COPENHAGEN – The physiological and emotion-processing abnormalities that underpin conduct disorder in teen girls are essentially the same as in teen boys, although the clinical presentation of conduct disorder in the two groups is often different, according to preliminary results from the large pan-European FemNAT-CD study, the first large study of conduct disorder in girls.

Bruce Jancin/MDedge News

“The main finding of the study, I think, is that we found no major differences in physiology between male and female conduct disorder. There are some differences, mainly related to having less LPE [low prosocial emotions] and more internalizing comorbidity in the girls, but when you look at conduct disorder overall, then you see that the physiological systems are about the same,” Lucres Nauta-Jansen, PhD, commented in presenting some of the early FemNAT-CD findings at the annual congress of the European College of Neuropsychopharmacology.

LPE is a term included in the DSM-5 as a descriptor of individuals with conduct disorder (CD) who exhibit callous-unemotional traits. The LPE specifier was present in 37% of the 296 adolescent girls with CD in FemNAT-CD, significantly less than the 50% prevalence in the 187 adolescent boys with CD in the study. This analysis from the ongoing study, which is being conducted at 13 universities across Europe, also included 363 age-matched girls and 164 age-matched boys without CD as controls. Average participant age was 14 years.

FemNAT-CD is a multidisciplinary study aimed at exploring sex differences between boys and girls with and without CD in terms of brain structure and function, genetics, hormone levels, emotion recognition and regulation, and autonomic nervous system (ANS) activity. At Amsterdam University Medical Center, where Dr. Nauta-Jansen serves as deputy head of the department of child and adolescent psychiatry, she and her coinvestigators have focused on the autonomic activity and emotion-processing portions of FemNAT-CD.

CD is less common in girls than boys, although the prevalence in girls is growing. The importance of FemNAT-CD lies in the fact that virtually all prior studies of CD were conducted in boys. As a result, there is no specific treatment intervention available for girls with CD.

“We actually don’t know anything about girls. There are a few previous studies, but they have small samples and contradictory results. We need to know more about the mechanisms that are involved in this kind of behavior to develop more specific treatments in the future,” Dr. Nauta-Jansen said.

In FemNAT-CD, the girls with CD not only had a lower rate of LPE symptoms than the boys with CD, they also had a significantly higher prevalence of anxiety and other internalizing comorbidities, by a margin of 32% to 22%. These differences are manifested in different expressions of antisocial behavior as described in the model of the neurobiology of CD developed by R. James Blair, PhD, director of the Center for Neurobehavioral Research at the Boys Town National Research Hospital in Omaha, Neb (Nat Rev Neurosci. 2013 Nov;14[11]:786-99).

According to the model’s low psychophysiological arousal theory, boys with the callous-unemotional form of CD have low basal ANS activity and low amygdala responsiveness to stressful events, making them more prone to sensation-seeking behavior.

“This might make them want to do ice climbing or sky diving. Or, in a more negative environment or in a bad neighborhood, it can also lead to aggressive and delinquent behavior,” Dr. Nauta-Jansen said.

The other core impairment that is common in a subset of CD patients as described in the Blair model – again, based upon studies in boys – involves a tendency to engage in threat-based reactive aggression with an increased ANS response to stress and a related difficulty in processing emotions.

Dr. Nauta-Jansen and coinvestigators conducted a series of tests of FemNAT-CD participants which demonstrated, for the first time, that both the callous-unemotional and threat-based reactive aggression forms of CD are present in girls as well as boys, albeit in different proportions.

The investigators found no differences in baseline ANS activity between girls and boys with CD and the controls as measured by heart rate, heart rate variability, and cardiac preejection period. Nor were there any differences in baseline ANS activity between boys and girls with CD and LPE. However, girls with CD and anxiety or other internalizing comorbidity displayed significantly lower heart rate variability than those without internalizing comorbidity or female controls.

Next, the investigators subjected study participants to an emotion provocation task in which they viewed two sadness-inducing film clips, including a heart-rending scene from the 1979 movie, “The Champ,” in which an ex-boxer played by Jon Voight returns to the ring to raise money to support his young son, played by Ricky Shroder. The champ wins by a knockout after taking such a beating that he subsequently dies in his dressing room as his son watches.

Both the girls and boys with CD had an increased heart rate response to “The Champ,” compared with the controls. And those with CD who did not have the LPE specifier showed the biggest ANS response of all. They were highly sensitive to negative emotions.

On a countdown task involving exposure to a loud, startling noise, the girls with CD did not learn to anticipate the pending startle at the autonomic level, whereas the boys with CD reacted no differently from controls.

On the Trier Social Stress Test, which entails public speaking and performing mental math calculations in front of a camera and a live audience of two, both the boys and girls with CD demonstrated a similarly lower heart rate response to the tasks than controls. Those with the LPE specifier had the lowest heart rate response of all.

“The conduct disorder subjects were impaired in their anticipatory response to fear and stress, but their responses to sadness were increased,” Dr. Nauta-Jansen observed.

“I think the main thing with these kids is they are mostly disturbed in their anticipation of bad situations. What you see in the countdown task is they don’t anticipate that there will be a bad event. And you see this also in clinical practice, that they sometimes get overwhelmed by things because they don’t learn from their previous experiences, including bad events. I think they don’t anticipate and therefore are more overwhelmed by bad events – especially the girls,” she said.

The take-home message from this phase of the FemNAT-CD study, she added, is straightforward: “When you’re treating conduct disorder in girls, I think it’s really important to know that it works about the same as in boys, although you have to be very aware that they show different symptomatology in terms of internalizing comorbidity.”

The FemNAT-CD investigators have developed a multifaceted therapeutic intervention for girls with CD that shows early promise in clinical settings. It includes aggression regulation training, medication in some cases, and emotion-processing training to teach patients how to deal with negative emotions without exploding into aggression.

FemNAT-CD is funded by the European Commission. Dr. Nauta-Jansen reported having no financial conflicts regarding the study.

[email protected]

COPENHAGEN – The physiological and emotion-processing abnormalities that underpin conduct disorder in teen girls are essentially the same as in teen boys, although the clinical presentation of conduct disorder in the two groups is often different, according to preliminary results from the large pan-European FemNAT-CD study, the first large study of conduct disorder in girls.

Bruce Jancin/MDedge News

“The main finding of the study, I think, is that we found no major differences in physiology between male and female conduct disorder. There are some differences, mainly related to having less LPE [low prosocial emotions] and more internalizing comorbidity in the girls, but when you look at conduct disorder overall, then you see that the physiological systems are about the same,” Lucres Nauta-Jansen, PhD, commented in presenting some of the early FemNAT-CD findings at the annual congress of the European College of Neuropsychopharmacology.

LPE is a term included in the DSM-5 as a descriptor of individuals with conduct disorder (CD) who exhibit callous-unemotional traits. The LPE specifier was present in 37% of the 296 adolescent girls with CD in FemNAT-CD, significantly less than the 50% prevalence in the 187 adolescent boys with CD in the study. This analysis from the ongoing study, which is being conducted at 13 universities across Europe, also included 363 age-matched girls and 164 age-matched boys without CD as controls. Average participant age was 14 years.

FemNAT-CD is a multidisciplinary study aimed at exploring sex differences between boys and girls with and without CD in terms of brain structure and function, genetics, hormone levels, emotion recognition and regulation, and autonomic nervous system (ANS) activity. At Amsterdam University Medical Center, where Dr. Nauta-Jansen serves as deputy head of the department of child and adolescent psychiatry, she and her coinvestigators have focused on the autonomic activity and emotion-processing portions of FemNAT-CD.

CD is less common in girls than boys, although the prevalence in girls is growing. The importance of FemNAT-CD lies in the fact that virtually all prior studies of CD were conducted in boys. As a result, there is no specific treatment intervention available for girls with CD.

“We actually don’t know anything about girls. There are a few previous studies, but they have small samples and contradictory results. We need to know more about the mechanisms that are involved in this kind of behavior to develop more specific treatments in the future,” Dr. Nauta-Jansen said.

In FemNAT-CD, the girls with CD not only had a lower rate of LPE symptoms than the boys with CD, they also had a significantly higher prevalence of anxiety and other internalizing comorbidities, by a margin of 32% to 22%. These differences are manifested in different expressions of antisocial behavior as described in the model of the neurobiology of CD developed by R. James Blair, PhD, director of the Center for Neurobehavioral Research at the Boys Town National Research Hospital in Omaha, Neb (Nat Rev Neurosci. 2013 Nov;14[11]:786-99).

According to the model’s low psychophysiological arousal theory, boys with the callous-unemotional form of CD have low basal ANS activity and low amygdala responsiveness to stressful events, making them more prone to sensation-seeking behavior.

“This might make them want to do ice climbing or sky diving. Or, in a more negative environment or in a bad neighborhood, it can also lead to aggressive and delinquent behavior,” Dr. Nauta-Jansen said.

The other core impairment that is common in a subset of CD patients as described in the Blair model – again, based upon studies in boys – involves a tendency to engage in threat-based reactive aggression with an increased ANS response to stress and a related difficulty in processing emotions.

Dr. Nauta-Jansen and coinvestigators conducted a series of tests of FemNAT-CD participants which demonstrated, for the first time, that both the callous-unemotional and threat-based reactive aggression forms of CD are present in girls as well as boys, albeit in different proportions.

The investigators found no differences in baseline ANS activity between girls and boys with CD and the controls as measured by heart rate, heart rate variability, and cardiac preejection period. Nor were there any differences in baseline ANS activity between boys and girls with CD and LPE. However, girls with CD and anxiety or other internalizing comorbidity displayed significantly lower heart rate variability than those without internalizing comorbidity or female controls.

Next, the investigators subjected study participants to an emotion provocation task in which they viewed two sadness-inducing film clips, including a heart-rending scene from the 1979 movie, “The Champ,” in which an ex-boxer played by Jon Voight returns to the ring to raise money to support his young son, played by Ricky Shroder. The champ wins by a knockout after taking such a beating that he subsequently dies in his dressing room as his son watches.

Both the girls and boys with CD had an increased heart rate response to “The Champ,” compared with the controls. And those with CD who did not have the LPE specifier showed the biggest ANS response of all. They were highly sensitive to negative emotions.

