“Bang, bang, you’re dead” has been uttered by millions of American children for generations. It is typical of the ordinary, angry, murderous thoughts of childhood; variations of it are universal. We expect children to learn to control their anger as they grow up and not to play out their angry wishes in reality. Unfortunately, this doesn’t always happen.

Following the many recent dramatic, crazed mass shootings, some commentators have called for restricting gun access for those with mental illness, but psychiatrists have rightly pointed out that murderers, including terror-inducing mass murderers, do not usually have a history of formally diagnosed mental illness. The psychiatrists are right for a reason: The potential for sudden, often unexpected, violence is widespread. This essay will employ a developmental perspective on how people handle anger, and on how we come to distinguish between fantasy and reality, to inform an understanding of gun violence.

Baby hyenas often try to kill their siblings shortly after birth. Human babies do not. They are not only motorically undeveloped, but their emotions appear to be mostly limited to the nonspecific states of distress and satisfaction. Distinct affects, such as anger, differentiate gradually. Babies smile by 2 months. Babies’ specific affection for and loyalty to their caregivers comes along a bit later, hence stranger anxiety commonly appears around 9 months. Facial expressions, sounds, and activity that look specifically like anger, and that occur when babies are frustrated or injured, are observed in the second half of the first year of human life. In the second year of life, feelings such as shame and guilt, which are dependent on the development of a distinct sense of self and other, appear. Shame and guilt, along with loving feelings, help form the basis for consideration of others and for the diminishment of young children’s omnipotence and egocentricity; they become a kind of social “glue,” tempering selfish, angry pursuits and tantrums.

There is a typical developmental sequence of how people come to handle their anger. Younger children express emotions directly, with little restraint; they hit, bite, and scream. Older children should be able to have more impulse control and be able to regulate the motor and verbal expression of their anger to a greater degree. At some point, most also become able to acknowledge their anger and not have to deny it. Adults, in principle, should be able both to inhibit the uncontrolled expression of anger and also, when appropriate, be able to use anger constructively. How tenuous this accomplishment is, and how often adults can function like overgrown children, can be readily observed at children’s sports matches, in which the children are often better behaved than their parents. In short, humans are endowed with the potential for enormous, destructive anger, but also, in our caring for others, a counterbalance to it.

The process of emotional development, and the regulation of anger, is intertwined with the development of the sense of self and of other. Evidence suggests that babies can start to distinguish self and other at birth, but that a full and reliable sense of self and other is a long, complicated developmental process.

The article by pediatrician and psychoanalyst Donald Winnicott, “Transitional Objects and Transitional Phenomena – A Study of the First Not-Me Possession,” one of the most frequently cited papers in the psychoanalytic literature, addresses this process (Int J Psychoanal. 1953;34[2]89-97). While transitional objects are not a human universal, the process of differentiating oneself from others, of finding out what is me and what is not-me, is. According to Dr. Winnicott, learning what is self and what is other assists babies in their related challenges of distinguishing animate from inanimate, wishes from causes, and fantasy from reality. Mother usually appears when I’m distressed – is she a part of me or a separate being? Does she appear because I wish, because I cry, or does she not appear despite my efforts? People never fully complete the developmental distinctions between self and other, and between wishes, fantasies, and magic, as opposed to reality.

Stressful events, such as a sudden loss, for example, commonly prompt a regressive denial of reality: “I don’t believe what I see” can be meant literally. When attending movies, we all “suspend disbelief” and participate, at least vicariously, in wishful magic. Further, although after early childhood, problems understanding material reality are characteristic of psychosis, all people are prone to at least occasional wishful or fearful errors in grasping social reality – we misperceive the meaning and intentions of others.

Combining the understanding of the development of how children handle anger and how they learn to differentiate self and other, and fantasy and reality, leads to an additional, important point. Suppose a person can’t tolerate his own angry wishes and he doesn’t distinguish well between self and other. He can easily attribute his own unwanted hatefulness to others, and he may then want to attack them for it. This process is extremely common, and we are all inclined to it to some degree. As childishly simplistic as it sounds, for humans, there is almost always an us and a them; we are good and they are bad. In addition to directing anger inappropriately at others, people can, of course, turn anger against themselves, and with just as much unreasonableness and venom. However much we grow up, development is never complete. We remain irrational, with a tenuous and incomplete perception of reality.

One would never give a weapon to an infant, but in light of these difficulties with respect to human development, should one give a weapon to an adult?

Whether or not humans have the self-control to possess weapons of great power and destructiveness, weapons are part of our evolution as a species. They have likely contributed to our remarkable success, protecting us from predators and enriching our diets. It is worth noting, however, that small-scale societies such as those we all evolved from often have high murder rates, and that lower rates of intra-societal violence tend to be found in larger, more highly regulated societies. People do not always adequately manage aggression themselves and benefit from external, societal assistance.

We humans all have the capacity to be mad: to be angry, to be crazy, to be crazed with anger. Fantasies of revenge are common when one is angry, and expectable when one has been hurt. Yet, expressions such as “blind with rage” and “seeing red” attest to the challenges to the sense of reality that rage can induce. The crucial distinction between having vengeful wishes and fantasies, and putting them into action, into reality, can crumble quickly. In addition to anger, fear is another emotion that can distort the perception of reality. Regular attention to the news suggests that police, whether they are aware of it or not, are more fearful of black men than of other people. They are more likely to perceive them as being armed and are quicker to shoot. For police and civilians alike, the presence of guns simultaneously requires greater impulse control and makes impulse control more difficult. The more guns, the more fear and anger, the more shootings – a vicious cycle.

Most people who commit crimes with guns, whether a singular “crime of passion” or a mass murder, have been crazed with anger. Some have been known to police as angry individuals with histories of getting into trouble, others not. But most have been angry, isolated individuals with problematic social relationships and little warm or respectful involvement with others to counterbalance their anger. Given the challenges inherent in human development, it is not surprising that in most societies there are a fair number of disaffected, angry, isolated individuals with inadequate realistic emotional regulation.

According to the anthropologist Scott Atran, who has studied both would-be and convicted terrorists, in addition to those individuals who are angry and disturbed, many recruits to terrorism are merely unsettled youth eager to find a sense of identity and belonging in a “band of brothers (and sisters).” He has described the “devoted actor,” who merges his identity with his combat unit and becomes willing to die for his comrades or their cause. These observations are consistent with both anthropological ideas about cultural influences on the sense of self in relation to groups, and with psychoanalytic emphasis on the difficulty of achieving a firm sense of self and other. In fusing with the group and its ideology, one gives up an independent self while feeling that one has gained a sense of self, belonging, and meaning. Whatever the psychological and social picture, it is obvious that the angry, isolated individuals who may regress and explode, and the countless unsettled youth of modern societies, cannot all be identified, tracked, and regulated by society, nor will they all seek help for their troubles. The United States’ decisions to allow massively destructive weapons to anyone and everyone are counter to everything we know about people.

Among many other things, Sigmund Freud is known for highlighting the comment that “The first man to hurl an insult rather than a spear was the founder of civilization.” Anger that is put into words is less destructive than anger put into violent action. From this point of view, the widespread presence of guns undermines civilization. Guns invite putting anger into action rather than conversation – they are a hindrance to impulse control and they shut down discussion. Democracy, a form of civilization contingent on impulse control, discussion, and voting, rather than submission to violent authority, is particularly undermined by guns. Congress should know: It has been so intimidated by the National Rifle Association that it has refused to outlaw private possession of military assault rifles and at the same time has submitted to outlawing the use of federal funds for research about gun violence. Despite this ban on research, there is overwhelming evidence that the presence of a gun in a home is associated not only with significantly increased murder rates, but also, as mental health professionals well know, greatly increased incidence of suicide.

As humans, we all have the ability to control ourselves to some degree. But, we all have the potential to become mad and to lose control. Our internal self-regulation is sometimes insufficient, and we need the restraining influence of our fellow humans. This can be in the form of a comforting word, a warning gesture, a carrot or a stick, or a law. The regulation of guns, assault rifles, and bomb-making materials is a mark of civilization.

Dr. Blum is a psychiatrist and psychoanalyst in private practice in Philadelphia. He teaches in the departments of anthropology and psychiatry at the University of Pennsylvania and at the Psychoanalytic Center of Philadelphia.

“Bang, bang, you’re dead” has been uttered by millions of American children for generations. It is typical of the ordinary, angry, murderous thoughts of childhood; variations of it are universal. We expect children to learn to control their anger as they grow up and not to play out their angry wishes in reality. Unfortunately, this doesn’t always happen.

Following the many recent dramatic, crazed mass shootings, some commentators have called for restricting gun access for those with mental illness, but psychiatrists have rightly pointed out that murderers, including terror-inducing mass murderers, do not usually have a history of formally diagnosed mental illness. The psychiatrists are right for a reason: The potential for sudden, often unexpected, violence is widespread. This essay will employ a developmental perspective on how people handle anger, and on how we come to distinguish between fantasy and reality, to inform an understanding of gun violence.

Baby hyenas often try to kill their siblings shortly after birth. Human babies do not. They are not only motorically undeveloped, but their emotions appear to be mostly limited to the nonspecific states of distress and satisfaction. Distinct affects, such as anger, differentiate gradually. Babies smile by 2 months. Babies’ specific affection for and loyalty to their caregivers comes along a bit later, hence stranger anxiety commonly appears around 9 months. Facial expressions, sounds, and activity that look specifically like anger, and that occur when babies are frustrated or injured, are observed in the second half of the first year of human life. In the second year of life, feelings such as shame and guilt, which are dependent on the development of a distinct sense of self and other, appear. Shame and guilt, along with loving feelings, help form the basis for consideration of others and for the diminishment of young children’s omnipotence and egocentricity; they become a kind of social “glue,” tempering selfish, angry pursuits and tantrums.

There is a typical developmental sequence of how people come to handle their anger. Younger children express emotions directly, with little restraint; they hit, bite, and scream. Older children should be able to have more impulse control and be able to regulate the motor and verbal expression of their anger to a greater degree. At some point, most also become able to acknowledge their anger and not have to deny it. Adults, in principle, should be able both to inhibit the uncontrolled expression of anger and also, when appropriate, be able to use anger constructively. How tenuous this accomplishment is, and how often adults can function like overgrown children, can be readily observed at children’s sports matches, in which the children are often better behaved than their parents. In short, humans are endowed with the potential for enormous, destructive anger, but also, in our caring for others, a counterbalance to it.

The process of emotional development, and the regulation of anger, is intertwined with the development of the sense of self and of other. Evidence suggests that babies can start to distinguish self and other at birth, but that a full and reliable sense of self and other is a long, complicated developmental process.

The article by pediatrician and psychoanalyst Donald Winnicott, “Transitional Objects and Transitional Phenomena – A Study of the First Not-Me Possession,” one of the most frequently cited papers in the psychoanalytic literature, addresses this process (Int J Psychoanal. 1953;34[2]89-97). While transitional objects are not a human universal, the process of differentiating oneself from others, of finding out what is me and what is not-me, is. According to Dr. Winnicott, learning what is self and what is other assists babies in their related challenges of distinguishing animate from inanimate, wishes from causes, and fantasy from reality. Mother usually appears when I’m distressed – is she a part of me or a separate being? Does she appear because I wish, because I cry, or does she not appear despite my efforts? People never fully complete the developmental distinctions between self and other, and between wishes, fantasies, and magic, as opposed to reality.

