembrane Conductance Regulator (CFTR) gene, can develop diverse dermatologic manifestations.
- Researchers reviewed the literature and provided their own clinical experience regarding dermatologic manifestations of CF.
- They also reviewed the cutaneous side effects of CFTR modulators and antibiotics used to treat CF.
TAKEAWAY:
- Aquagenic wrinkling of the palm is common in individuals with CF, affecting up to 80% of patients (and 25% of CF gene carriers), and can be an early manifestation of CF. Treatments include topical medications (such as aluminum chloride, corticosteroids, and salicylic acid), botulinum toxin injections, and recently, CFTR-modulating treatments.
- CF nutrient deficiency dermatitis, often in a diaper distribution, usually appears in infancy and, before newborn screening was available, was sometimes the first sign of CF in some cases. It usually resolves with an adequate diet, pancreatic enzymes, and/or nutritional supplements. Zinc and essential fatty acid deficiencies can lead to acrodermatitis enteropathica–like symptoms and psoriasiform rashes, respectively.
- CF is also associated with vascular disorders, including cutaneous and, rarely, systemic vasculitis. Treatment includes topical and oral steroids and immune-modulating therapies.
- CFTR modulators, now the most common and highly effective treatment for CF, are associated with several skin reactions, which can be managed with treatments that include topical steroids and oral antihistamines. Frequent antibiotic treatment can also trigger skin reactions.
IN PRACTICE:
“Recognition and familiarity with dermatologic clinical manifestations of CF are important for multidisciplinary care” for patients with CF, the authors wrote, adding that “dermatology providers may play a significant role in the diagnosis and management of CF cutaneous comorbidities.”
SOURCE:
Aaron D. Smith, BS, from the University of Virginia (UVA) School of Medicine, Charlottesville, and coauthors were from the departments of dermatology and pulmonology/critical care medicine at UVA. The study was published online in the Journal of the American Academy of Dermatology.
LIMITATIONS:
The authors did not make a comment about the limitations of their review.
DISCLOSURES:
No funding was received for the review. The authors had no disclosures.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Patients with CF, caused by a mutation in the CF Transmembrane Conductance Regulator (CFTR) gene, can develop diverse dermatologic manifestations.
- Researchers reviewed the literature and provided their own clinical experience regarding dermatologic manifestations of CF.
- They also reviewed the cutaneous side effects of CFTR modulators and antibiotics used to treat CF.
TAKEAWAY:
- Aquagenic wrinkling of the palm is common in individuals with CF, affecting up to 80% of patients (and 25% of CF gene carriers), and can be an early manifestation of CF. Treatments include topical medications (such as aluminum chloride, corticosteroids, and salicylic acid), botulinum toxin injections, and recently, CFTR-modulating treatments.
- CF nutrient deficiency dermatitis, often in a diaper distribution, usually appears in infancy and, before newborn screening was available, was sometimes the first sign of CF in some cases. It usually resolves with an adequate diet, pancreatic enzymes, and/or nutritional supplements. Zinc and essential fatty acid deficiencies can lead to acrodermatitis enteropathica–like symptoms and psoriasiform rashes, respectively.
- CF is also associated with vascular disorders, including cutaneous and, rarely, systemic vasculitis. Treatment includes topical and oral steroids and immune-modulating therapies.
- CFTR modulators, now the most common and highly effective treatment for CF, are associated with several skin reactions, which can be managed with treatments that include topical steroids and oral antihistamines. Frequent antibiotic treatment can also trigger skin reactions.
IN PRACTICE:
“Recognition and familiarity with dermatologic clinical manifestations of CF are important for multidisciplinary care” for patients with CF, the authors wrote, adding that “dermatology providers may play a significant role in the diagnosis and management of CF cutaneous comorbidities.”
SOURCE:
Aaron D. Smith, BS, from the University of Virginia (UVA) School of Medicine, Charlottesville, and coauthors were from the departments of dermatology and pulmonology/critical care medicine at UVA. The study was published online in the Journal of the American Academy of Dermatology.
LIMITATIONS:
The authors did not make a comment about the limitations of their review.
DISCLOSURES:
No funding was received for the review. The authors had no disclosures.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Patients with CF, caused by a mutation in the CF Transmembrane Conductance Regulator (CFTR) gene, can develop diverse dermatologic manifestations.
- Researchers reviewed the literature and provided their own clinical experience regarding dermatologic manifestations of CF.
- They also reviewed the cutaneous side effects of CFTR modulators and antibiotics used to treat CF.
TAKEAWAY:
- Aquagenic wrinkling of the palm is common in individuals with CF, affecting up to 80% of patients (and 25% of CF gene carriers), and can be an early manifestation of CF. Treatments include topical medications (such as aluminum chloride, corticosteroids, and salicylic acid), botulinum toxin injections, and recently, CFTR-modulating treatments.
- CF nutrient deficiency dermatitis, often in a diaper distribution, usually appears in infancy and, before newborn screening was available, was sometimes the first sign of CF in some cases. It usually resolves with an adequate diet, pancreatic enzymes, and/or nutritional supplements. Zinc and essential fatty acid deficiencies can lead to acrodermatitis enteropathica–like symptoms and psoriasiform rashes, respectively.
- CF is also associated with vascular disorders, including cutaneous and, rarely, systemic vasculitis. Treatment includes topical and oral steroids and immune-modulating therapies.
- CFTR modulators, now the most common and highly effective treatment for CF, are associated with several skin reactions, which can be managed with treatments that include topical steroids and oral antihistamines. Frequent antibiotic treatment can also trigger skin reactions.
IN PRACTICE:
“Recognition and familiarity with dermatologic clinical manifestations of CF are important for multidisciplinary care” for patients with CF, the authors wrote, adding that “dermatology providers may play a significant role in the diagnosis and management of CF cutaneous comorbidities.”
SOURCE:
Aaron D. Smith, BS, from the University of Virginia (UVA) School of Medicine, Charlottesville, and coauthors were from the departments of dermatology and pulmonology/critical care medicine at UVA. The study was published online in the Journal of the American Academy of Dermatology.
LIMITATIONS:
The authors did not make a comment about the limitations of their review.
DISCLOSURES:
No funding was received for the review. The authors had no disclosures.
A version of this article first appeared on Medscape.com.
New mRNA Vaccines in Development for Cancer and Infections
Martina Prelog, MD, a pediatric and adolescent medicine specialist at the University Hospital of Würzburg in Germany, reported on the principles, research status, and perspectives for these vaccines at the 25th Travel and Health Forum of the Center for Travel Medicine in Berlin.
To understand the future, the immunologist first examined the past. “The induction of cellular and humoral immune responses by externally injected mRNA was discovered in the 1990s,” she said.
Instability Challenge
Significant hurdles in mRNA vaccinations included the instability of mRNA and the immune system’s ability to identify foreign mRNA as a threat and destroy mRNA fragments. “The breakthrough toward vaccination came through Dr. Katalin Karikó, who, along with Dr. Drew Weissman, both of the University of Pennsylvania School of Medicine, discovered in 2005 that modifications of mRNA (replacing the nucleoside uridine with pseudouridine) enable better stability of mRNA, reduced immunogenicity, and higher translational capacity at the ribosomes,” said Dr. Prelog.
With this discovery, the two researchers paved the way for the development of mRNA vaccines against COVID-19 and other diseases. They were awarded the Nobel Prize in medicine for their discovery last year.
Improved Scalability
“Since 2009, mRNA vaccines have been studied as a treatment option for cancer,” said Dr. Prelog. “Since 2012, they have been studied for the influenza virus and respiratory syncytial virus [RSV].” Consequently, several mRNA vaccines are currently in development or in approval studies. “The mRNA technology offers the advantage of quickly and flexibly responding to new variants of pathogens and the ability to scale up production when there is high demand for a particular vaccine.”
Different forms and designations of mRNA vaccines are used, depending on the application and desired effect, said Dr. Prelog.
In nucleoside-modified mRNA vaccines, modifications in the mRNA sequence enable the mRNA to remain in the body longer and to induce protein synthesis more effectively.
Lipid nanoparticle (LNP)–encapsulated mRNA vaccines protect the coding mRNA sequences against degradation by the body’s enzymes and facilitate the uptake of mRNA into cells, where it then triggers the production of the desired protein. In addition, LNPs are involved in cell stimulation and support the self-adjuvant effect of mRNA vaccines, thus eliminating the need for adjuvants.
Self-amplifying mRNA vaccines include a special mRNA that replicates itself in the cell and contains a sequence for RNA replicase, in addition to the coding sequence for the protein. This composition enables increased production of the target protein without the need for a high amount of external mRNA administration. Such vaccines could trigger a longer and stronger immune response because the immune system has more time to interact with the protein.
Cancer Immunotherapy
Dr. Prelog also discussed personalized vaccines for cancer immunotherapy. Personalized mRNA vaccines are tailored to the patient’s genetic characteristics and antigens. They could be used in cancer immunotherapy to activate the immune system selectively against tumor cells.
Multivalent mRNA vaccines contain mRNA that codes for multiple antigens rather than just one protein to generate an immune response. These vaccines could be particularly useful in fighting pathogens with variable or changing surface structures or in eliciting protection against multiple pathogens simultaneously.
The technology of mRNA-encoded antibodies involves introducing mRNA into the cell, which creates light and heavy chains of antibodies. This step leads to the formation of antibodies targeted against toxins (eg, diphtheria and tetanus), animal venoms, infectious agents, or tumor cells.
Genetic Engineering
Dr. Prelog also reviewed genetic engineering techniques. In regenerative therapy or protein replacement therapy, skin fibroblasts or other cells are transfected with mRNA to enable conversion into induced pluripotent stem cells. This approach avoids the risk for DNA integration into the genome and associated mutation risks.
Another approach is making post-transcriptional modifications through RNA interference. For example, RNA structures can be used to inhibit the translation of disease-causing proteins. This technique is currently being tested against HIV and tumors such as melanoma.
In addition, mRNA technologies can be combined with CRISPR/Cas9 technology (“gene scissors”) to influence the creation of gene products even more precisely. The advantage of this technique is that mRNA is only transiently expressed, thus preventing unwanted side effects. Furthermore, mRNA is translated directly in the cytoplasm, leading to a faster initiation of gene editing.
Of the numerous ongoing clinical mRNA vaccine studies, around 70% focus on infections, about 12% on cancer, and the rest on autoimmune diseases and neurodegenerative disorders, said Dr. Prelog.
Research in Infections
Research in the fields of infectious diseases and oncology is the most advanced: mRNA vaccines against influenza and RSV are already in advanced clinical trials, Dr. Prelog told this news organization.
“Conventional influenza vaccines contain immunogenic surface molecules against hemagglutinin and neuraminidase in various combinations of influenza strains A and B and are produced in egg or cell cultures,” she said. “This is a time-consuming manufacturing process that takes months and, particularly with the egg-based process, bears the risk of changing the vaccine strain.”
“Additionally, influenza viruses undergo antigenic shift and drift through recombination, thus requiring annual adjustments to the vaccines. Thus, these influenza vaccines often lose accuracy in targeting circulating seasonal influenza strains.”
Several mRNA vaccines being tested contain not only coding sequences against hemagglutinin and neuraminidase but also for structural proteins of influenza viruses. “These are more conserved and mutate less easily, meaning they could serve as the basis for universal pandemic influenza vaccines,” said Dr. Prelog.
An advantage of mRNA vaccines, she added, is the strong cellular immune response that they elicit. This response is intended to provide additional protection alongside specific antibodies. An mRNA vaccine with coding sequences for the pre-fusion protein of RSV is in phase 3 trials for approval for vaccination in patients aged 60 years and older. It shows high effectiveness even in older patients and those with comorbidities.
Elaborate Purification Process
Bacterial origin plasmid DNA is used to produce mRNA vaccines. The mRNA vaccines for COVID-19 raised concerns that production-related DNA residues could pose a safety risk and cause autoimmune diseases.
These vaccines “typically undergo a very elaborate purification process,” said Dr. Prelog. “This involves enzymatic digestion with DNase to fragment and deplete plasmid DNA, followed by purification using chromatography columns, so that no safety-relevant DNA fragments should remain afterward.”
Thus, the Paul-Ehrlich-Institut also pointed out the very small, fragmented plasmid DNA residues of bacterial origin in mRNA COVID-19 vaccines pose no risk, unlike residual DNA from animal cell culture might pose in other vaccines.
Prevention and Therapy
In addition to the numerous advantages of mRNA vaccines (such as rapid adaptability to new or mutated pathogens, scalability, rapid production capability, self-adjuvant effect, strong induction of cellular immune responses, and safety), there are also challenges in RNA technology as a preventive and therapeutic measure, according to Dr. Prelog.
“Stability and storability, as well as the costs of new vaccine developments, play a role, as do the long-term effects regarding the persistence of antibody and cellular responses,” she said. The COVID-19 mRNA vaccines, for example, showed a well-maintained cellular immune response despite a tendency toward a rapid decline in humoral immune response.
“The experience with COVID-19 mRNA vaccines and the new vaccine developments based on mRNA technology give hope for an efficient and safe preventive and therapeutic use, particularly in the fields of infectious diseases and oncology,” Dr. Prelog concluded.
This story was translated from the Medscape German edition 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.
Martina Prelog, MD, a pediatric and adolescent medicine specialist at the University Hospital of Würzburg in Germany, reported on the principles, research status, and perspectives for these vaccines at the 25th Travel and Health Forum of the Center for Travel Medicine in Berlin.