On a countdown task involving exposure to a loud, startling noise, the girls with CD did not learn to anticipate the pending startle at the autonomic level, whereas the boys with CD reacted no differently from controls.

On the Trier Social Stress Test, which entails public speaking and performing mental math calculations in front of a camera and a live audience of two, both the boys and girls with CD demonstrated a similarly lower heart rate response to the tasks than controls. Those with the LPE specifier had the lowest heart rate response of all.

“The conduct disorder subjects were impaired in their anticipatory response to fear and stress, but their responses to sadness were increased,” Dr. Nauta-Jansen observed.

“I think the main thing with these kids is they are mostly disturbed in their anticipation of bad situations. What you see in the countdown task is they don’t anticipate that there will be a bad event. And you see this also in clinical practice, that they sometimes get overwhelmed by things because they don’t learn from their previous experiences, including bad events. I think they don’t anticipate and therefore are more overwhelmed by bad events – especially the girls,” she said.

The take-home message from this phase of the FemNAT-CD study, she added, is straightforward: “When you’re treating conduct disorder in girls, I think it’s really important to know that it works about the same as in boys, although you have to be very aware that they show different symptomatology in terms of internalizing comorbidity.”

The FemNAT-CD investigators have developed a multifaceted therapeutic intervention for girls with CD that shows early promise in clinical settings. It includes aggression regulation training, medication in some cases, and emotion-processing training to teach patients how to deal with negative emotions without exploding into aggression.

FemNAT-CD is funded by the European Commission. Dr. Nauta-Jansen reported having no financial conflicts regarding the study.

[email protected]

COPENHAGEN – The physiological and emotion-processing abnormalities that underpin conduct disorder in teen girls are essentially the same as in teen boys, although the clinical presentation of conduct disorder in the two groups is often different, according to preliminary results from the large pan-European FemNAT-CD study, the first large study of conduct disorder in girls.

Bruce Jancin/MDedge News

“The main finding of the study, I think, is that we found no major differences in physiology between male and female conduct disorder. There are some differences, mainly related to having less LPE [low prosocial emotions] and more internalizing comorbidity in the girls, but when you look at conduct disorder overall, then you see that the physiological systems are about the same,” Lucres Nauta-Jansen, PhD, commented in presenting some of the early FemNAT-CD findings at the annual congress of the European College of Neuropsychopharmacology.

LPE is a term included in the DSM-5 as a descriptor of individuals with conduct disorder (CD) who exhibit callous-unemotional traits. The LPE specifier was present in 37% of the 296 adolescent girls with CD in FemNAT-CD, significantly less than the 50% prevalence in the 187 adolescent boys with CD in the study. This analysis from the ongoing study, which is being conducted at 13 universities across Europe, also included 363 age-matched girls and 164 age-matched boys without CD as controls. Average participant age was 14 years.

FemNAT-CD is a multidisciplinary study aimed at exploring sex differences between boys and girls with and without CD in terms of brain structure and function, genetics, hormone levels, emotion recognition and regulation, and autonomic nervous system (ANS) activity. At Amsterdam University Medical Center, where Dr. Nauta-Jansen serves as deputy head of the department of child and adolescent psychiatry, she and her coinvestigators have focused on the autonomic activity and emotion-processing portions of FemNAT-CD.

CD is less common in girls than boys, although the prevalence in girls is growing. The importance of FemNAT-CD lies in the fact that virtually all prior studies of CD were conducted in boys. As a result, there is no specific treatment intervention available for girls with CD.

“We actually don’t know anything about girls. There are a few previous studies, but they have small samples and contradictory results. We need to know more about the mechanisms that are involved in this kind of behavior to develop more specific treatments in the future,” Dr. Nauta-Jansen said.

In FemNAT-CD, the girls with CD not only had a lower rate of LPE symptoms than the boys with CD, they also had a significantly higher prevalence of anxiety and other internalizing comorbidities, by a margin of 32% to 22%. These differences are manifested in different expressions of antisocial behavior as described in the model of the neurobiology of CD developed by R. James Blair, PhD, director of the Center for Neurobehavioral Research at the Boys Town National Research Hospital in Omaha, Neb (Nat Rev Neurosci. 2013 Nov;14[11]:786-99).

According to the model’s low psychophysiological arousal theory, boys with the callous-unemotional form of CD have low basal ANS activity and low amygdala responsiveness to stressful events, making them more prone to sensation-seeking behavior.

“This might make them want to do ice climbing or sky diving. Or, in a more negative environment or in a bad neighborhood, it can also lead to aggressive and delinquent behavior,” Dr. Nauta-Jansen said.

The other core impairment that is common in a subset of CD patients as described in the Blair model – again, based upon studies in boys – involves a tendency to engage in threat-based reactive aggression with an increased ANS response to stress and a related difficulty in processing emotions.

Dr. Nauta-Jansen and coinvestigators conducted a series of tests of FemNAT-CD participants which demonstrated, for the first time, that both the callous-unemotional and threat-based reactive aggression forms of CD are present in girls as well as boys, albeit in different proportions.

The investigators found no differences in baseline ANS activity between girls and boys with CD and the controls as measured by heart rate, heart rate variability, and cardiac preejection period. Nor were there any differences in baseline ANS activity between boys and girls with CD and LPE. However, girls with CD and anxiety or other internalizing comorbidity displayed significantly lower heart rate variability than those without internalizing comorbidity or female controls.

Next, the investigators subjected study participants to an emotion provocation task in which they viewed two sadness-inducing film clips, including a heart-rending scene from the 1979 movie, “The Champ,” in which an ex-boxer played by Jon Voight returns to the ring to raise money to support his young son, played by Ricky Shroder. The champ wins by a knockout after taking such a beating that he subsequently dies in his dressing room as his son watches.

Both the girls and boys with CD had an increased heart rate response to “The Champ,” compared with the controls. And those with CD who did not have the LPE specifier showed the biggest ANS response of all. They were highly sensitive to negative emotions.

On a countdown task involving exposure to a loud, startling noise, the girls with CD did not learn to anticipate the pending startle at the autonomic level, whereas the boys with CD reacted no differently from controls.

On the Trier Social Stress Test, which entails public speaking and performing mental math calculations in front of a camera and a live audience of two, both the boys and girls with CD demonstrated a similarly lower heart rate response to the tasks than controls. Those with the LPE specifier had the lowest heart rate response of all.

“The conduct disorder subjects were impaired in their anticipatory response to fear and stress, but their responses to sadness were increased,” Dr. Nauta-Jansen observed.

“I think the main thing with these kids is they are mostly disturbed in their anticipation of bad situations. What you see in the countdown task is they don’t anticipate that there will be a bad event. And you see this also in clinical practice, that they sometimes get overwhelmed by things because they don’t learn from their previous experiences, including bad events. I think they don’t anticipate and therefore are more overwhelmed by bad events – especially the girls,” she said.

The take-home message from this phase of the FemNAT-CD study, she added, is straightforward: “When you’re treating conduct disorder in girls, I think it’s really important to know that it works about the same as in boys, although you have to be very aware that they show different symptomatology in terms of internalizing comorbidity.”

The FemNAT-CD investigators have developed a multifaceted therapeutic intervention for girls with CD that shows early promise in clinical settings. It includes aggression regulation training, medication in some cases, and emotion-processing training to teach patients how to deal with negative emotions without exploding into aggression.

FemNAT-CD is funded by the European Commission. Dr. Nauta-Jansen reported having no financial conflicts regarding the study.

[email protected]

SAN FRANCISCO – Opioids may not always be necessary following elective colorectal surgery. That’s the message coming from a retrospective study of medical records at the University of Massachusetts Medical Center, Worcester, which found that over half of patients never even filled out their prescription after colorectal surgery.

“We found that over half of the patients took no opioid pills after discharge, and 60% of the prescribed pills were left over,” said David Meyer, MD, during a presentation of the study at the annual clinical congress of the American College of Surgeons. Dr. Meyer is a surgical resident at the University of Massachusetts.

The team also used the results of their analysis to develop a guideline for the amount of opioid to prescribe following major colorectal surgery, with specific amounts of pills recommended based on the amount of opioid use during the last 24 hours of hospitalization.

“It shows a real interest in tailoring our postoperative care in pain management. They’re trying to find a way to hit a sweet spot to get patients the right amount of pain control,” said Jonathan Mitchem, MD, in an interview. Dr. Mitchem is an assistant professor at University of Missouri–Columbia, and comoderated the session where the research was presented.

The researchers performed a retrospective analysis of major elective colorectal procedures at their institution, including colectomy, rectal resection, and ostomy reversal. The analysis included 100 patients (55 female), with a mean age of 59 years. A total of 71% were opioid naive, meaning there was no evidence of an opioid prescription in the year prior to surgery. A total of 74% underwent a laparoscopic procedure, and 75% had a partial colectomy. The postoperative stay averaged 4.5 days.

The researchers converted in-hospital opioid use categories (IOUC) to equianalgesic 5-mg oxycodone pills (EOPs). In the last 24 hours before release, 53% of patients had no opioids at all (no IOUC, 0 EOPs), 25% received low amounts of opioids (low IOUC, 0.1-3.0 EOPs), and 22% high amounts (high IOUC, more than 3.1 EOPs). Overall, prescribed EOP was 17.5, and just 38% was consumed. These numbers were lowest in the no-IOUC group (15.7, 16%), followed by the low-IOUC group (16.0, 32%), and the high group (23.7, 79%; P less than .01).

The researchers then looked at the 85th percentile of EOPs for each group, and used that to develop a guideline for opioid prescription. For the no-IOUC group, they recommend 3 EOPs, for the low-IOUC group they recommend 12 EOPs, and for the high-IOUC group they recommend 30 EOPs.

The researchers examined various factors that might have influenced opioid use, correcting for whether the patient was opioid naive, case type, postoperative length of stay, and new ostomy creation. The only factor with a significant association for excessive opioid use was inflammatory bowel disease, which was linked to a nearly 900% increased risk of using more than the guideline amounts (adjusted odds ratio, 8.3; P less than .01; area under the curve, 0.85).