Stressful events, such as a sudden loss, for example, commonly prompt a regressive denial of reality: “I don’t believe what I see” can be meant literally. When attending movies, we all “suspend disbelief” and participate, at least vicariously, in wishful magic. Further, although after early childhood, problems understanding material reality are characteristic of psychosis, all people are prone to at least occasional wishful or fearful errors in grasping social reality – we misperceive the meaning and intentions of others.

Combining the understanding of the development of how children handle anger and how they learn to differentiate self and other, and fantasy and reality, leads to an additional, important point. Suppose a person can’t tolerate his own angry wishes and he doesn’t distinguish well between self and other. He can easily attribute his own unwanted hatefulness to others, and he may then want to attack them for it. This process is extremely common, and we are all inclined to it to some degree. As childishly simplistic as it sounds, for humans, there is almost always an us and a them; we are good and they are bad. In addition to directing anger inappropriately at others, people can, of course, turn anger against themselves, and with just as much unreasonableness and venom. However much we grow up, development is never complete. We remain irrational, with a tenuous and incomplete perception of reality.

One would never give a weapon to an infant, but in light of these difficulties with respect to human development, should one give a weapon to an adult?

Whether or not humans have the self-control to possess weapons of great power and destructiveness, weapons are part of our evolution as a species. They have likely contributed to our remarkable success, protecting us from predators and enriching our diets. It is worth noting, however, that small-scale societies such as those we all evolved from often have high murder rates, and that lower rates of intra-societal violence tend to be found in larger, more highly regulated societies. People do not always adequately manage aggression themselves and benefit from external, societal assistance.

We humans all have the capacity to be mad: to be angry, to be crazy, to be crazed with anger. Fantasies of revenge are common when one is angry, and expectable when one has been hurt. Yet, expressions such as “blind with rage” and “seeing red” attest to the challenges to the sense of reality that rage can induce. The crucial distinction between having vengeful wishes and fantasies, and putting them into action, into reality, can crumble quickly. In addition to anger, fear is another emotion that can distort the perception of reality. Regular attention to the news suggests that police, whether they are aware of it or not, are more fearful of black men than of other people. They are more likely to perceive them as being armed and are quicker to shoot. For police and civilians alike, the presence of guns simultaneously requires greater impulse control and makes impulse control more difficult. The more guns, the more fear and anger, the more shootings – a vicious cycle.

Most people who commit crimes with guns, whether a singular “crime of passion” or a mass murder, have been crazed with anger. Some have been known to police as angry individuals with histories of getting into trouble, others not. But most have been angry, isolated individuals with problematic social relationships and little warm or respectful involvement with others to counterbalance their anger. Given the challenges inherent in human development, it is not surprising that in most societies there are a fair number of disaffected, angry, isolated individuals with inadequate realistic emotional regulation.

According to the anthropologist Scott Atran, who has studied both would-be and convicted terrorists, in addition to those individuals who are angry and disturbed, many recruits to terrorism are merely unsettled youth eager to find a sense of identity and belonging in a “band of brothers (and sisters).” He has described the “devoted actor,” who merges his identity with his combat unit and becomes willing to die for his comrades or their cause. These observations are consistent with both anthropological ideas about cultural influences on the sense of self in relation to groups, and with psychoanalytic emphasis on the difficulty of achieving a firm sense of self and other. In fusing with the group and its ideology, one gives up an independent self while feeling that one has gained a sense of self, belonging, and meaning. Whatever the psychological and social picture, it is obvious that the angry, isolated individuals who may regress and explode, and the countless unsettled youth of modern societies, cannot all be identified, tracked, and regulated by society, nor will they all seek help for their troubles. The United States’ decisions to allow massively destructive weapons to anyone and everyone are counter to everything we know about people.

Among many other things, Sigmund Freud is known for highlighting the comment that “The first man to hurl an insult rather than a spear was the founder of civilization.” Anger that is put into words is less destructive than anger put into violent action. From this point of view, the widespread presence of guns undermines civilization. Guns invite putting anger into action rather than conversation – they are a hindrance to impulse control and they shut down discussion. Democracy, a form of civilization contingent on impulse control, discussion, and voting, rather than submission to violent authority, is particularly undermined by guns. Congress should know: It has been so intimidated by the National Rifle Association that it has refused to outlaw private possession of military assault rifles and at the same time has submitted to outlawing the use of federal funds for research about gun violence. Despite this ban on research, there is overwhelming evidence that the presence of a gun in a home is associated not only with significantly increased murder rates, but also, as mental health professionals well know, greatly increased incidence of suicide.

As humans, we all have the ability to control ourselves to some degree. But, we all have the potential to become mad and to lose control. Our internal self-regulation is sometimes insufficient, and we need the restraining influence of our fellow humans. This can be in the form of a comforting word, a warning gesture, a carrot or a stick, or a law. The regulation of guns, assault rifles, and bomb-making materials is a mark of civilization.

Dr. Blum is a psychiatrist and psychoanalyst in private practice in Philadelphia. He teaches in the departments of anthropology and psychiatry at the University of Pennsylvania and at the Psychoanalytic Center of Philadelphia.

“Bang, bang, you’re dead” has been uttered by millions of American children for generations. It is typical of the ordinary, angry, murderous thoughts of childhood; variations of it are universal. We expect children to learn to control their anger as they grow up and not to play out their angry wishes in reality. Unfortunately, this doesn’t always happen.

Following the many recent dramatic, crazed mass shootings, some commentators have called for restricting gun access for those with mental illness, but psychiatrists have rightly pointed out that murderers, including terror-inducing mass murderers, do not usually have a history of formally diagnosed mental illness. The psychiatrists are right for a reason: The potential for sudden, often unexpected, violence is widespread. This essay will employ a developmental perspective on how people handle anger, and on how we come to distinguish between fantasy and reality, to inform an understanding of gun violence.

Baby hyenas often try to kill their siblings shortly after birth. Human babies do not. They are not only motorically undeveloped, but their emotions appear to be mostly limited to the nonspecific states of distress and satisfaction. Distinct affects, such as anger, differentiate gradually. Babies smile by 2 months. Babies’ specific affection for and loyalty to their caregivers comes along a bit later, hence stranger anxiety commonly appears around 9 months. Facial expressions, sounds, and activity that look specifically like anger, and that occur when babies are frustrated or injured, are observed in the second half of the first year of human life. In the second year of life, feelings such as shame and guilt, which are dependent on the development of a distinct sense of self and other, appear. Shame and guilt, along with loving feelings, help form the basis for consideration of others and for the diminishment of young children’s omnipotence and egocentricity; they become a kind of social “glue,” tempering selfish, angry pursuits and tantrums.

There is a typical developmental sequence of how people come to handle their anger. Younger children express emotions directly, with little restraint; they hit, bite, and scream. Older children should be able to have more impulse control and be able to regulate the motor and verbal expression of their anger to a greater degree. At some point, most also become able to acknowledge their anger and not have to deny it. Adults, in principle, should be able both to inhibit the uncontrolled expression of anger and also, when appropriate, be able to use anger constructively. How tenuous this accomplishment is, and how often adults can function like overgrown children, can be readily observed at children’s sports matches, in which the children are often better behaved than their parents. In short, humans are endowed with the potential for enormous, destructive anger, but also, in our caring for others, a counterbalance to it.

The process of emotional development, and the regulation of anger, is intertwined with the development of the sense of self and of other. Evidence suggests that babies can start to distinguish self and other at birth, but that a full and reliable sense of self and other is a long, complicated developmental process.

The article by pediatrician and psychoanalyst Donald Winnicott, “Transitional Objects and Transitional Phenomena – A Study of the First Not-Me Possession,” one of the most frequently cited papers in the psychoanalytic literature, addresses this process (Int J Psychoanal. 1953;34[2]89-97). While transitional objects are not a human universal, the process of differentiating oneself from others, of finding out what is me and what is not-me, is. According to Dr. Winnicott, learning what is self and what is other assists babies in their related challenges of distinguishing animate from inanimate, wishes from causes, and fantasy from reality. Mother usually appears when I’m distressed – is she a part of me or a separate being? Does she appear because I wish, because I cry, or does she not appear despite my efforts? People never fully complete the developmental distinctions between self and other, and between wishes, fantasies, and magic, as opposed to reality.

Stressful events, such as a sudden loss, for example, commonly prompt a regressive denial of reality: “I don’t believe what I see” can be meant literally. When attending movies, we all “suspend disbelief” and participate, at least vicariously, in wishful magic. Further, although after early childhood, problems understanding material reality are characteristic of psychosis, all people are prone to at least occasional wishful or fearful errors in grasping social reality – we misperceive the meaning and intentions of others.

Combining the understanding of the development of how children handle anger and how they learn to differentiate self and other, and fantasy and reality, leads to an additional, important point. Suppose a person can’t tolerate his own angry wishes and he doesn’t distinguish well between self and other. He can easily attribute his own unwanted hatefulness to others, and he may then want to attack them for it. This process is extremely common, and we are all inclined to it to some degree. As childishly simplistic as it sounds, for humans, there is almost always an us and a them; we are good and they are bad. In addition to directing anger inappropriately at others, people can, of course, turn anger against themselves, and with just as much unreasonableness and venom. However much we grow up, development is never complete. We remain irrational, with a tenuous and incomplete perception of reality.

One would never give a weapon to an infant, but in light of these difficulties with respect to human development, should one give a weapon to an adult?

Whether or not humans have the self-control to possess weapons of great power and destructiveness, weapons are part of our evolution as a species. They have likely contributed to our remarkable success, protecting us from predators and enriching our diets. It is worth noting, however, that small-scale societies such as those we all evolved from often have high murder rates, and that lower rates of intra-societal violence tend to be found in larger, more highly regulated societies. People do not always adequately manage aggression themselves and benefit from external, societal assistance.

We humans all have the capacity to be mad: to be angry, to be crazy, to be crazed with anger. Fantasies of revenge are common when one is angry, and expectable when one has been hurt. Yet, expressions such as “blind with rage” and “seeing red” attest to the challenges to the sense of reality that rage can induce. The crucial distinction between having vengeful wishes and fantasies, and putting them into action, into reality, can crumble quickly. In addition to anger, fear is another emotion that can distort the perception of reality. Regular attention to the news suggests that police, whether they are aware of it or not, are more fearful of black men than of other people. They are more likely to perceive them as being armed and are quicker to shoot. For police and civilians alike, the presence of guns simultaneously requires greater impulse control and makes impulse control more difficult. The more guns, the more fear and anger, the more shootings – a vicious cycle.

Most people who commit crimes with guns, whether a singular “crime of passion” or a mass murder, have been crazed with anger. Some have been known to police as angry individuals with histories of getting into trouble, others not. But most have been angry, isolated individuals with problematic social relationships and little warm or respectful involvement with others to counterbalance their anger. Given the challenges inherent in human development, it is not surprising that in most societies there are a fair number of disaffected, angry, isolated individuals with inadequate realistic emotional regulation.

