Nobel Prize in Medicine Awarded to MicroRNA Researchers

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Changed
Tue, 10/08/2024 - 15:15

In 2024, the Royal Swedish Academy of Sciences is honoring two US researchers with the Nobel Prize in Medicine for the discovery of a fundamental principle of how gene activity is regulated. Victor Ambros, PhD, a researcher at the University of Massachusetts Chan Medical School, Worcester, and Gary Ruvkun, PhD, professor of genetics at Harvard Medical School in Boston, Massachusetts, discovered microRNAs, a new class of RNA molecules.

“Their groundbreaking discovery in the small worm Caenorhabditis elegans revealed a completely new principle of gene regulation. This turned out to be essential for multicellular organisms, including humans,” said the Nobel Assembly in a statement.
 

Protein Expression 

Genetic information flows from DNA during transcription to messenger RNA (mRNA) and then to protein biosynthesis. In that stage, mRNAs are translated so that proteins are produced according to the genetic instructions stored in the DNA.

Different cell types or tissues express unique sets of proteins, however. This specialized expression results from precise regulation of gene activity, so that in each cell type, only the correct set of genes is active. In this way, for example, muscle cells, intestinal cells, and various types of nerve cells can fulfill their functions.

Furthermore, gene activity must constantly be fine-tuned to adapt cell functions to changing conditions in our body and environment. When gene regulation goes awry, it can lead to serious outcomes such as cancer, diabetes, or autoimmune diseases. Therefore, understanding the regulation of gene activity has been an important goal for many decades.

In the 1960s, researchers had shown that specialized proteins called transcription factors bind to specific regions of DNA and control the flow of genetic information by determining which mRNAs are produced. Since that time, thousands of transcription factors have been identified. For a long time, scientists thought that the main principles of gene regulation were understood. 
 

Roundworm Research 

In the late 1980s, Dr. Ambros and Dr. Ruvkun were postdoctoral researchers in the laboratory of Robert Horvitz, PhD, who received the Nobel Prize in 2002 with Sydney Brenner and John Sulston. In Dr. Horvitz’s laboratory, they studied the relatively inconspicuous, 1-mm long roundworm C elegans.

Despite its small size, C elegans has many specialized cell types such as nerve and muscle cells that are also found in larger, more complex animals. These features make it a popular animal model.

Dr. Ambros and Dr. Ruvkun were interested in genes that ensure that different cell types develop at the right time. They examined two mutated worm strains, lin-4 and lin-14, that exhibited defects in the temporal activation of specific genes during development. The laureates wanted to identify mutated genes and understand their function.

Dr. Ambros had previously shown that lin-4 appeared to be a negative regulator of lin-14. But how lin-14 activity was blocked was unknown.
 

Collaboration Yields Breakthrough

After his postdoctoral years, Dr. Ambros analyzed the lin-4 mutant in his newly established laboratory at Harvard University. Systematic mapping allowed the cloning of the gene and led to an unexpected result: lin-4 produced an unusually short RNA molecule that lacked a code for protein synthesis. These surprising results suggested that this small RNA from lin-4 was responsible for inhibiting lin-14. 

At the same time, Dr. Ruvkun, in his newly founded laboratory at Massachusetts General Hospital and Harvard Medical School, studied the regulation of lin-14. In contradiction to the current understanding of gene regulation, he showed that it was not the production of lin-14 mRNA that was inhibited by lin-4. The regulation seems to occur at a later stage in the gene expression process, namely through the shutdown of protein synthesis. In addition, a section in lin-14 mRNA was discovered to be necessary for inhibition by lin-4.

The two laureates compared their results, leading to a groundbreaking discovery. The short lin-4 sequence matched complementary sequences in the relevant section of the lin-14 mRNA. Dr. Ambros and Dr. Ruvkun conducted further experiments showing that the lin-4 microRNA silences lin-14 by binding to the complementary sequences of its mRNA, thus blocking the production of the lin-14 protein. A new principle of gene regulation, mediated by a previously unknown type of RNA, the microRNA, had been discovered.
 

 

 

Subdued Initial Response

The results were published in Cell in 1993 and initially received little attention. However, interest grew in 2000 when Dr. Ruvkun’s research group published the discovery of another microRNA encoded by let-7.

In contrast to lin-4, let-7 was highly conserved and present throughout the animal kingdom. The article sparked great interest. In the following years, hundreds of microRNAs were identified. Today, researchers know that there are more than 1000 genes for various microRNAs in humans and that gene regulation by microRNAs is found in all multicellular organisms.

In addition to mapping new microRNAs, experiments by several research groups have elucidated fundamental mechanisms. Their binding leads to inhibition of protein synthesis or degradation of mRNA. Interestingly, a single microRNA can regulate the expression of many genes. Conversely, a single gene can be regulated by multiple microRNAs, thus coordinating and fine-tuning entire gene networks.

The cellular machinery for producing functional microRNAs is also used to produce other small RNA molecules in plants and animals, for example, as a means of protecting plants from viral infections. Andrew Z. Fire and Craig C. Mello, who were awarded the Nobel Prize in 2006, described RNA interference, in which specific mRNA molecules are inactivated by the addition of double-stranded RNA molecules to cells.
 