The study is limited by the fact that it was conducted at a single center, and that patient opioid use was self-reported. The guidelines need to be validated prospectively.

No funding information was disclosed. Dr. Meyer and Dr. Mitchem had no relevant financial disclosures.

SOURCE: Meyer D et al. Clinical Congress 2019, Abstract.

SAN FRANCISCO – Opioids may not always be necessary following elective colorectal surgery. That’s the message coming from a retrospective study of medical records at the University of Massachusetts Medical Center, Worcester, which found that over half of patients never even filled out their prescription after colorectal surgery.

“We found that over half of the patients took no opioid pills after discharge, and 60% of the prescribed pills were left over,” said David Meyer, MD, during a presentation of the study at the annual clinical congress of the American College of Surgeons. Dr. Meyer is a surgical resident at the University of Massachusetts.

The team also used the results of their analysis to develop a guideline for the amount of opioid to prescribe following major colorectal surgery, with specific amounts of pills recommended based on the amount of opioid use during the last 24 hours of hospitalization.

“It shows a real interest in tailoring our postoperative care in pain management. They’re trying to find a way to hit a sweet spot to get patients the right amount of pain control,” said Jonathan Mitchem, MD, in an interview. Dr. Mitchem is an assistant professor at University of Missouri–Columbia, and comoderated the session where the research was presented.

The researchers performed a retrospective analysis of major elective colorectal procedures at their institution, including colectomy, rectal resection, and ostomy reversal. The analysis included 100 patients (55 female), with a mean age of 59 years. A total of 71% were opioid naive, meaning there was no evidence of an opioid prescription in the year prior to surgery. A total of 74% underwent a laparoscopic procedure, and 75% had a partial colectomy. The postoperative stay averaged 4.5 days.

The researchers converted in-hospital opioid use categories (IOUC) to equianalgesic 5-mg oxycodone pills (EOPs). In the last 24 hours before release, 53% of patients had no opioids at all (no IOUC, 0 EOPs), 25% received low amounts of opioids (low IOUC, 0.1-3.0 EOPs), and 22% high amounts (high IOUC, more than 3.1 EOPs). Overall, prescribed EOP was 17.5, and just 38% was consumed. These numbers were lowest in the no-IOUC group (15.7, 16%), followed by the low-IOUC group (16.0, 32%), and the high group (23.7, 79%; P less than .01).

The researchers then looked at the 85th percentile of EOPs for each group, and used that to develop a guideline for opioid prescription. For the no-IOUC group, they recommend 3 EOPs, for the low-IOUC group they recommend 12 EOPs, and for the high-IOUC group they recommend 30 EOPs.

The researchers examined various factors that might have influenced opioid use, correcting for whether the patient was opioid naive, case type, postoperative length of stay, and new ostomy creation. The only factor with a significant association for excessive opioid use was inflammatory bowel disease, which was linked to a nearly 900% increased risk of using more than the guideline amounts (adjusted odds ratio, 8.3; P less than .01; area under the curve, 0.85).

The study is limited by the fact that it was conducted at a single center, and that patient opioid use was self-reported. The guidelines need to be validated prospectively.

No funding information was disclosed. Dr. Meyer and Dr. Mitchem had no relevant financial disclosures.

SOURCE: Meyer D et al. Clinical Congress 2019, Abstract.

SAN FRANCISCO – Opioids may not always be necessary following elective colorectal surgery. That’s the message coming from a retrospective study of medical records at the University of Massachusetts Medical Center, Worcester, which found that over half of patients never even filled out their prescription after colorectal surgery.

“We found that over half of the patients took no opioid pills after discharge, and 60% of the prescribed pills were left over,” said David Meyer, MD, during a presentation of the study at the annual clinical congress of the American College of Surgeons. Dr. Meyer is a surgical resident at the University of Massachusetts.

The team also used the results of their analysis to develop a guideline for the amount of opioid to prescribe following major colorectal surgery, with specific amounts of pills recommended based on the amount of opioid use during the last 24 hours of hospitalization.

“It shows a real interest in tailoring our postoperative care in pain management. They’re trying to find a way to hit a sweet spot to get patients the right amount of pain control,” said Jonathan Mitchem, MD, in an interview. Dr. Mitchem is an assistant professor at University of Missouri–Columbia, and comoderated the session where the research was presented.

The researchers performed a retrospective analysis of major elective colorectal procedures at their institution, including colectomy, rectal resection, and ostomy reversal. The analysis included 100 patients (55 female), with a mean age of 59 years. A total of 71% were opioid naive, meaning there was no evidence of an opioid prescription in the year prior to surgery. A total of 74% underwent a laparoscopic procedure, and 75% had a partial colectomy. The postoperative stay averaged 4.5 days.

The researchers converted in-hospital opioid use categories (IOUC) to equianalgesic 5-mg oxycodone pills (EOPs). In the last 24 hours before release, 53% of patients had no opioids at all (no IOUC, 0 EOPs), 25% received low amounts of opioids (low IOUC, 0.1-3.0 EOPs), and 22% high amounts (high IOUC, more than 3.1 EOPs). Overall, prescribed EOP was 17.5, and just 38% was consumed. These numbers were lowest in the no-IOUC group (15.7, 16%), followed by the low-IOUC group (16.0, 32%), and the high group (23.7, 79%; P less than .01).

The researchers then looked at the 85th percentile of EOPs for each group, and used that to develop a guideline for opioid prescription. For the no-IOUC group, they recommend 3 EOPs, for the low-IOUC group they recommend 12 EOPs, and for the high-IOUC group they recommend 30 EOPs.

The researchers examined various factors that might have influenced opioid use, correcting for whether the patient was opioid naive, case type, postoperative length of stay, and new ostomy creation. The only factor with a significant association for excessive opioid use was inflammatory bowel disease, which was linked to a nearly 900% increased risk of using more than the guideline amounts (adjusted odds ratio, 8.3; P less than .01; area under the curve, 0.85).

The study is limited by the fact that it was conducted at a single center, and that patient opioid use was self-reported. The guidelines need to be validated prospectively.

No funding information was disclosed. Dr. Meyer and Dr. Mitchem had no relevant financial disclosures.

SOURCE: Meyer D et al. Clinical Congress 2019, Abstract.

NEW ORLEANS – When looking specifically at the subgroup patients with no recent exacerbations, the triple fixed-dose combination budesonide/glycopyrrolate/formoterol fumarate metered-dose inhaler (BGF MDI) improved lung function and exacerbations, compared with dual therapy in patients with moderate to very severe chronic obstructive pulmonary disorder (COPD), an analysis of the phase 3 KRONOS study shows.

For that subgroup of patients with no moderate to severe exacerbations in the past year, BGF MDI was associated with a nominally significant reduction in the rate of subsequent COPD exacerbations, compared with glycopyrrolate/formoterol fumarate (GFF) MDI, according to investigator Fernando J. Martinez MD, of Weill Cornell Medical College, New York.

Results for the COPD patients with no recent history of exacerbation were consistent with the overall results of KRONOS, suggesting that the benefits of BGF MDI shown in that study were not driven by patients with a recent exacerbation history, Dr. Martinez said at the annual meeting of the American College of Chest Physicians.

“It was clear that the effect of this particular triple did not really appear to be dramatically different by the prior history or not in the comparison of the triple versus dual bronchodilator,” he said in a late-breaking clinical trial session.

About three-quarters of the patients in KRONOS (1,411 out of 1,896) lacked a recent exacerbation history. These patients had a mean age of 65.5 years, 72.8% were male, and 69.9% used inhaled corticosteroids at screening, which are demographics were similar to the overall KRONOS patient population, Dr. Martinez said.

In this subset of patients with no recent exacerbation history, treatment with BGF MDI significantly reduced the rate of moderate or severe exacerbations, compared with GFF MDI, with a treatment incidence rate ratio of 0.52 (95% confidence interval, 0.37-0.72; P = .0001).

“The results were remarkably similar,” Dr. Martinez said. “I was surprised, to be honest with you, when I saw these results. I did not anticipate that would be the case.”

By contrast, BGF MDI did not significantly reduce the rate of moderate or severe exacerbations, compared with budesonide/formoterol fumarate (BFF) MDI or open-label budesonide/formoterol fumarate dihydrate dry-powder inhaler (BUD/FORM DPI) as studied in KRONOS, Dr. Martinez said.

The change from baseline in morning predose trough forced expiratory volume in 1 second (FEV₁) at week 24 was significantly improved for BGF MDI, compared with BFF MDI and BUD/FORM DPI, but not compared with GFF MDI, according to the investigator. Similarly, the FEV₁ area under the curve from 0 to 4 hours was significantly improved for BGF MDI, compared with BFF MDI and BUD/FORM DPI, but not compared with GFF MDI.

Dr. Martinez reported disclosures related to AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Chiesi, Sunovion, and Teva.

SOURCE: Martinez FJ et al. CHEST 2019, Abstract.

NEW ORLEANS – When looking specifically at the subgroup patients with no recent exacerbations, the triple fixed-dose combination budesonide/glycopyrrolate/formoterol fumarate metered-dose inhaler (BGF MDI) improved lung function and exacerbations, compared with dual therapy in patients with moderate to very severe chronic obstructive pulmonary disorder (COPD), an analysis of the phase 3 KRONOS study shows.

For that subgroup of patients with no moderate to severe exacerbations in the past year, BGF MDI was associated with a nominally significant reduction in the rate of subsequent COPD exacerbations, compared with glycopyrrolate/formoterol fumarate (GFF) MDI, according to investigator Fernando J. Martinez MD, of Weill Cornell Medical College, New York.

Results for the COPD patients with no recent history of exacerbation were consistent with the overall results of KRONOS, suggesting that the benefits of BGF MDI shown in that study were not driven by patients with a recent exacerbation history, Dr. Martinez said at the annual meeting of the American College of Chest Physicians.

“It was clear that the effect of this particular triple did not really appear to be dramatically different by the prior history or not in the comparison of the triple versus dual bronchodilator,” he said in a late-breaking clinical trial session.