To understand the future, the immunologist first examined the past. “The induction of cellular and humoral immune responses by externally injected mRNA was discovered in the 1990s,” she said.
Instability Challenge
Significant hurdles in mRNA vaccinations included the instability of mRNA and the immune system’s ability to identify foreign mRNA as a threat and destroy mRNA fragments. “The breakthrough toward vaccination came through Dr. Katalin Karikó, who, along with Dr. Drew Weissman, both of the University of Pennsylvania School of Medicine, discovered in 2005 that modifications of mRNA (replacing the nucleoside uridine with pseudouridine) enable better stability of mRNA, reduced immunogenicity, and higher translational capacity at the ribosomes,” said Dr. Prelog.
With this discovery, the two researchers paved the way for the development of mRNA vaccines against COVID-19 and other diseases. They were awarded the Nobel Prize in medicine for their discovery last year.
Improved Scalability
“Since 2009, mRNA vaccines have been studied as a treatment option for cancer,” said Dr. Prelog. “Since 2012, they have been studied for the influenza virus and respiratory syncytial virus [RSV].” Consequently, several mRNA vaccines are currently in development or in approval studies. “The mRNA technology offers the advantage of quickly and flexibly responding to new variants of pathogens and the ability to scale up production when there is high demand for a particular vaccine.”
Different forms and designations of mRNA vaccines are used, depending on the application and desired effect, said Dr. Prelog.
In nucleoside-modified mRNA vaccines, modifications in the mRNA sequence enable the mRNA to remain in the body longer and to induce protein synthesis more effectively.
Lipid nanoparticle (LNP)–encapsulated mRNA vaccines protect the coding mRNA sequences against degradation by the body’s enzymes and facilitate the uptake of mRNA into cells, where it then triggers the production of the desired protein. In addition, LNPs are involved in cell stimulation and support the self-adjuvant effect of mRNA vaccines, thus eliminating the need for adjuvants.
Self-amplifying mRNA vaccines include a special mRNA that replicates itself in the cell and contains a sequence for RNA replicase, in addition to the coding sequence for the protein. This composition enables increased production of the target protein without the need for a high amount of external mRNA administration. Such vaccines could trigger a longer and stronger immune response because the immune system has more time to interact with the protein.
Cancer Immunotherapy
Dr. Prelog also discussed personalized vaccines for cancer immunotherapy. Personalized mRNA vaccines are tailored to the patient’s genetic characteristics and antigens. They could be used in cancer immunotherapy to activate the immune system selectively against tumor cells.
Multivalent mRNA vaccines contain mRNA that codes for multiple antigens rather than just one protein to generate an immune response. These vaccines could be particularly useful in fighting pathogens with variable or changing surface structures or in eliciting protection against multiple pathogens simultaneously.
The technology of mRNA-encoded antibodies involves introducing mRNA into the cell, which creates light and heavy chains of antibodies. This step leads to the formation of antibodies targeted against toxins (eg, diphtheria and tetanus), animal venoms, infectious agents, or tumor cells.
Genetic Engineering
Dr. Prelog also reviewed genetic engineering techniques. In regenerative therapy or protein replacement therapy, skin fibroblasts or other cells are transfected with mRNA to enable conversion into induced pluripotent stem cells. This approach avoids the risk for DNA integration into the genome and associated mutation risks.
Another approach is making post-transcriptional modifications through RNA interference. For example, RNA structures can be used to inhibit the translation of disease-causing proteins. This technique is currently being tested against HIV and tumors such as melanoma.
In addition, mRNA technologies can be combined with CRISPR/Cas9 technology (“gene scissors”) to influence the creation of gene products even more precisely. The advantage of this technique is that mRNA is only transiently expressed, thus preventing unwanted side effects. Furthermore, mRNA is translated directly in the cytoplasm, leading to a faster initiation of gene editing.
Of the numerous ongoing clinical mRNA vaccine studies, around 70% focus on infections, about 12% on cancer, and the rest on autoimmune diseases and neurodegenerative disorders, said Dr. Prelog.
Research in Infections
Research in the fields of infectious diseases and oncology is the most advanced: mRNA vaccines against influenza and RSV are already in advanced clinical trials, Dr. Prelog told this news organization.
“Conventional influenza vaccines contain immunogenic surface molecules against hemagglutinin and neuraminidase in various combinations of influenza strains A and B and are produced in egg or cell cultures,” she said. “This is a time-consuming manufacturing process that takes months and, particularly with the egg-based process, bears the risk of changing the vaccine strain.”
“Additionally, influenza viruses undergo antigenic shift and drift through recombination, thus requiring annual adjustments to the vaccines. Thus, these influenza vaccines often lose accuracy in targeting circulating seasonal influenza strains.”
Several mRNA vaccines being tested contain not only coding sequences against hemagglutinin and neuraminidase but also for structural proteins of influenza viruses. “These are more conserved and mutate less easily, meaning they could serve as the basis for universal pandemic influenza vaccines,” said Dr. Prelog.
An advantage of mRNA vaccines, she added, is the strong cellular immune response that they elicit. This response is intended to provide additional protection alongside specific antibodies. An mRNA vaccine with coding sequences for the pre-fusion protein of RSV is in phase 3 trials for approval for vaccination in patients aged 60 years and older. It shows high effectiveness even in older patients and those with comorbidities.
Elaborate Purification Process
Bacterial origin plasmid DNA is used to produce mRNA vaccines. The mRNA vaccines for COVID-19 raised concerns that production-related DNA residues could pose a safety risk and cause autoimmune diseases.
These vaccines “typically undergo a very elaborate purification process,” said Dr. Prelog. “This involves enzymatic digestion with DNase to fragment and deplete plasmid DNA, followed by purification using chromatography columns, so that no safety-relevant DNA fragments should remain afterward.”
Thus, the Paul-Ehrlich-Institut also pointed out the very small, fragmented plasmid DNA residues of bacterial origin in mRNA COVID-19 vaccines pose no risk, unlike residual DNA from animal cell culture might pose in other vaccines.
Prevention and Therapy
In addition to the numerous advantages of mRNA vaccines (such as rapid adaptability to new or mutated pathogens, scalability, rapid production capability, self-adjuvant effect, strong induction of cellular immune responses, and safety), there are also challenges in RNA technology as a preventive and therapeutic measure, according to Dr. Prelog.
“Stability and storability, as well as the costs of new vaccine developments, play a role, as do the long-term effects regarding the persistence of antibody and cellular responses,” she said. The COVID-19 mRNA vaccines, for example, showed a well-maintained cellular immune response despite a tendency toward a rapid decline in humoral immune response.
“The experience with COVID-19 mRNA vaccines and the new vaccine developments based on mRNA technology give hope for an efficient and safe preventive and therapeutic use, particularly in the fields of infectious diseases and oncology,” Dr. Prelog concluded.
This story was translated from the Medscape German edition 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.
Martina Prelog, MD, a pediatric and adolescent medicine specialist at the University Hospital of Würzburg in Germany, reported on the principles, research status, and perspectives for these vaccines at the 25th Travel and Health Forum of the Center for Travel Medicine in Berlin.
To understand the future, the immunologist first examined the past. “The induction of cellular and humoral immune responses by externally injected mRNA was discovered in the 1990s,” she said.
Instability Challenge
Significant hurdles in mRNA vaccinations included the instability of mRNA and the immune system’s ability to identify foreign mRNA as a threat and destroy mRNA fragments. “The breakthrough toward vaccination came through Dr. Katalin Karikó, who, along with Dr. Drew Weissman, both of the University of Pennsylvania School of Medicine, discovered in 2005 that modifications of mRNA (replacing the nucleoside uridine with pseudouridine) enable better stability of mRNA, reduced immunogenicity, and higher translational capacity at the ribosomes,” said Dr. Prelog.
With this discovery, the two researchers paved the way for the development of mRNA vaccines against COVID-19 and other diseases. They were awarded the Nobel Prize in medicine for their discovery last year.
Improved Scalability
“Since 2009, mRNA vaccines have been studied as a treatment option for cancer,” said Dr. Prelog. “Since 2012, they have been studied for the influenza virus and respiratory syncytial virus [RSV].” Consequently, several mRNA vaccines are currently in development or in approval studies. “The mRNA technology offers the advantage of quickly and flexibly responding to new variants of pathogens and the ability to scale up production when there is high demand for a particular vaccine.”
Different forms and designations of mRNA vaccines are used, depending on the application and desired effect, said Dr. Prelog.
In nucleoside-modified mRNA vaccines, modifications in the mRNA sequence enable the mRNA to remain in the body longer and to induce protein synthesis more effectively.
Lipid nanoparticle (LNP)–encapsulated mRNA vaccines protect the coding mRNA sequences against degradation by the body’s enzymes and facilitate the uptake of mRNA into cells, where it then triggers the production of the desired protein. In addition, LNPs are involved in cell stimulation and support the self-adjuvant effect of mRNA vaccines, thus eliminating the need for adjuvants.
Self-amplifying mRNA vaccines include a special mRNA that replicates itself in the cell and contains a sequence for RNA replicase, in addition to the coding sequence for the protein. This composition enables increased production of the target protein without the need for a high amount of external mRNA administration. Such vaccines could trigger a longer and stronger immune response because the immune system has more time to interact with the protein.
Cancer Immunotherapy
Dr. Prelog also discussed personalized vaccines for cancer immunotherapy. Personalized mRNA vaccines are tailored to the patient’s genetic characteristics and antigens. They could be used in cancer immunotherapy to activate the immune system selectively against tumor cells.
Multivalent mRNA vaccines contain mRNA that codes for multiple antigens rather than just one protein to generate an immune response. These vaccines could be particularly useful in fighting pathogens with variable or changing surface structures or in eliciting protection against multiple pathogens simultaneously.
The technology of mRNA-encoded antibodies involves introducing mRNA into the cell, which creates light and heavy chains of antibodies. This step leads to the formation of antibodies targeted against toxins (eg, diphtheria and tetanus), animal venoms, infectious agents, or tumor cells.
Genetic Engineering
Dr. Prelog also reviewed genetic engineering techniques. In regenerative therapy or protein replacement therapy, skin fibroblasts or other cells are transfected with mRNA to enable conversion into induced pluripotent stem cells. This approach avoids the risk for DNA integration into the genome and associated mutation risks.
Another approach is making post-transcriptional modifications through RNA interference. For example, RNA structures can be used to inhibit the translation of disease-causing proteins. This technique is currently being tested against HIV and tumors such as melanoma.
In addition, mRNA technologies can be combined with CRISPR/Cas9 technology (“gene scissors”) to influence the creation of gene products even more precisely. The advantage of this technique is that mRNA is only transiently expressed, thus preventing unwanted side effects. Furthermore, mRNA is translated directly in the cytoplasm, leading to a faster initiation of gene editing.
Of the numerous ongoing clinical mRNA vaccine studies, around 70% focus on infections, about 12% on cancer, and the rest on autoimmune diseases and neurodegenerative disorders, said Dr. Prelog.
Research in Infections
Research in the fields of infectious diseases and oncology is the most advanced: mRNA vaccines against influenza and RSV are already in advanced clinical trials, Dr. Prelog told this news organization.
“Conventional influenza vaccines contain immunogenic surface molecules against hemagglutinin and neuraminidase in various combinations of influenza strains A and B and are produced in egg or cell cultures,” she said. “This is a time-consuming manufacturing process that takes months and, particularly with the egg-based process, bears the risk of changing the vaccine strain.”
“Additionally, influenza viruses undergo antigenic shift and drift through recombination, thus requiring annual adjustments to the vaccines. Thus, these influenza vaccines often lose accuracy in targeting circulating seasonal influenza strains.”
Several mRNA vaccines being tested contain not only coding sequences against hemagglutinin and neuraminidase but also for structural proteins of influenza viruses. “These are more conserved and mutate less easily, meaning they could serve as the basis for universal pandemic influenza vaccines,” said Dr. Prelog.
An advantage of mRNA vaccines, she added, is the strong cellular immune response that they elicit. This response is intended to provide additional protection alongside specific antibodies. An mRNA vaccine with coding sequences for the pre-fusion protein of RSV is in phase 3 trials for approval for vaccination in patients aged 60 years and older. It shows high effectiveness even in older patients and those with comorbidities.
Elaborate Purification Process
Bacterial origin plasmid DNA is used to produce mRNA vaccines. The mRNA vaccines for COVID-19 raised concerns that production-related DNA residues could pose a safety risk and cause autoimmune diseases.
These vaccines “typically undergo a very elaborate purification process,” said Dr. Prelog. “This involves enzymatic digestion with DNase to fragment and deplete plasmid DNA, followed by purification using chromatography columns, so that no safety-relevant DNA fragments should remain afterward.”
Thus, the Paul-Ehrlich-Institut also pointed out the very small, fragmented plasmid DNA residues of bacterial origin in mRNA COVID-19 vaccines pose no risk, unlike residual DNA from animal cell culture might pose in other vaccines.
Prevention and Therapy
In addition to the numerous advantages of mRNA vaccines (such as rapid adaptability to new or mutated pathogens, scalability, rapid production capability, self-adjuvant effect, strong induction of cellular immune responses, and safety), there are also challenges in RNA technology as a preventive and therapeutic measure, according to Dr. Prelog.
“Stability and storability, as well as the costs of new vaccine developments, play a role, as do the long-term effects regarding the persistence of antibody and cellular responses,” she said. The COVID-19 mRNA vaccines, for example, showed a well-maintained cellular immune response despite a tendency toward a rapid decline in humoral immune response.