Small RNAs, Great Importance

Gene regulation by microRNA has likely existed for hundreds of millions of years. This mechanism has enabled the evolution of increasingly complex organisms.

From genetic research, it is known that cells and tissues do not develop normally without microRNAs. Abnormal regulation can lead to cancer. Mutations in genes encoding microRNAs cause, among other things, congenital deafness and eye and skeletal diseases. And mutations in one of the proteins required for microRNA production lead to the DICER1 syndrome, a rare but severe syndrome associated with cancer in various organs and tissues.

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.

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In 2024, the Royal Swedish Academy of Sciences is honoring two US researchers with the Nobel Prize in Medicine for the discovery of a fundamental principle of how gene activity is regulated. Victor Ambros, PhD, a researcher at the University of Massachusetts Chan Medical School, Worcester, and Gary Ruvkun, PhD, professor of genetics at Harvard Medical School in Boston, Massachusetts, discovered microRNAs, a new class of RNA molecules.

“Their groundbreaking discovery in the small worm Caenorhabditis elegans revealed a completely new principle of gene regulation. This turned out to be essential for multicellular organisms, including humans,” said the Nobel Assembly in a statement.
 

Protein Expression 

Genetic information flows from DNA during transcription to messenger RNA (mRNA) and then to protein biosynthesis. In that stage, mRNAs are translated so that proteins are produced according to the genetic instructions stored in the DNA.

Different cell types or tissues express unique sets of proteins, however. This specialized expression results from precise regulation of gene activity, so that in each cell type, only the correct set of genes is active. In this way, for example, muscle cells, intestinal cells, and various types of nerve cells can fulfill their functions.

Furthermore, gene activity must constantly be fine-tuned to adapt cell functions to changing conditions in our body and environment. When gene regulation goes awry, it can lead to serious outcomes such as cancer, diabetes, or autoimmune diseases. Therefore, understanding the regulation of gene activity has been an important goal for many decades.

In the 1960s, researchers had shown that specialized proteins called transcription factors bind to specific regions of DNA and control the flow of genetic information by determining which mRNAs are produced. Since that time, thousands of transcription factors have been identified. For a long time, scientists thought that the main principles of gene regulation were understood. 
 

Roundworm Research 

In the late 1980s, Dr. Ambros and Dr. Ruvkun were postdoctoral researchers in the laboratory of Robert Horvitz, PhD, who received the Nobel Prize in 2002 with Sydney Brenner and John Sulston. In Dr. Horvitz’s laboratory, they studied the relatively inconspicuous, 1-mm long roundworm C elegans.

Despite its small size, C elegans has many specialized cell types such as nerve and muscle cells that are also found in larger, more complex animals. These features make it a popular animal model.

Dr. Ambros and Dr. Ruvkun were interested in genes that ensure that different cell types develop at the right time. They examined two mutated worm strains, lin-4 and lin-14, that exhibited defects in the temporal activation of specific genes during development. The laureates wanted to identify mutated genes and understand their function.

Dr. Ambros had previously shown that lin-4 appeared to be a negative regulator of lin-14. But how lin-14 activity was blocked was unknown.
 

Collaboration Yields Breakthrough

After his postdoctoral years, Dr. Ambros analyzed the lin-4 mutant in his newly established laboratory at Harvard University. Systematic mapping allowed the cloning of the gene and led to an unexpected result: lin-4 produced an unusually short RNA molecule that lacked a code for protein synthesis. These surprising results suggested that this small RNA from lin-4 was responsible for inhibiting lin-14. 

At the same time, Dr. Ruvkun, in his newly founded laboratory at Massachusetts General Hospital and Harvard Medical School, studied the regulation of lin-14. In contradiction to the current understanding of gene regulation, he showed that it was not the production of lin-14 mRNA that was inhibited by lin-4. The regulation seems to occur at a later stage in the gene expression process, namely through the shutdown of protein synthesis. In addition, a section in lin-14 mRNA was discovered to be necessary for inhibition by lin-4.

The two laureates compared their results, leading to a groundbreaking discovery. The short lin-4 sequence matched complementary sequences in the relevant section of the lin-14 mRNA. Dr. Ambros and Dr. Ruvkun conducted further experiments showing that the lin-4 microRNA silences lin-14 by binding to the complementary sequences of its mRNA, thus blocking the production of the lin-14 protein. A new principle of gene regulation, mediated by a previously unknown type of RNA, the microRNA, had been discovered.
 

 

 

Subdued Initial Response

The results were published in Cell in 1993 and initially received little attention. However, interest grew in 2000 when Dr. Ruvkun’s research group published the discovery of another microRNA encoded by let-7.

In contrast to lin-4, let-7 was highly conserved and present throughout the animal kingdom. The article sparked great interest. In the following years, hundreds of microRNAs were identified. Today, researchers know that there are more than 1000 genes for various microRNAs in humans and that gene regulation by microRNAs is found in all multicellular organisms.

In addition to mapping new microRNAs, experiments by several research groups have elucidated fundamental mechanisms. Their binding leads to inhibition of protein synthesis or degradation of mRNA. Interestingly, a single microRNA can regulate the expression of many genes. Conversely, a single gene can be regulated by multiple microRNAs, thus coordinating and fine-tuning entire gene networks.