According to the anthropologist Scott Atran, who has studied both would-be and convicted terrorists, in addition to those individuals who are angry and disturbed, many recruits to terrorism are merely unsettled youth eager to find a sense of identity and belonging in a “band of brothers (and sisters).” He has described the “devoted actor,” who merges his identity with his combat unit and becomes willing to die for his comrades or their cause. These observations are consistent with both anthropological ideas about cultural influences on the sense of self in relation to groups, and with psychoanalytic emphasis on the difficulty of achieving a firm sense of self and other. In fusing with the group and its ideology, one gives up an independent self while feeling that one has gained a sense of self, belonging, and meaning. Whatever the psychological and social picture, it is obvious that the angry, isolated individuals who may regress and explode, and the countless unsettled youth of modern societies, cannot all be identified, tracked, and regulated by society, nor will they all seek help for their troubles. The United States’ decisions to allow massively destructive weapons to anyone and everyone are counter to everything we know about people.

Among many other things, Sigmund Freud is known for highlighting the comment that “The first man to hurl an insult rather than a spear was the founder of civilization.” Anger that is put into words is less destructive than anger put into violent action. From this point of view, the widespread presence of guns undermines civilization. Guns invite putting anger into action rather than conversation – they are a hindrance to impulse control and they shut down discussion. Democracy, a form of civilization contingent on impulse control, discussion, and voting, rather than submission to violent authority, is particularly undermined by guns. Congress should know: It has been so intimidated by the National Rifle Association that it has refused to outlaw private possession of military assault rifles and at the same time has submitted to outlawing the use of federal funds for research about gun violence. Despite this ban on research, there is overwhelming evidence that the presence of a gun in a home is associated not only with significantly increased murder rates, but also, as mental health professionals well know, greatly increased incidence of suicide.

As humans, we all have the ability to control ourselves to some degree. But, we all have the potential to become mad and to lose control. Our internal self-regulation is sometimes insufficient, and we need the restraining influence of our fellow humans. This can be in the form of a comforting word, a warning gesture, a carrot or a stick, or a law. The regulation of guns, assault rifles, and bomb-making materials is a mark of civilization.

Dr. Blum is a psychiatrist and psychoanalyst in private practice in Philadelphia. He teaches in the departments of anthropology and psychiatry at the University of Pennsylvania and at the Psychoanalytic Center of Philadelphia.

MIAMI – As patients with psoriasis develop psoriatic arthritis, the abundance of particular genera in the skin microbiome decreases, according to a preliminary study characterizing cutaneous microbiota in these populations.

“The big overall message is there might be a decrease in microbiota diversity as you progress through the disease spectrum,” Julia Manasson, MD, a fellow in the division of rheumatology at New York University said. “This is the first study characterizing the cutaneous microbial compositions of subjects with psoriasis and psoriatic arthritis in both psoriatic lesions and unaffected skin.”

Damian McNamara/Frontline Medical News

A previous study that revealed changes in gut microbiome between psoriasis and psoriatic arthritis patient stool samples (Arthritis Rheumatol. 2015;67:128-39) prompted the current research, which is “trying to see if the skin has a similar manifestation,” Dr. Manasson said during an oral presentation of her poster at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

“The microbiome has been implicated as a potential trigger for inflammation and autoimmune disease,” Dr. Manasson noted.

To investigate a potential role of the skin microbiome, the investigators swabbed lesions and unaffected skin (on a contralateral site) in 29 people with psoriasis and 62 others with psoriatic arthritis. They extracted, amplified, and sequenced DNA from the samples. No participants in the study were on treatment with biologics, disease-modifying antirheumatic drugs, or steroids at the time of assessment. The psoriasis group was 66% men and had an average age of 45 years; the psoriatic arthritis group was 55% men and the average age was 42.

Dr. Manasson and her colleagues calculated the taxonomic relative abundance and contrasted their prevalence among the four skin phenotypes examined: lesions and unaffected skin of psoriasis patients and lesions and unaffected skin of psoriatic arthritis patients. Alpha diversity plots revealed a similar number of operational taxonomic units (OTUs) between psoriasis and psoriatic arthritis samples. Beta diversity analysis showed no distinct clustering or significant difference in microbiota communities among different phenotypes.

“We saw more of a decrease in nonlesional skin and across clinical severity, too,” Dr. Manasson said. “Globally, we didn’t see significant differences [in microbiota present].”

Staphylococcus and Corynebacterium were the predominant bacteria in all samples, but there were also specific genera that were less common in psoriatic arthritis patients and in lesional skin. These less abundant genera included unclassified Bradyrhizobiaceae, Rahnella, unclassified Prevotellaceae, and Parvibaculum.

“It looks like you had some differences between lesion and nonlesional skin,” Alice Gottlieb, MD, chair and dermatologist in chief at Tufts Medical Center in Boston. “In psoriasis, the barrier function is not normal. You may want to look at atopic dermatitis where you clearly have altered barrier function.”

Dr. Manasson said they used a skin swab, so they did not assess barrier function.

“The nonlesional skin may be more interesting to look at,” Dr. Gottlieb added. “If you see a difference in nonlesional skin, it could be more [conclusive].”

Microbiome stability often changes in individuals from week to week, commented Philip Helliwell, DM, PhD, a rheumatologist at the University of Leeds in England and president of GRAPPA. Dr. Manasson said she could assess variability over time in the future. She also would like to evaluate how therapies, including antibiotics, alter the skin microbiome.

Lack of a healthy control group is a potential limitation of the study. Some unanswered questions remain, Dr. Manasson said, such as what are the regional differences in skin microbiota, for example, between a patient’s scalp and forearm? She added, “The most interesting question is what does this actually mean? What are the downstream effects?”

If a decrease in skin microbiome flora diversity is verified in future research as a sign that a patient with psoriasis is at elevated risk for developing psoriatic arthritis, it could help physicians predict who will progress. Currently, about 30% of psoriatic patients go on to develop joint disease, but methods to identify this subpopulation remain elusive.

Dr. Manasson, Dr. Gottlieb, and Dr. Helliwell had no relevant financial disclosures.

MIAMI – As patients with psoriasis develop psoriatic arthritis, the abundance of particular genera in the skin microbiome decreases, according to a preliminary study characterizing cutaneous microbiota in these populations.

“The big overall message is there might be a decrease in microbiota diversity as you progress through the disease spectrum,” Julia Manasson, MD, a fellow in the division of rheumatology at New York University said. “This is the first study characterizing the cutaneous microbial compositions of subjects with psoriasis and psoriatic arthritis in both psoriatic lesions and unaffected skin.”

Damian McNamara/Frontline Medical News

A previous study that revealed changes in gut microbiome between psoriasis and psoriatic arthritis patient stool samples (Arthritis Rheumatol. 2015;67:128-39) prompted the current research, which is “trying to see if the skin has a similar manifestation,” Dr. Manasson said during an oral presentation of her poster at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

“The microbiome has been implicated as a potential trigger for inflammation and autoimmune disease,” Dr. Manasson noted.

To investigate a potential role of the skin microbiome, the investigators swabbed lesions and unaffected skin (on a contralateral site) in 29 people with psoriasis and 62 others with psoriatic arthritis. They extracted, amplified, and sequenced DNA from the samples. No participants in the study were on treatment with biologics, disease-modifying antirheumatic drugs, or steroids at the time of assessment. The psoriasis group was 66% men and had an average age of 45 years; the psoriatic arthritis group was 55% men and the average age was 42.

Dr. Manasson and her colleagues calculated the taxonomic relative abundance and contrasted their prevalence among the four skin phenotypes examined: lesions and unaffected skin of psoriasis patients and lesions and unaffected skin of psoriatic arthritis patients. Alpha diversity plots revealed a similar number of operational taxonomic units (OTUs) between psoriasis and psoriatic arthritis samples. Beta diversity analysis showed no distinct clustering or significant difference in microbiota communities among different phenotypes.

“We saw more of a decrease in nonlesional skin and across clinical severity, too,” Dr. Manasson said. “Globally, we didn’t see significant differences [in microbiota present].”

Staphylococcus and Corynebacterium were the predominant bacteria in all samples, but there were also specific genera that were less common in psoriatic arthritis patients and in lesional skin. These less abundant genera included unclassified Bradyrhizobiaceae, Rahnella, unclassified Prevotellaceae, and Parvibaculum.

“It looks like you had some differences between lesion and nonlesional skin,” Alice Gottlieb, MD, chair and dermatologist in chief at Tufts Medical Center in Boston. “In psoriasis, the barrier function is not normal. You may want to look at atopic dermatitis where you clearly have altered barrier function.”

Dr. Manasson said they used a skin swab, so they did not assess barrier function.

“The nonlesional skin may be more interesting to look at,” Dr. Gottlieb added. “If you see a difference in nonlesional skin, it could be more [conclusive].”

Microbiome stability often changes in individuals from week to week, commented Philip Helliwell, DM, PhD, a rheumatologist at the University of Leeds in England and president of GRAPPA. Dr. Manasson said she could assess variability over time in the future. She also would like to evaluate how therapies, including antibiotics, alter the skin microbiome.

Lack of a healthy control group is a potential limitation of the study. Some unanswered questions remain, Dr. Manasson said, such as what are the regional differences in skin microbiota, for example, between a patient’s scalp and forearm? She added, “The most interesting question is what does this actually mean? What are the downstream effects?”

If a decrease in skin microbiome flora diversity is verified in future research as a sign that a patient with psoriasis is at elevated risk for developing psoriatic arthritis, it could help physicians predict who will progress. Currently, about 30% of psoriatic patients go on to develop joint disease, but methods to identify this subpopulation remain elusive.

Dr. Manasson, Dr. Gottlieb, and Dr. Helliwell had no relevant financial disclosures.

MIAMI – As patients with psoriasis develop psoriatic arthritis, the abundance of particular genera in the skin microbiome decreases, according to a preliminary study characterizing cutaneous microbiota in these populations.

“The big overall message is there might be a decrease in microbiota diversity as you progress through the disease spectrum,” Julia Manasson, MD, a fellow in the division of rheumatology at New York University said. “This is the first study characterizing the cutaneous microbial compositions of subjects with psoriasis and psoriatic arthritis in both psoriatic lesions and unaffected skin.”

Damian McNamara/Frontline Medical News

A previous study that revealed changes in gut microbiome between psoriasis and psoriatic arthritis patient stool samples (Arthritis Rheumatol. 2015;67:128-39) prompted the current research, which is “trying to see if the skin has a similar manifestation,” Dr. Manasson said during an oral presentation of her poster at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

“The microbiome has been implicated as a potential trigger for inflammation and autoimmune disease,” Dr. Manasson noted.

To investigate a potential role of the skin microbiome, the investigators swabbed lesions and unaffected skin (on a contralateral site) in 29 people with psoriasis and 62 others with psoriatic arthritis. They extracted, amplified, and sequenced DNA from the samples. No participants in the study were on treatment with biologics, disease-modifying antirheumatic drugs, or steroids at the time of assessment. The psoriasis group was 66% men and had an average age of 45 years; the psoriatic arthritis group was 55% men and the average age was 42.

Dr. Manasson and her colleagues calculated the taxonomic relative abundance and contrasted their prevalence among the four skin phenotypes examined: lesions and unaffected skin of psoriasis patients and lesions and unaffected skin of psoriatic arthritis patients. Alpha diversity plots revealed a similar number of operational taxonomic units (OTUs) between psoriasis and psoriatic arthritis samples. Beta diversity analysis showed no distinct clustering or significant difference in microbiota communities among different phenotypes.