About three-quarters of the patients in KRONOS (1,411 out of 1,896) lacked a recent exacerbation history. These patients had a mean age of 65.5 years, 72.8% were male, and 69.9% used inhaled corticosteroids at screening, which are demographics were similar to the overall KRONOS patient population, Dr. Martinez said.

In this subset of patients with no recent exacerbation history, treatment with BGF MDI significantly reduced the rate of moderate or severe exacerbations, compared with GFF MDI, with a treatment incidence rate ratio of 0.52 (95% confidence interval, 0.37-0.72; P = .0001).

“The results were remarkably similar,” Dr. Martinez said. “I was surprised, to be honest with you, when I saw these results. I did not anticipate that would be the case.”

By contrast, BGF MDI did not significantly reduce the rate of moderate or severe exacerbations, compared with budesonide/formoterol fumarate (BFF) MDI or open-label budesonide/formoterol fumarate dihydrate dry-powder inhaler (BUD/FORM DPI) as studied in KRONOS, Dr. Martinez said.

The change from baseline in morning predose trough forced expiratory volume in 1 second (FEV₁) at week 24 was significantly improved for BGF MDI, compared with BFF MDI and BUD/FORM DPI, but not compared with GFF MDI, according to the investigator. Similarly, the FEV₁ area under the curve from 0 to 4 hours was significantly improved for BGF MDI, compared with BFF MDI and BUD/FORM DPI, but not compared with GFF MDI.

Dr. Martinez reported disclosures related to AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Chiesi, Sunovion, and Teva.

SOURCE: Martinez FJ et al. CHEST 2019, Abstract.

NEW ORLEANS – When looking specifically at the subgroup patients with no recent exacerbations, the triple fixed-dose combination budesonide/glycopyrrolate/formoterol fumarate metered-dose inhaler (BGF MDI) improved lung function and exacerbations, compared with dual therapy in patients with moderate to very severe chronic obstructive pulmonary disorder (COPD), an analysis of the phase 3 KRONOS study shows.

For that subgroup of patients with no moderate to severe exacerbations in the past year, BGF MDI was associated with a nominally significant reduction in the rate of subsequent COPD exacerbations, compared with glycopyrrolate/formoterol fumarate (GFF) MDI, according to investigator Fernando J. Martinez MD, of Weill Cornell Medical College, New York.

Results for the COPD patients with no recent history of exacerbation were consistent with the overall results of KRONOS, suggesting that the benefits of BGF MDI shown in that study were not driven by patients with a recent exacerbation history, Dr. Martinez said at the annual meeting of the American College of Chest Physicians.

“It was clear that the effect of this particular triple did not really appear to be dramatically different by the prior history or not in the comparison of the triple versus dual bronchodilator,” he said in a late-breaking clinical trial session.

About three-quarters of the patients in KRONOS (1,411 out of 1,896) lacked a recent exacerbation history. These patients had a mean age of 65.5 years, 72.8% were male, and 69.9% used inhaled corticosteroids at screening, which are demographics were similar to the overall KRONOS patient population, Dr. Martinez said.

In this subset of patients with no recent exacerbation history, treatment with BGF MDI significantly reduced the rate of moderate or severe exacerbations, compared with GFF MDI, with a treatment incidence rate ratio of 0.52 (95% confidence interval, 0.37-0.72; P = .0001).

“The results were remarkably similar,” Dr. Martinez said. “I was surprised, to be honest with you, when I saw these results. I did not anticipate that would be the case.”

By contrast, BGF MDI did not significantly reduce the rate of moderate or severe exacerbations, compared with budesonide/formoterol fumarate (BFF) MDI or open-label budesonide/formoterol fumarate dihydrate dry-powder inhaler (BUD/FORM DPI) as studied in KRONOS, Dr. Martinez said.

The change from baseline in morning predose trough forced expiratory volume in 1 second (FEV₁) at week 24 was significantly improved for BGF MDI, compared with BFF MDI and BUD/FORM DPI, but not compared with GFF MDI, according to the investigator. Similarly, the FEV₁ area under the curve from 0 to 4 hours was significantly improved for BGF MDI, compared with BFF MDI and BUD/FORM DPI, but not compared with GFF MDI.

Dr. Martinez reported disclosures related to AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Chiesi, Sunovion, and Teva.

SOURCE: Martinez FJ et al. CHEST 2019, Abstract.

ATLANTA – Concomitant use of even low-dose steroids increases the risk of serious infections with antirheumatic drugs, according to a review of 170,357 Medicare patients by investigators at the University of Pennsylvania, Philadelphia.

Infections are a well-known side effect of high-dose glucocorticoids, but there’s been debate about prednisone doses in the 5-10 mg/day range. Guidelines generally advise tapering RA patients off steroids after they start a biologic or methotrexate, but that doesn’t always happen because there’s a common perception that low-dose steroids are safe, said lead investigator Michael George, MD, assistant professor of medicine and epidemiology at the university.

“Many people continue low-dose steroids over the long term, but even low dose seems to be associated with infection. It’s a small risk, but it should be something you are aware of; for some patients, it might be quite important,” he said in an interview at the annual meeting of the American College of Rheumatology.

The team wanted to mimic real-world practice, so they compared infection incidence between the 53% of patients who were not on low-dose steroids with the 47% who were after at least 6 months of disease-modifying antirheumatic drug (DMARD) therapy. About 56% of patients were on methotrexate, with the rest on biologics or a targeted synthetic DMARD (tsDMARD). Average follow up was an additional 6 months, but some people were followed for several years; prednisone 5 mg/day or less was the most common dose.

There were 20,630 serious infections requiring hospitalization, most often urinary tract infection, pneumonia, bacteremia/septicemia, and skin or soft-tissue infections. The crude incidence was 11 per 100 person-years.

After propensity-score weighting to balance out about 50 potential confounders, the predicted 1-year incidence of infection was 9.3% among patients not on steroids. Among those on up to 5 mg/day of prednisone, it was 12.5%; among those on 5-10 mg/day, 17.2%; and among those on more than 10 mg/day, 23.9%.

Glucocorticoids were associated with a 37% increased rate of serious infections, even with doses at or below 5mg/day. The effect “was really similar” whether people were on a biologic, tsDMARD, or methotrexate, which was “surprising,” Dr. George said.

“When I see a patient now who is on long-term, low-dose prednisone, I don’t just say ‘okay, that’s probably safe.’ I think really hard about how much benefit they’re getting. For some people, that means I try to get them off it,” he said. For those who flare otherwise, “I might continue them on it, but recognize there is likely some risk.”

The magnitude of the infection risk was similar to that reported with tumor necrosis factors inhibitors, which might reassure patients who are reluctant to switch to a tumor necrosis factor inhibitor.

“Now I can say you’ve been taking 10 mg prednisone a day, and that’s probably at least as risky,” Dr. George said.

Frequency of office visits, hospitalizations, and ED visits, as well as prior infections, comorbidities, nursing-home admissions, and use of durable medical equipment were among the potential confounders controlled for in the analysis. They stood in for direct markers of RA severity, which weren’t available in the data. “We spent a lot of time trying to make sure our groups were as similar as possible in every way except prednisone use,” he said.

Patients were in their late 60s on average, 71% white, and 81% were women. People with other autoimmune rheumatic diseases, cancer, or HIV were excluded. Dr. George said the next step is to run the same analysis in a younger cohort.

The work was funded by the National Institutes of Health. Dr. George disclosed relationships with AbbVie and Bristol-Myers Squibb.

[email protected]

SOURCE: George M et al. ACR 2019, Abstract 848

ATLANTA – Concomitant use of even low-dose steroids increases the risk of serious infections with antirheumatic drugs, according to a review of 170,357 Medicare patients by investigators at the University of Pennsylvania, Philadelphia.

Infections are a well-known side effect of high-dose glucocorticoids, but there’s been debate about prednisone doses in the 5-10 mg/day range. Guidelines generally advise tapering RA patients off steroids after they start a biologic or methotrexate, but that doesn’t always happen because there’s a common perception that low-dose steroids are safe, said lead investigator Michael George, MD, assistant professor of medicine and epidemiology at the university.

“Many people continue low-dose steroids over the long term, but even low dose seems to be associated with infection. It’s a small risk, but it should be something you are aware of; for some patients, it might be quite important,” he said in an interview at the annual meeting of the American College of Rheumatology.

The team wanted to mimic real-world practice, so they compared infection incidence between the 53% of patients who were not on low-dose steroids with the 47% who were after at least 6 months of disease-modifying antirheumatic drug (DMARD) therapy. About 56% of patients were on methotrexate, with the rest on biologics or a targeted synthetic DMARD (tsDMARD). Average follow up was an additional 6 months, but some people were followed for several years; prednisone 5 mg/day or less was the most common dose.

There were 20,630 serious infections requiring hospitalization, most often urinary tract infection, pneumonia, bacteremia/septicemia, and skin or soft-tissue infections. The crude incidence was 11 per 100 person-years.

After propensity-score weighting to balance out about 50 potential confounders, the predicted 1-year incidence of infection was 9.3% among patients not on steroids. Among those on up to 5 mg/day of prednisone, it was 12.5%; among those on 5-10 mg/day, 17.2%; and among those on more than 10 mg/day, 23.9%.

Glucocorticoids were associated with a 37% increased rate of serious infections, even with doses at or below 5mg/day. The effect “was really similar” whether people were on a biologic, tsDMARD, or methotrexate, which was “surprising,” Dr. George said.

“When I see a patient now who is on long-term, low-dose prednisone, I don’t just say ‘okay, that’s probably safe.’ I think really hard about how much benefit they’re getting. For some people, that means I try to get them off it,” he said. For those who flare otherwise, “I might continue them on it, but recognize there is likely some risk.”

The magnitude of the infection risk was similar to that reported with tumor necrosis factors inhibitors, which might reassure patients who are reluctant to switch to a tumor necrosis factor inhibitor.

“Now I can say you’ve been taking 10 mg prednisone a day, and that’s probably at least as risky,” Dr. George said.

Frequency of office visits, hospitalizations, and ED visits, as well as prior infections, comorbidities, nursing-home admissions, and use of durable medical equipment were among the potential confounders controlled for in the analysis. They stood in for direct markers of RA severity, which weren’t available in the data. “We spent a lot of time trying to make sure our groups were as similar as possible in every way except prednisone use,” he said.