The cellular machinery for producing functional microRNAs is also used to produce other small RNA molecules in plants and animals, for example, as a means of protecting plants from viral infections. Andrew Z. Fire and Craig C. Mello, who were awarded the Nobel Prize in 2006, described RNA interference, in which specific mRNA molecules are inactivated by the addition of double-stranded RNA molecules to cells.
 

Small RNAs, Great Importance

Gene regulation by microRNA has likely existed for hundreds of millions of years. This mechanism has enabled the evolution of increasingly complex organisms.

From genetic research, it is known that cells and tissues do not develop normally without microRNAs. Abnormal regulation can lead to cancer. Mutations in genes encoding microRNAs cause, among other things, congenital deafness and eye and skeletal diseases. And mutations in one of the proteins required for microRNA production lead to the DICER1 syndrome, a rare but severe syndrome associated with cancer in various organs and tissues.

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.

In 2024, the Royal Swedish Academy of Sciences is honoring two US researchers with the Nobel Prize in Medicine for the discovery of a fundamental principle of how gene activity is regulated. Victor Ambros, PhD, a researcher at the University of Massachusetts Chan Medical School, Worcester, and Gary Ruvkun, PhD, professor of genetics at Harvard Medical School in Boston, Massachusetts, discovered microRNAs, a new class of RNA molecules.

“Their groundbreaking discovery in the small worm Caenorhabditis elegans revealed a completely new principle of gene regulation. This turned out to be essential for multicellular organisms, including humans,” said the Nobel Assembly in a statement.
 

Protein Expression 

Genetic information flows from DNA during transcription to messenger RNA (mRNA) and then to protein biosynthesis. In that stage, mRNAs are translated so that proteins are produced according to the genetic instructions stored in the DNA.

Different cell types or tissues express unique sets of proteins, however. This specialized expression results from precise regulation of gene activity, so that in each cell type, only the correct set of genes is active. In this way, for example, muscle cells, intestinal cells, and various types of nerve cells can fulfill their functions.

Furthermore, gene activity must constantly be fine-tuned to adapt cell functions to changing conditions in our body and environment. When gene regulation goes awry, it can lead to serious outcomes such as cancer, diabetes, or autoimmune diseases. Therefore, understanding the regulation of gene activity has been an important goal for many decades.

In the 1960s, researchers had shown that specialized proteins called transcription factors bind to specific regions of DNA and control the flow of genetic information by determining which mRNAs are produced. Since that time, thousands of transcription factors have been identified. For a long time, scientists thought that the main principles of gene regulation were understood. 
 

Roundworm Research 

In the late 1980s, Dr. Ambros and Dr. Ruvkun were postdoctoral researchers in the laboratory of Robert Horvitz, PhD, who received the Nobel Prize in 2002 with Sydney Brenner and John Sulston. In Dr. Horvitz’s laboratory, they studied the relatively inconspicuous, 1-mm long roundworm C elegans.

Despite its small size, C elegans has many specialized cell types such as nerve and muscle cells that are also found in larger, more complex animals. These features make it a popular animal model.

Dr. Ambros and Dr. Ruvkun were interested in genes that ensure that different cell types develop at the right time. They examined two mutated worm strains, lin-4 and lin-14, that exhibited defects in the temporal activation of specific genes during development. The laureates wanted to identify mutated genes and understand their function.

Dr. Ambros had previously shown that lin-4 appeared to be a negative regulator of lin-14. But how lin-14 activity was blocked was unknown.
 

Collaboration Yields Breakthrough

After his postdoctoral years, Dr. Ambros analyzed the lin-4 mutant in his newly established laboratory at Harvard University. Systematic mapping allowed the cloning of the gene and led to an unexpected result: lin-4 produced an unusually short RNA molecule that lacked a code for protein synthesis. These surprising results suggested that this small RNA from lin-4 was responsible for inhibiting lin-14. 

At the same time, Dr. Ruvkun, in his newly founded laboratory at Massachusetts General Hospital and Harvard Medical School, studied the regulation of lin-14. In contradiction to the current understanding of gene regulation, he showed that it was not the production of lin-14 mRNA that was inhibited by lin-4. The regulation seems to occur at a later stage in the gene expression process, namely through the shutdown of protein synthesis. In addition, a section in lin-14 mRNA was discovered to be necessary for inhibition by lin-4.

The two laureates compared their results, leading to a groundbreaking discovery. The short lin-4 sequence matched complementary sequences in the relevant section of the lin-14 mRNA. Dr. Ambros and Dr. Ruvkun conducted further experiments showing that the lin-4 microRNA silences lin-14 by binding to the complementary sequences of its mRNA, thus blocking the production of the lin-14 protein. A new principle of gene regulation, mediated by a previously unknown type of RNA, the microRNA, had been discovered.
 

 

 

Subdued Initial Response

The results were published in Cell in 1993 and initially received little attention. However, interest grew in 2000 when Dr. Ruvkun’s research group published the discovery of another microRNA encoded by let-7.

In contrast to lin-4, let-7 was highly conserved and present throughout the animal kingdom. The article sparked great interest. In the following years, hundreds of microRNAs were identified. Today, researchers know that there are more than 1000 genes for various microRNAs in humans and that gene regulation by microRNAs is found in all multicellular organisms.