“The experience with COVID-19 mRNA vaccines and the new vaccine developments based on mRNA technology give hope for an efficient and safe preventive and therapeutic use, particularly in the fields of infectious diseases and oncology,” Dr. Prelog concluded.
This story was translated from the Medscape German edition 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.
Climate Change’s Impact on Respiratory Care to Increase
Extreme heat, wildfires, and particulate matter not from wildfires were the most studied climate issues in conjunction with increased respiratory care, based on data from more than 60 studies.
Recent local events prompted Dr. Lewy and colleagues to examine the current landscape of climate change studies and respiratory healthcare.
“Last summer, when Canadian wildfire smoke enveloped the Midwest and the East Coast, patients presented with exacerbations of asthma and COPD to our clinics,” corresponding author Alexander S. Rabin, MD, of the University of Michigan, said in an interview.
“The event was a reminder of the increasing health threats that our most vulnerable patients face from climate change,” he said. “The smoke events also got us thinking about how health systems around the world are preparing, and we wanted to better understand what is known about the impacts of climate change on healthcare delivery to patients with lung disease and look for blind spots in the research,” he explained.
In the review, published in The Journal of Climate Change and Health, the researchers identified 67 studies related to climate and respiratory care; 50 of these were published between 2020 and 2023.
The most frequently studied climate and weather topics were extreme heat (31 studies), particulate matter not from wildfires (22 studies), and wildfires (19 studies).
The most common respiratory-related outcomes were respiratory-related hospital admissions (33 studies) and respiratory-related emergency department (ED) visits (24 studies).
Few studies addressed the potential impact of climate on telehealth, facility energy distribution, and pharmaceutical supplies, the researchers wrote. Notably, only one study in the review showed an association between power outages in New York City and higher chronic obstructive pulmonary disease (COPD)-related hospital admission rates, and no primary research emerged on the effects of climate change on respiratory medicine supply or distribution, they said.
Findings from studies with demographic breakdowns included evidence of greater effects of extreme weather on elderly populations compared with younger groups, and data from the seven studies focused on children showed a particular risk for climate-related respiratory exacerbations among those younger than 5 years.
The findings of the review were limited by several factors including the targeted article selection and potential misclassification bias, as respiratory outcomes often overlapped with cardiac or other outcomes, the researchers noted.
However, the results highlighted three key areas for future research. First, more studies are needed on the impact of climate on understudied populations in areas such as Africa, South America, Asia, and the Caribbean. Second, studies are needed on the impact of climate on respiratory care beyond acute care, with attention to primary and specialty respiratory care use, supply chain impacts, and effects on long-term pulmonary care and rehabilitation. Finally, more research is needed to explore solutions to the increased demands on pulmonary care in the context of climate change, including the use of telehealth, the authors wrote.
Limitations and Research Gaps
“While we found extensive published research chronicling the acute respiratory health impacts of climate change and extreme weather, such as heat waves and wildfires, we were surprised to find few studies on health system adaptation,” Dr. Rabin told this news organization.
“Although we know that prevention and long-term disease management are critical, studies looking at primary care impacts on respiratory care, healthcare infrastructure hardening, and medication supply chain resilience were largely absent from the literature,” he said. “We were further struck by the limited amount of research originating from the most climate-affected areas such as in the Global South, where outdoor air pollution already results in over 4 million deaths per year,” he noted.
Although clinicians increasingly recognize that climate change and extreme weather threaten lung health, solutions are needed to make health systems resilient, accessible, and adaptable, especially with the likely increase in demand for respiratory care, Dr. Rabin emphasized.
More research is needed on preventive measures that could mitigate the risk for bad air quality, heat, and other extreme climate change events on vulnerable populations, said Dr. Rabin. “Every domain of healthcare delivery, from pharmaceutical procurement to hospital heating and cooling system design, must account for these environmental changes,” he said. “More collaboration is needed with researchers and clinicians in areas of the world that are underrepresented and underresourced to help share knowledge and tools to build health system resilience.”
Takeaways and Next Steps
“I was struck by how many studies used healthcare metrics as a way to measure health outcomes but not to measure resilience and efficiency of healthcare systems themselves,” Dr. Lewy said in an interview. “For example, many studies used ED visits or hospital admissions as ways to measure severity of disease associated with a climate event, but the strain that increased visits or admissions have on healthcare systems was barely mentioned,” she noted.
Looking ahead, more studies that focus specifically on infrastructure as it relates to healthcare would be valuable, said Dr. Lewy. Recent research has explored virtual care as a way to mitigate climate change-associated COPD exacerbations, but virtual care may not be reliably accessible in cases of the widespread power and network outages that often accompany storms, heat waves, and other catastrophic weather events, she noted. “More research into these types of logistical factors affecting healthcare systems would be helpful,” she added.
Dr. Rabin disclosed support for the study from the US Department of Veterans Affairs but had no other financial conflicts to disclose. Dr. Lewy had no financial conflicts to disclose.
A version of this article appeared on Medscape.com.
Extreme heat, wildfires, and particulate matter not from wildfires were the most studied climate issues in conjunction with increased respiratory care, based on data from more than 60 studies.
Recent local events prompted Dr. Lewy and colleagues to examine the current landscape of climate change studies and respiratory healthcare.
“Last summer, when Canadian wildfire smoke enveloped the Midwest and the East Coast, patients presented with exacerbations of asthma and COPD to our clinics,” corresponding author Alexander S. Rabin, MD, of the University of Michigan, said in an interview.
“The event was a reminder of the increasing health threats that our most vulnerable patients face from climate change,” he said. “The smoke events also got us thinking about how health systems around the world are preparing, and we wanted to better understand what is known about the impacts of climate change on healthcare delivery to patients with lung disease and look for blind spots in the research,” he explained.
In the review, published in The Journal of Climate Change and Health, the researchers identified 67 studies related to climate and respiratory care; 50 of these were published between 2020 and 2023.
The most frequently studied climate and weather topics were extreme heat (31 studies), particulate matter not from wildfires (22 studies), and wildfires (19 studies).
The most common respiratory-related outcomes were respiratory-related hospital admissions (33 studies) and respiratory-related emergency department (ED) visits (24 studies).
Few studies addressed the potential impact of climate on telehealth, facility energy distribution, and pharmaceutical supplies, the researchers wrote. Notably, only one study in the review showed an association between power outages in New York City and higher chronic obstructive pulmonary disease (COPD)-related hospital admission rates, and no primary research emerged on the effects of climate change on respiratory medicine supply or distribution, they said.
Findings from studies with demographic breakdowns included evidence of greater effects of extreme weather on elderly populations compared with younger groups, and data from the seven studies focused on children showed a particular risk for climate-related respiratory exacerbations among those younger than 5 years.
The findings of the review were limited by several factors including the targeted article selection and potential misclassification bias, as respiratory outcomes often overlapped with cardiac or other outcomes, the researchers noted.
However, the results highlighted three key areas for future research. First, more studies are needed on the impact of climate on understudied populations in areas such as Africa, South America, Asia, and the Caribbean. Second, studies are needed on the impact of climate on respiratory care beyond acute care, with attention to primary and specialty respiratory care use, supply chain impacts, and effects on long-term pulmonary care and rehabilitation. Finally, more research is needed to explore solutions to the increased demands on pulmonary care in the context of climate change, including the use of telehealth, the authors wrote.
Limitations and Research Gaps
“While we found extensive published research chronicling the acute respiratory health impacts of climate change and extreme weather, such as heat waves and wildfires, we were surprised to find few studies on health system adaptation,” Dr. Rabin told this news organization.
“Although we know that prevention and long-term disease management are critical, studies looking at primary care impacts on respiratory care, healthcare infrastructure hardening, and medication supply chain resilience were largely absent from the literature,” he said. “We were further struck by the limited amount of research originating from the most climate-affected areas such as in the Global South, where outdoor air pollution already results in over 4 million deaths per year,” he noted.
Although clinicians increasingly recognize that climate change and extreme weather threaten lung health, solutions are needed to make health systems resilient, accessible, and adaptable, especially with the likely increase in demand for respiratory care, Dr. Rabin emphasized.
More research is needed on preventive measures that could mitigate the risk for bad air quality, heat, and other extreme climate change events on vulnerable populations, said Dr. Rabin. “Every domain of healthcare delivery, from pharmaceutical procurement to hospital heating and cooling system design, must account for these environmental changes,” he said. “More collaboration is needed with researchers and clinicians in areas of the world that are underrepresented and underresourced to help share knowledge and tools to build health system resilience.”
Takeaways and Next Steps
“I was struck by how many studies used healthcare metrics as a way to measure health outcomes but not to measure resilience and efficiency of healthcare systems themselves,” Dr. Lewy said in an interview. “For example, many studies used ED visits or hospital admissions as ways to measure severity of disease associated with a climate event, but the strain that increased visits or admissions have on healthcare systems was barely mentioned,” she noted.
Looking ahead, more studies that focus specifically on infrastructure as it relates to healthcare would be valuable, said Dr. Lewy. Recent research has explored virtual care as a way to mitigate climate change-associated COPD exacerbations, but virtual care may not be reliably accessible in cases of the widespread power and network outages that often accompany storms, heat waves, and other catastrophic weather events, she noted. “More research into these types of logistical factors affecting healthcare systems would be helpful,” she added.
Dr. Rabin disclosed support for the study from the US Department of Veterans Affairs but had no other financial conflicts to disclose. Dr. Lewy had no financial conflicts to disclose.
A version of this article appeared on Medscape.com.
Extreme heat, wildfires, and particulate matter not from wildfires were the most studied climate issues in conjunction with increased respiratory care, based on data from more than 60 studies.
Recent local events prompted Dr. Lewy and colleagues to examine the current landscape of climate change studies and respiratory healthcare.
“Last summer, when Canadian wildfire smoke enveloped the Midwest and the East Coast, patients presented with exacerbations of asthma and COPD to our clinics,” corresponding author Alexander S. Rabin, MD, of the University of Michigan, said in an interview.
“The event was a reminder of the increasing health threats that our most vulnerable patients face from climate change,” he said. “The smoke events also got us thinking about how health systems around the world are preparing, and we wanted to better understand what is known about the impacts of climate change on healthcare delivery to patients with lung disease and look for blind spots in the research,” he explained.
In the review, published in The Journal of Climate Change and Health, the researchers identified 67 studies related to climate and respiratory care; 50 of these were published between 2020 and 2023.
The most frequently studied climate and weather topics were extreme heat (31 studies), particulate matter not from wildfires (22 studies), and wildfires (19 studies).
The most common respiratory-related outcomes were respiratory-related hospital admissions (33 studies) and respiratory-related emergency department (ED) visits (24 studies).
Few studies addressed the potential impact of climate on telehealth, facility energy distribution, and pharmaceutical supplies, the researchers wrote. Notably, only one study in the review showed an association between power outages in New York City and higher chronic obstructive pulmonary disease (COPD)-related hospital admission rates, and no primary research emerged on the effects of climate change on respiratory medicine supply or distribution, they said.
Findings from studies with demographic breakdowns included evidence of greater effects of extreme weather on elderly populations compared with younger groups, and data from the seven studies focused on children showed a particular risk for climate-related respiratory exacerbations among those younger than 5 years.
The findings of the review were limited by several factors including the targeted article selection and potential misclassification bias, as respiratory outcomes often overlapped with cardiac or other outcomes, the researchers noted.
However, the results highlighted three key areas for future research. First, more studies are needed on the impact of climate on understudied populations in areas such as Africa, South America, Asia, and the Caribbean. Second, studies are needed on the impact of climate on respiratory care beyond acute care, with attention to primary and specialty respiratory care use, supply chain impacts, and effects on long-term pulmonary care and rehabilitation. Finally, more research is needed to explore solutions to the increased demands on pulmonary care in the context of climate change, including the use of telehealth, the authors wrote.
Limitations and Research Gaps
“While we found extensive published research chronicling the acute respiratory health impacts of climate change and extreme weather, such as heat waves and wildfires, we were surprised to find few studies on health system adaptation,” Dr. Rabin told this news organization.
“Although we know that prevention and long-term disease management are critical, studies looking at primary care impacts on respiratory care, healthcare infrastructure hardening, and medication supply chain resilience were largely absent from the literature,” he said. “We were further struck by the limited amount of research originating from the most climate-affected areas such as in the Global South, where outdoor air pollution already results in over 4 million deaths per year,” he noted.
Although clinicians increasingly recognize that climate change and extreme weather threaten lung health, solutions are needed to make health systems resilient, accessible, and adaptable, especially with the likely increase in demand for respiratory care, Dr. Rabin emphasized.
More research is needed on preventive measures that could mitigate the risk for bad air quality, heat, and other extreme climate change events on vulnerable populations, said Dr. Rabin. “Every domain of healthcare delivery, from pharmaceutical procurement to hospital heating and cooling system design, must account for these environmental changes,” he said. “More collaboration is needed with researchers and clinicians in areas of the world that are underrepresented and underresourced to help share knowledge and tools to build health system resilience.”
Takeaways and Next Steps
“I was struck by how many studies used healthcare metrics as a way to measure health outcomes but not to measure resilience and efficiency of healthcare systems themselves,” Dr. Lewy said in an interview. “For example, many studies used ED visits or hospital admissions as ways to measure severity of disease associated with a climate event, but the strain that increased visits or admissions have on healthcare systems was barely mentioned,” she noted.