Patients were in their late 60s on average, 71% white, and 81% were women. People with other autoimmune rheumatic diseases, cancer, or HIV were excluded. Dr. George said the next step is to run the same analysis in a younger cohort.

The work was funded by the National Institutes of Health. Dr. George disclosed relationships with AbbVie and Bristol-Myers Squibb.

[email protected]

SOURCE: George M et al. ACR 2019, Abstract 848

ATLANTA – Concomitant use of even low-dose steroids increases the risk of serious infections with antirheumatic drugs, according to a review of 170,357 Medicare patients by investigators at the University of Pennsylvania, Philadelphia.

Infections are a well-known side effect of high-dose glucocorticoids, but there’s been debate about prednisone doses in the 5-10 mg/day range. Guidelines generally advise tapering RA patients off steroids after they start a biologic or methotrexate, but that doesn’t always happen because there’s a common perception that low-dose steroids are safe, said lead investigator Michael George, MD, assistant professor of medicine and epidemiology at the university.

“Many people continue low-dose steroids over the long term, but even low dose seems to be associated with infection. It’s a small risk, but it should be something you are aware of; for some patients, it might be quite important,” he said in an interview at the annual meeting of the American College of Rheumatology.

The team wanted to mimic real-world practice, so they compared infection incidence between the 53% of patients who were not on low-dose steroids with the 47% who were after at least 6 months of disease-modifying antirheumatic drug (DMARD) therapy. About 56% of patients were on methotrexate, with the rest on biologics or a targeted synthetic DMARD (tsDMARD). Average follow up was an additional 6 months, but some people were followed for several years; prednisone 5 mg/day or less was the most common dose.

There were 20,630 serious infections requiring hospitalization, most often urinary tract infection, pneumonia, bacteremia/septicemia, and skin or soft-tissue infections. The crude incidence was 11 per 100 person-years.

After propensity-score weighting to balance out about 50 potential confounders, the predicted 1-year incidence of infection was 9.3% among patients not on steroids. Among those on up to 5 mg/day of prednisone, it was 12.5%; among those on 5-10 mg/day, 17.2%; and among those on more than 10 mg/day, 23.9%.

Glucocorticoids were associated with a 37% increased rate of serious infections, even with doses at or below 5mg/day. The effect “was really similar” whether people were on a biologic, tsDMARD, or methotrexate, which was “surprising,” Dr. George said.

“When I see a patient now who is on long-term, low-dose prednisone, I don’t just say ‘okay, that’s probably safe.’ I think really hard about how much benefit they’re getting. For some people, that means I try to get them off it,” he said. For those who flare otherwise, “I might continue them on it, but recognize there is likely some risk.”

The magnitude of the infection risk was similar to that reported with tumor necrosis factors inhibitors, which might reassure patients who are reluctant to switch to a tumor necrosis factor inhibitor.

“Now I can say you’ve been taking 10 mg prednisone a day, and that’s probably at least as risky,” Dr. George said.

Frequency of office visits, hospitalizations, and ED visits, as well as prior infections, comorbidities, nursing-home admissions, and use of durable medical equipment were among the potential confounders controlled for in the analysis. They stood in for direct markers of RA severity, which weren’t available in the data. “We spent a lot of time trying to make sure our groups were as similar as possible in every way except prednisone use,” he said.

Patients were in their late 60s on average, 71% white, and 81% were women. People with other autoimmune rheumatic diseases, cancer, or HIV were excluded. Dr. George said the next step is to run the same analysis in a younger cohort.

The work was funded by the National Institutes of Health. Dr. George disclosed relationships with AbbVie and Bristol-Myers Squibb.

[email protected]

SOURCE: George M et al. ACR 2019, Abstract 848

A few years ago, my seemingly indestructible 94-year-old mother suffered a series of medical setbacks. As her health problems accumulated, so did the complexity and cost of her care, progressing from her home to an assisted-living facility to a nursing home. It was heartbreaking – and expensive. My wife likened it to “putting another kid through college” – an elite private college, at that.

designer451/iStock/Getty Images Plus

Medicare, of course, did not cover any of this, except for physician visits and some of her medications. When it was finally over, my wife and I resolved that, should we face a similar situation in our final years, we could not put ourselves or our children through a similar financial ordeal.

Long-term care insurance (LTCI) is designed to prevent such situations by covering hospice services, nursing home stays, assisted living facilities, in-home services, and other end-of-life expenses. (Covered services vary by policy; and as always, I have no financial interest in any product or service mentioned here.)

According to the American Association for Long-Term Care Insurance (AALTCI), the average annual LTCI premium for a 60-year-old couple is $3,490. Not cheap; but there are ways to lower premiums without gutting your coverage.

The best way to keep costs down is to get in early. In general, the younger you are and the better health you are in, the lower your premiums will be. For example – again according to the AALTCI – that “average” annual premium of $3,490 for a hypothetical 60-year-old couple would increase 34%, to $4,675, if they waited until they were 65 to buy the policy. And if their health were to decline in the interim, they might not be able to obtain adequate coverage at all.

You can also lower premiums by decreasing daily benefits, or increasing the “elimination period” – the length of time after you become eligible for benefits that the policy starts paying them; 30-, 60-, and 90-day periods are common. As long as you have sufficient savings to realistically cover costs until the elimination period is over, choosing a longer one can reduce your costs significantly.

Another variable is the maximum length of time the policy will pay out benefits. Ideally, you would want a payout to continue for as long as necessary, but few if any companies are willing to write uncapped policies anymore. Two to five years of benefits is a common time frame. (The “average” premiums quoted above assume a benefit of $150 per day with a 3-year cap and a 90-day elimination period.)

As with any insurance, it is important not to overbuy LTCI. It isn’t necessary to obtain coverage that will pay for 100% of your long-term care costs – just the portion that your projected retirement income (Social Security, pensions, income from savings) may not be sufficient to cover. Buying only the amount of coverage you need will substantially reduce your premium costs over the life of the policy.

If you work for a hospital or a large group, it’s worth checking to see if your employer offers LTCI. Employer-sponsored plans are often offered at discounted group rates, and you can usually keep the policy even if you leave. If you’re a member of any social or religious groups, check their insurance plans as well.

To be sure, there is considerable debate about whether LTCI is worth the cost. Premiums for new policies are rising at a steep clip – 9% annually, according to the AALTCI – and insurers are allowed to raise premiums even after you buy the policy, so you’ll need to factor that possibility into your budget.

But forgoing coverage can be costly too: If you know you will have to cover your own long-term care costs, you won’t be able to spend that money on things you really care about – like your grandkids, or travel, or charitable work. You might even forgo necessary medical care for fear of running out of money.

Everyone must make their own decision. My wife and I decided that a few thousand dollars per year is a fair price to pay for the peace of mind of knowing we will be able to afford proper supportive care, without help from our children or anyone else, regardless of what happens in the years to come.
 

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

A few years ago, my seemingly indestructible 94-year-old mother suffered a series of medical setbacks. As her health problems accumulated, so did the complexity and cost of her care, progressing from her home to an assisted-living facility to a nursing home. It was heartbreaking – and expensive. My wife likened it to “putting another kid through college” – an elite private college, at that.

designer451/iStock/Getty Images Plus

Medicare, of course, did not cover any of this, except for physician visits and some of her medications. When it was finally over, my wife and I resolved that, should we face a similar situation in our final years, we could not put ourselves or our children through a similar financial ordeal.

Long-term care insurance (LTCI) is designed to prevent such situations by covering hospice services, nursing home stays, assisted living facilities, in-home services, and other end-of-life expenses. (Covered services vary by policy; and as always, I have no financial interest in any product or service mentioned here.)

According to the American Association for Long-Term Care Insurance (AALTCI), the average annual LTCI premium for a 60-year-old couple is $3,490. Not cheap; but there are ways to lower premiums without gutting your coverage.

The best way to keep costs down is to get in early. In general, the younger you are and the better health you are in, the lower your premiums will be. For example – again according to the AALTCI – that “average” annual premium of $3,490 for a hypothetical 60-year-old couple would increase 34%, to $4,675, if they waited until they were 65 to buy the policy. And if their health were to decline in the interim, they might not be able to obtain adequate coverage at all.

You can also lower premiums by decreasing daily benefits, or increasing the “elimination period” – the length of time after you become eligible for benefits that the policy starts paying them; 30-, 60-, and 90-day periods are common. As long as you have sufficient savings to realistically cover costs until the elimination period is over, choosing a longer one can reduce your costs significantly.

Another variable is the maximum length of time the policy will pay out benefits. Ideally, you would want a payout to continue for as long as necessary, but few if any companies are willing to write uncapped policies anymore. Two to five years of benefits is a common time frame. (The “average” premiums quoted above assume a benefit of $150 per day with a 3-year cap and a 90-day elimination period.)

As with any insurance, it is important not to overbuy LTCI. It isn’t necessary to obtain coverage that will pay for 100% of your long-term care costs – just the portion that your projected retirement income (Social Security, pensions, income from savings) may not be sufficient to cover. Buying only the amount of coverage you need will substantially reduce your premium costs over the life of the policy.

If you work for a hospital or a large group, it’s worth checking to see if your employer offers LTCI. Employer-sponsored plans are often offered at discounted group rates, and you can usually keep the policy even if you leave. If you’re a member of any social or religious groups, check their insurance plans as well.

To be sure, there is considerable debate about whether LTCI is worth the cost. Premiums for new policies are rising at a steep clip – 9% annually, according to the AALTCI – and insurers are allowed to raise premiums even after you buy the policy, so you’ll need to factor that possibility into your budget.

But forgoing coverage can be costly too: If you know you will have to cover your own long-term care costs, you won’t be able to spend that money on things you really care about – like your grandkids, or travel, or charitable work. You might even forgo necessary medical care for fear of running out of money.

Everyone must make their own decision. My wife and I decided that a few thousand dollars per year is a fair price to pay for the peace of mind of knowing we will be able to afford proper supportive care, without help from our children or anyone else, regardless of what happens in the years to come.
 