In addition to mapping new microRNAs, experiments by several research groups have elucidated fundamental mechanisms. Their binding leads to inhibition of protein synthesis or degradation of mRNA. Interestingly, a single microRNA can regulate the expression of many genes. Conversely, a single gene can be regulated by multiple microRNAs, thus coordinating and fine-tuning entire gene networks.

The cellular machinery for producing functional microRNAs is also used to produce other small RNA molecules in plants and animals, for example, as a means of protecting plants from viral infections. Andrew Z. Fire and Craig C. Mello, who were awarded the Nobel Prize in 2006, described RNA interference, in which specific mRNA molecules are inactivated by the addition of double-stranded RNA molecules to cells.
 

Small RNAs, Great Importance

Gene regulation by microRNA has likely existed for hundreds of millions of years. This mechanism has enabled the evolution of increasingly complex organisms.

From genetic research, it is known that cells and tissues do not develop normally without microRNAs. Abnormal regulation can lead to cancer. Mutations in genes encoding microRNAs cause, among other things, congenital deafness and eye and skeletal diseases. And mutations in one of the proteins required for microRNA production lead to the DICER1 syndrome, a rare but severe syndrome associated with cancer in various organs and tissues.

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.

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Six Tips on Coronavirus Testing for Doctors and Patients

Article Type
Changed
Fri, 10/04/2024 - 13:14

In Germany, the activity of acute respiratory diseases is at a higher level than usual for this time of year because of rhinoviruses and SARS-CoV-2, according to the Robert Koch Institute, Germany. If a patient has a fever and cough and feels exhausted, it could be COVID-19. What significance do rapid tests have? And when should doctors advise their patients about them?

When to Test

People at a higher risk for severe COVID-19 benefit from tests. This population includes the following groups:

  • Older patients
  • Immunocompromised patients
  • Patients with respiratory diseases
  • Patients with cardiovascular diseases
  • Patients with liver and kidney diseases
  • Patients with neurological diseases
  • Patients with obesity

If doctors detect SARS-CoV-2 infection early, they can prescribe Paxlovid, for example, to reduce morbidity and mortality risks. Conversely, people without specific risks should test themselves if they plan to visit vulnerable individuals.
 

Detecting New Variants

A comprehensive study from the fall of 2022 provides evidence that antigen tests targeting the nucleocapsid (N) protein of SARS-CoV-2 also detect new variants.

The researchers built a library of various versions of the SARS-CoV-2 N protein. Their collection included nearly 8000 individual amino acid substitutions, representing more than 99.5% of all statistically possible mutations of the N protein.

They then examined how these N proteins interacted with 17 antibodies used in 11 commercially available antigen rapid tests.

All antibodies were able to recognize altered N proteins. Since the researchers successfully investigated diagnostic antibodies against nearly all possible N-protein mutations, rapid tests should be able to detect future virus variants. However, sensitivity and specificity may still change.
 

Test Timing

Uncertainty about what time of day to test can be mitigated by performing multiple COVID-19 rapid tests over time. The Food and Drug Administration (FDA) and similar organizations make this recommendation. Studies of symptomatic individuals show that serial tests increase accuracy.

In the early stages of infection, swabs may contain too little virus material because of widespread immunity against SARS-CoV-2. That is, they may contain inadequate levels of the relevant antigen. Especially in asymptomatic individuals or patients in the incubation phase, a single test may therefore yield a false-negative result. Therefore, the FDA recommends conducting at least two additional tests 48 hours apart in case of a negative test result.

 

Costs of Rapid Tests

The days of free tests are long gone. In Germany, the distribution of free preventive coronavirus tests was discontinued on March 1, 2023.

Test kits are still available in pharmacies or drugstores. In packages with 5-10 tests, the individual test costs between €0.90 and €1.50, depending on the provider. If a patient still has old rapid coronavirus tests in his or her medicine cabinet, are they still suitable?
 

Expired Tests

Properly stored tests that have not passed their expiration dates can still be used. But microbiologist and pathologist Daniel Rhoads, MD, from the Cleveland Clinic in Ohio warns against expired rapid tests.

 

 

The chemicals may have decomposed, the solvent may have evaporated, or antibodies may have lost their effectiveness, thus making false negative results more likely. “These are proteins that can decompose over time,” said Dr. Rhoads.
 

Ordering PCR Tests

The polymerase chain reaction (PCR) test remains the gold standard for diagnosing COVID-19. It is still available within statutory health insurance coverage. As Germany’s National Association of Statutory Health Insurance Physicians observes, form Muster 10 is used to order the test in that country.

The fee for the swab is included in the insured patient’s basic flat rate. Laboratories bill the PCR test using fee schedule position (GOP) 32816, according to the Uniform Value Scale (EBM).

There is no possibility for billing rapid tests for SARS-CoV-2 in medical practices within the EBM. A laboratory-based SARS-CoV-2 antigen detection test (GOP 32779) can be requested via the Muster 10 form.

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 first appeared on Medscape.com.

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In Germany, the activity of acute respiratory diseases is at a higher level than usual for this time of year because of rhinoviruses and SARS-CoV-2, according to the Robert Koch Institute, Germany. If a patient has a fever and cough and feels exhausted, it could be COVID-19. What significance do rapid tests have? And when should doctors advise their patients about them?