“We saw more of a decrease in nonlesional skin and across clinical severity, too,” Dr. Manasson said. “Globally, we didn’t see significant differences [in microbiota present].”

Staphylococcus and Corynebacterium were the predominant bacteria in all samples, but there were also specific genera that were less common in psoriatic arthritis patients and in lesional skin. These less abundant genera included unclassified Bradyrhizobiaceae, Rahnella, unclassified Prevotellaceae, and Parvibaculum.

“It looks like you had some differences between lesion and nonlesional skin,” Alice Gottlieb, MD, chair and dermatologist in chief at Tufts Medical Center in Boston. “In psoriasis, the barrier function is not normal. You may want to look at atopic dermatitis where you clearly have altered barrier function.”

Dr. Manasson said they used a skin swab, so they did not assess barrier function.

“The nonlesional skin may be more interesting to look at,” Dr. Gottlieb added. “If you see a difference in nonlesional skin, it could be more [conclusive].”

Microbiome stability often changes in individuals from week to week, commented Philip Helliwell, DM, PhD, a rheumatologist at the University of Leeds in England and president of GRAPPA. Dr. Manasson said she could assess variability over time in the future. She also would like to evaluate how therapies, including antibiotics, alter the skin microbiome.

Lack of a healthy control group is a potential limitation of the study. Some unanswered questions remain, Dr. Manasson said, such as what are the regional differences in skin microbiota, for example, between a patient’s scalp and forearm? She added, “The most interesting question is what does this actually mean? What are the downstream effects?”

If a decrease in skin microbiome flora diversity is verified in future research as a sign that a patient with psoriasis is at elevated risk for developing psoriatic arthritis, it could help physicians predict who will progress. Currently, about 30% of psoriatic patients go on to develop joint disease, but methods to identify this subpopulation remain elusive.

Dr. Manasson, Dr. Gottlieb, and Dr. Helliwell had no relevant financial disclosures.

TORONTO – Hallucinations – especially auditory hallucinations – triple the risk that a risperidone-controlled Alzheimer’s patient with psychoses will relapse if the drug is withdrawn.

“I think the clinical impact we see here is that for patients with hallucinations, and particularly auditory hallucinations, antipsychotic discontinuation should be done very, very cautiously because they do have a very high risk of relapse,” Anjali Patel, DO, said at the Alzheimer’s Association International Conference 2016. “Close monitoring will be necessary and antipsychotic medications promptly reinstated if relapse occurs.”

The findings come from a responder analysis of an open-label study of risperidone (Risperdal) use in Alzheimer’s patients who express neuropsychiatric symptoms. The primary results of the multicenter Antipsychotic Discontinuation in Alzheimer’s Disease (ADAD) trial were published in 2012 (N Engl J Med. 2012;367:1497-507). The 48-week study administered open-label, flexible-dose risperidone for 16 weeks to 180 patients with Alzheimer’s dementia, with agitation and/or aggression. The patients in this study had a mean age of 79 years at baseline. Most (62%) were taking a cholinesterase inhibitor, and many took memantine (35%). Patients commonly used anxiolytics (17%) and antidepressants (24%). The mean Neuropsychiatric Inventory (NPI) score at baseline was 36. Patients were moderately impaired, with a mean Mini Mental State Exam score of 14.

At 16 weeks, patients who had not responded left the study. After 16 weeks of open-label treatment, 110 patients who had responded well continued the dosing schedule for 32 weeks, continued risperidone for 16 weeks and then went on placebo for 16 weeks, or were switched to placebo for 32 weeks. Discontinuation of risperidone was associated with a two- to four-fold increased risk of relapse over 16-32 weeks.

Dr. Patel of Columbia University, New York, presented the preplanned post-hoc analysis that examined the association between the 12 NPI symptom domains and the likelihood of relapse at week 32. In a univariate analysis, only hallucinations posted a significant association with discontinuation of risperidone. Hallucinations of any severity at baseline were present in 43 patients (39%). The relapse rates were similar among patients without baseline hallucinations (35%) and those with mild baseline hallucinations (37%). But 78% of those with severe hallucinations relapsed when risperidone was withdrawn.

Baseline hallucinations remained a strong predictor of relapse in a multivariate model as well, with a risk ratio of 2.96 for relapse among patients who had severe baseline hallucinations, compared with those with mild or no hallucinations. Age, gender, race, and nursing home placement had no significant impact on relapse rate.

Of the 17 patients with any baseline hallucinations who were switched to placebo, 13 (77%) relapsed, compared with 38% of the patients with hallucinations who continued risperidone (risk ratio, 1.98).

The risk for relapse was particularly high when the hallucinations were primarily auditory, Dr. Patel said. “In fact, visual hallucinations were not predictive of relapse.”

Among the 11 patients with severe baseline hallucinations, 10 relapsed when risperidone was withdrawn (91%; RR, 2.88), compared with 57% of patients with severe hallucinations who stayed on the drug (RR, 1.59).

The ADAD trial was funded by the National Institutes of Health and the Department of Veterans Affairs. Dr. Patel had no financial disclosures for the subanalysis.

TORONTO – Hallucinations – especially auditory hallucinations – triple the risk that a risperidone-controlled Alzheimer’s patient with psychoses will relapse if the drug is withdrawn.

“I think the clinical impact we see here is that for patients with hallucinations, and particularly auditory hallucinations, antipsychotic discontinuation should be done very, very cautiously because they do have a very high risk of relapse,” Anjali Patel, DO, said at the Alzheimer’s Association International Conference 2016. “Close monitoring will be necessary and antipsychotic medications promptly reinstated if relapse occurs.”

The findings come from a responder analysis of an open-label study of risperidone (Risperdal) use in Alzheimer’s patients who express neuropsychiatric symptoms. The primary results of the multicenter Antipsychotic Discontinuation in Alzheimer’s Disease (ADAD) trial were published in 2012 (N Engl J Med. 2012;367:1497-507). The 48-week study administered open-label, flexible-dose risperidone for 16 weeks to 180 patients with Alzheimer’s dementia, with agitation and/or aggression. The patients in this study had a mean age of 79 years at baseline. Most (62%) were taking a cholinesterase inhibitor, and many took memantine (35%). Patients commonly used anxiolytics (17%) and antidepressants (24%). The mean Neuropsychiatric Inventory (NPI) score at baseline was 36. Patients were moderately impaired, with a mean Mini Mental State Exam score of 14.

At 16 weeks, patients who had not responded left the study. After 16 weeks of open-label treatment, 110 patients who had responded well continued the dosing schedule for 32 weeks, continued risperidone for 16 weeks and then went on placebo for 16 weeks, or were switched to placebo for 32 weeks. Discontinuation of risperidone was associated with a two- to four-fold increased risk of relapse over 16-32 weeks.

Dr. Patel of Columbia University, New York, presented the preplanned post-hoc analysis that examined the association between the 12 NPI symptom domains and the likelihood of relapse at week 32. In a univariate analysis, only hallucinations posted a significant association with discontinuation of risperidone. Hallucinations of any severity at baseline were present in 43 patients (39%). The relapse rates were similar among patients without baseline hallucinations (35%) and those with mild baseline hallucinations (37%). But 78% of those with severe hallucinations relapsed when risperidone was withdrawn.

Baseline hallucinations remained a strong predictor of relapse in a multivariate model as well, with a risk ratio of 2.96 for relapse among patients who had severe baseline hallucinations, compared with those with mild or no hallucinations. Age, gender, race, and nursing home placement had no significant impact on relapse rate.

Of the 17 patients with any baseline hallucinations who were switched to placebo, 13 (77%) relapsed, compared with 38% of the patients with hallucinations who continued risperidone (risk ratio, 1.98).

The risk for relapse was particularly high when the hallucinations were primarily auditory, Dr. Patel said. “In fact, visual hallucinations were not predictive of relapse.”

Among the 11 patients with severe baseline hallucinations, 10 relapsed when risperidone was withdrawn (91%; RR, 2.88), compared with 57% of patients with severe hallucinations who stayed on the drug (RR, 1.59).

The ADAD trial was funded by the National Institutes of Health and the Department of Veterans Affairs. Dr. Patel had no financial disclosures for the subanalysis.

TORONTO – Hallucinations – especially auditory hallucinations – triple the risk that a risperidone-controlled Alzheimer’s patient with psychoses will relapse if the drug is withdrawn.

“I think the clinical impact we see here is that for patients with hallucinations, and particularly auditory hallucinations, antipsychotic discontinuation should be done very, very cautiously because they do have a very high risk of relapse,” Anjali Patel, DO, said at the Alzheimer’s Association International Conference 2016. “Close monitoring will be necessary and antipsychotic medications promptly reinstated if relapse occurs.”

The findings come from a responder analysis of an open-label study of risperidone (Risperdal) use in Alzheimer’s patients who express neuropsychiatric symptoms. The primary results of the multicenter Antipsychotic Discontinuation in Alzheimer’s Disease (ADAD) trial were published in 2012 (N Engl J Med. 2012;367:1497-507). The 48-week study administered open-label, flexible-dose risperidone for 16 weeks to 180 patients with Alzheimer’s dementia, with agitation and/or aggression. The patients in this study had a mean age of 79 years at baseline. Most (62%) were taking a cholinesterase inhibitor, and many took memantine (35%). Patients commonly used anxiolytics (17%) and antidepressants (24%). The mean Neuropsychiatric Inventory (NPI) score at baseline was 36. Patients were moderately impaired, with a mean Mini Mental State Exam score of 14.

At 16 weeks, patients who had not responded left the study. After 16 weeks of open-label treatment, 110 patients who had responded well continued the dosing schedule for 32 weeks, continued risperidone for 16 weeks and then went on placebo for 16 weeks, or were switched to placebo for 32 weeks. Discontinuation of risperidone was associated with a two- to four-fold increased risk of relapse over 16-32 weeks.

Dr. Patel of Columbia University, New York, presented the preplanned post-hoc analysis that examined the association between the 12 NPI symptom domains and the likelihood of relapse at week 32. In a univariate analysis, only hallucinations posted a significant association with discontinuation of risperidone. Hallucinations of any severity at baseline were present in 43 patients (39%). The relapse rates were similar among patients without baseline hallucinations (35%) and those with mild baseline hallucinations (37%). But 78% of those with severe hallucinations relapsed when risperidone was withdrawn.

Baseline hallucinations remained a strong predictor of relapse in a multivariate model as well, with a risk ratio of 2.96 for relapse among patients who had severe baseline hallucinations, compared with those with mild or no hallucinations. Age, gender, race, and nursing home placement had no significant impact on relapse rate.

Of the 17 patients with any baseline hallucinations who were switched to placebo, 13 (77%) relapsed, compared with 38% of the patients with hallucinations who continued risperidone (risk ratio, 1.98).

The risk for relapse was particularly high when the hallucinations were primarily auditory, Dr. Patel said. “In fact, visual hallucinations were not predictive of relapse.”

Among the 11 patients with severe baseline hallucinations, 10 relapsed when risperidone was withdrawn (91%; RR, 2.88), compared with 57% of patients with severe hallucinations who stayed on the drug (RR, 1.59).

The ADAD trial was funded by the National Institutes of Health and the Department of Veterans Affairs. Dr. Patel had no financial disclosures for the subanalysis.