Looking ahead, more studies that focus specifically on infrastructure as it relates to healthcare would be valuable, said Dr. Lewy. Recent research has explored virtual care as a way to mitigate climate change-associated COPD exacerbations, but virtual care may not be reliably accessible in cases of the widespread power and network outages that often accompany storms, heat waves, and other catastrophic weather events, she noted. “More research into these types of logistical factors affecting healthcare systems would be helpful,” she added.
Dr. Rabin disclosed support for the study from the US Department of Veterans Affairs but had no other financial conflicts to disclose. Dr. Lewy had no financial conflicts to disclose.
A version of this article appeared on Medscape.com.
National Mine Safety Group Issues Rule to Reduce Silica Exposure
The Mine Safety and Health Administration (MSHA) has announced a new final rule designed to protect miners from the dangers of exposure to silica dust, according to a press release from the US Department of Labor.
including silicosis, lung cancer, progressive massive fibrosis, chronic bronchitis, and kidney disease.
The MSHA final rule reduces the permissible exposure limit of respirable crystalline silica to 50 micrograms per cubic meter of air for a miner›s full-shift exposure, which was calculated as an 8-hour time-weighted average. If a miner’s exposure exceeds this limit, mine operators must take immediate action to comply with it, according to the new final rule.
“It is unconscionable that our nation’s miners have worked without adequate protection from silica dust despite it being a known health hazard for decades,” said Department of Labor acting secretary Julie Su, in the press release. “The Department of Labor has taken an important action to finally reduce miners’ exposure to toxic silica dust and protect them from suffering from preventable diseases,” she said.
The final rule requires mine operators to prevent miners’ overexposures by using engineering controls and to use environmental evaluations and dust samplings to monitor their exposures. The rule also updates standards for respiratory protection to include the latest advances in equipment and practices to safeguard miners against a range of airborne hazards including silica dust, diesel particulate matter, and asbestos.
In addition, the rule requires metal and nonmetal mine operators to establish medical surveillance programs and provide periodic health examinations to minors at no cost, similar to existing programs for coal miners, according to the press release.
Implementation of the rule will result in approximately 1067 lifetime avoided deaths and 3746 lifetime avoided cases of silica-related illness, according to MSHA.
“Congress gave MSHA the authority to regulate toxic substances to protect miners from health hazards and made clear in the Mine Act that miners’ health and safety must always be our first priority and concern,” said Chris Williamson, assistant secretary for mine safety and health, in the press release. “To further advance this directive, MSHA is committed to working together with everyone in the mining community to implement this rule successfully. No miner should ever have to sacrifice their health or lungs to provide for their family,” he said.
A version of this article appeared on Medscape.com.
The Mine Safety and Health Administration (MSHA) has announced a new final rule designed to protect miners from the dangers of exposure to silica dust, according to a press release from the US Department of Labor.
including silicosis, lung cancer, progressive massive fibrosis, chronic bronchitis, and kidney disease.
The MSHA final rule reduces the permissible exposure limit of respirable crystalline silica to 50 micrograms per cubic meter of air for a miner›s full-shift exposure, which was calculated as an 8-hour time-weighted average. If a miner’s exposure exceeds this limit, mine operators must take immediate action to comply with it, according to the new final rule.
“It is unconscionable that our nation’s miners have worked without adequate protection from silica dust despite it being a known health hazard for decades,” said Department of Labor acting secretary Julie Su, in the press release. “The Department of Labor has taken an important action to finally reduce miners’ exposure to toxic silica dust and protect them from suffering from preventable diseases,” she said.
The final rule requires mine operators to prevent miners’ overexposures by using engineering controls and to use environmental evaluations and dust samplings to monitor their exposures. The rule also updates standards for respiratory protection to include the latest advances in equipment and practices to safeguard miners against a range of airborne hazards including silica dust, diesel particulate matter, and asbestos.
In addition, the rule requires metal and nonmetal mine operators to establish medical surveillance programs and provide periodic health examinations to minors at no cost, similar to existing programs for coal miners, according to the press release.
Implementation of the rule will result in approximately 1067 lifetime avoided deaths and 3746 lifetime avoided cases of silica-related illness, according to MSHA.
“Congress gave MSHA the authority to regulate toxic substances to protect miners from health hazards and made clear in the Mine Act that miners’ health and safety must always be our first priority and concern,” said Chris Williamson, assistant secretary for mine safety and health, in the press release. “To further advance this directive, MSHA is committed to working together with everyone in the mining community to implement this rule successfully. No miner should ever have to sacrifice their health or lungs to provide for their family,” he said.
A version of this article appeared on Medscape.com.
The Mine Safety and Health Administration (MSHA) has announced a new final rule designed to protect miners from the dangers of exposure to silica dust, according to a press release from the US Department of Labor.
including silicosis, lung cancer, progressive massive fibrosis, chronic bronchitis, and kidney disease.
The MSHA final rule reduces the permissible exposure limit of respirable crystalline silica to 50 micrograms per cubic meter of air for a miner›s full-shift exposure, which was calculated as an 8-hour time-weighted average. If a miner’s exposure exceeds this limit, mine operators must take immediate action to comply with it, according to the new final rule.
“It is unconscionable that our nation’s miners have worked without adequate protection from silica dust despite it being a known health hazard for decades,” said Department of Labor acting secretary Julie Su, in the press release. “The Department of Labor has taken an important action to finally reduce miners’ exposure to toxic silica dust and protect them from suffering from preventable diseases,” she said.
The final rule requires mine operators to prevent miners’ overexposures by using engineering controls and to use environmental evaluations and dust samplings to monitor their exposures. The rule also updates standards for respiratory protection to include the latest advances in equipment and practices to safeguard miners against a range of airborne hazards including silica dust, diesel particulate matter, and asbestos.
In addition, the rule requires metal and nonmetal mine operators to establish medical surveillance programs and provide periodic health examinations to minors at no cost, similar to existing programs for coal miners, according to the press release.
Implementation of the rule will result in approximately 1067 lifetime avoided deaths and 3746 lifetime avoided cases of silica-related illness, according to MSHA.
“Congress gave MSHA the authority to regulate toxic substances to protect miners from health hazards and made clear in the Mine Act that miners’ health and safety must always be our first priority and concern,” said Chris Williamson, assistant secretary for mine safety and health, in the press release. “To further advance this directive, MSHA is committed to working together with everyone in the mining community to implement this rule successfully. No miner should ever have to sacrifice their health or lungs to provide for their family,” he said.
A version of this article appeared on Medscape.com.
Avian Flu Threat Still Low and Vaccine Measures Are Ready
After cow-to-cow transmission of avian influenza A subtype H5N1 in US dairy herds led to a cow-to-human transmission in Texas, the Association of State and Territorial Health Officials convened a panel of experts for a scientific symposium on Thursday to talk about the public health implications.
From the sequencing data, “we can expect and anticipate that [the candidate vaccine viruses] will provide good protection,” she explained.
Establishing candidate vaccine viruses “are the precursor to moving into large-scale vaccine production,” Dr. Dugan explained. Should that be needed, the candidate viruses can be used by manufacturers to produce new vaccines.
The CDC is also actively partnering with commercial diagnostic developers and testing companies in case there is a need to scale-up testing, Dr. Dugan said.
The only current human case in the United States was reported on April 1 and confirmed by the CDC within 24 hours, reported Sonja Olsen, PhD, associate director for preparedness and response of the Influenza Division at the CDC.
The person had direct exposure to cattle and reported eye redness, consistent with conjunctivitis, as the only symptom. The person received treatment and has recovered, and there were no reports of illness among the person’s household contacts, Dr. Olsen said.
Person With the Virus Has Recovered
The only other detection of the virus in a human in the United States was in 2022 and it was associated with infected poultry exposure. That person also had mild illness and recovered, Dr. Olsen explained.
Since 1997, when the first case of human infection was reported globally, “there have been 909 [human cases] reported from 23 countries,” Dr. Olsen said. “About half [52%] of the human cases have resulted in death.” Only a small number of human cases have been reported since 2015, but since 2022, more than two dozen human cases have been reported to the World Health Organization.
Experience with the virus in the United States has been about a year behind that in Europe, said Rosemary Sifford, DVM, chief veterinary officer at the US Department of Agriculture. In the United States, the first detection — in January 2022 — was in wild birds; this was followed the next month by the first detection in a commercial poultry flock.
In March of this year, the United States had its first detection in cattle, specifically dairy cattle. But testing has shown that “it remains very much an avian virus. It’s not becoming a bovine virus,” Dr. Sifford reported.
Detected in Cattle
Earlier this week, in an effort to minimize the risk of disease spread, the USDA issued a federal order that requires the reporting of positive influenza tests in livestock and mandatory testing for influenza of dairy cattle before interstate movement.
“As of today, there are affected herds in 33 farms across eight states,” reported Dr. Olsen.
Tests are ongoing to determine how the virus is traveling, but “what we can say is that there’s a high viral load in the milk in the cattle, and it appears that the transmission is happening mostly within the lactating herds,” Dr. Sifford reported. It is unclear whether that is happening during the milking of the cows or whether contaminated milk from a cow with a high viral load is transmitting the virus to other cattle.
“We are strongly encouraging producers to limit the movement of cattle, particularly lactating cattle, as much as possible,” she says.
Milk Is Likely the Source of Transmission
“We haven’t seen anything that would change our assessment that the commercial milk supply is safe,” says Donald Prater, DVM, acting director of the Center for Food Safety and Applied Nutrition at the US Food and Drug Administration (FDA).
In the federal and state milk safety system, he explained, nearly 99% of the commercial milk supply comes from farms that participate in the Grade A program and follow the Pasteurized Milk Ordinance, which outlines pasteurization requirements.
Because detection of the virus in dairy cattle is new, there are many questions to be answered in research, he reported. Among them:
- What level of virus might be leaving the farms from shedding by apparently healthy cows?
- Does any live virus survive the pasteurization process?
- Do different methods of pasteurization and dairy production have different effects on the viability of H5N1?
- Are effects different in various forms of dairy products, such as cheese and cream?
A critical question regarding the potential risk to humans is how much milk would have to be consumed for the virus to become an established infection. That information is essential to determine “what type of pasteurization criteria” are needed to provide “acceptable public health outcomes,” Dr. Prater said.
The CDC is currently using the flu surveillance system to monitor for H5N1 activity in people. The systems show no current indicators of unusual influenza activity in people.
A version of this article appeared on Medscape.com.
After cow-to-cow transmission of avian influenza A subtype H5N1 in US dairy herds led to a cow-to-human transmission in Texas, the Association of State and Territorial Health Officials convened a panel of experts for a scientific symposium on Thursday to talk about the public health implications.
From the sequencing data, “we can expect and anticipate that [the candidate vaccine viruses] will provide good protection,” she explained.
Establishing candidate vaccine viruses “are the precursor to moving into large-scale vaccine production,” Dr. Dugan explained. Should that be needed, the candidate viruses can be used by manufacturers to produce new vaccines.
The CDC is also actively partnering with commercial diagnostic developers and testing companies in case there is a need to scale-up testing, Dr. Dugan said.
The only current human case in the United States was reported on April 1 and confirmed by the CDC within 24 hours, reported Sonja Olsen, PhD, associate director for preparedness and response of the Influenza Division at the CDC.
The person had direct exposure to cattle and reported eye redness, consistent with conjunctivitis, as the only symptom. The person received treatment and has recovered, and there were no reports of illness among the person’s household contacts, Dr. Olsen said.
Person With the Virus Has Recovered
The only other detection of the virus in a human in the United States was in 2022 and it was associated with infected poultry exposure. That person also had mild illness and recovered, Dr. Olsen explained.
Since 1997, when the first case of human infection was reported globally, “there have been 909 [human cases] reported from 23 countries,” Dr. Olsen said. “About half [52%] of the human cases have resulted in death.” Only a small number of human cases have been reported since 2015, but since 2022, more than two dozen human cases have been reported to the World Health Organization.
Experience with the virus in the United States has been about a year behind that in Europe, said Rosemary Sifford, DVM, chief veterinary officer at the US Department of Agriculture. In the United States, the first detection — in January 2022 — was in wild birds; this was followed the next month by the first detection in a commercial poultry flock.
In March of this year, the United States had its first detection in cattle, specifically dairy cattle. But testing has shown that “it remains very much an avian virus. It’s not becoming a bovine virus,” Dr. Sifford reported.
Detected in Cattle
Earlier this week, in an effort to minimize the risk of disease spread, the USDA issued a federal order that requires the reporting of positive influenza tests in livestock and mandatory testing for influenza of dairy cattle before interstate movement.
“As of today, there are affected herds in 33 farms across eight states,” reported Dr. Olsen.
Tests are ongoing to determine how the virus is traveling, but “what we can say is that there’s a high viral load in the milk in the cattle, and it appears that the transmission is happening mostly within the lactating herds,” Dr. Sifford reported. It is unclear whether that is happening during the milking of the cows or whether contaminated milk from a cow with a high viral load is transmitting the virus to other cattle.
“We are strongly encouraging producers to limit the movement of cattle, particularly lactating cattle, as much as possible,” she says.
Milk Is Likely the Source of Transmission
“We haven’t seen anything that would change our assessment that the commercial milk supply is safe,” says Donald Prater, DVM, acting director of the Center for Food Safety and Applied Nutrition at the US Food and Drug Administration (FDA).
In the federal and state milk safety system, he explained, nearly 99% of the commercial milk supply comes from farms that participate in the Grade A program and follow the Pasteurized Milk Ordinance, which outlines pasteurization requirements.