When to Test

People at a higher risk for severe COVID-19 benefit from tests. This population includes the following groups:

  • Older patients
  • Immunocompromised patients
  • Patients with respiratory diseases
  • Patients with cardiovascular diseases
  • Patients with liver and kidney diseases
  • Patients with neurological diseases
  • Patients with obesity

If doctors detect SARS-CoV-2 infection early, they can prescribe Paxlovid, for example, to reduce morbidity and mortality risks. Conversely, people without specific risks should test themselves if they plan to visit vulnerable individuals.
 

Detecting New Variants

A comprehensive study from the fall of 2022 provides evidence that antigen tests targeting the nucleocapsid (N) protein of SARS-CoV-2 also detect new variants.

The researchers built a library of various versions of the SARS-CoV-2 N protein. Their collection included nearly 8000 individual amino acid substitutions, representing more than 99.5% of all statistically possible mutations of the N protein.

They then examined how these N proteins interacted with 17 antibodies used in 11 commercially available antigen rapid tests.

All antibodies were able to recognize altered N proteins. Since the researchers successfully investigated diagnostic antibodies against nearly all possible N-protein mutations, rapid tests should be able to detect future virus variants. However, sensitivity and specificity may still change.
 

Test Timing

Uncertainty about what time of day to test can be mitigated by performing multiple COVID-19 rapid tests over time. The Food and Drug Administration (FDA) and similar organizations make this recommendation. Studies of symptomatic individuals show that serial tests increase accuracy.

In the early stages of infection, swabs may contain too little virus material because of widespread immunity against SARS-CoV-2. That is, they may contain inadequate levels of the relevant antigen. Especially in asymptomatic individuals or patients in the incubation phase, a single test may therefore yield a false-negative result. Therefore, the FDA recommends conducting at least two additional tests 48 hours apart in case of a negative test result.

 

Costs of Rapid Tests

The days of free tests are long gone. In Germany, the distribution of free preventive coronavirus tests was discontinued on March 1, 2023.

Test kits are still available in pharmacies or drugstores. In packages with 5-10 tests, the individual test costs between €0.90 and €1.50, depending on the provider. If a patient still has old rapid coronavirus tests in his or her medicine cabinet, are they still suitable?
 

Expired Tests

Properly stored tests that have not passed their expiration dates can still be used. But microbiologist and pathologist Daniel Rhoads, MD, from the Cleveland Clinic in Ohio warns against expired rapid tests.

 

 

The chemicals may have decomposed, the solvent may have evaporated, or antibodies may have lost their effectiveness, thus making false negative results more likely. “These are proteins that can decompose over time,” said Dr. Rhoads.
 

Ordering PCR Tests

The polymerase chain reaction (PCR) test remains the gold standard for diagnosing COVID-19. It is still available within statutory health insurance coverage. As Germany’s National Association of Statutory Health Insurance Physicians observes, form Muster 10 is used to order the test in that country.

The fee for the swab is included in the insured patient’s basic flat rate. Laboratories bill the PCR test using fee schedule position (GOP) 32816, according to the Uniform Value Scale (EBM).

There is no possibility for billing rapid tests for SARS-CoV-2 in medical practices within the EBM. A laboratory-based SARS-CoV-2 antigen detection test (GOP 32779) can be requested via the Muster 10 form.

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 first appeared on Medscape.com.

In Germany, the activity of acute respiratory diseases is at a higher level than usual for this time of year because of rhinoviruses and SARS-CoV-2, according to the Robert Koch Institute, Germany. If a patient has a fever and cough and feels exhausted, it could be COVID-19. What significance do rapid tests have? And when should doctors advise their patients about them?

When to Test

People at a higher risk for severe COVID-19 benefit from tests. This population includes the following groups:

  • Older patients
  • Immunocompromised patients
  • Patients with respiratory diseases
  • Patients with cardiovascular diseases
  • Patients with liver and kidney diseases
  • Patients with neurological diseases
  • Patients with obesity

If doctors detect SARS-CoV-2 infection early, they can prescribe Paxlovid, for example, to reduce morbidity and mortality risks. Conversely, people without specific risks should test themselves if they plan to visit vulnerable individuals.
 

Detecting New Variants

A comprehensive study from the fall of 2022 provides evidence that antigen tests targeting the nucleocapsid (N) protein of SARS-CoV-2 also detect new variants.

The researchers built a library of various versions of the SARS-CoV-2 N protein. Their collection included nearly 8000 individual amino acid substitutions, representing more than 99.5% of all statistically possible mutations of the N protein.

They then examined how these N proteins interacted with 17 antibodies used in 11 commercially available antigen rapid tests.

All antibodies were able to recognize altered N proteins. Since the researchers successfully investigated diagnostic antibodies against nearly all possible N-protein mutations, rapid tests should be able to detect future virus variants. However, sensitivity and specificity may still change.
 

Test Timing

Uncertainty about what time of day to test can be mitigated by performing multiple COVID-19 rapid tests over time. The Food and Drug Administration (FDA) and similar organizations make this recommendation. Studies of symptomatic individuals show that serial tests increase accuracy.

