The FP suspected melanoma and recommended immediate biopsy. The patient consented, and the physician performed a broad shave biopsy that included most of the pigmented lesion. Pathology revealed a lentigo maligna melanoma with a Breslow depth of 0.3 mm.

Lentigo maligna melanoma occurs in 4% to 15% of cutaneous melanomas. It’s similar to the superficial spreading type and appears as a flat (or mildly elevated) mottled tan, brown, or dark-brown discoloration. This type of melanoma is found most often in the elderly and arises on chronically sun-exposed, damaged skin on the face, ears, arms, and upper trunk. The average age of onset is 65 years and it grows slowly over 5 to 20 years.

When melanoma is suspected, it’s best to provide a specimen with adequate depth and breadth. Unfortunately, choosing the darkest and most raised area does not guarantee the correct diagnosis in a partial biopsy.

In cases of suspected lentigo maligna melanoma on the face, a broad shave provides a better sample than a punch biopsy. The broad shave biopsy (also known as saucerization) is best performed with a razor blade. (See the Watch & Learn video on “Shave biopsy.”)

In this case, the relatively small size of the lesion and the high risk for melanoma would make an elliptical excisional biopsy a good alternative. The saucerization has the advantage of being quick and easy to perform so that it can be done on the day that the melanoma is suspected.

This patient was referred for Mohs surgery for complete excision and repair. A sentinel lymph node biopsy was not indicated, and the prognosis for this stage Ia melanoma was relatively good.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Mayeaux, EJ, Usatine, R. Lentigo maligna. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:981-984.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

The FP suspected melanoma and recommended immediate biopsy. The patient consented, and the physician performed a broad shave biopsy that included most of the pigmented lesion. Pathology revealed a lentigo maligna melanoma with a Breslow depth of 0.3 mm.

Lentigo maligna melanoma occurs in 4% to 15% of cutaneous melanomas. It’s similar to the superficial spreading type and appears as a flat (or mildly elevated) mottled tan, brown, or dark-brown discoloration. This type of melanoma is found most often in the elderly and arises on chronically sun-exposed, damaged skin on the face, ears, arms, and upper trunk. The average age of onset is 65 years and it grows slowly over 5 to 20 years.

When melanoma is suspected, it’s best to provide a specimen with adequate depth and breadth. Unfortunately, choosing the darkest and most raised area does not guarantee the correct diagnosis in a partial biopsy.

In cases of suspected lentigo maligna melanoma on the face, a broad shave provides a better sample than a punch biopsy. The broad shave biopsy (also known as saucerization) is best performed with a razor blade. (See the Watch & Learn video on “Shave biopsy.”)

In this case, the relatively small size of the lesion and the high risk for melanoma would make an elliptical excisional biopsy a good alternative. The saucerization has the advantage of being quick and easy to perform so that it can be done on the day that the melanoma is suspected.

This patient was referred for Mohs surgery for complete excision and repair. A sentinel lymph node biopsy was not indicated, and the prognosis for this stage Ia melanoma was relatively good.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Mayeaux, EJ, Usatine, R. Lentigo maligna. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:981-984.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

The FP suspected melanoma and recommended immediate biopsy. The patient consented, and the physician performed a broad shave biopsy that included most of the pigmented lesion. Pathology revealed a lentigo maligna melanoma with a Breslow depth of 0.3 mm.

Lentigo maligna melanoma occurs in 4% to 15% of cutaneous melanomas. It’s similar to the superficial spreading type and appears as a flat (or mildly elevated) mottled tan, brown, or dark-brown discoloration. This type of melanoma is found most often in the elderly and arises on chronically sun-exposed, damaged skin on the face, ears, arms, and upper trunk. The average age of onset is 65 years and it grows slowly over 5 to 20 years.

When melanoma is suspected, it’s best to provide a specimen with adequate depth and breadth. Unfortunately, choosing the darkest and most raised area does not guarantee the correct diagnosis in a partial biopsy.

In cases of suspected lentigo maligna melanoma on the face, a broad shave provides a better sample than a punch biopsy. The broad shave biopsy (also known as saucerization) is best performed with a razor blade. (See the Watch & Learn video on “Shave biopsy.”)

In this case, the relatively small size of the lesion and the high risk for melanoma would make an elliptical excisional biopsy a good alternative. The saucerization has the advantage of being quick and easy to perform so that it can be done on the day that the melanoma is suspected.

This patient was referred for Mohs surgery for complete excision and repair. A sentinel lymph node biopsy was not indicated, and the prognosis for this stage Ia melanoma was relatively good.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Mayeaux, EJ, Usatine, R. Lentigo maligna. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:981-984.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

What is the largest endocrine organ in the human body?

Here is a clue: It is also the largest immune organ in humans!

Still scratching your head? Here is another clue: This organ also contains a “second brain,” which is connected to big brain inside the head by the vagus nerve.

Okay, enough guessing: It’s the 30-foot long gastrointestinal (GI) tract, which is generally associated only with eating and digestion. But it is far more than a digestive tract. It is home to about 100 trillion diverse bacteria, including 1,000 known species, which together are known as “microbiota.” Its combined DNA is called the “microbiome” and is 10,000% larger than the human genome. Those trillions of bacteria in our guts are a symbiotic (commensal) organ that is vital for the normal functions of the human body.¹

While this vast array of microorganisms is vital to sustaining a healthy human existence, it can also be involved in multiple psychiatric disorders, including depression, psychosis, anxiety, autism, and attention-deficit/hyperactivity disorder (ADHD). Humans acquire their unique sets of microbiota as they pass through the mother’s vagina at birth and while breastfeeding, as well as from exposure to various environmental sources in the first few months of life.²

The microbiota in the GI tract are an intimate neighbor of the “enteric brain,” comprised of 100 million neurons plus glia-like support cell structures. This “second brain” produces over 30 neuro­transmitters, several of which (dopamine, serotonin, γ-aminobutyric acid [GABA], acetylcholine) have been implicated in major psychiatric disorders.³

The brain and gut have a dynamic bidirectional communication system, mediated by neural, hormonal, and immunological crosstalk and influences. The GI tract secretes dozens of peptides and other signaling molecules that influence the brain. The microbiota also interact with and are regulated by gut hormones such as oxytocin, ghrelin, neuropeptide Y, cholecystokinin, corticotrophin-releasing factor, and pancreatic polypeptide.⁴ The microbiota modulate brain development, functions, and behavior, and maintain the intestinal barrier, which, if disrupted, would result in the gut becoming “leaky” and triggering low-grade inflammation such as that associated with depression.⁵

Continue to: But don't overlook the importance of...

But don’t overlook the importance of diet. It is a major factor in shaping the composition of the microbiota. What we eat can have a preventative or reparative effect on neuroimmune or neuroinflammatory disease. An emerging body of evidence suggests that the diet and its effects on the gut microbiota can modify a person’s genes by epi­genetic mechanisms (altering DNA methylation and histone effects). Probiotics can exert epigenetic effects by influencing cytokines, by producing short-chain fatty acids (SCFAs), by vitamin synthesis, and by producing several well-known neurotransmitters.⁶

The bidirectional trafficking across the microbiome-gut-brain axis includes reciprocal effects. The brain influences the microbiome composition by regulating satiety, the hypothalamic-pituitary axis, and with neuropeptides.⁷ In return, the microbiome conveys information to the brain about the intestinal status via infectious agents, intestinal neuro­transmitters and modulators, cytokines, sensory vagal fibers, and various metabolites. Failure of these normal interactions can lead to a variety of pathological processes, including inflammatory, autoimmune, degenerative, metabolic, cognitive, mood, and behavioral adverse effects. Therapeutic interventions for these adverse consequences can be implemented through microbiome manipulations (such as fecal transplants), nutritional strategies, and reinforcement of the enteric and brain barriers.

Alterations in the microbiota, such as by the intake of antibiotics or by intestinal inflammation, can lead to psychiatric disorders.⁸ The following findings link gut microbiome disruptions with several psychiatric disorders:

Schizophrenia prodrome. Fecal bacteria show an increase in SCFAs, which can activate microglia (the initial step in triggering psychosis).⁹ These bacteria have been shown to lead to an increase in choline levels in the anterior cingulate, a known biomarker for membrane dysfunction, which is one of the biological models of schizophrenia.

Schizophrenia—first-episode. A recent study reported abnormalities in the gut microbiota of patients with first-episode psychosis, with a lower number of certain fecal bacteria (including bifidobacterium, E. coli, and lactobacillus) and high levels of Clostridium coccoides. After 6 months of risperidone treatment, the above changes were reversed.¹⁰

Continue to: Another study of fecal microbiota...

Another study of fecal microbiota in a first-episode psychosis cohort found significant differences in several bacterial strains compared with a healthy control group, and those with the strongest difference had more severe psychotic symptoms and poorer response after 12 months of antipsychotic treatment.¹¹

Autism has been linked to increased microbiota diversity, and an excess of bacteroides has been associated with a higher diversity of autism. Fecal samples from autistic children were reported to have an increase in SCFAs. Interestingly, a certain strain of lactobacillus can modulate oxytocin or reverse some autistic symptoms.