Because detection of the virus in dairy cattle is new, there are many questions to be answered in research, he reported. Among them:
- What level of virus might be leaving the farms from shedding by apparently healthy cows?
- Does any live virus survive the pasteurization process?
- Do different methods of pasteurization and dairy production have different effects on the viability of H5N1?
- Are effects different in various forms of dairy products, such as cheese and cream?
A critical question regarding the potential risk to humans is how much milk would have to be consumed for the virus to become an established infection. That information is essential to determine “what type of pasteurization criteria” are needed to provide “acceptable public health outcomes,” Dr. Prater said.
The CDC is currently using the flu surveillance system to monitor for H5N1 activity in people. The systems show no current indicators of unusual influenza activity in people.
A version of this article appeared on Medscape.com.
After cow-to-cow transmission of avian influenza A subtype H5N1 in US dairy herds led to a cow-to-human transmission in Texas, the Association of State and Territorial Health Officials convened a panel of experts for a scientific symposium on Thursday to talk about the public health implications.
From the sequencing data, “we can expect and anticipate that [the candidate vaccine viruses] will provide good protection,” she explained.
Establishing candidate vaccine viruses “are the precursor to moving into large-scale vaccine production,” Dr. Dugan explained. Should that be needed, the candidate viruses can be used by manufacturers to produce new vaccines.
The CDC is also actively partnering with commercial diagnostic developers and testing companies in case there is a need to scale-up testing, Dr. Dugan said.
The only current human case in the United States was reported on April 1 and confirmed by the CDC within 24 hours, reported Sonja Olsen, PhD, associate director for preparedness and response of the Influenza Division at the CDC.
The person had direct exposure to cattle and reported eye redness, consistent with conjunctivitis, as the only symptom. The person received treatment and has recovered, and there were no reports of illness among the person’s household contacts, Dr. Olsen said.
Person With the Virus Has Recovered
The only other detection of the virus in a human in the United States was in 2022 and it was associated with infected poultry exposure. That person also had mild illness and recovered, Dr. Olsen explained.
Since 1997, when the first case of human infection was reported globally, “there have been 909 [human cases] reported from 23 countries,” Dr. Olsen said. “About half [52%] of the human cases have resulted in death.” Only a small number of human cases have been reported since 2015, but since 2022, more than two dozen human cases have been reported to the World Health Organization.
Experience with the virus in the United States has been about a year behind that in Europe, said Rosemary Sifford, DVM, chief veterinary officer at the US Department of Agriculture. In the United States, the first detection — in January 2022 — was in wild birds; this was followed the next month by the first detection in a commercial poultry flock.
In March of this year, the United States had its first detection in cattle, specifically dairy cattle. But testing has shown that “it remains very much an avian virus. It’s not becoming a bovine virus,” Dr. Sifford reported.
Detected in Cattle
Earlier this week, in an effort to minimize the risk of disease spread, the USDA issued a federal order that requires the reporting of positive influenza tests in livestock and mandatory testing for influenza of dairy cattle before interstate movement.
“As of today, there are affected herds in 33 farms across eight states,” reported Dr. Olsen.
Tests are ongoing to determine how the virus is traveling, but “what we can say is that there’s a high viral load in the milk in the cattle, and it appears that the transmission is happening mostly within the lactating herds,” Dr. Sifford reported. It is unclear whether that is happening during the milking of the cows or whether contaminated milk from a cow with a high viral load is transmitting the virus to other cattle.
“We are strongly encouraging producers to limit the movement of cattle, particularly lactating cattle, as much as possible,” she says.
Milk Is Likely the Source of Transmission
“We haven’t seen anything that would change our assessment that the commercial milk supply is safe,” says Donald Prater, DVM, acting director of the Center for Food Safety and Applied Nutrition at the US Food and Drug Administration (FDA).
In the federal and state milk safety system, he explained, nearly 99% of the commercial milk supply comes from farms that participate in the Grade A program and follow the Pasteurized Milk Ordinance, which outlines pasteurization requirements.
Because detection of the virus in dairy cattle is new, there are many questions to be answered in research, he reported. Among them:
- What level of virus might be leaving the farms from shedding by apparently healthy cows?
- Does any live virus survive the pasteurization process?
- Do different methods of pasteurization and dairy production have different effects on the viability of H5N1?
- Are effects different in various forms of dairy products, such as cheese and cream?
A critical question regarding the potential risk to humans is how much milk would have to be consumed for the virus to become an established infection. That information is essential to determine “what type of pasteurization criteria” are needed to provide “acceptable public health outcomes,” Dr. Prater said.
The CDC is currently using the flu surveillance system to monitor for H5N1 activity in people. The systems show no current indicators of unusual influenza activity in people.
A version of this article appeared on Medscape.com.
Automated Risk Assessment Tool Reduces Antibiotic Prescribing Rates
An algorithm-driven risk assessment embedded in an electronic health record (EHR) helped clinicians reduce inappropriate broad-spectrum antibiotic prescribing by 17.4% and 28.4% in patients with UTIs and pneumonia, respectively, according to two related studies published in JAMA.
The randomized control trials included more than 200,000 adult patients with non–life threatening pneumonia or urinary tract infections (UTIs) in 59 hospitals owned by HCA Healthcare across the country.
Researchers analyzed baseline prescribing behaviors over an 18-month period starting in April 2017, and data from a 15-month period of implementation of the new antibiotic system starting in April 2019.
, according to lead author Shruti K. Gohil, MD, MPH, associate medical director of epidemiology and infection prevention, infectious diseases at the University of California Irvine School of Medicine.
“When a patient comes in with pneumonia or a UTI, it’s precisely because we are concerned that our patients have a multidrug-resistant organism that we end up using broad-spectrum antibiotics,” she said.
Despite growing awareness of the need to reduce unnecessary antibiotic use, clinicians have still been slow to adopt a more conservative approach to prescribing, Dr. Gohil said.
“What physicians have been needing is something to hang their hat on, to be able to say, ‘Okay, well, this one’s a low-risk person,’ ” Dr. Gohil said.
The trials compared the impact of routine antibiotic activities with a stewardship bundle, called INSPIRE (Intelligent Stewardship Prompts to Improve Real-time Empiric Antibiotic Selection).
Both groups received educational materials, quarterly coaching calls, prospective evaluations for antibiotic use, and were required to select a reason for prescribing an antibiotic.
But prescribers in the intervention group took part in monthly coaching calls and feedback reports. In addition, if a clinician ordered a broad-spectrum antibiotic to treat pneumonia or a UTI outside of the intensive care unit within 72 hours of admission, an EHR prompt would pop up. The pop-up suggested a standard-spectrum antibiotic instead if patient risk for developing a multidrug-resistant (MDRO) version of either condition was less than 10%.
An algorithm used data from the EHR calculated risk, using factors like patient demographics and history and MDRO infection at the community and hospital level.
Prescribing rates were based on the number of days a patient received a broad-spectrum antibiotic during the first 72 hours of hospitalization.
For the UTI intervention group, rates dropped by 17.4% (rate ratio [RR], 0.83; 95% CI, 0.77-0.89; P < .001), and 28.4% reduction in the pneumonia group (RR, 0.72; 95% CI, 0.66-0.78; P < .001).
“We cannot know which element — prompt, education, or feedback — worked, but the data suggests that the prompt was the main driver,” Dr. Gohil said.
“In antibiotic stewardship, we have learned not only that doctors want to do the right thing, but that we as stewards need to make it easy for them do the right thing,” said Paul Pottinger, MD, professor of medicine at the Division of Allergy and Infectious Diseases at the University of Washington Medical Center in Seattle.
The prompt “is your easy button,” said Dr. Pottinger, who was not involved with either study. “The researchers made it simple, fast, and straightforward, so people don’t have to think about it too much.”
The studies showed similar safety outcomes for the control and intervention groups. Among patients with a UTI, those in the control group were transferred to the ICU after an average of 6.6 days compared to 7 days in the intervention group. Among patients with pneumonia, the average days to ICU transfer were 6.5 for the control group and 7.1 for the intervention group.
“This study is a proof of concept that physicians want to do the right thing and are willing to trust this information,” Dr. Pottinger said. “And this also shows us that this tool can be refined and made even more precise over time.”
The study was funded by the US Centers for Disease Control and Prevention and was led by the University of California Irvine, Harvard Pilgrim Healthcare Institute, and HCA Healthcare System. Various authors report funding and support from entities outside the submitted work. The full list can be found with the original articles.
A version of this article appeared on Medscape.com.
An algorithm-driven risk assessment embedded in an electronic health record (EHR) helped clinicians reduce inappropriate broad-spectrum antibiotic prescribing by 17.4% and 28.4% in patients with UTIs and pneumonia, respectively, according to two related studies published in JAMA.
The randomized control trials included more than 200,000 adult patients with non–life threatening pneumonia or urinary tract infections (UTIs) in 59 hospitals owned by HCA Healthcare across the country.
Researchers analyzed baseline prescribing behaviors over an 18-month period starting in April 2017, and data from a 15-month period of implementation of the new antibiotic system starting in April 2019.
, according to lead author Shruti K. Gohil, MD, MPH, associate medical director of epidemiology and infection prevention, infectious diseases at the University of California Irvine School of Medicine.
“When a patient comes in with pneumonia or a UTI, it’s precisely because we are concerned that our patients have a multidrug-resistant organism that we end up using broad-spectrum antibiotics,” she said.
Despite growing awareness of the need to reduce unnecessary antibiotic use, clinicians have still been slow to adopt a more conservative approach to prescribing, Dr. Gohil said.
“What physicians have been needing is something to hang their hat on, to be able to say, ‘Okay, well, this one’s a low-risk person,’ ” Dr. Gohil said.
The trials compared the impact of routine antibiotic activities with a stewardship bundle, called INSPIRE (Intelligent Stewardship Prompts to Improve Real-time Empiric Antibiotic Selection).
Both groups received educational materials, quarterly coaching calls, prospective evaluations for antibiotic use, and were required to select a reason for prescribing an antibiotic.
But prescribers in the intervention group took part in monthly coaching calls and feedback reports. In addition, if a clinician ordered a broad-spectrum antibiotic to treat pneumonia or a UTI outside of the intensive care unit within 72 hours of admission, an EHR prompt would pop up. The pop-up suggested a standard-spectrum antibiotic instead if patient risk for developing a multidrug-resistant (MDRO) version of either condition was less than 10%.
An algorithm used data from the EHR calculated risk, using factors like patient demographics and history and MDRO infection at the community and hospital level.
Prescribing rates were based on the number of days a patient received a broad-spectrum antibiotic during the first 72 hours of hospitalization.
For the UTI intervention group, rates dropped by 17.4% (rate ratio [RR], 0.83; 95% CI, 0.77-0.89; P < .001), and 28.4% reduction in the pneumonia group (RR, 0.72; 95% CI, 0.66-0.78; P < .001).
“We cannot know which element — prompt, education, or feedback — worked, but the data suggests that the prompt was the main driver,” Dr. Gohil said.
“In antibiotic stewardship, we have learned not only that doctors want to do the right thing, but that we as stewards need to make it easy for them do the right thing,” said Paul Pottinger, MD, professor of medicine at the Division of Allergy and Infectious Diseases at the University of Washington Medical Center in Seattle.
The prompt “is your easy button,” said Dr. Pottinger, who was not involved with either study. “The researchers made it simple, fast, and straightforward, so people don’t have to think about it too much.”
The studies showed similar safety outcomes for the control and intervention groups. Among patients with a UTI, those in the control group were transferred to the ICU after an average of 6.6 days compared to 7 days in the intervention group. Among patients with pneumonia, the average days to ICU transfer were 6.5 for the control group and 7.1 for the intervention group.
“This study is a proof of concept that physicians want to do the right thing and are willing to trust this information,” Dr. Pottinger said. “And this also shows us that this tool can be refined and made even more precise over time.”
The study was funded by the US Centers for Disease Control and Prevention and was led by the University of California Irvine, Harvard Pilgrim Healthcare Institute, and HCA Healthcare System. Various authors report funding and support from entities outside the submitted work. The full list can be found with the original articles.
A version of this article appeared on Medscape.com.
An algorithm-driven risk assessment embedded in an electronic health record (EHR) helped clinicians reduce inappropriate broad-spectrum antibiotic prescribing by 17.4% and 28.4% in patients with UTIs and pneumonia, respectively, according to two related studies published in JAMA.
The randomized control trials included more than 200,000 adult patients with non–life threatening pneumonia or urinary tract infections (UTIs) in 59 hospitals owned by HCA Healthcare across the country.
Researchers analyzed baseline prescribing behaviors over an 18-month period starting in April 2017, and data from a 15-month period of implementation of the new antibiotic system starting in April 2019.
, according to lead author Shruti K. Gohil, MD, MPH, associate medical director of epidemiology and infection prevention, infectious diseases at the University of California Irvine School of Medicine.
“When a patient comes in with pneumonia or a UTI, it’s precisely because we are concerned that our patients have a multidrug-resistant organism that we end up using broad-spectrum antibiotics,” she said.
Despite growing awareness of the need to reduce unnecessary antibiotic use, clinicians have still been slow to adopt a more conservative approach to prescribing, Dr. Gohil said.
“What physicians have been needing is something to hang their hat on, to be able to say, ‘Okay, well, this one’s a low-risk person,’ ” Dr. Gohil said.
The trials compared the impact of routine antibiotic activities with a stewardship bundle, called INSPIRE (Intelligent Stewardship Prompts to Improve Real-time Empiric Antibiotic Selection).