In the early stages of infection, swabs may contain too little virus material because of widespread immunity against SARS-CoV-2. That is, they may contain inadequate levels of the relevant antigen. Especially in asymptomatic individuals or patients in the incubation phase, a single test may therefore yield a false-negative result. Therefore, the FDA recommends conducting at least two additional tests 48 hours apart in case of a negative test result.

 

Costs of Rapid Tests

The days of free tests are long gone. In Germany, the distribution of free preventive coronavirus tests was discontinued on March 1, 2023.

Test kits are still available in pharmacies or drugstores. In packages with 5-10 tests, the individual test costs between €0.90 and €1.50, depending on the provider. If a patient still has old rapid coronavirus tests in his or her medicine cabinet, are they still suitable?
 

Expired Tests

Properly stored tests that have not passed their expiration dates can still be used. But microbiologist and pathologist Daniel Rhoads, MD, from the Cleveland Clinic in Ohio warns against expired rapid tests.

 

 

The chemicals may have decomposed, the solvent may have evaporated, or antibodies may have lost their effectiveness, thus making false negative results more likely. “These are proteins that can decompose over time,” said Dr. Rhoads.
 

Ordering PCR Tests

The polymerase chain reaction (PCR) test remains the gold standard for diagnosing COVID-19. It is still available within statutory health insurance coverage. As Germany’s National Association of Statutory Health Insurance Physicians observes, form Muster 10 is used to order the test in that country.

The fee for the swab is included in the insured patient’s basic flat rate. Laboratories bill the PCR test using fee schedule position (GOP) 32816, according to the Uniform Value Scale (EBM).

There is no possibility for billing rapid tests for SARS-CoV-2 in medical practices within the EBM. A laboratory-based SARS-CoV-2 antigen detection test (GOP 32779) can be requested via the Muster 10 form.

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 first appeared on Medscape.com.

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EMA warns that omega-3-acid ethyl esters may cause AFib

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Changed
Tue, 10/17/2023 - 12:37

 

In its September meeting, the safety committee (Pharmacovigilance Risk Assessment Committee) of the European Medicines Agency confirmed that atrial fibrillation will now be included as a common side effect in the Summary of Product Characteristics for medicinal products containing omega-3-acid ethyl esters. Should atrial fibrillation develop, intake of the medication must be stopped permanently.

Omega-3-acid ethyl esters are used to treat hypertriglyceridemia if lifestyle changes, particularly those related to nutrition, have not been sufficient to lower the blood triglyceride level. Hypertriglyceridemia is a risk factor for coronary heart disease.

During a Periodic Safety Update Single Assessment Procedure, the EMA safety committee analyzed systematic overviews and meta-analyses of randomized, controlled clinical studies. Experts found a dose-dependent increase in the risk for atrial fibrillation in patients with cardiovascular diseases or cardiovascular risk factors who were being treated with omega-3-acid ethyl esters, compared with those treated with placebo. The observed risk was at its highest at a dose of 4 g/d.

The PRAC will recommend an update to the Summary of Product Characteristics for preparations that contain omega-3-acid ethyl esters. The aim is to inform physicians, pharmacists, and patients of the risk for atrial fibrillation. A notification will be sent to health care professionals soon to inform them of further details.

This article was translated from the Medscape German Edition. A version appeared on Medscape.com.

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In its September meeting, the safety committee (Pharmacovigilance Risk Assessment Committee) of the European Medicines Agency confirmed that atrial fibrillation will now be included as a common side effect in the Summary of Product Characteristics for medicinal products containing omega-3-acid ethyl esters. Should atrial fibrillation develop, intake of the medication must be stopped permanently.

Omega-3-acid ethyl esters are used to treat hypertriglyceridemia if lifestyle changes, particularly those related to nutrition, have not been sufficient to lower the blood triglyceride level. Hypertriglyceridemia is a risk factor for coronary heart disease.

During a Periodic Safety Update Single Assessment Procedure, the EMA safety committee analyzed systematic overviews and meta-analyses of randomized, controlled clinical studies. Experts found a dose-dependent increase in the risk for atrial fibrillation in patients with cardiovascular diseases or cardiovascular risk factors who were being treated with omega-3-acid ethyl esters, compared with those treated with placebo. The observed risk was at its highest at a dose of 4 g/d.

The PRAC will recommend an update to the Summary of Product Characteristics for preparations that contain omega-3-acid ethyl esters. The aim is to inform physicians, pharmacists, and patients of the risk for atrial fibrillation. A notification will be sent to health care professionals soon to inform them of further details.

This article was translated from the Medscape German Edition. A version appeared on Medscape.com.

 

In its September meeting, the safety committee (Pharmacovigilance Risk Assessment Committee) of the European Medicines Agency confirmed that atrial fibrillation will now be included as a common side effect in the Summary of Product Characteristics for medicinal products containing omega-3-acid ethyl esters. Should atrial fibrillation develop, intake of the medication must be stopped permanently.

Omega-3-acid ethyl esters are used to treat hypertriglyceridemia if lifestyle changes, particularly those related to nutrition, have not been sufficient to lower the blood triglyceride level. Hypertriglyceridemia is a risk factor for coronary heart disease.