Depression has been associated with increased diversity of microbiota alpha. Patients with depression have been reported to have low numbers of bifidobacterium and lactobacillus. Certain strains have been reported to reduce depression and anxiety behaviors in animal studies. The microbiota-friendly Mediterranean diet, but not the Western diet, appears to mitigate the risk of depression. Certain probiotics have been reported to increase resilience to stress.^12,13

ADHD. Some studies suggest that ADHD may be linked to factors that can alter gut microbiota, including birthing mode, type of infant feeding, maternal health, and early stressors. In addition, dietary influences on gut microbiota can modify ADHD symptoms.¹⁴

Alzheimer’s disease. Metabolic dysregulation, such as obesity and diabetes, can inflame the gut microbiota, and are known risk factors for Alzheimer’s disease.¹⁵

Continue to: Irritable bowel sydrome...

Irritable bowel syndrome (IBS). Fecal microbiota transplantation has been shown to improve IBS by increasing the diversity of gut microbiota.¹⁶ It also improves patients’ mood, not just their IBS symptoms.

Alcohol use. Both alcohol consumption and alcohol withdrawal have been shown to cause immune dysregulation in the brain leading to neuroinflammation. This is attributed to the alteration in the composition of the microbiome (dysbiosis), which has a negative effect on the microbe-host homeostasis.¹⁷

The discovery of microbiome-gut-brain interactions and their bidirectional immune, endocrine, and neurotransmitter effects has been a momentous paradigm shift in health, neuroscience, and psychiatry.¹⁸ It has opened wide vistas of research for potential innovations in the prevention and treatment of various psychiatric disorders. Radical medical interventions that were previously inconceivable, such as fecal transplantation,¹⁹ are an example of the bold insights this new field of microbiome-gut-brain interaction is bringing to the landscape of medicine, including psychiatry. It has also highlighted the previously underappreciated importance of nutrition in health and disease.²⁰

What is the largest endocrine organ in the human body?

Here is a clue: It is also the largest immune organ in humans!

Still scratching your head? Here is another clue: This organ also contains a “second brain,” which is connected to big brain inside the head by the vagus nerve.

Okay, enough guessing: It’s the 30-foot long gastrointestinal (GI) tract, which is generally associated only with eating and digestion. But it is far more than a digestive tract. It is home to about 100 trillion diverse bacteria, including 1,000 known species, which together are known as “microbiota.” Its combined DNA is called the “microbiome” and is 10,000% larger than the human genome. Those trillions of bacteria in our guts are a symbiotic (commensal) organ that is vital for the normal functions of the human body.¹

While this vast array of microorganisms is vital to sustaining a healthy human existence, it can also be involved in multiple psychiatric disorders, including depression, psychosis, anxiety, autism, and attention-deficit/hyperactivity disorder (ADHD). Humans acquire their unique sets of microbiota as they pass through the mother’s vagina at birth and while breastfeeding, as well as from exposure to various environmental sources in the first few months of life.²

The microbiota in the GI tract are an intimate neighbor of the “enteric brain,” comprised of 100 million neurons plus glia-like support cell structures. This “second brain” produces over 30 neuro­transmitters, several of which (dopamine, serotonin, γ-aminobutyric acid [GABA], acetylcholine) have been implicated in major psychiatric disorders.³

The brain and gut have a dynamic bidirectional communication system, mediated by neural, hormonal, and immunological crosstalk and influences. The GI tract secretes dozens of peptides and other signaling molecules that influence the brain. The microbiota also interact with and are regulated by gut hormones such as oxytocin, ghrelin, neuropeptide Y, cholecystokinin, corticotrophin-releasing factor, and pancreatic polypeptide.⁴ The microbiota modulate brain development, functions, and behavior, and maintain the intestinal barrier, which, if disrupted, would result in the gut becoming “leaky” and triggering low-grade inflammation such as that associated with depression.⁵

Continue to: But don't overlook the importance of...

But don’t overlook the importance of diet. It is a major factor in shaping the composition of the microbiota. What we eat can have a preventative or reparative effect on neuroimmune or neuroinflammatory disease. An emerging body of evidence suggests that the diet and its effects on the gut microbiota can modify a person’s genes by epi­genetic mechanisms (altering DNA methylation and histone effects). Probiotics can exert epigenetic effects by influencing cytokines, by producing short-chain fatty acids (SCFAs), by vitamin synthesis, and by producing several well-known neurotransmitters.⁶

The bidirectional trafficking across the microbiome-gut-brain axis includes reciprocal effects. The brain influences the microbiome composition by regulating satiety, the hypothalamic-pituitary axis, and with neuropeptides.⁷ In return, the microbiome conveys information to the brain about the intestinal status via infectious agents, intestinal neuro­transmitters and modulators, cytokines, sensory vagal fibers, and various metabolites. Failure of these normal interactions can lead to a variety of pathological processes, including inflammatory, autoimmune, degenerative, metabolic, cognitive, mood, and behavioral adverse effects. Therapeutic interventions for these adverse consequences can be implemented through microbiome manipulations (such as fecal transplants), nutritional strategies, and reinforcement of the enteric and brain barriers.

Alterations in the microbiota, such as by the intake of antibiotics or by intestinal inflammation, can lead to psychiatric disorders.⁸ The following findings link gut microbiome disruptions with several psychiatric disorders:

Schizophrenia prodrome. Fecal bacteria show an increase in SCFAs, which can activate microglia (the initial step in triggering psychosis).⁹ These bacteria have been shown to lead to an increase in choline levels in the anterior cingulate, a known biomarker for membrane dysfunction, which is one of the biological models of schizophrenia.

Schizophrenia—first-episode. A recent study reported abnormalities in the gut microbiota of patients with first-episode psychosis, with a lower number of certain fecal bacteria (including bifidobacterium, E. coli, and lactobacillus) and high levels of Clostridium coccoides. After 6 months of risperidone treatment, the above changes were reversed.¹⁰

Continue to: Another study of fecal microbiota...

Another study of fecal microbiota in a first-episode psychosis cohort found significant differences in several bacterial strains compared with a healthy control group, and those with the strongest difference had more severe psychotic symptoms and poorer response after 12 months of antipsychotic treatment.¹¹

Autism has been linked to increased microbiota diversity, and an excess of bacteroides has been associated with a higher diversity of autism. Fecal samples from autistic children were reported to have an increase in SCFAs. Interestingly, a certain strain of lactobacillus can modulate oxytocin or reverse some autistic symptoms.

Depression has been associated with increased diversity of microbiota alpha. Patients with depression have been reported to have low numbers of bifidobacterium and lactobacillus. Certain strains have been reported to reduce depression and anxiety behaviors in animal studies. The microbiota-friendly Mediterranean diet, but not the Western diet, appears to mitigate the risk of depression. Certain probiotics have been reported to increase resilience to stress.^12,13

ADHD. Some studies suggest that ADHD may be linked to factors that can alter gut microbiota, including birthing mode, type of infant feeding, maternal health, and early stressors. In addition, dietary influences on gut microbiota can modify ADHD symptoms.¹⁴

Alzheimer’s disease. Metabolic dysregulation, such as obesity and diabetes, can inflame the gut microbiota, and are known risk factors for Alzheimer’s disease.¹⁵

Continue to: Irritable bowel sydrome...

Irritable bowel syndrome (IBS). Fecal microbiota transplantation has been shown to improve IBS by increasing the diversity of gut microbiota.¹⁶ It also improves patients’ mood, not just their IBS symptoms.

Alcohol use. Both alcohol consumption and alcohol withdrawal have been shown to cause immune dysregulation in the brain leading to neuroinflammation. This is attributed to the alteration in the composition of the microbiome (dysbiosis), which has a negative effect on the microbe-host homeostasis.¹⁷

The discovery of microbiome-gut-brain interactions and their bidirectional immune, endocrine, and neurotransmitter effects has been a momentous paradigm shift in health, neuroscience, and psychiatry.¹⁸ It has opened wide vistas of research for potential innovations in the prevention and treatment of various psychiatric disorders. Radical medical interventions that were previously inconceivable, such as fecal transplantation,¹⁹ are an example of the bold insights this new field of microbiome-gut-brain interaction is bringing to the landscape of medicine, including psychiatry. It has also highlighted the previously underappreciated importance of nutrition in health and disease.²⁰

What is the largest endocrine organ in the human body?

Here is a clue: It is also the largest immune organ in humans!

Still scratching your head? Here is another clue: This organ also contains a “second brain,” which is connected to big brain inside the head by the vagus nerve.

Okay, enough guessing: It’s the 30-foot long gastrointestinal (GI) tract, which is generally associated only with eating and digestion. But it is far more than a digestive tract. It is home to about 100 trillion diverse bacteria, including 1,000 known species, which together are known as “microbiota.” Its combined DNA is called the “microbiome” and is 10,000% larger than the human genome. Those trillions of bacteria in our guts are a symbiotic (commensal) organ that is vital for the normal functions of the human body.¹

While this vast array of microorganisms is vital to sustaining a healthy human existence, it can also be involved in multiple psychiatric disorders, including depression, psychosis, anxiety, autism, and attention-deficit/hyperactivity disorder (ADHD). Humans acquire their unique sets of microbiota as they pass through the mother’s vagina at birth and while breastfeeding, as well as from exposure to various environmental sources in the first few months of life.²

The microbiota in the GI tract are an intimate neighbor of the “enteric brain,” comprised of 100 million neurons plus glia-like support cell structures. This “second brain” produces over 30 neuro­transmitters, several of which (dopamine, serotonin, γ-aminobutyric acid [GABA], acetylcholine) have been implicated in major psychiatric disorders.³

The brain and gut have a dynamic bidirectional communication system, mediated by neural, hormonal, and immunological crosstalk and influences. The GI tract secretes dozens of peptides and other signaling molecules that influence the brain. The microbiota also interact with and are regulated by gut hormones such as oxytocin, ghrelin, neuropeptide Y, cholecystokinin, corticotrophin-releasing factor, and pancreatic polypeptide.⁴ The microbiota modulate brain development, functions, and behavior, and maintain the intestinal barrier, which, if disrupted, would result in the gut becoming “leaky” and triggering low-grade inflammation such as that associated with depression.⁵

Continue to: But don't overlook the importance of...