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

A few years ago, my seemingly indestructible 94-year-old mother suffered a series of medical setbacks. As her health problems accumulated, so did the complexity and cost of her care, progressing from her home to an assisted-living facility to a nursing home. It was heartbreaking – and expensive. My wife likened it to “putting another kid through college” – an elite private college, at that.

designer451/iStock/Getty Images Plus

Medicare, of course, did not cover any of this, except for physician visits and some of her medications. When it was finally over, my wife and I resolved that, should we face a similar situation in our final years, we could not put ourselves or our children through a similar financial ordeal.

Long-term care insurance (LTCI) is designed to prevent such situations by covering hospice services, nursing home stays, assisted living facilities, in-home services, and other end-of-life expenses. (Covered services vary by policy; and as always, I have no financial interest in any product or service mentioned here.)

According to the American Association for Long-Term Care Insurance (AALTCI), the average annual LTCI premium for a 60-year-old couple is $3,490. Not cheap; but there are ways to lower premiums without gutting your coverage.

The best way to keep costs down is to get in early. In general, the younger you are and the better health you are in, the lower your premiums will be. For example – again according to the AALTCI – that “average” annual premium of $3,490 for a hypothetical 60-year-old couple would increase 34%, to $4,675, if they waited until they were 65 to buy the policy. And if their health were to decline in the interim, they might not be able to obtain adequate coverage at all.

You can also lower premiums by decreasing daily benefits, or increasing the “elimination period” – the length of time after you become eligible for benefits that the policy starts paying them; 30-, 60-, and 90-day periods are common. As long as you have sufficient savings to realistically cover costs until the elimination period is over, choosing a longer one can reduce your costs significantly.

Another variable is the maximum length of time the policy will pay out benefits. Ideally, you would want a payout to continue for as long as necessary, but few if any companies are willing to write uncapped policies anymore. Two to five years of benefits is a common time frame. (The “average” premiums quoted above assume a benefit of $150 per day with a 3-year cap and a 90-day elimination period.)

As with any insurance, it is important not to overbuy LTCI. It isn’t necessary to obtain coverage that will pay for 100% of your long-term care costs – just the portion that your projected retirement income (Social Security, pensions, income from savings) may not be sufficient to cover. Buying only the amount of coverage you need will substantially reduce your premium costs over the life of the policy.

If you work for a hospital or a large group, it’s worth checking to see if your employer offers LTCI. Employer-sponsored plans are often offered at discounted group rates, and you can usually keep the policy even if you leave. If you’re a member of any social or religious groups, check their insurance plans as well.

To be sure, there is considerable debate about whether LTCI is worth the cost. Premiums for new policies are rising at a steep clip – 9% annually, according to the AALTCI – and insurers are allowed to raise premiums even after you buy the policy, so you’ll need to factor that possibility into your budget.

But forgoing coverage can be costly too: If you know you will have to cover your own long-term care costs, you won’t be able to spend that money on things you really care about – like your grandkids, or travel, or charitable work. You might even forgo necessary medical care for fear of running out of money.

Everyone must make their own decision. My wife and I decided that a few thousand dollars per year is a fair price to pay for the peace of mind of knowing we will be able to afford proper supportive care, without help from our children or anyone else, regardless of what happens in the years to come.
 

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

LAS VEGAS – Based on the best available data to date, certolizumab pegol is likely the best treatment choice for women with psoriasis who become pregnant, Francisco A. Kerdel, BSc, MBBS, said at the Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.

Doug Brunk/MDedge News

Dr. Kerdel, professor and vice chair of the department of dermatology at Florida International University, Miami, noted that, while tumor necrosis factor (TNF)–alpha inhibitors are category B drugs, inadequate data exist regarding lactation and exposure throughout pregnancy. “Rates of malformations and spontaneous abortions with therapy are similar to those in the general population, higher concentrations of infliximab and adalimumab have been found in infant and cord blood, compared with certolizumab pegol,” an anti-TNF biologic, he said.

In a prospective, postmarketing, multicenter pharmacokinetic study, researchers found a lack of placental transfer of certolizumab pegol during pregnancy (Ann Rheum Dis. 2018;77:228-33). Specifically, certolizumab levels were below the lower limit of quantification (less than 0.032 mcg/mL) in 13 of 14 infant samples at birth and in all infant samples at weeks 4 and 8. Only one infant had a minimal certolizumab level at birth (infant/mother ratio of 0.0009). No antibodies were detected at any time point during the study. Safety data in mothers were in line with the known safety profile of certolizumab and pregnancy profile of these underlying diseases. Adverse events experienced by the infants did not show any patterns or clusters of events suggesting a specific safety signal in children.

In a separate postmarketing pharmacokinetic study, investigators evaluated the transfer of certolizumab into breast milk (Ann Rheum Dis. 2017;76:1890-6). They found that the average daily infant dose of certolizumab was minimal. Specifically, the highest concentration of certolizumab in breast milk (0.0758 mcg/mL) was less than 1% of the expected mean plasma trough concentration of a therapeutic dose.

How do TNF-alpha inhibitors fare in the pediatric population? In a retrospective study of 390 children with psoriasis treated at 20 centers in the United States, Canada, and Europe, researchers evaluated the safety of systemic agents (JAMA Dermatol. 2017;153[11]:1147-57). Most (69%) were prescribed methotrexate, followed by biologics, acitretin, cyclosporine, and fumaric acid. Drug discontinuation (because of adverse events), which is sometimes used as an efficacy parameter, occurred in 12% of those who were on methotrexate, compared with 3% of those on biologics, 67% of those on acitretin, and 68% of those on fumaric acid.

At the other end of the age spectrum, biologic therapy is generally effective and well tolerated in elderly patients. “Sometimes, they may be more effective than other traditional drugs,” Dr. Kerdel said. “We’re a little bit concerned about immunosenescence, which can increase the risk for severe infections and malignancies. And, 90% of elderly patients with psoriasis may have comorbidities that need to be taken into account when treating psoriasis.”

Other factors come into play when choosing the right anti-TNF agent, including weight. While clinical trials show efficacy across weight groups, infliximab has weight-based dosing, “which may make it a better choice,” Dr. Kerdel said. “Patients taking etanercept may need a biweekly dose.”

Treatment flexibility also comes into play. For example, stopping therapy because of an infection or surgery may be problematic in drugs with a long half-life. Then there’s the issue of patient preference. “Some people don’t want to be injected frequently,” he said. “Some people don’t want to be injected at all and may require a simpler dosing regimen.”

Optimizing anti-TNF-alpha treatment starts with recognizing that there is a loss of response over time, Dr. Kerdel said, “or there may not be a response at all.” Contributing factors may include immunogenicity, suboptimal dosing, and poor patient adherence. In order to optimize treatment, clinicians can try switching agents or combination therapy, and explore continuous versus intermittent dosing.

“We really don’t have good data on the best protocol for switching treatment after failure of an anti-TNF-alpha agent,” he added. In cases of primary and secondary treatment failure, there is no consensus or guidelines on which second-line agent to use, nor good data on which measures to use.

No evidence-based guidelines are available for screening and monitoring patients receiving biologic therapy for psoriasis, either. “Evidence is strongest [grade B] for tuberculosis screening in patients treated with biologic agents,” Dr. Kerdel said. “Among known hepatitis B virus carriers, consider monitoring liver function tests and viral load [grade C]. High-grade evidence is lacking to support other routine testing. Physicians should use clinical judgment when screening and monitoring patients.”

He concluded his presentation by noting that there are a number of biosimilar agents available or in the pipeline for infliximab, adalimumab, and etanercept. This raises a number of questions for current and future consideration. For one, “will biosimilars show the same long-term efficacy and safety as the innovator products?” he asked. “Real-world, postmarketing, and registry data are needed. Will biosimilar agents offer significant cost benefits? Will biosimilar labeling be adequately transparent? Will we find biomarkers to help us target biologic agents to specific patients and subtypes of psoriasis?”

Dr. Kerdel reported that he is a member of the speaker’s bureau for AbbVie, Amgen, Celgene, Janssen, Novartis, Lilly, Leo, Ortho, and Novartis. He has also received grant/research support from AbbVie, Amgen, AstraZeneca, Celgene, Janssen, Leo, Lilly, Menlo Therapeutics, Novartis, Pfizer, and XBiotech.

SDEF and this news organization are owned by the same parent company.

[email protected]

LAS VEGAS – Based on the best available data to date, certolizumab pegol is likely the best treatment choice for women with psoriasis who become pregnant, Francisco A. Kerdel, BSc, MBBS, said at the Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.

Doug Brunk/MDedge News

Dr. Kerdel, professor and vice chair of the department of dermatology at Florida International University, Miami, noted that, while tumor necrosis factor (TNF)–alpha inhibitors are category B drugs, inadequate data exist regarding lactation and exposure throughout pregnancy. “Rates of malformations and spontaneous abortions with therapy are similar to those in the general population, higher concentrations of infliximab and adalimumab have been found in infant and cord blood, compared with certolizumab pegol,” an anti-TNF biologic, he said.

In a prospective, postmarketing, multicenter pharmacokinetic study, researchers found a lack of placental transfer of certolizumab pegol during pregnancy (Ann Rheum Dis. 2018;77:228-33). Specifically, certolizumab levels were below the lower limit of quantification (less than 0.032 mcg/mL) in 13 of 14 infant samples at birth and in all infant samples at weeks 4 and 8. Only one infant had a minimal certolizumab level at birth (infant/mother ratio of 0.0009). No antibodies were detected at any time point during the study. Safety data in mothers were in line with the known safety profile of certolizumab and pregnancy profile of these underlying diseases. Adverse events experienced by the infants did not show any patterns or clusters of events suggesting a specific safety signal in children.

In a separate postmarketing pharmacokinetic study, investigators evaluated the transfer of certolizumab into breast milk (Ann Rheum Dis. 2017;76:1890-6). They found that the average daily infant dose of certolizumab was minimal. Specifically, the highest concentration of certolizumab in breast milk (0.0758 mcg/mL) was less than 1% of the expected mean plasma trough concentration of a therapeutic dose.