During a Periodic Safety Update Single Assessment Procedure, the EMA safety committee analyzed systematic overviews and meta-analyses of randomized, controlled clinical studies. Experts found a dose-dependent increase in the risk for atrial fibrillation in patients with cardiovascular diseases or cardiovascular risk factors who were being treated with omega-3-acid ethyl esters, compared with those treated with placebo. The observed risk was at its highest at a dose of 4 g/d.

The PRAC will recommend an update to the Summary of Product Characteristics for preparations that contain omega-3-acid ethyl esters. The aim is to inform physicians, pharmacists, and patients of the risk for atrial fibrillation. A notification will be sent to health care professionals soon to inform them of further details.

This article was translated from the Medscape German Edition. A version appeared on Medscape.com.

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How can doctors protect their practices against monkeypox?

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Fri, 06/24/2022 - 15:00

Globally, as of June 22, the number of patients with monkeypox has risen to 3,308, according to the U.S. Centers for Disease Control and Prevention. In Germany, 521 people have been infected to date. “There does not seem to be a monkeypox pandemic,” wrote Germany’s Federal Minister of Health Karl Lauterbach, MD. At the moment, the probability that doctors will see a patient infected with the monkeypox virus is quite small. Nevertheless, health care professionals should be prepared. The Robert Koch Institute (RKI), a German federal government agency, has compiled suggestions for inpatient and outpatient sectors.

Characteristics of the virus

All hygiene measures are oriented around the currently known characteristics of the monkeypox virus. According to the RKI, skin or mucosal contact with infectious material from the skin lesions of an infected person plays a key role in human-to-human transmission.

The virus remains biologically active for a certain amount of time, even in dried flakes of skin or dried secretion. Therefore, in general, “careful and thorough cleaning and disinfection of the patient environment or surfaces is necessary,” wrote the RKI. Droplet infections or contaminated surfaces are less often of importance.
 

Basic hygiene measures

“Fundamentally, all basic hygiene measures should of course be followed when dealing with the infected,” said the RKI. Doctors and other health care professionals should use hand sanitizer with proven, at least viricidal, efficacy.

Manufacturers provide such details on the packaging. Both the RKI and the Association for Applied Hygiene (VAH) have published compilations.
 

Measures in medical practices

In the outpatient sector, there is the (currently still quite low) danger that patients with monkeypox will infect other patients or practice employees. To prevent this, the RKI advised organizational measures.

If employees suspect that patients have monkeypox when they first arrive at the practice, or when they first speak to them over the phone, they must be separated. Waiting and treatment rooms with surfaces that can be wipe disinfected are well suited for this. Even if only suspected, all employees should wear disposable gloves and mouth-and-nose protection, which has become standard during COVID.
 

Measures in the clinical sector

In terms of accommodation, the RKI recommends isolation rooms with a washroom and, if possible, an antechamber that doctors and nurses can use to put on and take off their personal protective equipment (PPE). PPE includes disposable gloves, mouth-and-nose protection (for direct treatment, at least an FFP2 mask), and protective eyeglasses.

Special attention should be paid to the disinfection of surfaces. In addition to the selection of suitable preparations, the RKI advised that the high stability of the virus, especially in skin particles, be taken into account. When cleaning, particular care should be taken not to disturb any particles, according to the recommendations. In addition, the manufacturer’s application time must be strictly observed.

In the inpatient sector, such measures are important for all surfaces close to patients, such as bedside tables, wet zones, or door handles.

Medical devices such as stethoscopes or electrodes should be disinfected immediately after use. If possible, thermal treatment is preferred, such as for surgical apparatus, as long as they are not disposable products. The RKI has compiled separate recommendations for medical devices.

For laundry such as towels or bed linen, there is the danger that infectious particles will be stirred up. They should be collected and transported for treatment in sealable bags. Details on the selection of preparations can be found in the RKI or VAH list.

Contaminated waste is classified under waste code ASN 18 01 03 (“Guidelines for disposal of waste from healthcare institutions”) and may only be destroyed thermally in suitable facilities.

This article was translated from the Medscape German edition. A version of this article first appeared on Medscape.com.

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Globally, as of June 22, the number of patients with monkeypox has risen to 3,308, according to the U.S. Centers for Disease Control and Prevention. In Germany, 521 people have been infected to date. “There does not seem to be a monkeypox pandemic,” wrote Germany’s Federal Minister of Health Karl Lauterbach, MD. At the moment, the probability that doctors will see a patient infected with the monkeypox virus is quite small. Nevertheless, health care professionals should be prepared. The Robert Koch Institute (RKI), a German federal government agency, has compiled suggestions for inpatient and outpatient sectors.

Characteristics of the virus

All hygiene measures are oriented around the currently known characteristics of the monkeypox virus. According to the RKI, skin or mucosal contact with infectious material from the skin lesions of an infected person plays a key role in human-to-human transmission.

The virus remains biologically active for a certain amount of time, even in dried flakes of skin or dried secretion. Therefore, in general, “careful and thorough cleaning and disinfection of the patient environment or surfaces is necessary,” wrote the RKI. Droplet infections or contaminated surfaces are less often of importance.
 

Basic hygiene measures

“Fundamentally, all basic hygiene measures should of course be followed when dealing with the infected,” said the RKI. Doctors and other health care professionals should use hand sanitizer with proven, at least viricidal, efficacy.