But don’t overlook the importance of diet. It is a major factor in shaping the composition of the microbiota. What we eat can have a preventative or reparative effect on neuroimmune or neuroinflammatory disease. An emerging body of evidence suggests that the diet and its effects on the gut microbiota can modify a person’s genes by epi­genetic mechanisms (altering DNA methylation and histone effects). Probiotics can exert epigenetic effects by influencing cytokines, by producing short-chain fatty acids (SCFAs), by vitamin synthesis, and by producing several well-known neurotransmitters.⁶

The bidirectional trafficking across the microbiome-gut-brain axis includes reciprocal effects. The brain influences the microbiome composition by regulating satiety, the hypothalamic-pituitary axis, and with neuropeptides.⁷ In return, the microbiome conveys information to the brain about the intestinal status via infectious agents, intestinal neuro­transmitters and modulators, cytokines, sensory vagal fibers, and various metabolites. Failure of these normal interactions can lead to a variety of pathological processes, including inflammatory, autoimmune, degenerative, metabolic, cognitive, mood, and behavioral adverse effects. Therapeutic interventions for these adverse consequences can be implemented through microbiome manipulations (such as fecal transplants), nutritional strategies, and reinforcement of the enteric and brain barriers.

Alterations in the microbiota, such as by the intake of antibiotics or by intestinal inflammation, can lead to psychiatric disorders.⁸ The following findings link gut microbiome disruptions with several psychiatric disorders:

Schizophrenia prodrome. Fecal bacteria show an increase in SCFAs, which can activate microglia (the initial step in triggering psychosis).⁹ These bacteria have been shown to lead to an increase in choline levels in the anterior cingulate, a known biomarker for membrane dysfunction, which is one of the biological models of schizophrenia.

Schizophrenia—first-episode. A recent study reported abnormalities in the gut microbiota of patients with first-episode psychosis, with a lower number of certain fecal bacteria (including bifidobacterium, E. coli, and lactobacillus) and high levels of Clostridium coccoides. After 6 months of risperidone treatment, the above changes were reversed.¹⁰

Continue to: Another study of fecal microbiota...

Another study of fecal microbiota in a first-episode psychosis cohort found significant differences in several bacterial strains compared with a healthy control group, and those with the strongest difference had more severe psychotic symptoms and poorer response after 12 months of antipsychotic treatment.¹¹

Autism has been linked to increased microbiota diversity, and an excess of bacteroides has been associated with a higher diversity of autism. Fecal samples from autistic children were reported to have an increase in SCFAs. Interestingly, a certain strain of lactobacillus can modulate oxytocin or reverse some autistic symptoms.

Depression has been associated with increased diversity of microbiota alpha. Patients with depression have been reported to have low numbers of bifidobacterium and lactobacillus. Certain strains have been reported to reduce depression and anxiety behaviors in animal studies. The microbiota-friendly Mediterranean diet, but not the Western diet, appears to mitigate the risk of depression. Certain probiotics have been reported to increase resilience to stress.^12,13

ADHD. Some studies suggest that ADHD may be linked to factors that can alter gut microbiota, including birthing mode, type of infant feeding, maternal health, and early stressors. In addition, dietary influences on gut microbiota can modify ADHD symptoms.¹⁴

Alzheimer’s disease. Metabolic dysregulation, such as obesity and diabetes, can inflame the gut microbiota, and are known risk factors for Alzheimer’s disease.¹⁵

Continue to: Irritable bowel sydrome...

Irritable bowel syndrome (IBS). Fecal microbiota transplantation has been shown to improve IBS by increasing the diversity of gut microbiota.¹⁶ It also improves patients’ mood, not just their IBS symptoms.

Alcohol use. Both alcohol consumption and alcohol withdrawal have been shown to cause immune dysregulation in the brain leading to neuroinflammation. This is attributed to the alteration in the composition of the microbiome (dysbiosis), which has a negative effect on the microbe-host homeostasis.¹⁷

The discovery of microbiome-gut-brain interactions and their bidirectional immune, endocrine, and neurotransmitter effects has been a momentous paradigm shift in health, neuroscience, and psychiatry.¹⁸ It has opened wide vistas of research for potential innovations in the prevention and treatment of various psychiatric disorders. Radical medical interventions that were previously inconceivable, such as fecal transplantation,¹⁹ are an example of the bold insights this new field of microbiome-gut-brain interaction is bringing to the landscape of medicine, including psychiatry. It has also highlighted the previously underappreciated importance of nutrition in health and disease.²⁰

Any benefit of statins for primary prevention in older adult populations may depend on whether or not type 2 diabetes is present, results of a retrospective cohort study suggest.

Statins had no protective effect overall in the study, which included adults older than 74 years who had no clinically recognized atherosclerotic cardiovascular disease (ASCVD).

In older patients with diabetes, statins were associated with reductions in CVD incidence and all-cause mortality. However, this benefit was substantially reduced in patients 85 years and older, and completely absent in those over 90, study authors said in the BMJ.

“These results do not support the widespread use of statins in old and very old populations, but they do support treatment in those with type 2 diabetes younger than 85 years,” said Rafael Ramos, MD, of the University of Girona, Spain, and his coauthors.

While meta-analyses support statins as primary prevention of CVD in individuals 65 years or older, evidence is lacking on those older than 74 years, according to the investigators.

Accordingly, they conducted the present retrospective cohort study based on data from a Spanish primary care database that included patient records for more than 6 million people. They looked specifically for individuals aged 75 years or older with no history of ASCVD who had at least one visit between July 2006 and December 2007.

They found 46,864 people meeting those criteria, of whom 7,502 (16.0%) had started statin treatment and 7,880 (16.8%) had type 2 diabetes.

With a median follow-up of 7.7 years, statin use had no benefit in reducing ASCVD incidence or all-cause mortality for the entire study population, statistical analyses showed.

In participants with diabetes, however, statins did appear protective, at least in the patients aged 75-84 years, with hazard ratios of 0.76 (95% confidence interval, 0.65-0.89) for CVD and 0.84 (95% CI, 0.75-0.94) for all-cause mortality, Dr. Ramos and his colleagues reported.

The 1-year number needed to treat in this 75-84 age group was 164 for atherosclerotic CVD, and 306 for all-cause mortality, they added.

By contrast, the hazard ratios for patients 85 years and older were 0.82 (95% CI, 0.53-1.26) for atherosclerotic CVD, and 1.05 (95% CI, 0.86-1.28) for all-cause mortality, the investigators reported.

The observed reductions in CVD in individuals with diabetes lost statistical significance at age 85 years when investigators looked at hazard ratios for each year of age. Similarly, reductions in all-cause mortality began to lose statistical significance at age 82 years and “definitively disappeared” in those aged 88 years or older, they said.

The project was supported by grants from the Ministerio de Salud, Spain’s Ministry of Science and Innovation through the Carlos III Health Institute and other entities.

Dr. Ramos and his coauthors declared no support in the previous 3 years from any organization related to, or that might have an interest in, the submitted work. They also declared no other relationships or activities that could appear to have influenced the work.
 

SOURCE: Ramos R et al. BMJ 2018 Sep 5;362:k3359.

Any benefit of statins for primary prevention in older adult populations may depend on whether or not type 2 diabetes is present, results of a retrospective cohort study suggest.

Statins had no protective effect overall in the study, which included adults older than 74 years who had no clinically recognized atherosclerotic cardiovascular disease (ASCVD).

In older patients with diabetes, statins were associated with reductions in CVD incidence and all-cause mortality. However, this benefit was substantially reduced in patients 85 years and older, and completely absent in those over 90, study authors said in the BMJ.

“These results do not support the widespread use of statins in old and very old populations, but they do support treatment in those with type 2 diabetes younger than 85 years,” said Rafael Ramos, MD, of the University of Girona, Spain, and his coauthors.

While meta-analyses support statins as primary prevention of CVD in individuals 65 years or older, evidence is lacking on those older than 74 years, according to the investigators.

Accordingly, they conducted the present retrospective cohort study based on data from a Spanish primary care database that included patient records for more than 6 million people. They looked specifically for individuals aged 75 years or older with no history of ASCVD who had at least one visit between July 2006 and December 2007.

They found 46,864 people meeting those criteria, of whom 7,502 (16.0%) had started statin treatment and 7,880 (16.8%) had type 2 diabetes.

With a median follow-up of 7.7 years, statin use had no benefit in reducing ASCVD incidence or all-cause mortality for the entire study population, statistical analyses showed.

In participants with diabetes, however, statins did appear protective, at least in the patients aged 75-84 years, with hazard ratios of 0.76 (95% confidence interval, 0.65-0.89) for CVD and 0.84 (95% CI, 0.75-0.94) for all-cause mortality, Dr. Ramos and his colleagues reported.

The 1-year number needed to treat in this 75-84 age group was 164 for atherosclerotic CVD, and 306 for all-cause mortality, they added.

By contrast, the hazard ratios for patients 85 years and older were 0.82 (95% CI, 0.53-1.26) for atherosclerotic CVD, and 1.05 (95% CI, 0.86-1.28) for all-cause mortality, the investigators reported.