How do TNF-alpha inhibitors fare in the pediatric population? In a retrospective study of 390 children with psoriasis treated at 20 centers in the United States, Canada, and Europe, researchers evaluated the safety of systemic agents (JAMA Dermatol. 2017;153[11]:1147-57). Most (69%) were prescribed methotrexate, followed by biologics, acitretin, cyclosporine, and fumaric acid. Drug discontinuation (because of adverse events), which is sometimes used as an efficacy parameter, occurred in 12% of those who were on methotrexate, compared with 3% of those on biologics, 67% of those on acitretin, and 68% of those on fumaric acid.

At the other end of the age spectrum, biologic therapy is generally effective and well tolerated in elderly patients. “Sometimes, they may be more effective than other traditional drugs,” Dr. Kerdel said. “We’re a little bit concerned about immunosenescence, which can increase the risk for severe infections and malignancies. And, 90% of elderly patients with psoriasis may have comorbidities that need to be taken into account when treating psoriasis.”

Other factors come into play when choosing the right anti-TNF agent, including weight. While clinical trials show efficacy across weight groups, infliximab has weight-based dosing, “which may make it a better choice,” Dr. Kerdel said. “Patients taking etanercept may need a biweekly dose.”

Treatment flexibility also comes into play. For example, stopping therapy because of an infection or surgery may be problematic in drugs with a long half-life. Then there’s the issue of patient preference. “Some people don’t want to be injected frequently,” he said. “Some people don’t want to be injected at all and may require a simpler dosing regimen.”

Optimizing anti-TNF-alpha treatment starts with recognizing that there is a loss of response over time, Dr. Kerdel said, “or there may not be a response at all.” Contributing factors may include immunogenicity, suboptimal dosing, and poor patient adherence. In order to optimize treatment, clinicians can try switching agents or combination therapy, and explore continuous versus intermittent dosing.

“We really don’t have good data on the best protocol for switching treatment after failure of an anti-TNF-alpha agent,” he added. In cases of primary and secondary treatment failure, there is no consensus or guidelines on which second-line agent to use, nor good data on which measures to use.

No evidence-based guidelines are available for screening and monitoring patients receiving biologic therapy for psoriasis, either. “Evidence is strongest [grade B] for tuberculosis screening in patients treated with biologic agents,” Dr. Kerdel said. “Among known hepatitis B virus carriers, consider monitoring liver function tests and viral load [grade C]. High-grade evidence is lacking to support other routine testing. Physicians should use clinical judgment when screening and monitoring patients.”

He concluded his presentation by noting that there are a number of biosimilar agents available or in the pipeline for infliximab, adalimumab, and etanercept. This raises a number of questions for current and future consideration. For one, “will biosimilars show the same long-term efficacy and safety as the innovator products?” he asked. “Real-world, postmarketing, and registry data are needed. Will biosimilar agents offer significant cost benefits? Will biosimilar labeling be adequately transparent? Will we find biomarkers to help us target biologic agents to specific patients and subtypes of psoriasis?”

Dr. Kerdel reported that he is a member of the speaker’s bureau for AbbVie, Amgen, Celgene, Janssen, Novartis, Lilly, Leo, Ortho, and Novartis. He has also received grant/research support from AbbVie, Amgen, AstraZeneca, Celgene, Janssen, Leo, Lilly, Menlo Therapeutics, Novartis, Pfizer, and XBiotech.

SDEF and this news organization are owned by the same parent company.

[email protected]

LAS VEGAS – Based on the best available data to date, certolizumab pegol is likely the best treatment choice for women with psoriasis who become pregnant, Francisco A. Kerdel, BSc, MBBS, said at the Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar.

Doug Brunk/MDedge News

Dr. Kerdel, professor and vice chair of the department of dermatology at Florida International University, Miami, noted that, while tumor necrosis factor (TNF)–alpha inhibitors are category B drugs, inadequate data exist regarding lactation and exposure throughout pregnancy. “Rates of malformations and spontaneous abortions with therapy are similar to those in the general population, higher concentrations of infliximab and adalimumab have been found in infant and cord blood, compared with certolizumab pegol,” an anti-TNF biologic, he said.

In a prospective, postmarketing, multicenter pharmacokinetic study, researchers found a lack of placental transfer of certolizumab pegol during pregnancy (Ann Rheum Dis. 2018;77:228-33). Specifically, certolizumab levels were below the lower limit of quantification (less than 0.032 mcg/mL) in 13 of 14 infant samples at birth and in all infant samples at weeks 4 and 8. Only one infant had a minimal certolizumab level at birth (infant/mother ratio of 0.0009). No antibodies were detected at any time point during the study. Safety data in mothers were in line with the known safety profile of certolizumab and pregnancy profile of these underlying diseases. Adverse events experienced by the infants did not show any patterns or clusters of events suggesting a specific safety signal in children.

In a separate postmarketing pharmacokinetic study, investigators evaluated the transfer of certolizumab into breast milk (Ann Rheum Dis. 2017;76:1890-6). They found that the average daily infant dose of certolizumab was minimal. Specifically, the highest concentration of certolizumab in breast milk (0.0758 mcg/mL) was less than 1% of the expected mean plasma trough concentration of a therapeutic dose.

How do TNF-alpha inhibitors fare in the pediatric population? In a retrospective study of 390 children with psoriasis treated at 20 centers in the United States, Canada, and Europe, researchers evaluated the safety of systemic agents (JAMA Dermatol. 2017;153[11]:1147-57). Most (69%) were prescribed methotrexate, followed by biologics, acitretin, cyclosporine, and fumaric acid. Drug discontinuation (because of adverse events), which is sometimes used as an efficacy parameter, occurred in 12% of those who were on methotrexate, compared with 3% of those on biologics, 67% of those on acitretin, and 68% of those on fumaric acid.

At the other end of the age spectrum, biologic therapy is generally effective and well tolerated in elderly patients. “Sometimes, they may be more effective than other traditional drugs,” Dr. Kerdel said. “We’re a little bit concerned about immunosenescence, which can increase the risk for severe infections and malignancies. And, 90% of elderly patients with psoriasis may have comorbidities that need to be taken into account when treating psoriasis.”

Other factors come into play when choosing the right anti-TNF agent, including weight. While clinical trials show efficacy across weight groups, infliximab has weight-based dosing, “which may make it a better choice,” Dr. Kerdel said. “Patients taking etanercept may need a biweekly dose.”

Treatment flexibility also comes into play. For example, stopping therapy because of an infection or surgery may be problematic in drugs with a long half-life. Then there’s the issue of patient preference. “Some people don’t want to be injected frequently,” he said. “Some people don’t want to be injected at all and may require a simpler dosing regimen.”

Optimizing anti-TNF-alpha treatment starts with recognizing that there is a loss of response over time, Dr. Kerdel said, “or there may not be a response at all.” Contributing factors may include immunogenicity, suboptimal dosing, and poor patient adherence. In order to optimize treatment, clinicians can try switching agents or combination therapy, and explore continuous versus intermittent dosing.

“We really don’t have good data on the best protocol for switching treatment after failure of an anti-TNF-alpha agent,” he added. In cases of primary and secondary treatment failure, there is no consensus or guidelines on which second-line agent to use, nor good data on which measures to use.

No evidence-based guidelines are available for screening and monitoring patients receiving biologic therapy for psoriasis, either. “Evidence is strongest [grade B] for tuberculosis screening in patients treated with biologic agents,” Dr. Kerdel said. “Among known hepatitis B virus carriers, consider monitoring liver function tests and viral load [grade C]. High-grade evidence is lacking to support other routine testing. Physicians should use clinical judgment when screening and monitoring patients.”

He concluded his presentation by noting that there are a number of biosimilar agents available or in the pipeline for infliximab, adalimumab, and etanercept. This raises a number of questions for current and future consideration. For one, “will biosimilars show the same long-term efficacy and safety as the innovator products?” he asked. “Real-world, postmarketing, and registry data are needed. Will biosimilar agents offer significant cost benefits? Will biosimilar labeling be adequately transparent? Will we find biomarkers to help us target biologic agents to specific patients and subtypes of psoriasis?”

Dr. Kerdel reported that he is a member of the speaker’s bureau for AbbVie, Amgen, Celgene, Janssen, Novartis, Lilly, Leo, Ortho, and Novartis. He has also received grant/research support from AbbVie, Amgen, AstraZeneca, Celgene, Janssen, Leo, Lilly, Menlo Therapeutics, Novartis, Pfizer, and XBiotech.

SDEF and this news organization are owned by the same parent company.

[email protected]

LAS VEGAS – Narrowband UVB phototherapy remains an effective and generally safe treatment for psoriasis, according to Kenneth B. Gordon, MD, professor and chair of dermatology at the Medical College of Wisconsin, Milwaukee.

Doug Brunk/MDedge News

At the Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar, Dr. Gordon said that he uses phototherapy most in patients “who can’t get to all of the spots without it,” and in those whose disease is not having a huge impact on day-to-day life. “In my experience it’s best in people with thinner plaques, though I have some question over whether we can figure out if morphology really does correlate to respond to phototherapy,” he added. “We’re in the process of conducting a study to try and figure that out.”

From an immunologic standpoint, UVB decreases responsiveness of the interleukin-17 pathway and increases both cutaneous and circulating FoxP3+ cells, he said. Activation of p38 mitogen–activated protein kinase during phototherapy inhibits proinflammatory T-cell activation. In Dr. Gordon’s opinion, phototherapy is absolutely contraindicated in patients who have a photosensitivity reaction related to the UVB spectrum, while it is relatively contraindicated in those at high risk for skin cancer, including patients with multiple squamous cell carcinomas and those who have undergone organ transplantation. “I would argue that [the use of] photosensitizing drugs are not a contraindication,” he said. “Would I prefer that someone who’s had 54 [squamous cell carcinomas] not use phototherapy? Of course. But if it’s the only weapon I have, I’ll use it.”

Although clinicians have used phototherapy for about 100 years, early standards for clinical trials were different, compared with the rigor required of those conducted in the current era. Outcomes were not standardized, he said, and they were generally smaller trials that did not incorporate proper monitoring of adverse events. “Even with these weaknesses, we can get a general impression of how well UV works,” he said. In a 6-week, split-body trial of 11 patients from 20 years ago, researchers were able to induce clinical clearing in 82% of patients after narrowband UVB (the type most commonly used today), but in only 9% of patients after broadband UVB treatment (P less than .01) (J Am Acad Dermatol. 1999 Jun;40[6 Pt 1]:893-900).