Manufacturers provide such details on the packaging. Both the RKI and the Association for Applied Hygiene (VAH) have published compilations.
 

Measures in medical practices

In the outpatient sector, there is the (currently still quite low) danger that patients with monkeypox will infect other patients or practice employees. To prevent this, the RKI advised organizational measures.

If employees suspect that patients have monkeypox when they first arrive at the practice, or when they first speak to them over the phone, they must be separated. Waiting and treatment rooms with surfaces that can be wipe disinfected are well suited for this. Even if only suspected, all employees should wear disposable gloves and mouth-and-nose protection, which has become standard during COVID.
 

Measures in the clinical sector

In terms of accommodation, the RKI recommends isolation rooms with a washroom and, if possible, an antechamber that doctors and nurses can use to put on and take off their personal protective equipment (PPE). PPE includes disposable gloves, mouth-and-nose protection (for direct treatment, at least an FFP2 mask), and protective eyeglasses.

Special attention should be paid to the disinfection of surfaces. In addition to the selection of suitable preparations, the RKI advised that the high stability of the virus, especially in skin particles, be taken into account. When cleaning, particular care should be taken not to disturb any particles, according to the recommendations. In addition, the manufacturer’s application time must be strictly observed.

In the inpatient sector, such measures are important for all surfaces close to patients, such as bedside tables, wet zones, or door handles.

Medical devices such as stethoscopes or electrodes should be disinfected immediately after use. If possible, thermal treatment is preferred, such as for surgical apparatus, as long as they are not disposable products. The RKI has compiled separate recommendations for medical devices.

For laundry such as towels or bed linen, there is the danger that infectious particles will be stirred up. They should be collected and transported for treatment in sealable bags. Details on the selection of preparations can be found in the RKI or VAH list.

Contaminated waste is classified under waste code ASN 18 01 03 (“Guidelines for disposal of waste from healthcare institutions”) and may only be destroyed thermally in suitable facilities.

This article was translated from the Medscape German edition. A version of this article first appeared on Medscape.com.

Globally, as of June 22, the number of patients with monkeypox has risen to 3,308, according to the U.S. Centers for Disease Control and Prevention. In Germany, 521 people have been infected to date. “There does not seem to be a monkeypox pandemic,” wrote Germany’s Federal Minister of Health Karl Lauterbach, MD. At the moment, the probability that doctors will see a patient infected with the monkeypox virus is quite small. Nevertheless, health care professionals should be prepared. The Robert Koch Institute (RKI), a German federal government agency, has compiled suggestions for inpatient and outpatient sectors.

Characteristics of the virus

All hygiene measures are oriented around the currently known characteristics of the monkeypox virus. According to the RKI, skin or mucosal contact with infectious material from the skin lesions of an infected person plays a key role in human-to-human transmission.

The virus remains biologically active for a certain amount of time, even in dried flakes of skin or dried secretion. Therefore, in general, “careful and thorough cleaning and disinfection of the patient environment or surfaces is necessary,” wrote the RKI. Droplet infections or contaminated surfaces are less often of importance.
 

Basic hygiene measures

“Fundamentally, all basic hygiene measures should of course be followed when dealing with the infected,” said the RKI. Doctors and other health care professionals should use hand sanitizer with proven, at least viricidal, efficacy.

Manufacturers provide such details on the packaging. Both the RKI and the Association for Applied Hygiene (VAH) have published compilations.
 

Measures in medical practices

In the outpatient sector, there is the (currently still quite low) danger that patients with monkeypox will infect other patients or practice employees. To prevent this, the RKI advised organizational measures.

If employees suspect that patients have monkeypox when they first arrive at the practice, or when they first speak to them over the phone, they must be separated. Waiting and treatment rooms with surfaces that can be wipe disinfected are well suited for this. Even if only suspected, all employees should wear disposable gloves and mouth-and-nose protection, which has become standard during COVID.
 

Measures in the clinical sector

In terms of accommodation, the RKI recommends isolation rooms with a washroom and, if possible, an antechamber that doctors and nurses can use to put on and take off their personal protective equipment (PPE). PPE includes disposable gloves, mouth-and-nose protection (for direct treatment, at least an FFP2 mask), and protective eyeglasses.

Special attention should be paid to the disinfection of surfaces. In addition to the selection of suitable preparations, the RKI advised that the high stability of the virus, especially in skin particles, be taken into account. When cleaning, particular care should be taken not to disturb any particles, according to the recommendations. In addition, the manufacturer’s application time must be strictly observed.

In the inpatient sector, such measures are important for all surfaces close to patients, such as bedside tables, wet zones, or door handles.

Medical devices such as stethoscopes or electrodes should be disinfected immediately after use. If possible, thermal treatment is preferred, such as for surgical apparatus, as long as they are not disposable products. The RKI has compiled separate recommendations for medical devices.

For laundry such as towels or bed linen, there is the danger that infectious particles will be stirred up. They should be collected and transported for treatment in sealable bags. Details on the selection of preparations can be found in the RKI or VAH list.

Contaminated waste is classified under waste code ASN 18 01 03 (“Guidelines for disposal of waste from healthcare institutions”) and may only be destroyed thermally in suitable facilities.

This article was translated from the Medscape German edition. A version of this article first appeared on Medscape.com.

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