The observed reductions in CVD in individuals with diabetes lost statistical significance at age 85 years when investigators looked at hazard ratios for each year of age. Similarly, reductions in all-cause mortality began to lose statistical significance at age 82 years and “definitively disappeared” in those aged 88 years or older, they said.

The project was supported by grants from the Ministerio de Salud, Spain’s Ministry of Science and Innovation through the Carlos III Health Institute and other entities.

Dr. Ramos and his coauthors declared no support in the previous 3 years from any organization related to, or that might have an interest in, the submitted work. They also declared no other relationships or activities that could appear to have influenced the work.
 

SOURCE: Ramos R et al. BMJ 2018 Sep 5;362:k3359.

Any benefit of statins for primary prevention in older adult populations may depend on whether or not type 2 diabetes is present, results of a retrospective cohort study suggest.

Statins had no protective effect overall in the study, which included adults older than 74 years who had no clinically recognized atherosclerotic cardiovascular disease (ASCVD).

In older patients with diabetes, statins were associated with reductions in CVD incidence and all-cause mortality. However, this benefit was substantially reduced in patients 85 years and older, and completely absent in those over 90, study authors said in the BMJ.

“These results do not support the widespread use of statins in old and very old populations, but they do support treatment in those with type 2 diabetes younger than 85 years,” said Rafael Ramos, MD, of the University of Girona, Spain, and his coauthors.

While meta-analyses support statins as primary prevention of CVD in individuals 65 years or older, evidence is lacking on those older than 74 years, according to the investigators.

Accordingly, they conducted the present retrospective cohort study based on data from a Spanish primary care database that included patient records for more than 6 million people. They looked specifically for individuals aged 75 years or older with no history of ASCVD who had at least one visit between July 2006 and December 2007.

They found 46,864 people meeting those criteria, of whom 7,502 (16.0%) had started statin treatment and 7,880 (16.8%) had type 2 diabetes.

With a median follow-up of 7.7 years, statin use had no benefit in reducing ASCVD incidence or all-cause mortality for the entire study population, statistical analyses showed.

In participants with diabetes, however, statins did appear protective, at least in the patients aged 75-84 years, with hazard ratios of 0.76 (95% confidence interval, 0.65-0.89) for CVD and 0.84 (95% CI, 0.75-0.94) for all-cause mortality, Dr. Ramos and his colleagues reported.

The 1-year number needed to treat in this 75-84 age group was 164 for atherosclerotic CVD, and 306 for all-cause mortality, they added.

By contrast, the hazard ratios for patients 85 years and older were 0.82 (95% CI, 0.53-1.26) for atherosclerotic CVD, and 1.05 (95% CI, 0.86-1.28) for all-cause mortality, the investigators reported.

The observed reductions in CVD in individuals with diabetes lost statistical significance at age 85 years when investigators looked at hazard ratios for each year of age. Similarly, reductions in all-cause mortality began to lose statistical significance at age 82 years and “definitively disappeared” in those aged 88 years or older, they said.

The project was supported by grants from the Ministerio de Salud, Spain’s Ministry of Science and Innovation through the Carlos III Health Institute and other entities.

Dr. Ramos and his coauthors declared no support in the previous 3 years from any organization related to, or that might have an interest in, the submitted work. They also declared no other relationships or activities that could appear to have influenced the work.
 

SOURCE: Ramos R et al. BMJ 2018 Sep 5;362:k3359.

The Centers for Medicare & Medicaid Services may be able to reduce spending through the Medicare Shared Savings Program (MSSP) without asking for health care professionals and organizations to take on penalties or so-called downside risk, according to a study published in Sept. 5 in the New England Journal of Medicine.

TheaDesign/Thinkstock

Researchers, using fee-for-service claims from 2009 through 2015 and performing difference-in-difference analyses to compare changes in Medicare spending, found that Accountable Care Organizations (ACOs) formed from physician practices were able to save money while hospital-based ACOs were not.

“Our results also suggest that shared-savings contracts that do not impose a downside risk of financial losses for spending above benchmarks – which may appeal to smaller organizations without sufficient reserves to withstand potential losses – may be effective in lowering Medicare spending,” J. Michael McWilliams, MD, PhD, of Harvard Medical School, Boston, and his colleagues wrote.

Researchers found that by 2015, groups participating in MSSP, as compared with those who did not participate, were “associated with a mean differential reduction of $302 in total Medicare spending per beneficiary in the 2012 entry of cohorts of ACOs,” without accounting for bonus payments.

“Accounting for shared-savings bonus payments, we determined that the differential spending reductions in the entry cohorts of physician-group ACOs from 2012 through 2014 constituted a net savings to Medicare of $256.4 million in 2015,” Dr. McWilliams and his colleagues wrote. “For hospital-integrated ACOs, bonus payments more than offset annual spending reductions.”

Dr. McWilliams and his colleagues noted that their findings were limited by a narrow focus on organizational structure (financial independence from hospitals), so other factors could have held to differences in savings; changes in coding practices for ACOs coming in as of 2013; lack of data on costs to ACOs or efforts to lower spending or improve quality; and the inability to assess the effects of the MSSP on many aspects of quality of care because of the nature of using claims-based measures.

“Our results probably underestimate savings to Medicare because they do not account for spillover effects of ACO efforts on nonattributed patients or effects of lower fee-for-service Medicare spending on payments to Medicare Advantage plans,” the researchers added.

The study was funded by a grant from the National Institute on Aging. Dr. McWilliams and Michael Chernew, PhD, also of Harvard Medical School, both have received consulting fees related to ACO research.

gtwachtman@mdedge.com

SOURCE: McWilliams JM et al. N Engl J Med. 2018 Sep 5. doi: 10.1056/NEJMsa1803388.

The Centers for Medicare & Medicaid Services may be able to reduce spending through the Medicare Shared Savings Program (MSSP) without asking for health care professionals and organizations to take on penalties or so-called downside risk, according to a study published in Sept. 5 in the New England Journal of Medicine.

TheaDesign/Thinkstock

Researchers, using fee-for-service claims from 2009 through 2015 and performing difference-in-difference analyses to compare changes in Medicare spending, found that Accountable Care Organizations (ACOs) formed from physician practices were able to save money while hospital-based ACOs were not.

“Our results also suggest that shared-savings contracts that do not impose a downside risk of financial losses for spending above benchmarks – which may appeal to smaller organizations without sufficient reserves to withstand potential losses – may be effective in lowering Medicare spending,” J. Michael McWilliams, MD, PhD, of Harvard Medical School, Boston, and his colleagues wrote.

Researchers found that by 2015, groups participating in MSSP, as compared with those who did not participate, were “associated with a mean differential reduction of $302 in total Medicare spending per beneficiary in the 2012 entry of cohorts of ACOs,” without accounting for bonus payments.

“Accounting for shared-savings bonus payments, we determined that the differential spending reductions in the entry cohorts of physician-group ACOs from 2012 through 2014 constituted a net savings to Medicare of $256.4 million in 2015,” Dr. McWilliams and his colleagues wrote. “For hospital-integrated ACOs, bonus payments more than offset annual spending reductions.”

Dr. McWilliams and his colleagues noted that their findings were limited by a narrow focus on organizational structure (financial independence from hospitals), so other factors could have held to differences in savings; changes in coding practices for ACOs coming in as of 2013; lack of data on costs to ACOs or efforts to lower spending or improve quality; and the inability to assess the effects of the MSSP on many aspects of quality of care because of the nature of using claims-based measures.

“Our results probably underestimate savings to Medicare because they do not account for spillover effects of ACO efforts on nonattributed patients or effects of lower fee-for-service Medicare spending on payments to Medicare Advantage plans,” the researchers added.

The study was funded by a grant from the National Institute on Aging. Dr. McWilliams and Michael Chernew, PhD, also of Harvard Medical School, both have received consulting fees related to ACO research.

gtwachtman@mdedge.com

SOURCE: McWilliams JM et al. N Engl J Med. 2018 Sep 5. doi: 10.1056/NEJMsa1803388.

The Centers for Medicare & Medicaid Services may be able to reduce spending through the Medicare Shared Savings Program (MSSP) without asking for health care professionals and organizations to take on penalties or so-called downside risk, according to a study published in Sept. 5 in the New England Journal of Medicine.

TheaDesign/Thinkstock

Researchers, using fee-for-service claims from 2009 through 2015 and performing difference-in-difference analyses to compare changes in Medicare spending, found that Accountable Care Organizations (ACOs) formed from physician practices were able to save money while hospital-based ACOs were not.

“Our results also suggest that shared-savings contracts that do not impose a downside risk of financial losses for spending above benchmarks – which may appeal to smaller organizations without sufficient reserves to withstand potential losses – may be effective in lowering Medicare spending,” J. Michael McWilliams, MD, PhD, of Harvard Medical School, Boston, and his colleagues wrote.

Researchers found that by 2015, groups participating in MSSP, as compared with those who did not participate, were “associated with a mean differential reduction of $302 in total Medicare spending per beneficiary in the 2012 entry of cohorts of ACOs,” without accounting for bonus payments.

“Accounting for shared-savings bonus payments, we determined that the differential spending reductions in the entry cohorts of physician-group ACOs from 2012 through 2014 constituted a net savings to Medicare of $256.4 million in 2015,” Dr. McWilliams and his colleagues wrote. “For hospital-integrated ACOs, bonus payments more than offset annual spending reductions.”