TORONTO – Hallucinations – especially auditory hallucinations – triple the risk that a risperidone-controlled Alzheimer’s patient with psychoses will relapse if the drug is withdrawn.

“I think the clinical impact we see here is that for patients with hallucinations, and particularly auditory hallucinations, antipsychotic discontinuation should be done very, very cautiously because they do have a very high risk of relapse,” Anjali Patel, DO, said at the Alzheimer’s Association International Conference 2016. “Close monitoring will be necessary and antipsychotic medications promptly reinstated if relapse occurs.”

The findings come from a responder analysis of an open-label study of risperidone (Risperdal) use in Alzheimer’s patients who express neuropsychiatric symptoms. The primary results of the multicenter Antipsychotic Discontinuation in Alzheimer’s Disease (ADAD) trial were published in 2012 (N Engl J Med. 2012;367:1497-507). The 48-week study administered open-label, flexible-dose risperidone for 16 weeks to 180 patients with Alzheimer’s dementia, with agitation and/or aggression. The patients in this study had a mean age of 79 years at baseline. Most (62%) were taking a cholinesterase inhibitor, and many took memantine (35%). Patients commonly used anxiolytics (17%) and antidepressants (24%). The mean Neuropsychiatric Inventory (NPI) score at baseline was 36. Patients were moderately impaired, with a mean Mini Mental State Exam score of 14.

At 16 weeks, patients who had not responded left the study. After 16 weeks of open-label treatment, 110 patients who had responded well continued the dosing schedule for 32 weeks, continued risperidone for 16 weeks and then went on placebo for 16 weeks, or were switched to placebo for 32 weeks. Discontinuation of risperidone was associated with a two- to four-fold increased risk of relapse over 16-32 weeks.

Dr. Patel of Columbia University, New York, presented the preplanned post-hoc analysis that examined the association between the 12 NPI symptom domains and the likelihood of relapse at week 32. In a univariate analysis, only hallucinations posted a significant association with discontinuation of risperidone. Hallucinations of any severity at baseline were present in 43 patients (39%). The relapse rates were similar among patients without baseline hallucinations (35%) and those with mild baseline hallucinations (37%). But 78% of those with severe hallucinations relapsed when risperidone was withdrawn.

Baseline hallucinations remained a strong predictor of relapse in a multivariate model as well, with a risk ratio of 2.96 for relapse among patients who had severe baseline hallucinations, compared with those with mild or no hallucinations. Age, gender, race, and nursing home placement had no significant impact on relapse rate.

Of the 17 patients with any baseline hallucinations who were switched to placebo, 13 (77%) relapsed, compared with 38% of the patients with hallucinations who continued risperidone (risk ratio, 1.98).

The risk for relapse was particularly high when the hallucinations were primarily auditory, Dr. Patel said. “In fact, visual hallucinations were not predictive of relapse.”

Among the 11 patients with severe baseline hallucinations, 10 relapsed when risperidone was withdrawn (91%; RR, 2.88), compared with 57% of patients with severe hallucinations who stayed on the drug (RR, 1.59).

The ADAD trial was funded by the National Institutes of Health and the Department of Veterans Affairs. Dr. Patel had no financial disclosures for the subanalysis.

[email protected]

On Twitter @alz_gal

TORONTO – Hallucinations – especially auditory hallucinations – triple the risk that a risperidone-controlled Alzheimer’s patient with psychoses will relapse if the drug is withdrawn.

“I think the clinical impact we see here is that for patients with hallucinations, and particularly auditory hallucinations, antipsychotic discontinuation should be done very, very cautiously because they do have a very high risk of relapse,” Anjali Patel, DO, said at the Alzheimer’s Association International Conference 2016. “Close monitoring will be necessary and antipsychotic medications promptly reinstated if relapse occurs.”

The findings come from a responder analysis of an open-label study of risperidone (Risperdal) use in Alzheimer’s patients who express neuropsychiatric symptoms. The primary results of the multicenter Antipsychotic Discontinuation in Alzheimer’s Disease (ADAD) trial were published in 2012 (N Engl J Med. 2012;367:1497-507). The 48-week study administered open-label, flexible-dose risperidone for 16 weeks to 180 patients with Alzheimer’s dementia, with agitation and/or aggression. The patients in this study had a mean age of 79 years at baseline. Most (62%) were taking a cholinesterase inhibitor, and many took memantine (35%). Patients commonly used anxiolytics (17%) and antidepressants (24%). The mean Neuropsychiatric Inventory (NPI) score at baseline was 36. Patients were moderately impaired, with a mean Mini Mental State Exam score of 14.

At 16 weeks, patients who had not responded left the study. After 16 weeks of open-label treatment, 110 patients who had responded well continued the dosing schedule for 32 weeks, continued risperidone for 16 weeks and then went on placebo for 16 weeks, or were switched to placebo for 32 weeks. Discontinuation of risperidone was associated with a two- to four-fold increased risk of relapse over 16-32 weeks.

Dr. Patel of Columbia University, New York, presented the preplanned post-hoc analysis that examined the association between the 12 NPI symptom domains and the likelihood of relapse at week 32. In a univariate analysis, only hallucinations posted a significant association with discontinuation of risperidone. Hallucinations of any severity at baseline were present in 43 patients (39%). The relapse rates were similar among patients without baseline hallucinations (35%) and those with mild baseline hallucinations (37%). But 78% of those with severe hallucinations relapsed when risperidone was withdrawn.

Baseline hallucinations remained a strong predictor of relapse in a multivariate model as well, with a risk ratio of 2.96 for relapse among patients who had severe baseline hallucinations, compared with those with mild or no hallucinations. Age, gender, race, and nursing home placement had no significant impact on relapse rate.

Of the 17 patients with any baseline hallucinations who were switched to placebo, 13 (77%) relapsed, compared with 38% of the patients with hallucinations who continued risperidone (risk ratio, 1.98).

The risk for relapse was particularly high when the hallucinations were primarily auditory, Dr. Patel said. “In fact, visual hallucinations were not predictive of relapse.”

Among the 11 patients with severe baseline hallucinations, 10 relapsed when risperidone was withdrawn (91%; RR, 2.88), compared with 57% of patients with severe hallucinations who stayed on the drug (RR, 1.59).

The ADAD trial was funded by the National Institutes of Health and the Department of Veterans Affairs. Dr. Patel had no financial disclosures for the subanalysis.

[email protected]

On Twitter @alz_gal

TORONTO – Hallucinations – especially auditory hallucinations – triple the risk that a risperidone-controlled Alzheimer’s patient with psychoses will relapse if the drug is withdrawn.

“I think the clinical impact we see here is that for patients with hallucinations, and particularly auditory hallucinations, antipsychotic discontinuation should be done very, very cautiously because they do have a very high risk of relapse,” Anjali Patel, DO, said at the Alzheimer’s Association International Conference 2016. “Close monitoring will be necessary and antipsychotic medications promptly reinstated if relapse occurs.”

The findings come from a responder analysis of an open-label study of risperidone (Risperdal) use in Alzheimer’s patients who express neuropsychiatric symptoms. The primary results of the multicenter Antipsychotic Discontinuation in Alzheimer’s Disease (ADAD) trial were published in 2012 (N Engl J Med. 2012;367:1497-507). The 48-week study administered open-label, flexible-dose risperidone for 16 weeks to 180 patients with Alzheimer’s dementia, with agitation and/or aggression. The patients in this study had a mean age of 79 years at baseline. Most (62%) were taking a cholinesterase inhibitor, and many took memantine (35%). Patients commonly used anxiolytics (17%) and antidepressants (24%). The mean Neuropsychiatric Inventory (NPI) score at baseline was 36. Patients were moderately impaired, with a mean Mini Mental State Exam score of 14.

At 16 weeks, patients who had not responded left the study. After 16 weeks of open-label treatment, 110 patients who had responded well continued the dosing schedule for 32 weeks, continued risperidone for 16 weeks and then went on placebo for 16 weeks, or were switched to placebo for 32 weeks. Discontinuation of risperidone was associated with a two- to four-fold increased risk of relapse over 16-32 weeks.

Dr. Patel of Columbia University, New York, presented the preplanned post-hoc analysis that examined the association between the 12 NPI symptom domains and the likelihood of relapse at week 32. In a univariate analysis, only hallucinations posted a significant association with discontinuation of risperidone. Hallucinations of any severity at baseline were present in 43 patients (39%). The relapse rates were similar among patients without baseline hallucinations (35%) and those with mild baseline hallucinations (37%). But 78% of those with severe hallucinations relapsed when risperidone was withdrawn.

Baseline hallucinations remained a strong predictor of relapse in a multivariate model as well, with a risk ratio of 2.96 for relapse among patients who had severe baseline hallucinations, compared with those with mild or no hallucinations. Age, gender, race, and nursing home placement had no significant impact on relapse rate.

Of the 17 patients with any baseline hallucinations who were switched to placebo, 13 (77%) relapsed, compared with 38% of the patients with hallucinations who continued risperidone (risk ratio, 1.98).

The risk for relapse was particularly high when the hallucinations were primarily auditory, Dr. Patel said. “In fact, visual hallucinations were not predictive of relapse.”

Among the 11 patients with severe baseline hallucinations, 10 relapsed when risperidone was withdrawn (91%; RR, 2.88), compared with 57% of patients with severe hallucinations who stayed on the drug (RR, 1.59).

The ADAD trial was funded by the National Institutes of Health and the Department of Veterans Affairs. Dr. Patel had no financial disclosures for the subanalysis.

[email protected]

On Twitter @alz_gal

MIAMI – Ultrasound-detected enthesitis was associated with both destructive and bone formation lesions on radiography of peripheral and axial joints in a study of 222 patients with psoriatic arthritis. But its lack of correlation to clinically detected enthesitis in this study and in others has made its clinical usefulness somewhat controversial.

“This is not first time we see this result in the literature,” Ari Polachek, MD, said when presenting the research at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). The findings suggest ultrasound reveals something different than a physical examination does, and because it’s more sensitive and specific, ultrasound is more accurate, he said.

Damian McNamara/Frontline Medical News

Diagnostic disagreement

Some differing opinions arose during a discussion after Dr. Polachek’s presentation. “When you look at the enthesitis measures [with ultrasound] ... you don’t necessarily measure the same enthesitis points you measure in clinical practice,” said Dafna D. Gladman, MD, a senior scientist at Toronto Western Hospital’s Krembil Research Institute and a rheumatologist at the University of Toronto. “We have to be careful. I don’t think we should immediately cancel the relationship between the ultrasound and clinical exam.”

“Well, I disagree entirely,” said Philip Helliwell, DM, PhD, senior lecturer in rheumatology at the University of Leeds, England, and president of GRAPPA. “We have looked at the Leeds [Enthesitis Index] with ultrasound and MRI and found no significant relationship at all.” Although Dr. Helliwell said there is a possible role for ultrasound to detect enthesitis in the Achilles, “We are fooling ourselves if we are measuring enthesitis as a pathologic entity. I don’t really know what we’re measuring when we do these scores.”