Both groups received educational materials, quarterly coaching calls, prospective evaluations for antibiotic use, and were required to select a reason for prescribing an antibiotic.
But prescribers in the intervention group took part in monthly coaching calls and feedback reports. In addition, if a clinician ordered a broad-spectrum antibiotic to treat pneumonia or a UTI outside of the intensive care unit within 72 hours of admission, an EHR prompt would pop up. The pop-up suggested a standard-spectrum antibiotic instead if patient risk for developing a multidrug-resistant (MDRO) version of either condition was less than 10%.
An algorithm used data from the EHR calculated risk, using factors like patient demographics and history and MDRO infection at the community and hospital level.
Prescribing rates were based on the number of days a patient received a broad-spectrum antibiotic during the first 72 hours of hospitalization.
For the UTI intervention group, rates dropped by 17.4% (rate ratio [RR], 0.83; 95% CI, 0.77-0.89; P < .001), and 28.4% reduction in the pneumonia group (RR, 0.72; 95% CI, 0.66-0.78; P < .001).
“We cannot know which element — prompt, education, or feedback — worked, but the data suggests that the prompt was the main driver,” Dr. Gohil said.
“In antibiotic stewardship, we have learned not only that doctors want to do the right thing, but that we as stewards need to make it easy for them do the right thing,” said Paul Pottinger, MD, professor of medicine at the Division of Allergy and Infectious Diseases at the University of Washington Medical Center in Seattle.
The prompt “is your easy button,” said Dr. Pottinger, who was not involved with either study. “The researchers made it simple, fast, and straightforward, so people don’t have to think about it too much.”
The studies showed similar safety outcomes for the control and intervention groups. Among patients with a UTI, those in the control group were transferred to the ICU after an average of 6.6 days compared to 7 days in the intervention group. Among patients with pneumonia, the average days to ICU transfer were 6.5 for the control group and 7.1 for the intervention group.
“This study is a proof of concept that physicians want to do the right thing and are willing to trust this information,” Dr. Pottinger said. “And this also shows us that this tool can be refined and made even more precise over time.”
The study was funded by the US Centers for Disease Control and Prevention and was led by the University of California Irvine, Harvard Pilgrim Healthcare Institute, and HCA Healthcare System. Various authors report funding and support from entities outside the submitted work. The full list can be found with the original articles.
A version of this article appeared on Medscape.com.
‘We Need to Rethink Our Options’: Lung Cancer Recurrence
This transcript has been edited for clarity.
Hello. It’s Mark Kris reporting back after attending the New York Lung Cancer Foundation Summit here in New York. A large amount of discussion went on, but as usual, I was most interested in the perioperative space.
In previous videos, I’ve talked about this ongoing discussion of whether you should operate and give adjuvant therapy or give neoadjuvant therapy, and I’ve addressed that already. One thing I want to bring up – and as we move off of that argument, which frankly doesn’t have an answer today, with neoadjuvant therapy, having all the data to support it – is
I was taught early on by my surgical mentors that the issue here was systemic control. While they could do very successful surgery to get high levels of local control, they could not control systemic disease. Sadly, the tools we had early on with chemotherapy were just not good enough. Suddenly, we have better tools to control systemic spread. In the past, the vast majority of occurrences were systemic; they’re now local.
What I think we need to do as a group of practitioners trying to deal with the problems getting in the way of curing our patients is look at what the issue is now. Frankly, the big issue now, as systemic therapy has controlled metastatic disease, is recurrence in the chest.
We give adjuvant osimertinib. Please remember what the numbers are. In the osimertinib arm, of the 11 recurrences reported in the European Society for Medical Oncology presentation a few years back, nine of them were in the chest or mediastinal nodes. In the arm that got no osimertinib afterward, there were 46 recurrences, and 32 of those 46 recurrences were in the chest, either the lung or mediastinal nodes. Therefore, 74% of the recurrences are suddenly in the chest. What’s the issue here?
The issue is we need to find strategies to give better disease control in the chest, as we have made inroads in controlling systemic disease with the targeted therapies in the endothelial growth factor receptor space, and very likely the checkpoint inhibitors, too, as that data kind of filters out. We need to think about how better to get local control.
I think rather than continue to get into this argument of neoadjuvant vs adjuvant, we should move to what’s really hurting our patients. Again, the data I quoted you was from the ADAURA trial, which was adjuvant therapy, and I’m sure the neoadjuvant is going to show the same thing. It’s better systemic therapy but now, more trouble in the chest.
How are we going to deal with that? I’d like to throw out one strategy, and that is to rethink the role of radiation in these patients. Again, if the problem is local in the chest, lung, and lymph nodes, we have to think about local therapy. Yes, we’re not recommending it routinely for everybody, but now that we have better systemic control, we need to rethink our options. The obvious one to rethink is about giving radiotherapy.
We should also use what we learned in the earlier trials, which is that there is harm in giving excessive radiation to the heart. If you avoid the heart, you avoid the harm. We have better planning strategies for stereotactic body radiotherapy and more traditional radiation, and of course, we have proton therapy as well.
As we continue to struggle with the idea of that patient with stage II or III disease, whether to give adjuvant vs neoadjuvant therapy, please remember to consider their risk in 2024. Their risk for first recurrence is in the chest.
What are we going to do to better control disease in the chest? We have a challenge. I’m sure we can meet it if we put our heads together.
Dr. Kris is professor of medicine at Weill Cornell Medical College, and attending physician, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York. He disclosed ties with AstraZeneca, Roche/Genentech, Ariad Pharmaceuticals, Pfizer, and PUMA.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Hello. It’s Mark Kris reporting back after attending the New York Lung Cancer Foundation Summit here in New York. A large amount of discussion went on, but as usual, I was most interested in the perioperative space.
In previous videos, I’ve talked about this ongoing discussion of whether you should operate and give adjuvant therapy or give neoadjuvant therapy, and I’ve addressed that already. One thing I want to bring up – and as we move off of that argument, which frankly doesn’t have an answer today, with neoadjuvant therapy, having all the data to support it – is
I was taught early on by my surgical mentors that the issue here was systemic control. While they could do very successful surgery to get high levels of local control, they could not control systemic disease. Sadly, the tools we had early on with chemotherapy were just not good enough. Suddenly, we have better tools to control systemic spread. In the past, the vast majority of occurrences were systemic; they’re now local.
What I think we need to do as a group of practitioners trying to deal with the problems getting in the way of curing our patients is look at what the issue is now. Frankly, the big issue now, as systemic therapy has controlled metastatic disease, is recurrence in the chest.
We give adjuvant osimertinib. Please remember what the numbers are. In the osimertinib arm, of the 11 recurrences reported in the European Society for Medical Oncology presentation a few years back, nine of them were in the chest or mediastinal nodes. In the arm that got no osimertinib afterward, there were 46 recurrences, and 32 of those 46 recurrences were in the chest, either the lung or mediastinal nodes. Therefore, 74% of the recurrences are suddenly in the chest. What’s the issue here?
The issue is we need to find strategies to give better disease control in the chest, as we have made inroads in controlling systemic disease with the targeted therapies in the endothelial growth factor receptor space, and very likely the checkpoint inhibitors, too, as that data kind of filters out. We need to think about how better to get local control.
I think rather than continue to get into this argument of neoadjuvant vs adjuvant, we should move to what’s really hurting our patients. Again, the data I quoted you was from the ADAURA trial, which was adjuvant therapy, and I’m sure the neoadjuvant is going to show the same thing. It’s better systemic therapy but now, more trouble in the chest.
How are we going to deal with that? I’d like to throw out one strategy, and that is to rethink the role of radiation in these patients. Again, if the problem is local in the chest, lung, and lymph nodes, we have to think about local therapy. Yes, we’re not recommending it routinely for everybody, but now that we have better systemic control, we need to rethink our options. The obvious one to rethink is about giving radiotherapy.
We should also use what we learned in the earlier trials, which is that there is harm in giving excessive radiation to the heart. If you avoid the heart, you avoid the harm. We have better planning strategies for stereotactic body radiotherapy and more traditional radiation, and of course, we have proton therapy as well.
As we continue to struggle with the idea of that patient with stage II or III disease, whether to give adjuvant vs neoadjuvant therapy, please remember to consider their risk in 2024. Their risk for first recurrence is in the chest.
What are we going to do to better control disease in the chest? We have a challenge. I’m sure we can meet it if we put our heads together.
Dr. Kris is professor of medicine at Weill Cornell Medical College, and attending physician, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York. He disclosed ties with AstraZeneca, Roche/Genentech, Ariad Pharmaceuticals, Pfizer, and PUMA.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Hello. It’s Mark Kris reporting back after attending the New York Lung Cancer Foundation Summit here in New York. A large amount of discussion went on, but as usual, I was most interested in the perioperative space.
In previous videos, I’ve talked about this ongoing discussion of whether you should operate and give adjuvant therapy or give neoadjuvant therapy, and I’ve addressed that already. One thing I want to bring up – and as we move off of that argument, which frankly doesn’t have an answer today, with neoadjuvant therapy, having all the data to support it – is
I was taught early on by my surgical mentors that the issue here was systemic control. While they could do very successful surgery to get high levels of local control, they could not control systemic disease. Sadly, the tools we had early on with chemotherapy were just not good enough. Suddenly, we have better tools to control systemic spread. In the past, the vast majority of occurrences were systemic; they’re now local.
What I think we need to do as a group of practitioners trying to deal with the problems getting in the way of curing our patients is look at what the issue is now. Frankly, the big issue now, as systemic therapy has controlled metastatic disease, is recurrence in the chest.
We give adjuvant osimertinib. Please remember what the numbers are. In the osimertinib arm, of the 11 recurrences reported in the European Society for Medical Oncology presentation a few years back, nine of them were in the chest or mediastinal nodes. In the arm that got no osimertinib afterward, there were 46 recurrences, and 32 of those 46 recurrences were in the chest, either the lung or mediastinal nodes. Therefore, 74% of the recurrences are suddenly in the chest. What’s the issue here?
The issue is we need to find strategies to give better disease control in the chest, as we have made inroads in controlling systemic disease with the targeted therapies in the endothelial growth factor receptor space, and very likely the checkpoint inhibitors, too, as that data kind of filters out. We need to think about how better to get local control.
I think rather than continue to get into this argument of neoadjuvant vs adjuvant, we should move to what’s really hurting our patients. Again, the data I quoted you was from the ADAURA trial, which was adjuvant therapy, and I’m sure the neoadjuvant is going to show the same thing. It’s better systemic therapy but now, more trouble in the chest.
How are we going to deal with that? I’d like to throw out one strategy, and that is to rethink the role of radiation in these patients. Again, if the problem is local in the chest, lung, and lymph nodes, we have to think about local therapy. Yes, we’re not recommending it routinely for everybody, but now that we have better systemic control, we need to rethink our options. The obvious one to rethink is about giving radiotherapy.
We should also use what we learned in the earlier trials, which is that there is harm in giving excessive radiation to the heart. If you avoid the heart, you avoid the harm. We have better planning strategies for stereotactic body radiotherapy and more traditional radiation, and of course, we have proton therapy as well.
As we continue to struggle with the idea of that patient with stage II or III disease, whether to give adjuvant vs neoadjuvant therapy, please remember to consider their risk in 2024. Their risk for first recurrence is in the chest.
What are we going to do to better control disease in the chest? We have a challenge. I’m sure we can meet it if we put our heads together.
Dr. Kris is professor of medicine at Weill Cornell Medical College, and attending physician, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York. He disclosed ties with AstraZeneca, Roche/Genentech, Ariad Pharmaceuticals, Pfizer, and PUMA.
A version of this article appeared on Medscape.com.
GLP-1s May Increase Post-Endoscopy Aspiration Pneumonia Risk
, according to a new large population-based study.
In June 2023, the American Society of Anesthesiologists (ASA) recommended holding GLP-1 RAs before an endoscopic or surgical procedure to reduce the risk for complications associated with anesthesia and delayed stomach emptying.
In response, the American Gastroenterological Association (AGA) published a rapid clinical practice update in November 2023 that found insufficient evidence to support patients stopping the medications before endoscopic procedures.
“It is known that GLP-1 RAs significantly reduce the motility of the stomach and small bowel. As more and more patients are being started on GLP-1 RAs at higher doses and longer half-life, the question became whether the current recommended fasting durations are enough to reasonably assume the stomach is empty prior to procedures that require sedation,” said senior author Ali Rezaie, MD, medical director of the GI Motility Program at Cedars-Sinai Medical Center in Los Angeles.
“We wanted to see if these medications in fact increased the chance of aspiration before the ASA suggestion went into effect,” he said. “However, this is not an easy task, as aspiration is a rare event and a large sample size is needed to confidently answer that question. That is why we evaluated nearly 1 million cases.”
The study was published online in Gastroenterology.
Analyzing GLP-1 RA Use
Dr. Rezaie and colleagues conducted a population-based, retrospective cohort study of the TriNetX dataset, which includes 114 million deidentified individual health records from 80 healthcare organizations. The research team analyzed nearly 1 million records for adult patients between ages 21 and 70 who underwent upper and lower endoscopies between January 2018 and December 2020.
The researchers defined GLP-1 RA users as those who had the medication for more than 6 months and two or more refills within 6 months before the procedure. They adjusted for 59 factors that could affect gut motility or aspiration risks, such as obesity, numerous chronic diseases, and dozens of medications. The primary outcome was aspiration pneumonia within a month after the procedure.