Dr. McWilliams and his colleagues noted that their findings were limited by a narrow focus on organizational structure (financial independence from hospitals), so other factors could have held to differences in savings; changes in coding practices for ACOs coming in as of 2013; lack of data on costs to ACOs or efforts to lower spending or improve quality; and the inability to assess the effects of the MSSP on many aspects of quality of care because of the nature of using claims-based measures.

“Our results probably underestimate savings to Medicare because they do not account for spillover effects of ACO efforts on nonattributed patients or effects of lower fee-for-service Medicare spending on payments to Medicare Advantage plans,” the researchers added.

The study was funded by a grant from the National Institute on Aging. Dr. McWilliams and Michael Chernew, PhD, also of Harvard Medical School, both have received consulting fees related to ACO research.

gtwachtman@mdedge.com

SOURCE: McWilliams JM et al. N Engl J Med. 2018 Sep 5. doi: 10.1056/NEJMsa1803388.

A new single-dose influenza antiviral drug appears significantly better than placebo at relieving the symptoms of infection, and reduces viral load faster than does oseltamivir, new research suggests.

Cynthia Goldsmith/CDC photo #10073

Baloxavir marboxil – a selective inhibitor of influenza cap-dependent endonuclease – was tested in two randomized, double-blind, controlled trials. The first was a double-blind, placebo-controlled, dose-ranging, phase 2 randomized trial of 389 Japanese adults aged 20-64 years with acute uncomplicated influenza from December 2015 through March 2016. The second was a phase 3 randomized controlled trial of 1,366 patients comparing baloxavir with placebo and oseltamivir.

The phase 2 study showed patients treated with 10 mg, 20 mg or 40 mg oral dose of baloxavir experienced a significantly shorter median time to symptom alleviation compared with placebo (54.2, 51, 49.5, and 77.7 hours, respectively), according to a paper published in the Sept. 6 edition of the New England Journal of Medicine.

In addition, all three doses showed significantly greater reductions in influenza virus titers on days 2 and 3, compared with placebo.

The phase 3 trial CAPSTONE-1 (NCT02954354) was a double-blind, placebo- and oseltamivir-controlled, randomized trial that enrolled outpatients aged 12-64 years with influenza-like illness in the United States and Japan from December 2016 through March 2017. Patients aged 20-64 years received a single, weight-based oral dose of baloxavir (40 mg for patients weighing more than 80 kg, 80 mg for those weighing 80 kg or less) on day 1 only or oseltamivir at a dose of 75 mg twice daily or matching placebos on a 5-day regimen.

Patients aged 12-19 years were randomly assigned to receive either baloxavir or placebo on day 1 only, according to the researchers.

The median time to alleviation of symptoms was similar in the baloxavir (53.5 hours) and oseltamivir group (53.8 hours). However, patients taking baloxavir had significantly faster declines in infectious viral load compared with those taking oseltamivir, which was taken as a 75-mg dose twice daily for 5 days. In addition, patients who were treated with baloxavir within 24 hours of symptom onset showed significantly shorter time to alleviation of symptoms compared with placebo than did those who started treatment more than 24 hours after symptoms began.

Adverse events related to the study drug were more common among patients taking oseltamivir (8.4%) compared with those taking baloxavir (4.4%) or placebo (3.9%). In the phase 2 study, the adverse event rate was lower in the three baloxavir dosage groups compared with the placebo group. The study also showed a similar low frequency of complications requiring antibiotic treatment in both the baloxavir, oseltamivir, and placebo arms.

Some patients did show evidence of decreased susceptibility to baloxavir; for example, PA I38T/M amino acid substitutions were seen in 9.7% of the patients taking baloxavir but none of randomly selected patients in the placebo group of the phase 3 trial.

“These trials showed that single doses of the cap-dependent endonuclease inhibitor baloxavir were superior to placebo in alleviating influenza symptoms in patients with uncomplicated influenza, without clinically significant side effects,” wrote Dr. Frederick G. Hayden of the University of Virginia, Charlottesville, and his coauthors.

“The antiviral effects that were observed with baloxavir in patients with uncomplicated influenza provide encouragement with respect to its potential value in treating complicated or severe influenza infections,” they noted.

Because the treatment was inhibitory for influenza virus strains that were resistant to neuraminidase inhibitors or M2 ion-channel inhibitors, it could be a treatment option for patients infected with those viruses, the researchers added.

CAPSTONE-2, a randomized, controlled trial involving patients at high risk for influenza complications (NCT02949011) is in progress.

The study was supported by Shionogi, which developed baloxavir. Seven authors declared fees from the pharmaceutical industry, including Shionogi. Six authors were employees of Shionogi, one also holding stock. No other conflicts of interest were declared.

SOURCE: Hayden F et al. N Engl J Med. 2018;379:913-23. doi: 10.1056/NEJMoa1716197.

A new single-dose influenza antiviral drug appears significantly better than placebo at relieving the symptoms of infection, and reduces viral load faster than does oseltamivir, new research suggests.

Cynthia Goldsmith/CDC photo #10073

Baloxavir marboxil – a selective inhibitor of influenza cap-dependent endonuclease – was tested in two randomized, double-blind, controlled trials. The first was a double-blind, placebo-controlled, dose-ranging, phase 2 randomized trial of 389 Japanese adults aged 20-64 years with acute uncomplicated influenza from December 2015 through March 2016. The second was a phase 3 randomized controlled trial of 1,366 patients comparing baloxavir with placebo and oseltamivir.

The phase 2 study showed patients treated with 10 mg, 20 mg or 40 mg oral dose of baloxavir experienced a significantly shorter median time to symptom alleviation compared with placebo (54.2, 51, 49.5, and 77.7 hours, respectively), according to a paper published in the Sept. 6 edition of the New England Journal of Medicine.

In addition, all three doses showed significantly greater reductions in influenza virus titers on days 2 and 3, compared with placebo.

The phase 3 trial CAPSTONE-1 (NCT02954354) was a double-blind, placebo- and oseltamivir-controlled, randomized trial that enrolled outpatients aged 12-64 years with influenza-like illness in the United States and Japan from December 2016 through March 2017. Patients aged 20-64 years received a single, weight-based oral dose of baloxavir (40 mg for patients weighing more than 80 kg, 80 mg for those weighing 80 kg or less) on day 1 only or oseltamivir at a dose of 75 mg twice daily or matching placebos on a 5-day regimen.

Patients aged 12-19 years were randomly assigned to receive either baloxavir or placebo on day 1 only, according to the researchers.

The median time to alleviation of symptoms was similar in the baloxavir (53.5 hours) and oseltamivir group (53.8 hours). However, patients taking baloxavir had significantly faster declines in infectious viral load compared with those taking oseltamivir, which was taken as a 75-mg dose twice daily for 5 days. In addition, patients who were treated with baloxavir within 24 hours of symptom onset showed significantly shorter time to alleviation of symptoms compared with placebo than did those who started treatment more than 24 hours after symptoms began.

Adverse events related to the study drug were more common among patients taking oseltamivir (8.4%) compared with those taking baloxavir (4.4%) or placebo (3.9%). In the phase 2 study, the adverse event rate was lower in the three baloxavir dosage groups compared with the placebo group. The study also showed a similar low frequency of complications requiring antibiotic treatment in both the baloxavir, oseltamivir, and placebo arms.

Some patients did show evidence of decreased susceptibility to baloxavir; for example, PA I38T/M amino acid substitutions were seen in 9.7% of the patients taking baloxavir but none of randomly selected patients in the placebo group of the phase 3 trial.

“These trials showed that single doses of the cap-dependent endonuclease inhibitor baloxavir were superior to placebo in alleviating influenza symptoms in patients with uncomplicated influenza, without clinically significant side effects,” wrote Dr. Frederick G. Hayden of the University of Virginia, Charlottesville, and his coauthors.

“The antiviral effects that were observed with baloxavir in patients with uncomplicated influenza provide encouragement with respect to its potential value in treating complicated or severe influenza infections,” they noted.

Because the treatment was inhibitory for influenza virus strains that were resistant to neuraminidase inhibitors or M2 ion-channel inhibitors, it could be a treatment option for patients infected with those viruses, the researchers added.

CAPSTONE-2, a randomized, controlled trial involving patients at high risk for influenza complications (NCT02949011) is in progress.

The study was supported by Shionogi, which developed baloxavir. Seven authors declared fees from the pharmaceutical industry, including Shionogi. Six authors were employees of Shionogi, one also holding stock. No other conflicts of interest were declared.

SOURCE: Hayden F et al. N Engl J Med. 2018;379:913-23. doi: 10.1056/NEJMoa1716197.

A new single-dose influenza antiviral drug appears significantly better than placebo at relieving the symptoms of infection, and reduces viral load faster than does oseltamivir, new research suggests.

Cynthia Goldsmith/CDC photo #10073

Baloxavir marboxil – a selective inhibitor of influenza cap-dependent endonuclease – was tested in two randomized, double-blind, controlled trials. The first was a double-blind, placebo-controlled, dose-ranging, phase 2 randomized trial of 389 Japanese adults aged 20-64 years with acute uncomplicated influenza from December 2015 through March 2016. The second was a phase 3 randomized controlled trial of 1,366 patients comparing baloxavir with placebo and oseltamivir.

The phase 2 study showed patients treated with 10 mg, 20 mg or 40 mg oral dose of baloxavir experienced a significantly shorter median time to symptom alleviation compared with placebo (54.2, 51, 49.5, and 77.7 hours, respectively), according to a paper published in the Sept. 6 edition of the New England Journal of Medicine.