“My message is you do not need to scan every patient,” Dr. Polachek said in an interview. If a physician remains unsure about the physical exam results, it can be useful. Dr. Polachek, who completed his medical training in Israel, added: “In Israel, we say that ultrasound is ‘the final judge.’ ”

Association with radiographic joint findings

The investigators achieved their study aim: demonstrating that the severity of sonographic enthesitis is a marker of radiographic peripheral and axial joint damage in psoriatic arthritis. They found an association for both destructive and bone formation lesions.

“These findings highlight the potential role of enthesitis in the pathogenesis of articular damage in psoriatic arthritis,” said Dr. Polachek, clinical and research fellow at the University of Toronto.

The researchers assessed 12 entheseal sites with ultrasound. They used the Madrid Sonography Enthesitis Index scoring system (MASEI) to determine the global extent of enthesitis in each patient. In addition, they used the modified Steinbrocker score to assess peripheral joint damage, and the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) to assess spinal damage. Patients also underwent a clinical exam and were asked about their medical history.

Multivariate analysis revealed a significant association between higher MASEI score and joint ankylosis (odds ratio, 2.09; P = .0001) and arthritis mutilans (OR, 1.73; P = .005). The total MASEI score was associated with the modified Steinbrocker score (OR, 9.3; P less than .0001) in a logistic regression analysis; total MASEI also significantly correlated with the mSASSS measure of spinal damage (OR, 1.55; P less than .0001) in a linear regression analysis.

Participants had a mean age of 56 years and a 17-year mean duration of psoriatic arthritis. They presented with a mean of 2.4 tender joints and 1.1 swollen joints. At study entry, their mean scores were 15.6 on MASEI, 18.1 on modified Steinbrocker, and 1.72 on mSASSS.

The strengths of the study included a large number of participants and control of multiple possible confounders (age, sex, body mass index, duration of psoriatic arthritis, and use of disease-modifying antirheumatic drugs and biologics). It is limited by its cross-sectional design, which rules out inferences of causality.

Clinical confirmation

“Traditionally, patients came in with a tender joint, and we might not see anything. Now I can put the sensor down and say they have inflammation,” Dr. Polachek said. In such cases, he may suggest more aggressive treatment. However, if an asymptomatic patient has ultrasound findings, “right now the recommendation is not to do anything. Otherwise, it could be overtreatment.”

“This is the future,” Dr. Polachek said. “I started doing ultrasound myself – it’s a game changer.”

Dr. Polachek has received funding from Janssen and the Krembil Research Institute.

MIAMI – Ultrasound-detected enthesitis was associated with both destructive and bone formation lesions on radiography of peripheral and axial joints in a study of 222 patients with psoriatic arthritis. But its lack of correlation to clinically detected enthesitis in this study and in others has made its clinical usefulness somewhat controversial.

“This is not first time we see this result in the literature,” Ari Polachek, MD, said when presenting the research at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). The findings suggest ultrasound reveals something different than a physical examination does, and because it’s more sensitive and specific, ultrasound is more accurate, he said.

Damian McNamara/Frontline Medical News

Diagnostic disagreement

Some differing opinions arose during a discussion after Dr. Polachek’s presentation. “When you look at the enthesitis measures [with ultrasound] ... you don’t necessarily measure the same enthesitis points you measure in clinical practice,” said Dafna D. Gladman, MD, a senior scientist at Toronto Western Hospital’s Krembil Research Institute and a rheumatologist at the University of Toronto. “We have to be careful. I don’t think we should immediately cancel the relationship between the ultrasound and clinical exam.”

“Well, I disagree entirely,” said Philip Helliwell, DM, PhD, senior lecturer in rheumatology at the University of Leeds, England, and president of GRAPPA. “We have looked at the Leeds [Enthesitis Index] with ultrasound and MRI and found no significant relationship at all.” Although Dr. Helliwell said there is a possible role for ultrasound to detect enthesitis in the Achilles, “We are fooling ourselves if we are measuring enthesitis as a pathologic entity. I don’t really know what we’re measuring when we do these scores.”

“My message is you do not need to scan every patient,” Dr. Polachek said in an interview. If a physician remains unsure about the physical exam results, it can be useful. Dr. Polachek, who completed his medical training in Israel, added: “In Israel, we say that ultrasound is ‘the final judge.’ ”

Association with radiographic joint findings

The investigators achieved their study aim: demonstrating that the severity of sonographic enthesitis is a marker of radiographic peripheral and axial joint damage in psoriatic arthritis. They found an association for both destructive and bone formation lesions.

“These findings highlight the potential role of enthesitis in the pathogenesis of articular damage in psoriatic arthritis,” said Dr. Polachek, clinical and research fellow at the University of Toronto.

The researchers assessed 12 entheseal sites with ultrasound. They used the Madrid Sonography Enthesitis Index scoring system (MASEI) to determine the global extent of enthesitis in each patient. In addition, they used the modified Steinbrocker score to assess peripheral joint damage, and the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) to assess spinal damage. Patients also underwent a clinical exam and were asked about their medical history.

Multivariate analysis revealed a significant association between higher MASEI score and joint ankylosis (odds ratio, 2.09; P = .0001) and arthritis mutilans (OR, 1.73; P = .005). The total MASEI score was associated with the modified Steinbrocker score (OR, 9.3; P less than .0001) in a logistic regression analysis; total MASEI also significantly correlated with the mSASSS measure of spinal damage (OR, 1.55; P less than .0001) in a linear regression analysis.

Participants had a mean age of 56 years and a 17-year mean duration of psoriatic arthritis. They presented with a mean of 2.4 tender joints and 1.1 swollen joints. At study entry, their mean scores were 15.6 on MASEI, 18.1 on modified Steinbrocker, and 1.72 on mSASSS.

The strengths of the study included a large number of participants and control of multiple possible confounders (age, sex, body mass index, duration of psoriatic arthritis, and use of disease-modifying antirheumatic drugs and biologics). It is limited by its cross-sectional design, which rules out inferences of causality.

Clinical confirmation

“Traditionally, patients came in with a tender joint, and we might not see anything. Now I can put the sensor down and say they have inflammation,” Dr. Polachek said. In such cases, he may suggest more aggressive treatment. However, if an asymptomatic patient has ultrasound findings, “right now the recommendation is not to do anything. Otherwise, it could be overtreatment.”

“This is the future,” Dr. Polachek said. “I started doing ultrasound myself – it’s a game changer.”

Dr. Polachek has received funding from Janssen and the Krembil Research Institute.

MIAMI – Ultrasound-detected enthesitis was associated with both destructive and bone formation lesions on radiography of peripheral and axial joints in a study of 222 patients with psoriatic arthritis. But its lack of correlation to clinically detected enthesitis in this study and in others has made its clinical usefulness somewhat controversial.

“This is not first time we see this result in the literature,” Ari Polachek, MD, said when presenting the research at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). The findings suggest ultrasound reveals something different than a physical examination does, and because it’s more sensitive and specific, ultrasound is more accurate, he said.

Damian McNamara/Frontline Medical News

Diagnostic disagreement

Some differing opinions arose during a discussion after Dr. Polachek’s presentation. “When you look at the enthesitis measures [with ultrasound] ... you don’t necessarily measure the same enthesitis points you measure in clinical practice,” said Dafna D. Gladman, MD, a senior scientist at Toronto Western Hospital’s Krembil Research Institute and a rheumatologist at the University of Toronto. “We have to be careful. I don’t think we should immediately cancel the relationship between the ultrasound and clinical exam.”

“Well, I disagree entirely,” said Philip Helliwell, DM, PhD, senior lecturer in rheumatology at the University of Leeds, England, and president of GRAPPA. “We have looked at the Leeds [Enthesitis Index] with ultrasound and MRI and found no significant relationship at all.” Although Dr. Helliwell said there is a possible role for ultrasound to detect enthesitis in the Achilles, “We are fooling ourselves if we are measuring enthesitis as a pathologic entity. I don’t really know what we’re measuring when we do these scores.”

“My message is you do not need to scan every patient,” Dr. Polachek said in an interview. If a physician remains unsure about the physical exam results, it can be useful. Dr. Polachek, who completed his medical training in Israel, added: “In Israel, we say that ultrasound is ‘the final judge.’ ”

Association with radiographic joint findings

The investigators achieved their study aim: demonstrating that the severity of sonographic enthesitis is a marker of radiographic peripheral and axial joint damage in psoriatic arthritis. They found an association for both destructive and bone formation lesions.

“These findings highlight the potential role of enthesitis in the pathogenesis of articular damage in psoriatic arthritis,” said Dr. Polachek, clinical and research fellow at the University of Toronto.

The researchers assessed 12 entheseal sites with ultrasound. They used the Madrid Sonography Enthesitis Index scoring system (MASEI) to determine the global extent of enthesitis in each patient. In addition, they used the modified Steinbrocker score to assess peripheral joint damage, and the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) to assess spinal damage. Patients also underwent a clinical exam and were asked about their medical history.

Multivariate analysis revealed a significant association between higher MASEI score and joint ankylosis (odds ratio, 2.09; P = .0001) and arthritis mutilans (OR, 1.73; P = .005). The total MASEI score was associated with the modified Steinbrocker score (OR, 9.3; P less than .0001) in a logistic regression analysis; total MASEI also significantly correlated with the mSASSS measure of spinal damage (OR, 1.55; P less than .0001) in a linear regression analysis.

Participants had a mean age of 56 years and a 17-year mean duration of psoriatic arthritis. They presented with a mean of 2.4 tender joints and 1.1 swollen joints. At study entry, their mean scores were 15.6 on MASEI, 18.1 on modified Steinbrocker, and 1.72 on mSASSS.

The strengths of the study included a large number of participants and control of multiple possible confounders (age, sex, body mass index, duration of psoriatic arthritis, and use of disease-modifying antirheumatic drugs and biologics). It is limited by its cross-sectional design, which rules out inferences of causality.

Clinical confirmation

“Traditionally, patients came in with a tender joint, and we might not see anything. Now I can put the sensor down and say they have inflammation,” Dr. Polachek said. In such cases, he may suggest more aggressive treatment. However, if an asymptomatic patient has ultrasound findings, “right now the recommendation is not to do anything. Otherwise, it could be overtreatment.”

“This is the future,” Dr. Polachek said. “I started doing ultrasound myself – it’s a game changer.”

Dr. Polachek has received funding from Janssen and the Krembil Research Institute.

NEW YORK - After two confirmed U.S. cases of a superbug that thwarts a last-resort antibiotic, infectious disease experts say they expect more cases in coming months because the bacterial gene behind it is likely far more widespread than previously believed.

Army scientists in May reported finding E. coli bacteria that harbor a gene which renders the antibiotic colistin useless. The gene, called mcr-1, was found in a urine sample of a Pennsylvania woman being treated for a urinary tract infection.

On Monday, researchers confirmed preliminary findings that E. coli carrying the same mcr-1 gene were found in a stored bacterial sample of a New York patient who had been treated for an infection last year, as well as in patient samples from nine other countries.

The report came from a global effort called the SENTRY Antimicrobial Surveillance Program, led by Mariana Castanheira of JMI Laboratories based in North Liberty, Iowa.

The mcr-1 superbug has been identified over the past six months in farm animals and people in about 20 countries, including China, Germany and Italy.

The bacteria can be transmitted by fecal contact and poor hygiene, which suggests a far wider likely presence than the documented cases so far, according to leading infectious disease experts.