Among 963,184 patients who underwent endoscopy, 46,935 (4.9%) were considered GLP-1 RA users. Among those, 20,099 GLP-1 RA users met the inclusion criteria and had their results compared with non-GLP-1 RA users.
After propensity score matching for the 59 potential confounders, GLP-1 RA use had a higher incidence rate of aspiration pneumonia (0.83% vs 0.63%) and was associated with a significantly higher risk for aspiration pneumonia, with a hazard ratio (HR) of 1.33.
An even higher risk was seen among patients with propofol-assisted endoscopies (HR, 1.49) but not among those without propofol (HR, 1.31).
In a subgroup analysis based on endoscopy type, an elevated risk was observed among patients who underwent upper endoscopy (HR, 1.82) and combined upper and lower endoscopy (HR, 2.26) but not lower endoscopy (HR, 0.56).
“The results were not necessarily surprising given the mechanism of action of GLP-1 RAs. However, for the first time, this was shown with a clinically relevant outcome, such as aspiration pneumonia,” Dr. Rezaie said. “Aspiration during sedation can have devastating consequences, and the 0.2% difference in risk of aspiration can have a significant effect on healthcare as well.”
More than 20 million endoscopies are performed across the United States annually. Based on the assumption that about 3% of those patients are taking GLP-1 RAs, about 1200 aspiration cases per year can be prevented by raising awareness, he said.
Considering Next Steps
The varying risk profiles observed with separate sedation and endoscopy types point to a need for more tailored guidance in managing GLP-1 RA use before a procedure, the study authors wrote.
Although holding the medications before endoscopy may disrupt diabetes management, the potential increased risk for aspiration could justify a change in practice, particularly for upper endoscopy and propofol-associated procedures, they added.
At the same time, additional studies are needed to understand the optimal drug withholding windows before endoscopies and other procedures, they concluded.
“We will need more data on what is the optimal duration of holding GLP-1 RAs,” Dr. Rezaie said. “But given our data and current ASA guidance, stopping these medications prior to elective procedures is the safe thing to do.”
For now, AGA guidance remains the same as offered in the November 2023 update, suggesting an individual approach for each patient on a GLP-1 RA rather than a “blanket statement” on how to manage all patients taking these medications.
“Overall, I believe that this study is important, but we require more high-level data to inform clinical decision-making regarding patients using GLP-1 receptor agonists prior to gastrointestinal endoscopy,” said Andrew Y. Wang, MD, AGAF, chief of gastroenterology and hepatology and director of interventional endoscopy at the University of Virginia in Charlottesville.
Dr. Wang, who wasn’t involved with this study, coauthored the AGA rapid clinical practice update. He and colleagues advised continuing with a procedure as planned for patients on GLP-1 RAs who followed standard preprocedure fasting instructions and didn’t have nausea, vomiting, dyspepsia, or abdominal distention.
Among patients with symptoms that suggest retained gastric contents, rapid sequence intubation may be considered, though it may not be possible in ambulatory or office-based endoscopy settings, Dr. Wang and colleagues wrote. As another option in lieu of stopping GLP-1 RAs, patients can be placed on a liquid diet for 1 day before the procedure.
“While this study found a signal suggesting that patients using GLP-1 RAs had an increased risk of aspiration pneumonia within 1 month following upper endoscopy or combined upper and lower endoscopy, it does not inform us if having patients stop GLP-1 RAs before endoscopic procedures — especially for a single dose — will mitigate this potential risk,” Dr. Wang said.
“It was also interesting that these investigators found that patients taking GLP-1 RAs who underwent lower endoscopy alone were not at increased risk for aspiration pneumonia,” Dr. Wang noted.
The authors didn’t report a funding source and disclosed no potential conflicts. Dr. Wang reported no relevant disclosures.
A version of this article appeared on Medscape.com.
, according to a new large population-based study.
In June 2023, the American Society of Anesthesiologists (ASA) recommended holding GLP-1 RAs before an endoscopic or surgical procedure to reduce the risk for complications associated with anesthesia and delayed stomach emptying.
In response, the American Gastroenterological Association (AGA) published a rapid clinical practice update in November 2023 that found insufficient evidence to support patients stopping the medications before endoscopic procedures.
“It is known that GLP-1 RAs significantly reduce the motility of the stomach and small bowel. As more and more patients are being started on GLP-1 RAs at higher doses and longer half-life, the question became whether the current recommended fasting durations are enough to reasonably assume the stomach is empty prior to procedures that require sedation,” said senior author Ali Rezaie, MD, medical director of the GI Motility Program at Cedars-Sinai Medical Center in Los Angeles.
“We wanted to see if these medications in fact increased the chance of aspiration before the ASA suggestion went into effect,” he said. “However, this is not an easy task, as aspiration is a rare event and a large sample size is needed to confidently answer that question. That is why we evaluated nearly 1 million cases.”
The study was published online in Gastroenterology.
Analyzing GLP-1 RA Use
Dr. Rezaie and colleagues conducted a population-based, retrospective cohort study of the TriNetX dataset, which includes 114 million deidentified individual health records from 80 healthcare organizations. The research team analyzed nearly 1 million records for adult patients between ages 21 and 70 who underwent upper and lower endoscopies between January 2018 and December 2020.
The researchers defined GLP-1 RA users as those who had the medication for more than 6 months and two or more refills within 6 months before the procedure. They adjusted for 59 factors that could affect gut motility or aspiration risks, such as obesity, numerous chronic diseases, and dozens of medications. The primary outcome was aspiration pneumonia within a month after the procedure.
Among 963,184 patients who underwent endoscopy, 46,935 (4.9%) were considered GLP-1 RA users. Among those, 20,099 GLP-1 RA users met the inclusion criteria and had their results compared with non-GLP-1 RA users.
After propensity score matching for the 59 potential confounders, GLP-1 RA use had a higher incidence rate of aspiration pneumonia (0.83% vs 0.63%) and was associated with a significantly higher risk for aspiration pneumonia, with a hazard ratio (HR) of 1.33.
An even higher risk was seen among patients with propofol-assisted endoscopies (HR, 1.49) but not among those without propofol (HR, 1.31).
In a subgroup analysis based on endoscopy type, an elevated risk was observed among patients who underwent upper endoscopy (HR, 1.82) and combined upper and lower endoscopy (HR, 2.26) but not lower endoscopy (HR, 0.56).
“The results were not necessarily surprising given the mechanism of action of GLP-1 RAs. However, for the first time, this was shown with a clinically relevant outcome, such as aspiration pneumonia,” Dr. Rezaie said. “Aspiration during sedation can have devastating consequences, and the 0.2% difference in risk of aspiration can have a significant effect on healthcare as well.”
More than 20 million endoscopies are performed across the United States annually. Based on the assumption that about 3% of those patients are taking GLP-1 RAs, about 1200 aspiration cases per year can be prevented by raising awareness, he said.
Considering Next Steps
The varying risk profiles observed with separate sedation and endoscopy types point to a need for more tailored guidance in managing GLP-1 RA use before a procedure, the study authors wrote.
Although holding the medications before endoscopy may disrupt diabetes management, the potential increased risk for aspiration could justify a change in practice, particularly for upper endoscopy and propofol-associated procedures, they added.
At the same time, additional studies are needed to understand the optimal drug withholding windows before endoscopies and other procedures, they concluded.
“We will need more data on what is the optimal duration of holding GLP-1 RAs,” Dr. Rezaie said. “But given our data and current ASA guidance, stopping these medications prior to elective procedures is the safe thing to do.”
For now, AGA guidance remains the same as offered in the November 2023 update, suggesting an individual approach for each patient on a GLP-1 RA rather than a “blanket statement” on how to manage all patients taking these medications.
“Overall, I believe that this study is important, but we require more high-level data to inform clinical decision-making regarding patients using GLP-1 receptor agonists prior to gastrointestinal endoscopy,” said Andrew Y. Wang, MD, AGAF, chief of gastroenterology and hepatology and director of interventional endoscopy at the University of Virginia in Charlottesville.
Dr. Wang, who wasn’t involved with this study, coauthored the AGA rapid clinical practice update. He and colleagues advised continuing with a procedure as planned for patients on GLP-1 RAs who followed standard preprocedure fasting instructions and didn’t have nausea, vomiting, dyspepsia, or abdominal distention.
Among patients with symptoms that suggest retained gastric contents, rapid sequence intubation may be considered, though it may not be possible in ambulatory or office-based endoscopy settings, Dr. Wang and colleagues wrote. As another option in lieu of stopping GLP-1 RAs, patients can be placed on a liquid diet for 1 day before the procedure.
“While this study found a signal suggesting that patients using GLP-1 RAs had an increased risk of aspiration pneumonia within 1 month following upper endoscopy or combined upper and lower endoscopy, it does not inform us if having patients stop GLP-1 RAs before endoscopic procedures — especially for a single dose — will mitigate this potential risk,” Dr. Wang said.
“It was also interesting that these investigators found that patients taking GLP-1 RAs who underwent lower endoscopy alone were not at increased risk for aspiration pneumonia,” Dr. Wang noted.
The authors didn’t report a funding source and disclosed no potential conflicts. Dr. Wang reported no relevant disclosures.
A version of this article appeared on Medscape.com.
, according to a new large population-based study.
In June 2023, the American Society of Anesthesiologists (ASA) recommended holding GLP-1 RAs before an endoscopic or surgical procedure to reduce the risk for complications associated with anesthesia and delayed stomach emptying.
In response, the American Gastroenterological Association (AGA) published a rapid clinical practice update in November 2023 that found insufficient evidence to support patients stopping the medications before endoscopic procedures.
“It is known that GLP-1 RAs significantly reduce the motility of the stomach and small bowel. As more and more patients are being started on GLP-1 RAs at higher doses and longer half-life, the question became whether the current recommended fasting durations are enough to reasonably assume the stomach is empty prior to procedures that require sedation,” said senior author Ali Rezaie, MD, medical director of the GI Motility Program at Cedars-Sinai Medical Center in Los Angeles.
“We wanted to see if these medications in fact increased the chance of aspiration before the ASA suggestion went into effect,” he said. “However, this is not an easy task, as aspiration is a rare event and a large sample size is needed to confidently answer that question. That is why we evaluated nearly 1 million cases.”
The study was published online in Gastroenterology.
Analyzing GLP-1 RA Use
Dr. Rezaie and colleagues conducted a population-based, retrospective cohort study of the TriNetX dataset, which includes 114 million deidentified individual health records from 80 healthcare organizations. The research team analyzed nearly 1 million records for adult patients between ages 21 and 70 who underwent upper and lower endoscopies between January 2018 and December 2020.
The researchers defined GLP-1 RA users as those who had the medication for more than 6 months and two or more refills within 6 months before the procedure. They adjusted for 59 factors that could affect gut motility or aspiration risks, such as obesity, numerous chronic diseases, and dozens of medications. The primary outcome was aspiration pneumonia within a month after the procedure.
Among 963,184 patients who underwent endoscopy, 46,935 (4.9%) were considered GLP-1 RA users. Among those, 20,099 GLP-1 RA users met the inclusion criteria and had their results compared with non-GLP-1 RA users.
After propensity score matching for the 59 potential confounders, GLP-1 RA use had a higher incidence rate of aspiration pneumonia (0.83% vs 0.63%) and was associated with a significantly higher risk for aspiration pneumonia, with a hazard ratio (HR) of 1.33.
An even higher risk was seen among patients with propofol-assisted endoscopies (HR, 1.49) but not among those without propofol (HR, 1.31).
In a subgroup analysis based on endoscopy type, an elevated risk was observed among patients who underwent upper endoscopy (HR, 1.82) and combined upper and lower endoscopy (HR, 2.26) but not lower endoscopy (HR, 0.56).
“The results were not necessarily surprising given the mechanism of action of GLP-1 RAs. However, for the first time, this was shown with a clinically relevant outcome, such as aspiration pneumonia,” Dr. Rezaie said. “Aspiration during sedation can have devastating consequences, and the 0.2% difference in risk of aspiration can have a significant effect on healthcare as well.”
More than 20 million endoscopies are performed across the United States annually. Based on the assumption that about 3% of those patients are taking GLP-1 RAs, about 1200 aspiration cases per year can be prevented by raising awareness, he said.
Considering Next Steps
The varying risk profiles observed with separate sedation and endoscopy types point to a need for more tailored guidance in managing GLP-1 RA use before a procedure, the study authors wrote.
Although holding the medications before endoscopy may disrupt diabetes management, the potential increased risk for aspiration could justify a change in practice, particularly for upper endoscopy and propofol-associated procedures, they added.
At the same time, additional studies are needed to understand the optimal drug withholding windows before endoscopies and other procedures, they concluded.
“We will need more data on what is the optimal duration of holding GLP-1 RAs,” Dr. Rezaie said. “But given our data and current ASA guidance, stopping these medications prior to elective procedures is the safe thing to do.”
For now, AGA guidance remains the same as offered in the November 2023 update, suggesting an individual approach for each patient on a GLP-1 RA rather than a “blanket statement” on how to manage all patients taking these medications.
“Overall, I believe that this study is important, but we require more high-level data to inform clinical decision-making regarding patients using GLP-1 receptor agonists prior to gastrointestinal endoscopy,” said Andrew Y. Wang, MD, AGAF, chief of gastroenterology and hepatology and director of interventional endoscopy at the University of Virginia in Charlottesville.
Dr. Wang, who wasn’t involved with this study, coauthored the AGA rapid clinical practice update. He and colleagues advised continuing with a procedure as planned for patients on GLP-1 RAs who followed standard preprocedure fasting instructions and didn’t have nausea, vomiting, dyspepsia, or abdominal distention.