In addition, all three doses showed significantly greater reductions in influenza virus titers on days 2 and 3, compared with placebo.

The phase 3 trial CAPSTONE-1 (NCT02954354) was a double-blind, placebo- and oseltamivir-controlled, randomized trial that enrolled outpatients aged 12-64 years with influenza-like illness in the United States and Japan from December 2016 through March 2017. Patients aged 20-64 years received a single, weight-based oral dose of baloxavir (40 mg for patients weighing more than 80 kg, 80 mg for those weighing 80 kg or less) on day 1 only or oseltamivir at a dose of 75 mg twice daily or matching placebos on a 5-day regimen.

Patients aged 12-19 years were randomly assigned to receive either baloxavir or placebo on day 1 only, according to the researchers.

The median time to alleviation of symptoms was similar in the baloxavir (53.5 hours) and oseltamivir group (53.8 hours). However, patients taking baloxavir had significantly faster declines in infectious viral load compared with those taking oseltamivir, which was taken as a 75-mg dose twice daily for 5 days. In addition, patients who were treated with baloxavir within 24 hours of symptom onset showed significantly shorter time to alleviation of symptoms compared with placebo than did those who started treatment more than 24 hours after symptoms began.

Adverse events related to the study drug were more common among patients taking oseltamivir (8.4%) compared with those taking baloxavir (4.4%) or placebo (3.9%). In the phase 2 study, the adverse event rate was lower in the three baloxavir dosage groups compared with the placebo group. The study also showed a similar low frequency of complications requiring antibiotic treatment in both the baloxavir, oseltamivir, and placebo arms.

Some patients did show evidence of decreased susceptibility to baloxavir; for example, PA I38T/M amino acid substitutions were seen in 9.7% of the patients taking baloxavir but none of randomly selected patients in the placebo group of the phase 3 trial.

“These trials showed that single doses of the cap-dependent endonuclease inhibitor baloxavir were superior to placebo in alleviating influenza symptoms in patients with uncomplicated influenza, without clinically significant side effects,” wrote Dr. Frederick G. Hayden of the University of Virginia, Charlottesville, and his coauthors.

“The antiviral effects that were observed with baloxavir in patients with uncomplicated influenza provide encouragement with respect to its potential value in treating complicated or severe influenza infections,” they noted.

Because the treatment was inhibitory for influenza virus strains that were resistant to neuraminidase inhibitors or M2 ion-channel inhibitors, it could be a treatment option for patients infected with those viruses, the researchers added.

CAPSTONE-2, a randomized, controlled trial involving patients at high risk for influenza complications (NCT02949011) is in progress.

The study was supported by Shionogi, which developed baloxavir. Seven authors declared fees from the pharmaceutical industry, including Shionogi. Six authors were employees of Shionogi, one also holding stock. No other conflicts of interest were declared.

SOURCE: Hayden F et al. N Engl J Med. 2018;379:913-23. doi: 10.1056/NEJMoa1716197.

Janssen has announced its submission of a new drug application to the Food and Drug Administration for esketamine nasal spray, which is intended for adult patients with treatment-resistant depression.

About 30% of people with depression do not respond to currently available interventions (Biol Psychiatry. 2016 Sep 15;80[6]:424-31). “This represents a major unmet public health need,” Mathai Mammen, MD, PhD, global head, Janssen Research & Development, said in a Sept. 4 press release announcing the NDA.

The application submitted by Janssen is based on data from five phase 3 trials, all of which demonstrated rapid reduction of depressive symptoms, as well as delayed time to relapse of symptoms, in patients with treatment-resistant depression, Janssen said in the release. Those studies compared treatment with esketamine plus a newly initiated oral antidepressant with that of placebo plus a newly initiated oral antidepressant. One of the studies evaluated long-term safety associated with esketamine treatment and found no new safety signals at 52 weeks of treatment, compared with those seen in short-term studies of the drug.

Esketamine nasal spray is meant to be self-administered under supervision of health care professionals. Previously, it received Breakthrough Therapy Designations for both treatment-resistant depression and major depressive disorder with imminent risk for suicide. Phase 3 clinical studies for the latter indication are ongoing. According to Janssen, the company plans to submit a Marketing Authorization Application to the European Medicines Agency later in 2018 for the treatment-resistant depression indication.

cpalmer@mdedge.com

Janssen has announced its submission of a new drug application to the Food and Drug Administration for esketamine nasal spray, which is intended for adult patients with treatment-resistant depression.

About 30% of people with depression do not respond to currently available interventions (Biol Psychiatry. 2016 Sep 15;80[6]:424-31). “This represents a major unmet public health need,” Mathai Mammen, MD, PhD, global head, Janssen Research & Development, said in a Sept. 4 press release announcing the NDA.

The application submitted by Janssen is based on data from five phase 3 trials, all of which demonstrated rapid reduction of depressive symptoms, as well as delayed time to relapse of symptoms, in patients with treatment-resistant depression, Janssen said in the release. Those studies compared treatment with esketamine plus a newly initiated oral antidepressant with that of placebo plus a newly initiated oral antidepressant. One of the studies evaluated long-term safety associated with esketamine treatment and found no new safety signals at 52 weeks of treatment, compared with those seen in short-term studies of the drug.

Esketamine nasal spray is meant to be self-administered under supervision of health care professionals. Previously, it received Breakthrough Therapy Designations for both treatment-resistant depression and major depressive disorder with imminent risk for suicide. Phase 3 clinical studies for the latter indication are ongoing. According to Janssen, the company plans to submit a Marketing Authorization Application to the European Medicines Agency later in 2018 for the treatment-resistant depression indication.

cpalmer@mdedge.com

Janssen has announced its submission of a new drug application to the Food and Drug Administration for esketamine nasal spray, which is intended for adult patients with treatment-resistant depression.

About 30% of people with depression do not respond to currently available interventions (Biol Psychiatry. 2016 Sep 15;80[6]:424-31). “This represents a major unmet public health need,” Mathai Mammen, MD, PhD, global head, Janssen Research & Development, said in a Sept. 4 press release announcing the NDA.

The application submitted by Janssen is based on data from five phase 3 trials, all of which demonstrated rapid reduction of depressive symptoms, as well as delayed time to relapse of symptoms, in patients with treatment-resistant depression, Janssen said in the release. Those studies compared treatment with esketamine plus a newly initiated oral antidepressant with that of placebo plus a newly initiated oral antidepressant. One of the studies evaluated long-term safety associated with esketamine treatment and found no new safety signals at 52 weeks of treatment, compared with those seen in short-term studies of the drug.

Esketamine nasal spray is meant to be self-administered under supervision of health care professionals. Previously, it received Breakthrough Therapy Designations for both treatment-resistant depression and major depressive disorder with imminent risk for suicide. Phase 3 clinical studies for the latter indication are ongoing. According to Janssen, the company plans to submit a Marketing Authorization Application to the European Medicines Agency later in 2018 for the treatment-resistant depression indication.

cpalmer@mdedge.com

Antidepressants often are used to treat depressive symptoms in patients with dementia, but this practice is not backed by strong evidence, according to a systematic review published in the Cochrane Database of Systematic Reviews.

“On the only measure of efficacy for which we had high-quality evidence (depression rating scale scores), antidepressants showed little or no effect,” reported Robert Dudas, MD, PhD, of the University of Cambridge (England), and his associates. “The evidence on remission rates favored antidepressants but was of moderate quality, so future research may find a different result.”

For the review, a total of 10 studies – which altogether included of 1,592 patients – were examined, of which 8 included enough information to enter into analyses about antidepressant efficacy, Dr. Dudas and his associates reported. The average age in the studies was 75 years, and study participants had mild or moderate dementia.

After 6-13 weeks, little difference in depression symptom rating scale scores was found between antidepressant- and placebo-treated groups (standardized mean difference, –0.10 points; 95% confidence interval, –0.26 to 0.06). Similar results were found after 6-9 months (SMD, 0.59 points; 95% CI, –1.12 to 2.30).

Antidepressants did not significantly improve response rates (odds ratio, 1.71; 95% CI, 0.80-3.67) but were associated with a higher remission rate (OR, 2.57; 95% CI, 1.44-4.59). After 6-13 weeks, no difference was found between antidepressants and placebo on performance of daily activities (SMD, –0.05; 95% CI, –0.36 to 0.25) or in cognition (mean difference of 0.33 in Mini-Mental State Examination scores; 95% CI, –1.31 to 1.96).

In addition to experiencing no significant improvement in depression symptoms, patients who received antidepressants were more likely to drop out of treatment than were those receiving placebo (OR, 1.51; 95% CI, 1.07-2.14) and to experience at least one adverse event (OR, 1.55; 95% CI, 1.21-1.98). Adverse events more likely to occur in patients receiving antidepressants included dry mouth (OR, 1.80; 95% CI, 1.23-2.63) and dizziness (OR, 2.00; 95% CI, 1.34-2.98).

“With an expanding aging population and a resultant increase in the prevalence of dementia, more research is needed in this important clinical area. There is a need for well-conducted, randomized, controlled trials, using scales validated in older people with depression and dementia, of modern, frequently used drugs and sufficient sample sizes that would allow a study of treatment response and detailed adverse event profile according to dementia etiology and severity and depression severity,” the investigators concluded.