Health officials fear the mcr-1 gene, carried by a highly mobile piece of DNA called a plasmid, will soon be found in bacteria already resistant to all or virtually all other types of antibiotics, potentially making infections untreatable.

"You can be sure (mcr-1) is already in the guts of people throughout the United States and will continue to spread," said Dr. Brad Spellberg, professor of medicine at the University of Southern California.

Dr. David Van Duin, an infectious disease expert at the University of North Carolina in Chapel Hill, said he expects more documented U.S. cases of mcr-1 in coming months because it is already here and will spread from abroad. "We will see a lot more of this gene."

Colistin causes kidney damage, but doctors have opted for it as other antibiotics increasingly fail. Its overuse, especially in overseas farm animals, has allowed bacteria to develop resistance to it.

PAST AND PRESENT INFECTIONS

To track the mcr-1 gene, U.S. hospitals are working together with state and federal agencies to test bacteria samples of patients that have recently been treated for infections. Many of the largest research hospitals are examining samples of antibiotic-resistant bacteria that have long been stored in their freezers.

Gautam Dantas, associate professor of pathology at Washington University Medical Center in St. Louis, has tested hundreds of U.S. samples of archived bacteria in recent months and has not yet detected mcr-1. But he expects dozens of confirmed cases of the gene will be documented by next year in the country, mostly among current patients.

The concern of many disease experts is that mcr-1 could soon show up in bacteria also resistant to carbapenems, one of the few remaining dependable classes of antibiotics. In that event, with colistin no longer a last-ditch option, some patients would have to rely on their immune systems to fight off infection.

"Within the next two to three years, it's going to be fairly routine for infections to occur in the United States for which we have no (effective) drugs available," Dantas said.

Castanheira also believes mcr-1 will find its way into carbapenem-resistant enterobacteriaceae (CRE).

In an interview, she said the resulting virtually impervious bacterium would likely spread slowly inside the United States because CRE themselves are not yet widespread in the country, giving drugmakers some time to create new antibiotics.

Beginning in August, the U.S. Centers for Disease Control and Prevention will use $21 million to expand surveillance at laboratories operated by all 50 state health departments and seven larger regional labs. The federal funding will help pay for more-sensitive equipment to test for antibiotic resistance in bacteria samples provided by hospitals.

Jean Patel, deputy director of the CDC's Office of Antimicrobial Resistance, said the effort will provide the CDC improved national surveillance of antibiotic-resistance trends, including any spread of mcr-1.

"This is data for action," she said, adding that special procedures to prevent infections from spreading in hospitals could be taken once a patient is identified with mcr-1 related infections or with multidrug-resistant bacteria.

SOURCE: http://bit.ly/29yFekw

Antimicrob Agents Chemother 2016.

NEW YORK - After two confirmed U.S. cases of a superbug that thwarts a last-resort antibiotic, infectious disease experts say they expect more cases in coming months because the bacterial gene behind it is likely far more widespread than previously believed.

Army scientists in May reported finding E. coli bacteria that harbor a gene which renders the antibiotic colistin useless. The gene, called mcr-1, was found in a urine sample of a Pennsylvania woman being treated for a urinary tract infection.

On Monday, researchers confirmed preliminary findings that E. coli carrying the same mcr-1 gene were found in a stored bacterial sample of a New York patient who had been treated for an infection last year, as well as in patient samples from nine other countries.

The report came from a global effort called the SENTRY Antimicrobial Surveillance Program, led by Mariana Castanheira of JMI Laboratories based in North Liberty, Iowa.

The mcr-1 superbug has been identified over the past six months in farm animals and people in about 20 countries, including China, Germany and Italy.

The bacteria can be transmitted by fecal contact and poor hygiene, which suggests a far wider likely presence than the documented cases so far, according to leading infectious disease experts.

Health officials fear the mcr-1 gene, carried by a highly mobile piece of DNA called a plasmid, will soon be found in bacteria already resistant to all or virtually all other types of antibiotics, potentially making infections untreatable.

"You can be sure (mcr-1) is already in the guts of people throughout the United States and will continue to spread," said Dr. Brad Spellberg, professor of medicine at the University of Southern California.

Dr. David Van Duin, an infectious disease expert at the University of North Carolina in Chapel Hill, said he expects more documented U.S. cases of mcr-1 in coming months because it is already here and will spread from abroad. "We will see a lot more of this gene."

Colistin causes kidney damage, but doctors have opted for it as other antibiotics increasingly fail. Its overuse, especially in overseas farm animals, has allowed bacteria to develop resistance to it.

PAST AND PRESENT INFECTIONS

To track the mcr-1 gene, U.S. hospitals are working together with state and federal agencies to test bacteria samples of patients that have recently been treated for infections. Many of the largest research hospitals are examining samples of antibiotic-resistant bacteria that have long been stored in their freezers.

Gautam Dantas, associate professor of pathology at Washington University Medical Center in St. Louis, has tested hundreds of U.S. samples of archived bacteria in recent months and has not yet detected mcr-1. But he expects dozens of confirmed cases of the gene will be documented by next year in the country, mostly among current patients.

The concern of many disease experts is that mcr-1 could soon show up in bacteria also resistant to carbapenems, one of the few remaining dependable classes of antibiotics. In that event, with colistin no longer a last-ditch option, some patients would have to rely on their immune systems to fight off infection.

"Within the next two to three years, it's going to be fairly routine for infections to occur in the United States for which we have no (effective) drugs available," Dantas said.

Castanheira also believes mcr-1 will find its way into carbapenem-resistant enterobacteriaceae (CRE).

In an interview, she said the resulting virtually impervious bacterium would likely spread slowly inside the United States because CRE themselves are not yet widespread in the country, giving drugmakers some time to create new antibiotics.

Beginning in August, the U.S. Centers for Disease Control and Prevention will use $21 million to expand surveillance at laboratories operated by all 50 state health departments and seven larger regional labs. The federal funding will help pay for more-sensitive equipment to test for antibiotic resistance in bacteria samples provided by hospitals.

Jean Patel, deputy director of the CDC's Office of Antimicrobial Resistance, said the effort will provide the CDC improved national surveillance of antibiotic-resistance trends, including any spread of mcr-1.

"This is data for action," she said, adding that special procedures to prevent infections from spreading in hospitals could be taken once a patient is identified with mcr-1 related infections or with multidrug-resistant bacteria.

SOURCE: http://bit.ly/29yFekw

Antimicrob Agents Chemother 2016.

NEW YORK - After two confirmed U.S. cases of a superbug that thwarts a last-resort antibiotic, infectious disease experts say they expect more cases in coming months because the bacterial gene behind it is likely far more widespread than previously believed.

Army scientists in May reported finding E. coli bacteria that harbor a gene which renders the antibiotic colistin useless. The gene, called mcr-1, was found in a urine sample of a Pennsylvania woman being treated for a urinary tract infection.

On Monday, researchers confirmed preliminary findings that E. coli carrying the same mcr-1 gene were found in a stored bacterial sample of a New York patient who had been treated for an infection last year, as well as in patient samples from nine other countries.

The report came from a global effort called the SENTRY Antimicrobial Surveillance Program, led by Mariana Castanheira of JMI Laboratories based in North Liberty, Iowa.

The mcr-1 superbug has been identified over the past six months in farm animals and people in about 20 countries, including China, Germany and Italy.

The bacteria can be transmitted by fecal contact and poor hygiene, which suggests a far wider likely presence than the documented cases so far, according to leading infectious disease experts.

Health officials fear the mcr-1 gene, carried by a highly mobile piece of DNA called a plasmid, will soon be found in bacteria already resistant to all or virtually all other types of antibiotics, potentially making infections untreatable.

"You can be sure (mcr-1) is already in the guts of people throughout the United States and will continue to spread," said Dr. Brad Spellberg, professor of medicine at the University of Southern California.

Dr. David Van Duin, an infectious disease expert at the University of North Carolina in Chapel Hill, said he expects more documented U.S. cases of mcr-1 in coming months because it is already here and will spread from abroad. "We will see a lot more of this gene."

Colistin causes kidney damage, but doctors have opted for it as other antibiotics increasingly fail. Its overuse, especially in overseas farm animals, has allowed bacteria to develop resistance to it.

PAST AND PRESENT INFECTIONS

To track the mcr-1 gene, U.S. hospitals are working together with state and federal agencies to test bacteria samples of patients that have recently been treated for infections. Many of the largest research hospitals are examining samples of antibiotic-resistant bacteria that have long been stored in their freezers.

Gautam Dantas, associate professor of pathology at Washington University Medical Center in St. Louis, has tested hundreds of U.S. samples of archived bacteria in recent months and has not yet detected mcr-1. But he expects dozens of confirmed cases of the gene will be documented by next year in the country, mostly among current patients.

The concern of many disease experts is that mcr-1 could soon show up in bacteria also resistant to carbapenems, one of the few remaining dependable classes of antibiotics. In that event, with colistin no longer a last-ditch option, some patients would have to rely on their immune systems to fight off infection.

"Within the next two to three years, it's going to be fairly routine for infections to occur in the United States for which we have no (effective) drugs available," Dantas said.

Castanheira also believes mcr-1 will find its way into carbapenem-resistant enterobacteriaceae (CRE).

In an interview, she said the resulting virtually impervious bacterium would likely spread slowly inside the United States because CRE themselves are not yet widespread in the country, giving drugmakers some time to create new antibiotics.

Beginning in August, the U.S. Centers for Disease Control and Prevention will use $21 million to expand surveillance at laboratories operated by all 50 state health departments and seven larger regional labs. The federal funding will help pay for more-sensitive equipment to test for antibiotic resistance in bacteria samples provided by hospitals.

Jean Patel, deputy director of the CDC's Office of Antimicrobial Resistance, said the effort will provide the CDC improved national surveillance of antibiotic-resistance trends, including any spread of mcr-1.

"This is data for action," she said, adding that special procedures to prevent infections from spreading in hospitals could be taken once a patient is identified with mcr-1 related infections or with multidrug-resistant bacteria.

SOURCE: http://bit.ly/29yFekw

Antimicrob Agents Chemother 2016.

Acute lymphoblastic leukemia is a neoplastic proliferation of lymphoblasts in the bone marrow. Normal hematopoiesis is affected, and symptoms from anemia (fatigue, breathlessness), leukopenia (recurrent infections) or thrombocytopenia (easy bruising, mucosal bleeding) are typically described in ALL. Hepatosplenomegaly and B-symptoms (fever, weight loss, and night sweats) are frequently seen. Presence of lymphoblasts in the peripheral smear is indicative of ALL, and a bone marrow biopsy finding of >25% lymphoblasts is confirmatory. Absence of peripheral lymphoblasts in a patient with acute leukemia is known as aleukemic leukemia. Aleukemic leukemia is uncommon, and most cases have described skin lesions from lymphoblast infiltration (leukemia cutis) in addition to bone marrow involvement.¹ We report a case of aleukemic ALL in an adult presenting with unusual clinical features including bone pain, osteolytic lesions, hypercalcemia, and normal blood counts. To our knowledge, this is fifth such case ever reported in an adult patient.

Click on the PDF icon at the top of this introduction to read the full article.