Among patients with symptoms that suggest retained gastric contents, rapid sequence intubation may be considered, though it may not be possible in ambulatory or office-based endoscopy settings, Dr. Wang and colleagues wrote. As another option in lieu of stopping GLP-1 RAs, patients can be placed on a liquid diet for 1 day before the procedure.
“While this study found a signal suggesting that patients using GLP-1 RAs had an increased risk of aspiration pneumonia within 1 month following upper endoscopy or combined upper and lower endoscopy, it does not inform us if having patients stop GLP-1 RAs before endoscopic procedures — especially for a single dose — will mitigate this potential risk,” Dr. Wang said.
“It was also interesting that these investigators found that patients taking GLP-1 RAs who underwent lower endoscopy alone were not at increased risk for aspiration pneumonia,” Dr. Wang noted.
The authors didn’t report a funding source and disclosed no potential conflicts. Dr. Wang reported no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM GASTROENTEROLOGY
Which Emergencies Are Genuine Emergencies?
WIESBADEN, GERMANY — Crowded waiting rooms, long wait times, irritable patients, and aggression toward nursing staff and doctors are increasingly the reality in German emergency rooms. Clearly, emergencies belong in the emergency room. However, “In about half of all patients in the emergency room, there is no urgent medical emergency,” Norbert Schütz, MD, director of geriatrics and rheumatology at Helios Dr. Horst Schmidt Hospital in Wiesbaden, Germany, said at a press conference for the 130th Annual Meeting of the German Society of Internal Medicine (DGIM).
“In our daily medical practice, we repeatedly experience people either accessing our emergency departments and ambulances too quickly or lingering at home for too long when they have severe symptoms,” said Dr. Schütz, who organized the Patient Day during the Internist Congress.
DGIM Educates Patients
What is an emergency? “I think the public is quite well informed about conditions associated with loss of consciousness, severe pain, chest pain, or paralysis: Think stroke or heart attack. This is undoubtedly a success of recent years. The difficulty arises with everything in between. For instance, should I go to the hospital with severe headaches?” asked Dr. Schütz.
When is a patient a case for the emergency room, the physician on-call service, or the general practitioner? At the Patient Day in Wiesbaden, DGIM aims to educate and train interested parties with a dedicated lecture. The focus is on recognizing an emergency, specifically emergencies in children and mental illnesses.
“Our Patient Day aims to contribute to making the right decisions. We want to inform, answer questions, and alleviate fears,” said Dr. Schütz. Interested parties can refresh their emergency knowledge, tour ambulances, and have the equipment explained. The public also has the opportunity to learn about resuscitation techniques theoretically and practically.
“Should, for whatever reason, the general practitioner not be reachable, the physician on-call service can be reached,” said Dr. Schütz. It may happen, however, that neither the general practitioner nor the on-call physician is immediately available.
What Are Emergencies?
In cases of severe health impairment, urgency is required, and a severe emergency should be assumed in the following cases:
- Chest pain
- Circulatory disorder
- Disorders of consciousness
- Breathing difficulties
- Sudden weakness or numbness/paralysis
- Severe bleeding
- Allergic shock
“In such cases, the emergency departments of the hospitals are available around the clock, and if necessary, an emergency doctor should be present during transportation to the hospital,” said Dr. Schütz.
Classifying emergencies is challenging, especially with children. “Children often find it difficult to clearly categorize or describe symptoms,” said Dr. Schütz. A situation is critical if, for example, the child’s breathing or consciousness is impaired.
Mental emergencies pose a particular challenge for patients and relatives because the patient and relatives are often overwhelmed by the situation. If there are suicidal thoughts, the patient should present him- or herself immediately to an emergency room.
“Patients who come to the emergency room because they cannot get appointments with their general practitioner or specialist, for whatever reason, are no emergency. We also see this in the emergency room from time to time,” said Dr. Schütz. Emergency rooms are not intended for this purpose. “And generally, these are not emergencies.”
Four of 10 Cases
The number of patients in emergency rooms has steadily increased in recent years. Statistically, only 4 out of 10 cases are genuine emergencies, as detailed surveys of patients in the emergency rooms of northern German hospitals have shown.
In the PiNo Nord cross-sectional study, Martin Scherer, MD, of University Hospital Hamburg-Eppendorf in Hamburg, Germany, and his team examined the reasons why patients visit the emergency room. They interviewed 1175 patients in five hospitals and documented the medical diagnoses. Patients classified as “immediately” or “very urgently” in need of treatment were excluded.
The surveyed patients were on average 41.8 years old, 52.9% were men, and 54.7% of the patients indicated a low urgency of treatment. About 41% of the patients visited the emergency room on their own initiative, 17% stated they were referred or entrusted by their general practitioner, and 8% were referred by a specialist in the emergency room.
The strongest predictors for low subjective treatment urgency were musculoskeletal trauma (odds ratio [OR], 2.18), skin afflictions (OR, 2.15), and the unavailability of an open general practitioner’s office (OR, 1.70).
According to Dr. Scherer and his colleagues, the reasons for visiting an emergency room are diverse and can be based on the perceived structural conditions and individual patient preferences in addition to the urgency of the health problem.
This story was translated from the Medscape German edition 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.
WIESBADEN, GERMANY — Crowded waiting rooms, long wait times, irritable patients, and aggression toward nursing staff and doctors are increasingly the reality in German emergency rooms. Clearly, emergencies belong in the emergency room. However, “In about half of all patients in the emergency room, there is no urgent medical emergency,” Norbert Schütz, MD, director of geriatrics and rheumatology at Helios Dr. Horst Schmidt Hospital in Wiesbaden, Germany, said at a press conference for the 130th Annual Meeting of the German Society of Internal Medicine (DGIM).
“In our daily medical practice, we repeatedly experience people either accessing our emergency departments and ambulances too quickly or lingering at home for too long when they have severe symptoms,” said Dr. Schütz, who organized the Patient Day during the Internist Congress.
DGIM Educates Patients
What is an emergency? “I think the public is quite well informed about conditions associated with loss of consciousness, severe pain, chest pain, or paralysis: Think stroke or heart attack. This is undoubtedly a success of recent years. The difficulty arises with everything in between. For instance, should I go to the hospital with severe headaches?” asked Dr. Schütz.
When is a patient a case for the emergency room, the physician on-call service, or the general practitioner? At the Patient Day in Wiesbaden, DGIM aims to educate and train interested parties with a dedicated lecture. The focus is on recognizing an emergency, specifically emergencies in children and mental illnesses.
“Our Patient Day aims to contribute to making the right decisions. We want to inform, answer questions, and alleviate fears,” said Dr. Schütz. Interested parties can refresh their emergency knowledge, tour ambulances, and have the equipment explained. The public also has the opportunity to learn about resuscitation techniques theoretically and practically.
“Should, for whatever reason, the general practitioner not be reachable, the physician on-call service can be reached,” said Dr. Schütz. It may happen, however, that neither the general practitioner nor the on-call physician is immediately available.
What Are Emergencies?
In cases of severe health impairment, urgency is required, and a severe emergency should be assumed in the following cases:
- Chest pain
- Circulatory disorder
- Disorders of consciousness
- Breathing difficulties
- Sudden weakness or numbness/paralysis
- Severe bleeding
- Allergic shock
“In such cases, the emergency departments of the hospitals are available around the clock, and if necessary, an emergency doctor should be present during transportation to the hospital,” said Dr. Schütz.
Classifying emergencies is challenging, especially with children. “Children often find it difficult to clearly categorize or describe symptoms,” said Dr. Schütz. A situation is critical if, for example, the child’s breathing or consciousness is impaired.
Mental emergencies pose a particular challenge for patients and relatives because the patient and relatives are often overwhelmed by the situation. If there are suicidal thoughts, the patient should present him- or herself immediately to an emergency room.
“Patients who come to the emergency room because they cannot get appointments with their general practitioner or specialist, for whatever reason, are no emergency. We also see this in the emergency room from time to time,” said Dr. Schütz. Emergency rooms are not intended for this purpose. “And generally, these are not emergencies.”
Four of 10 Cases
The number of patients in emergency rooms has steadily increased in recent years. Statistically, only 4 out of 10 cases are genuine emergencies, as detailed surveys of patients in the emergency rooms of northern German hospitals have shown.
In the PiNo Nord cross-sectional study, Martin Scherer, MD, of University Hospital Hamburg-Eppendorf in Hamburg, Germany, and his team examined the reasons why patients visit the emergency room. They interviewed 1175 patients in five hospitals and documented the medical diagnoses. Patients classified as “immediately” or “very urgently” in need of treatment were excluded.
The surveyed patients were on average 41.8 years old, 52.9% were men, and 54.7% of the patients indicated a low urgency of treatment. About 41% of the patients visited the emergency room on their own initiative, 17% stated they were referred or entrusted by their general practitioner, and 8% were referred by a specialist in the emergency room.
The strongest predictors for low subjective treatment urgency were musculoskeletal trauma (odds ratio [OR], 2.18), skin afflictions (OR, 2.15), and the unavailability of an open general practitioner’s office (OR, 1.70).
According to Dr. Scherer and his colleagues, the reasons for visiting an emergency room are diverse and can be based on the perceived structural conditions and individual patient preferences in addition to the urgency of the health problem.
This story was translated from the Medscape German edition 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.
WIESBADEN, GERMANY — Crowded waiting rooms, long wait times, irritable patients, and aggression toward nursing staff and doctors are increasingly the reality in German emergency rooms. Clearly, emergencies belong in the emergency room. However, “In about half of all patients in the emergency room, there is no urgent medical emergency,” Norbert Schütz, MD, director of geriatrics and rheumatology at Helios Dr. Horst Schmidt Hospital in Wiesbaden, Germany, said at a press conference for the 130th Annual Meeting of the German Society of Internal Medicine (DGIM).
“In our daily medical practice, we repeatedly experience people either accessing our emergency departments and ambulances too quickly or lingering at home for too long when they have severe symptoms,” said Dr. Schütz, who organized the Patient Day during the Internist Congress.
DGIM Educates Patients
What is an emergency? “I think the public is quite well informed about conditions associated with loss of consciousness, severe pain, chest pain, or paralysis: Think stroke or heart attack. This is undoubtedly a success of recent years. The difficulty arises with everything in between. For instance, should I go to the hospital with severe headaches?” asked Dr. Schütz.
When is a patient a case for the emergency room, the physician on-call service, or the general practitioner? At the Patient Day in Wiesbaden, DGIM aims to educate and train interested parties with a dedicated lecture. The focus is on recognizing an emergency, specifically emergencies in children and mental illnesses.
“Our Patient Day aims to contribute to making the right decisions. We want to inform, answer questions, and alleviate fears,” said Dr. Schütz. Interested parties can refresh their emergency knowledge, tour ambulances, and have the equipment explained. The public also has the opportunity to learn about resuscitation techniques theoretically and practically.
“Should, for whatever reason, the general practitioner not be reachable, the physician on-call service can be reached,” said Dr. Schütz. It may happen, however, that neither the general practitioner nor the on-call physician is immediately available.
What Are Emergencies?
In cases of severe health impairment, urgency is required, and a severe emergency should be assumed in the following cases:
- Chest pain
- Circulatory disorder
- Disorders of consciousness
- Breathing difficulties
- Sudden weakness or numbness/paralysis
- Severe bleeding
- Allergic shock
“In such cases, the emergency departments of the hospitals are available around the clock, and if necessary, an emergency doctor should be present during transportation to the hospital,” said Dr. Schütz.
Classifying emergencies is challenging, especially with children. “Children often find it difficult to clearly categorize or describe symptoms,” said Dr. Schütz. A situation is critical if, for example, the child’s breathing or consciousness is impaired.
Mental emergencies pose a particular challenge for patients and relatives because the patient and relatives are often overwhelmed by the situation. If there are suicidal thoughts, the patient should present him- or herself immediately to an emergency room.
“Patients who come to the emergency room because they cannot get appointments with their general practitioner or specialist, for whatever reason, are no emergency. We also see this in the emergency room from time to time,” said Dr. Schütz. Emergency rooms are not intended for this purpose. “And generally, these are not emergencies.”
Four of 10 Cases
The number of patients in emergency rooms has steadily increased in recent years. Statistically, only 4 out of 10 cases are genuine emergencies, as detailed surveys of patients in the emergency rooms of northern German hospitals have shown.
In the PiNo Nord cross-sectional study, Martin Scherer, MD, of University Hospital Hamburg-Eppendorf in Hamburg, Germany, and his team examined the reasons why patients visit the emergency room. They interviewed 1175 patients in five hospitals and documented the medical diagnoses. Patients classified as “immediately” or “very urgently” in need of treatment were excluded.
The surveyed patients were on average 41.8 years old, 52.9% were men, and 54.7% of the patients indicated a low urgency of treatment. About 41% of the patients visited the emergency room on their own initiative, 17% stated they were referred or entrusted by their general practitioner, and 8% were referred by a specialist in the emergency room.
The strongest predictors for low subjective treatment urgency were musculoskeletal trauma (odds ratio [OR], 2.18), skin afflictions (OR, 2.15), and the unavailability of an open general practitioner’s office (OR, 1.70).
According to Dr. Scherer and his colleagues, the reasons for visiting an emergency room are diverse and can be based on the perceived structural conditions and individual patient preferences in addition to the urgency of the health problem.
This story was translated from the Medscape German edition 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.