The study was supported by several entities, including the Cambridgeshire and Petersborough NHS Foundation Trust, Collaborations for Leadership in Applied Health Research and Care, and the National Institute for Health Research, all in the United Kingdom. Dr. Dudas and his associates declared no conflicts of interest.

lfranki@mdedge.com

SOURCE: Dudas R et al. Cochrane Database Syst Rev. 2018 Aug 31. doi: 10.1002/14651858.CD003944.pub2.

Antidepressants often are used to treat depressive symptoms in patients with dementia, but this practice is not backed by strong evidence, according to a systematic review published in the Cochrane Database of Systematic Reviews.

“On the only measure of efficacy for which we had high-quality evidence (depression rating scale scores), antidepressants showed little or no effect,” reported Robert Dudas, MD, PhD, of the University of Cambridge (England), and his associates. “The evidence on remission rates favored antidepressants but was of moderate quality, so future research may find a different result.”

For the review, a total of 10 studies – which altogether included of 1,592 patients – were examined, of which 8 included enough information to enter into analyses about antidepressant efficacy, Dr. Dudas and his associates reported. The average age in the studies was 75 years, and study participants had mild or moderate dementia.

After 6-13 weeks, little difference in depression symptom rating scale scores was found between antidepressant- and placebo-treated groups (standardized mean difference, –0.10 points; 95% confidence interval, –0.26 to 0.06). Similar results were found after 6-9 months (SMD, 0.59 points; 95% CI, –1.12 to 2.30).

Antidepressants did not significantly improve response rates (odds ratio, 1.71; 95% CI, 0.80-3.67) but were associated with a higher remission rate (OR, 2.57; 95% CI, 1.44-4.59). After 6-13 weeks, no difference was found between antidepressants and placebo on performance of daily activities (SMD, –0.05; 95% CI, –0.36 to 0.25) or in cognition (mean difference of 0.33 in Mini-Mental State Examination scores; 95% CI, –1.31 to 1.96).

In addition to experiencing no significant improvement in depression symptoms, patients who received antidepressants were more likely to drop out of treatment than were those receiving placebo (OR, 1.51; 95% CI, 1.07-2.14) and to experience at least one adverse event (OR, 1.55; 95% CI, 1.21-1.98). Adverse events more likely to occur in patients receiving antidepressants included dry mouth (OR, 1.80; 95% CI, 1.23-2.63) and dizziness (OR, 2.00; 95% CI, 1.34-2.98).

“With an expanding aging population and a resultant increase in the prevalence of dementia, more research is needed in this important clinical area. There is a need for well-conducted, randomized, controlled trials, using scales validated in older people with depression and dementia, of modern, frequently used drugs and sufficient sample sizes that would allow a study of treatment response and detailed adverse event profile according to dementia etiology and severity and depression severity,” the investigators concluded.

The study was supported by several entities, including the Cambridgeshire and Petersborough NHS Foundation Trust, Collaborations for Leadership in Applied Health Research and Care, and the National Institute for Health Research, all in the United Kingdom. Dr. Dudas and his associates declared no conflicts of interest.

lfranki@mdedge.com

SOURCE: Dudas R et al. Cochrane Database Syst Rev. 2018 Aug 31. doi: 10.1002/14651858.CD003944.pub2.

Antidepressants often are used to treat depressive symptoms in patients with dementia, but this practice is not backed by strong evidence, according to a systematic review published in the Cochrane Database of Systematic Reviews.

“On the only measure of efficacy for which we had high-quality evidence (depression rating scale scores), antidepressants showed little or no effect,” reported Robert Dudas, MD, PhD, of the University of Cambridge (England), and his associates. “The evidence on remission rates favored antidepressants but was of moderate quality, so future research may find a different result.”

For the review, a total of 10 studies – which altogether included of 1,592 patients – were examined, of which 8 included enough information to enter into analyses about antidepressant efficacy, Dr. Dudas and his associates reported. The average age in the studies was 75 years, and study participants had mild or moderate dementia.

After 6-13 weeks, little difference in depression symptom rating scale scores was found between antidepressant- and placebo-treated groups (standardized mean difference, –0.10 points; 95% confidence interval, –0.26 to 0.06). Similar results were found after 6-9 months (SMD, 0.59 points; 95% CI, –1.12 to 2.30).

Antidepressants did not significantly improve response rates (odds ratio, 1.71; 95% CI, 0.80-3.67) but were associated with a higher remission rate (OR, 2.57; 95% CI, 1.44-4.59). After 6-13 weeks, no difference was found between antidepressants and placebo on performance of daily activities (SMD, –0.05; 95% CI, –0.36 to 0.25) or in cognition (mean difference of 0.33 in Mini-Mental State Examination scores; 95% CI, –1.31 to 1.96).

In addition to experiencing no significant improvement in depression symptoms, patients who received antidepressants were more likely to drop out of treatment than were those receiving placebo (OR, 1.51; 95% CI, 1.07-2.14) and to experience at least one adverse event (OR, 1.55; 95% CI, 1.21-1.98). Adverse events more likely to occur in patients receiving antidepressants included dry mouth (OR, 1.80; 95% CI, 1.23-2.63) and dizziness (OR, 2.00; 95% CI, 1.34-2.98).

“With an expanding aging population and a resultant increase in the prevalence of dementia, more research is needed in this important clinical area. There is a need for well-conducted, randomized, controlled trials, using scales validated in older people with depression and dementia, of modern, frequently used drugs and sufficient sample sizes that would allow a study of treatment response and detailed adverse event profile according to dementia etiology and severity and depression severity,” the investigators concluded.

The study was supported by several entities, including the Cambridgeshire and Petersborough NHS Foundation Trust, Collaborations for Leadership in Applied Health Research and Care, and the National Institute for Health Research, all in the United Kingdom. Dr. Dudas and his associates declared no conflicts of interest.

lfranki@mdedge.com

SOURCE: Dudas R et al. Cochrane Database Syst Rev. 2018 Aug 31. doi: 10.1002/14651858.CD003944.pub2.

Inpatients with pneumonia are just slightly more likely to receive chest x-rays than those in the ED, but there are considerable discrepancies between the two settings for other services, the National Center for Health Statistics (NCHS) reported.

rfranki@mdedge.com

Inpatients with pneumonia are just slightly more likely to receive chest x-rays than those in the ED, but there are considerable discrepancies between the two settings for other services, the National Center for Health Statistics (NCHS) reported.

rfranki@mdedge.com

Inpatients with pneumonia are just slightly more likely to receive chest x-rays than those in the ED, but there are considerable discrepancies between the two settings for other services, the National Center for Health Statistics (NCHS) reported.

rfranki@mdedge.com

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Pancreatic cancer screening may be worthwhile for high-risk individuals who have germline genetic mutations predisposing them to the disease, according to a recent study. However, screening individuals under the age of 50 years, even those with risk factors, is a low-yield strategy.

In a retrospective analysis of 86 asymptomatic adult patients with high-risk germline mutations followed at a single center, screening by a variety of imaging modalities showed a pancreatic abnormality in about one-quarter of patients (23 of 86, 26.7%). No cancers were detected on initial screening or during a median 29.8-month follow-up period, though the investigators saw more abnormalities in patients over the age of 60 years (P = .043).

The mutations were detected through genetic screening at the University of Texas MD Anderson Cancer Center, Houston, where the study was conducted.

“At our institution, based on oncology and/or medical genetics assessments, patients with a personal history of breast cancer and/or family history of [pancreatic cancer] are screened for BRCAs and BRCA1 mutations. Patients with other types of cancers in the family are screened for P53, STK11, MSH2, ATM, and APC mutations,” explained first author R. Tomás DaVee, MD, of the division of gastroenterology, hepatology, and nutrition at the University of Texas, Houston, and his collaborators.

Patients were considered to have a family history of pancreatic cancer (PC) if any first-, second-, or third-degree relative had PC; overall, this amounted to 37 patients (43%). For the study, familial PC was defined as having either two first-degree or three or more relatives of any degree diagnosed with PC.

Patients, who were a median age of 48.5 years, were included in the study if they had any of the germline mutations, which are associated with an increase in relative risk of PC ranging from 2.26 for BRCA1 to 132 for STK11/LKB1, the mutation that causes Peutz-Jeghers syndrome. Patients who had a family history alone, without high-risk germline mutations, were excluded from the study. Most participants (79.8%) were women, and most of the participants were BRCA2 or BRCA1 positive (58.1% and 16.3%, respectively).

Of the abnormalities found, almost half (47.8%) were cysts, and almost as many (43.5%) were hyperechoic strands and foci. Two patients (8.7% of abnormalities) had mild pancreatic duct dilation. Patients who had only fatty infiltration or pancreas divisum were classified as having normal variations rather than abnormalities.

The pancreatic abnormalities had been found through endoscopic ultrasound (EUS), CT, or MRI, though the study’s primary aim was to look at outcomes and diagnostic yield for high-risk germline mutation patients receiving EUS. A secondary aim of the study, said the authors, was to compare EUS with both MRI and CT as methods to screen for early PC.

In this regard, Dr. DaVee and his coauthors wrote that “EUS-based screening conferred a higher yield in detecting abnormal pancreatic findings, compared with MRI [P = .007].” For MRI in comparison with EUS as the criterion standard, sensitivity and specificity were 55.6% and 93.8% for detecting pancreatic abnormalities. CT fared a little worse, with sensitivity of 50% and specificity of 89.5% for detecting pancreatic abnormalities.