Acute lymphoblastic leukemia is a neoplastic proliferation of lymphoblasts in the bone marrow. Normal hematopoiesis is affected, and symptoms from anemia (fatigue, breathlessness), leukopenia (recurrent infections) or thrombocytopenia (easy bruising, mucosal bleeding) are typically described in ALL. Hepatosplenomegaly and B-symptoms (fever, weight loss, and night sweats) are frequently seen. Presence of lymphoblasts in the peripheral smear is indicative of ALL, and a bone marrow biopsy finding of >25% lymphoblasts is confirmatory. Absence of peripheral lymphoblasts in a patient with acute leukemia is known as aleukemic leukemia. Aleukemic leukemia is uncommon, and most cases have described skin lesions from lymphoblast infiltration (leukemia cutis) in addition to bone marrow involvement.¹ We report a case of aleukemic ALL in an adult presenting with unusual clinical features including bone pain, osteolytic lesions, hypercalcemia, and normal blood counts. To our knowledge, this is fifth such case ever reported in an adult patient.

Click on the PDF icon at the top of this introduction to read the full article.

Acute lymphoblastic leukemia is a neoplastic proliferation of lymphoblasts in the bone marrow. Normal hematopoiesis is affected, and symptoms from anemia (fatigue, breathlessness), leukopenia (recurrent infections) or thrombocytopenia (easy bruising, mucosal bleeding) are typically described in ALL. Hepatosplenomegaly and B-symptoms (fever, weight loss, and night sweats) are frequently seen. Presence of lymphoblasts in the peripheral smear is indicative of ALL, and a bone marrow biopsy finding of >25% lymphoblasts is confirmatory. Absence of peripheral lymphoblasts in a patient with acute leukemia is known as aleukemic leukemia. Aleukemic leukemia is uncommon, and most cases have described skin lesions from lymphoblast infiltration (leukemia cutis) in addition to bone marrow involvement.¹ We report a case of aleukemic ALL in an adult presenting with unusual clinical features including bone pain, osteolytic lesions, hypercalcemia, and normal blood counts. To our knowledge, this is fifth such case ever reported in an adult patient.

Click on the PDF icon at the top of this introduction to read the full article.

Background The cost of medicines may prove prohibitive for some cancer patients, potentially reducing the ability of a health system to fully deliver best practice care. 

Objective To identify nonuse or nonpurchase of cancer-related medicines due to cost, and to describe the perceived financial burden of such medicines and associated patient characteristics.

Methods A cross-sectional pen-and-paper questionnaire was completed by oncology outpatients at 2 hospitals in Australia; 1 in regional New South Wales and 1 in metropolitan Victoria.

Results Almost 1 in 10 study participants had used over-the-counter medicines rather than prescribed medicines for cancer and obtained some but not all of the medicines prescribed in relation to their cancer. 63% of the sample reported some level of financial burden associated with obtaining these medicines, with 34% reporting a moderate or heavy financial burden. 11.8% reported using alternatives to prescribed medicines. People reporting reduced income after being diagnosed with cancer had almost 4 times the odds (OR, 3.73; 95% CI, 1.1-12.1) of reporting a heavy or extreme financial burden associated with prescribed medicines for cancer.

Limitations Study response rate, narrow survey population, self-reported survey used.

Conclusion This study identifies that a number of cancer patients, especially those with a reduced income after their diagnosis, experience financial burden associated with the purchase of medicines and that some go as far as to not use or to not purchase medicines. It seems likely that limiting the cost of medicines for cancer may improve patient ability to fully participate in the intended treatment.

Funding Cancer Council NSW, National Health and Medical Research Council, and Hunter Medical Research Institute, Australia

Click on the PDF icon at the top of this introduction to read the full article.

Background The cost of medicines may prove prohibitive for some cancer patients, potentially reducing the ability of a health system to fully deliver best practice care. 

Objective To identify nonuse or nonpurchase of cancer-related medicines due to cost, and to describe the perceived financial burden of such medicines and associated patient characteristics.

Methods A cross-sectional pen-and-paper questionnaire was completed by oncology outpatients at 2 hospitals in Australia; 1 in regional New South Wales and 1 in metropolitan Victoria.

Results Almost 1 in 10 study participants had used over-the-counter medicines rather than prescribed medicines for cancer and obtained some but not all of the medicines prescribed in relation to their cancer. 63% of the sample reported some level of financial burden associated with obtaining these medicines, with 34% reporting a moderate or heavy financial burden. 11.8% reported using alternatives to prescribed medicines. People reporting reduced income after being diagnosed with cancer had almost 4 times the odds (OR, 3.73; 95% CI, 1.1-12.1) of reporting a heavy or extreme financial burden associated with prescribed medicines for cancer.

Limitations Study response rate, narrow survey population, self-reported survey used.

Conclusion This study identifies that a number of cancer patients, especially those with a reduced income after their diagnosis, experience financial burden associated with the purchase of medicines and that some go as far as to not use or to not purchase medicines. It seems likely that limiting the cost of medicines for cancer may improve patient ability to fully participate in the intended treatment.

Funding Cancer Council NSW, National Health and Medical Research Council, and Hunter Medical Research Institute, Australia

Click on the PDF icon at the top of this introduction to read the full article.

Background The cost of medicines may prove prohibitive for some cancer patients, potentially reducing the ability of a health system to fully deliver best practice care. 

Objective To identify nonuse or nonpurchase of cancer-related medicines due to cost, and to describe the perceived financial burden of such medicines and associated patient characteristics.

Methods A cross-sectional pen-and-paper questionnaire was completed by oncology outpatients at 2 hospitals in Australia; 1 in regional New South Wales and 1 in metropolitan Victoria.

Results Almost 1 in 10 study participants had used over-the-counter medicines rather than prescribed medicines for cancer and obtained some but not all of the medicines prescribed in relation to their cancer. 63% of the sample reported some level of financial burden associated with obtaining these medicines, with 34% reporting a moderate or heavy financial burden. 11.8% reported using alternatives to prescribed medicines. People reporting reduced income after being diagnosed with cancer had almost 4 times the odds (OR, 3.73; 95% CI, 1.1-12.1) of reporting a heavy or extreme financial burden associated with prescribed medicines for cancer.

Limitations Study response rate, narrow survey population, self-reported survey used.

Conclusion This study identifies that a number of cancer patients, especially those with a reduced income after their diagnosis, experience financial burden associated with the purchase of medicines and that some go as far as to not use or to not purchase medicines. It seems likely that limiting the cost of medicines for cancer may improve patient ability to fully participate in the intended treatment.

Funding Cancer Council NSW, National Health and Medical Research Council, and Hunter Medical Research Institute, Australia

Click on the PDF icon at the top of this introduction to read the full article.

Background Improvements in cancer therapy have led to an increasing number of adolescent and young adult (AYA) survivors of childhood cancers. Many survivors have ongoing needs for support and information that are not being met.

Objective To conduct a program evaluation to identify AYAs’ perceptions of survivor care services.

Methods Using a community-based approach, 157 AYA childhood cancer survivors (aged 15-30 years) completed a program evaluation survey to assess perceptions of the importance of survivor patient care services and supportive programming using a Likert scale (1, Not At All Important; 2, Of Little Importance; 3, Somewhat Important; 4, Important; 5, Very Important).

Results Receipt of a medical summary was ranked as the most important survivor patient care service (mean, 4.5; SD, 0.91). 70% of respondents reported interest in late-effects education. Informational mailings were the most valued form of supportive programming and were endorsed by 62% of AYAs. Older survivors were more likely to value workshops (P = .01-0.05), whereas those aged 19-22 years valued weekend retreats (P < .01) and social activities (P < .01). Survivors of brain/CNS tumors were more likely to value social activities (P = .03) and support groups (P = .03), compared with leukemia survivors.

Limitations Contact information from the hospital tumor registry was used, which limited the number of correct addresses.

Conclusion The greatest care needs reported by AYA survivors of childhood cancer are services such as generation of a medical summary, late-effects education, and survivor-focused follow-up care, which are provided through cancer survivor programs. Development of additional programming to engage and further educate and encourage AYA survivors will be important to reinforce their adherence with survivor care throughout adulthood.

Funding/Sponsorship LiveStrong Community Based Participatory Research Planning Grant

Click on the PDF icon at the top of this introduction to read the full article.

Background Improvements in cancer therapy have led to an increasing number of adolescent and young adult (AYA) survivors of childhood cancers. Many survivors have ongoing needs for support and information that are not being met.

Objective To conduct a program evaluation to identify AYAs’ perceptions of survivor care services.

Methods Using a community-based approach, 157 AYA childhood cancer survivors (aged 15-30 years) completed a program evaluation survey to assess perceptions of the importance of survivor patient care services and supportive programming using a Likert scale (1, Not At All Important; 2, Of Little Importance; 3, Somewhat Important; 4, Important; 5, Very Important).

Results Receipt of a medical summary was ranked as the most important survivor patient care service (mean, 4.5; SD, 0.91). 70% of respondents reported interest in late-effects education. Informational mailings were the most valued form of supportive programming and were endorsed by 62% of AYAs. Older survivors were more likely to value workshops (P = .01-0.05), whereas those aged 19-22 years valued weekend retreats (P < .01) and social activities (P < .01). Survivors of brain/CNS tumors were more likely to value social activities (P = .03) and support groups (P = .03), compared with leukemia survivors.

Limitations Contact information from the hospital tumor registry was used, which limited the number of correct addresses.

Conclusion The greatest care needs reported by AYA survivors of childhood cancer are services such as generation of a medical summary, late-effects education, and survivor-focused follow-up care, which are provided through cancer survivor programs. Development of additional programming to engage and further educate and encourage AYA survivors will be important to reinforce their adherence with survivor care throughout adulthood.

Funding/Sponsorship LiveStrong Community Based Participatory Research Planning Grant

Click on the PDF icon at the top of this introduction to read the full article.

Background Improvements in cancer therapy have led to an increasing number of adolescent and young adult (AYA) survivors of childhood cancers. Many survivors have ongoing needs for support and information that are not being met.

Objective To conduct a program evaluation to identify AYAs’ perceptions of survivor care services.

Methods Using a community-based approach, 157 AYA childhood cancer survivors (aged 15-30 years) completed a program evaluation survey to assess perceptions of the importance of survivor patient care services and supportive programming using a Likert scale (1, Not At All Important; 2, Of Little Importance; 3, Somewhat Important; 4, Important; 5, Very Important).

Results Receipt of a medical summary was ranked as the most important survivor patient care service (mean, 4.5; SD, 0.91). 70% of respondents reported interest in late-effects education. Informational mailings were the most valued form of supportive programming and were endorsed by 62% of AYAs. Older survivors were more likely to value workshops (P = .01-0.05), whereas those aged 19-22 years valued weekend retreats (P < .01) and social activities (P < .01). Survivors of brain/CNS tumors were more likely to value social activities (P = .03) and support groups (P = .03), compared with leukemia survivors.

Limitations Contact information from the hospital tumor registry was used, which limited the number of correct addresses.

Conclusion The greatest care needs reported by AYA survivors of childhood cancer are services such as generation of a medical summary, late-effects education, and survivor-focused follow-up care, which are provided through cancer survivor programs. Development of additional programming to engage and further educate and encourage AYA survivors will be important to reinforce their adherence with survivor care throughout adulthood.

Funding/Sponsorship LiveStrong Community Based Participatory Research Planning Grant

Click on the PDF icon at the top of this introduction to read the full article.