Overall, the investigators noted that “the frequency of [pancreatic abnormalities] in our study is lower than reported in some studies using alternate criteria.” The relatively young age of the study cohort may be partly responsible for this finding, they said, adding that “our data further support evidence that abnormal pancreatic findings increase with age ... in asymptomatic [high-risk individuals], including the subtle finding of hyperechoic strands and foci.”

To improve survival, “premalignant and early PC identification is key,” wrote Dr. DaVee and his coauthors, pointing out that, of the 10% of patients diagnosed with PC when it is still localized, the 5-year survival rate is about 31.5%, compared with the overall 8.2% of individuals with PC who are still alive 5 years after their diagnosis. The latter figure, they noted, is a small improvement over the 3% 5-year survival figure from 1975.

Since population-wide screening for PC would not have a favorable cost-benefit profile, the challenge is identifying which individuals might benefit from targeted screening for PC. Dr. DaVee and his colleagues suggested that, as a general rule, high-risk individuals aged younger than 50 years need not be screened, and that EUS be used for the index screening, with MRI used to follow individuals with unremarkable initial screenings.

None of the authors reported relevant conflicts of interest, and no outside source of funding was reported.

koakes@mdedge.com

SOURCE: DaVee RT et al. Gastrointest Endosc. 2018 Jun; 87(6):1443-50.

Pancreatic cancer screening may be worthwhile for high-risk individuals who have germline genetic mutations predisposing them to the disease, according to a recent study. However, screening individuals under the age of 50 years, even those with risk factors, is a low-yield strategy.

In a retrospective analysis of 86 asymptomatic adult patients with high-risk germline mutations followed at a single center, screening by a variety of imaging modalities showed a pancreatic abnormality in about one-quarter of patients (23 of 86, 26.7%). No cancers were detected on initial screening or during a median 29.8-month follow-up period, though the investigators saw more abnormalities in patients over the age of 60 years (P = .043).

The mutations were detected through genetic screening at the University of Texas MD Anderson Cancer Center, Houston, where the study was conducted.

“At our institution, based on oncology and/or medical genetics assessments, patients with a personal history of breast cancer and/or family history of [pancreatic cancer] are screened for BRCAs and BRCA1 mutations. Patients with other types of cancers in the family are screened for P53, STK11, MSH2, ATM, and APC mutations,” explained first author R. Tomás DaVee, MD, of the division of gastroenterology, hepatology, and nutrition at the University of Texas, Houston, and his collaborators.

Patients were considered to have a family history of pancreatic cancer (PC) if any first-, second-, or third-degree relative had PC; overall, this amounted to 37 patients (43%). For the study, familial PC was defined as having either two first-degree or three or more relatives of any degree diagnosed with PC.

Patients, who were a median age of 48.5 years, were included in the study if they had any of the germline mutations, which are associated with an increase in relative risk of PC ranging from 2.26 for BRCA1 to 132 for STK11/LKB1, the mutation that causes Peutz-Jeghers syndrome. Patients who had a family history alone, without high-risk germline mutations, were excluded from the study. Most participants (79.8%) were women, and most of the participants were BRCA2 or BRCA1 positive (58.1% and 16.3%, respectively).

Of the abnormalities found, almost half (47.8%) were cysts, and almost as many (43.5%) were hyperechoic strands and foci. Two patients (8.7% of abnormalities) had mild pancreatic duct dilation. Patients who had only fatty infiltration or pancreas divisum were classified as having normal variations rather than abnormalities.

The pancreatic abnormalities had been found through endoscopic ultrasound (EUS), CT, or MRI, though the study’s primary aim was to look at outcomes and diagnostic yield for high-risk germline mutation patients receiving EUS. A secondary aim of the study, said the authors, was to compare EUS with both MRI and CT as methods to screen for early PC.

In this regard, Dr. DaVee and his coauthors wrote that “EUS-based screening conferred a higher yield in detecting abnormal pancreatic findings, compared with MRI [P = .007].” For MRI in comparison with EUS as the criterion standard, sensitivity and specificity were 55.6% and 93.8% for detecting pancreatic abnormalities. CT fared a little worse, with sensitivity of 50% and specificity of 89.5% for detecting pancreatic abnormalities.

Overall, the investigators noted that “the frequency of [pancreatic abnormalities] in our study is lower than reported in some studies using alternate criteria.” The relatively young age of the study cohort may be partly responsible for this finding, they said, adding that “our data further support evidence that abnormal pancreatic findings increase with age ... in asymptomatic [high-risk individuals], including the subtle finding of hyperechoic strands and foci.”

To improve survival, “premalignant and early PC identification is key,” wrote Dr. DaVee and his coauthors, pointing out that, of the 10% of patients diagnosed with PC when it is still localized, the 5-year survival rate is about 31.5%, compared with the overall 8.2% of individuals with PC who are still alive 5 years after their diagnosis. The latter figure, they noted, is a small improvement over the 3% 5-year survival figure from 1975.

Since population-wide screening for PC would not have a favorable cost-benefit profile, the challenge is identifying which individuals might benefit from targeted screening for PC. Dr. DaVee and his colleagues suggested that, as a general rule, high-risk individuals aged younger than 50 years need not be screened, and that EUS be used for the index screening, with MRI used to follow individuals with unremarkable initial screenings.

None of the authors reported relevant conflicts of interest, and no outside source of funding was reported.

koakes@mdedge.com

SOURCE: DaVee RT et al. Gastrointest Endosc. 2018 Jun; 87(6):1443-50.

Pancreatic cancer screening may be worthwhile for high-risk individuals who have germline genetic mutations predisposing them to the disease, according to a recent study. However, screening individuals under the age of 50 years, even those with risk factors, is a low-yield strategy.

In a retrospective analysis of 86 asymptomatic adult patients with high-risk germline mutations followed at a single center, screening by a variety of imaging modalities showed a pancreatic abnormality in about one-quarter of patients (23 of 86, 26.7%). No cancers were detected on initial screening or during a median 29.8-month follow-up period, though the investigators saw more abnormalities in patients over the age of 60 years (P = .043).

The mutations were detected through genetic screening at the University of Texas MD Anderson Cancer Center, Houston, where the study was conducted.

“At our institution, based on oncology and/or medical genetics assessments, patients with a personal history of breast cancer and/or family history of [pancreatic cancer] are screened for BRCAs and BRCA1 mutations. Patients with other types of cancers in the family are screened for P53, STK11, MSH2, ATM, and APC mutations,” explained first author R. Tomás DaVee, MD, of the division of gastroenterology, hepatology, and nutrition at the University of Texas, Houston, and his collaborators.

Patients were considered to have a family history of pancreatic cancer (PC) if any first-, second-, or third-degree relative had PC; overall, this amounted to 37 patients (43%). For the study, familial PC was defined as having either two first-degree or three or more relatives of any degree diagnosed with PC.

Patients, who were a median age of 48.5 years, were included in the study if they had any of the germline mutations, which are associated with an increase in relative risk of PC ranging from 2.26 for BRCA1 to 132 for STK11/LKB1, the mutation that causes Peutz-Jeghers syndrome. Patients who had a family history alone, without high-risk germline mutations, were excluded from the study. Most participants (79.8%) were women, and most of the participants were BRCA2 or BRCA1 positive (58.1% and 16.3%, respectively).

Of the abnormalities found, almost half (47.8%) were cysts, and almost as many (43.5%) were hyperechoic strands and foci. Two patients (8.7% of abnormalities) had mild pancreatic duct dilation. Patients who had only fatty infiltration or pancreas divisum were classified as having normal variations rather than abnormalities.

The pancreatic abnormalities had been found through endoscopic ultrasound (EUS), CT, or MRI, though the study’s primary aim was to look at outcomes and diagnostic yield for high-risk germline mutation patients receiving EUS. A secondary aim of the study, said the authors, was to compare EUS with both MRI and CT as methods to screen for early PC.

In this regard, Dr. DaVee and his coauthors wrote that “EUS-based screening conferred a higher yield in detecting abnormal pancreatic findings, compared with MRI [P = .007].” For MRI in comparison with EUS as the criterion standard, sensitivity and specificity were 55.6% and 93.8% for detecting pancreatic abnormalities. CT fared a little worse, with sensitivity of 50% and specificity of 89.5% for detecting pancreatic abnormalities.

Overall, the investigators noted that “the frequency of [pancreatic abnormalities] in our study is lower than reported in some studies using alternate criteria.” The relatively young age of the study cohort may be partly responsible for this finding, they said, adding that “our data further support evidence that abnormal pancreatic findings increase with age ... in asymptomatic [high-risk individuals], including the subtle finding of hyperechoic strands and foci.”

To improve survival, “premalignant and early PC identification is key,” wrote Dr. DaVee and his coauthors, pointing out that, of the 10% of patients diagnosed with PC when it is still localized, the 5-year survival rate is about 31.5%, compared with the overall 8.2% of individuals with PC who are still alive 5 years after their diagnosis. The latter figure, they noted, is a small improvement over the 3% 5-year survival figure from 1975.

Since population-wide screening for PC would not have a favorable cost-benefit profile, the challenge is identifying which individuals might benefit from targeted screening for PC. Dr. DaVee and his colleagues suggested that, as a general rule, high-risk individuals aged younger than 50 years need not be screened, and that EUS be used for the index screening, with MRI used to follow individuals with unremarkable initial screenings.

None of the authors reported relevant conflicts of interest, and no outside source of funding was reported.

koakes@mdedge.com

SOURCE: DaVee RT et al. Gastrointest Endosc. 2018 Jun; 87(6):1443-50.