Most clinicians commence narrowband UVB phototherapy treatment with three sessions per week and safely increase the dose to reach an effective level. Erythema can develop with overdosing. “If a patient can only come in twice weekly [for phototherapy treatment], that is okay,” Dr. Gordon said. “It takes a longer time getting to treatment goals. In my opinion, going down to once a week during the escalating phase of using phototherapy doesn’t work. Three times a week is better than twice a week during the escalating phase, but one time a week isn’t enough.”

Even for maintenance therapy, it remains a question whether limiting phototherapy to once every 2 or 4 weeks is sufficient for disease control. “I let the patient choose, but I like to go down to no less than once a week and hold people steady at that dose,” he said.

Purported risks of narrowband UVB phototherapy include photoaging, sunburn, herpes simplex virus reactivation, loss of the patient’s productive time, and development of skin cancer. “I don’t think we have good data about the effect of phototherapy on photoaging,” Dr. Gordon said. “Loss of productive time is my single biggest [complaint]. People are having trouble getting to work and having bosses who are not pleased with them [leaving work for treatment].”

As for the association between phototherapy and skin cancer, he noted that published studies that show statistical differences all incorporate psoralen-UVA photochemotherapy into their analyses. “There’s really no study that has demonstrated a significant impact on nonmelanoma skin cancers with the use of phototherapy [alone],” Dr. Gordon said. A British study of 3,867 psoriasis patients found no significant association between narrowband UVB treatment and basal cell cancer, squamous cell cancer, or melanoma (Br J Dermatol. 2008 Sep;159[4]:931-5). However, among those who also were treated with psoralen-UVA photochemotherapy, there was a small increase in basal cell cancer.

In a more recent Swedish study of 162 psoriasis patients who were treated with UVB phototherapy, researchers found that, after controlling for age, the risk of skin cancer was associated with the number of treatments, but not with the type of UVB lamp used (Acta Derm Venereol. 2014 Jul;94[4]:425-30). They reported that overall, the risk of malignancy in the UVB-treated patients did not exceed that in the general population.

Dr. Gordon concluded his presentation by noting that home-based UVB phototherapy is gaining in popularity and is comparable with in-office UVB in terms of accuracy and efficacy (BMJ. 2009;338:b1542). Because of convenience and decreased time away from work, he said, “it’s easier for patients ... and it’s probably cheaper in the long run.” The National Psoriasis Foundation web site includes a list of home UVB equipment.

Dr. Gordon disclosed that he is a consultant with AbbVie, Almirall, Amgen, Bristol-Meyers Squibb, Celgene, Dermavant, Eli Lilly, Janssen, Leo, Novartis, Ortho Dermatologics, Pfizer, Sun Pharma, and UCB. He has also received grant/research support from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, and Novartis.

SDEF and this news organization are owned by the same parent company.

[email protected]

LAS VEGAS – Narrowband UVB phototherapy remains an effective and generally safe treatment for psoriasis, according to Kenneth B. Gordon, MD, professor and chair of dermatology at the Medical College of Wisconsin, Milwaukee.

Doug Brunk/MDedge News

At the Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar, Dr. Gordon said that he uses phototherapy most in patients “who can’t get to all of the spots without it,” and in those whose disease is not having a huge impact on day-to-day life. “In my experience it’s best in people with thinner plaques, though I have some question over whether we can figure out if morphology really does correlate to respond to phototherapy,” he added. “We’re in the process of conducting a study to try and figure that out.”

From an immunologic standpoint, UVB decreases responsiveness of the interleukin-17 pathway and increases both cutaneous and circulating FoxP3+ cells, he said. Activation of p38 mitogen–activated protein kinase during phototherapy inhibits proinflammatory T-cell activation. In Dr. Gordon’s opinion, phototherapy is absolutely contraindicated in patients who have a photosensitivity reaction related to the UVB spectrum, while it is relatively contraindicated in those at high risk for skin cancer, including patients with multiple squamous cell carcinomas and those who have undergone organ transplantation. “I would argue that [the use of] photosensitizing drugs are not a contraindication,” he said. “Would I prefer that someone who’s had 54 [squamous cell carcinomas] not use phototherapy? Of course. But if it’s the only weapon I have, I’ll use it.”

Although clinicians have used phototherapy for about 100 years, early standards for clinical trials were different, compared with the rigor required of those conducted in the current era. Outcomes were not standardized, he said, and they were generally smaller trials that did not incorporate proper monitoring of adverse events. “Even with these weaknesses, we can get a general impression of how well UV works,” he said. In a 6-week, split-body trial of 11 patients from 20 years ago, researchers were able to induce clinical clearing in 82% of patients after narrowband UVB (the type most commonly used today), but in only 9% of patients after broadband UVB treatment (P less than .01) (J Am Acad Dermatol. 1999 Jun;40[6 Pt 1]:893-900).

Most clinicians commence narrowband UVB phototherapy treatment with three sessions per week and safely increase the dose to reach an effective level. Erythema can develop with overdosing. “If a patient can only come in twice weekly [for phototherapy treatment], that is okay,” Dr. Gordon said. “It takes a longer time getting to treatment goals. In my opinion, going down to once a week during the escalating phase of using phototherapy doesn’t work. Three times a week is better than twice a week during the escalating phase, but one time a week isn’t enough.”

Even for maintenance therapy, it remains a question whether limiting phototherapy to once every 2 or 4 weeks is sufficient for disease control. “I let the patient choose, but I like to go down to no less than once a week and hold people steady at that dose,” he said.

Purported risks of narrowband UVB phototherapy include photoaging, sunburn, herpes simplex virus reactivation, loss of the patient’s productive time, and development of skin cancer. “I don’t think we have good data about the effect of phototherapy on photoaging,” Dr. Gordon said. “Loss of productive time is my single biggest [complaint]. People are having trouble getting to work and having bosses who are not pleased with them [leaving work for treatment].”

As for the association between phototherapy and skin cancer, he noted that published studies that show statistical differences all incorporate psoralen-UVA photochemotherapy into their analyses. “There’s really no study that has demonstrated a significant impact on nonmelanoma skin cancers with the use of phototherapy [alone],” Dr. Gordon said. A British study of 3,867 psoriasis patients found no significant association between narrowband UVB treatment and basal cell cancer, squamous cell cancer, or melanoma (Br J Dermatol. 2008 Sep;159[4]:931-5). However, among those who also were treated with psoralen-UVA photochemotherapy, there was a small increase in basal cell cancer.

In a more recent Swedish study of 162 psoriasis patients who were treated with UVB phototherapy, researchers found that, after controlling for age, the risk of skin cancer was associated with the number of treatments, but not with the type of UVB lamp used (Acta Derm Venereol. 2014 Jul;94[4]:425-30). They reported that overall, the risk of malignancy in the UVB-treated patients did not exceed that in the general population.

Dr. Gordon concluded his presentation by noting that home-based UVB phototherapy is gaining in popularity and is comparable with in-office UVB in terms of accuracy and efficacy (BMJ. 2009;338:b1542). Because of convenience and decreased time away from work, he said, “it’s easier for patients ... and it’s probably cheaper in the long run.” The National Psoriasis Foundation web site includes a list of home UVB equipment.

Dr. Gordon disclosed that he is a consultant with AbbVie, Almirall, Amgen, Bristol-Meyers Squibb, Celgene, Dermavant, Eli Lilly, Janssen, Leo, Novartis, Ortho Dermatologics, Pfizer, Sun Pharma, and UCB. He has also received grant/research support from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, and Novartis.

SDEF and this news organization are owned by the same parent company.

[email protected]

LAS VEGAS – Narrowband UVB phototherapy remains an effective and generally safe treatment for psoriasis, according to Kenneth B. Gordon, MD, professor and chair of dermatology at the Medical College of Wisconsin, Milwaukee.

Doug Brunk/MDedge News

At the Skin Disease Education Foundation’s annual Las Vegas Dermatology Seminar, Dr. Gordon said that he uses phototherapy most in patients “who can’t get to all of the spots without it,” and in those whose disease is not having a huge impact on day-to-day life. “In my experience it’s best in people with thinner plaques, though I have some question over whether we can figure out if morphology really does correlate to respond to phototherapy,” he added. “We’re in the process of conducting a study to try and figure that out.”

From an immunologic standpoint, UVB decreases responsiveness of the interleukin-17 pathway and increases both cutaneous and circulating FoxP3+ cells, he said. Activation of p38 mitogen–activated protein kinase during phototherapy inhibits proinflammatory T-cell activation. In Dr. Gordon’s opinion, phototherapy is absolutely contraindicated in patients who have a photosensitivity reaction related to the UVB spectrum, while it is relatively contraindicated in those at high risk for skin cancer, including patients with multiple squamous cell carcinomas and those who have undergone organ transplantation. “I would argue that [the use of] photosensitizing drugs are not a contraindication,” he said. “Would I prefer that someone who’s had 54 [squamous cell carcinomas] not use phototherapy? Of course. But if it’s the only weapon I have, I’ll use it.”

Although clinicians have used phototherapy for about 100 years, early standards for clinical trials were different, compared with the rigor required of those conducted in the current era. Outcomes were not standardized, he said, and they were generally smaller trials that did not incorporate proper monitoring of adverse events. “Even with these weaknesses, we can get a general impression of how well UV works,” he said. In a 6-week, split-body trial of 11 patients from 20 years ago, researchers were able to induce clinical clearing in 82% of patients after narrowband UVB (the type most commonly used today), but in only 9% of patients after broadband UVB treatment (P less than .01) (J Am Acad Dermatol. 1999 Jun;40[6 Pt 1]:893-900).

Most clinicians commence narrowband UVB phototherapy treatment with three sessions per week and safely increase the dose to reach an effective level. Erythema can develop with overdosing. “If a patient can only come in twice weekly [for phototherapy treatment], that is okay,” Dr. Gordon said. “It takes a longer time getting to treatment goals. In my opinion, going down to once a week during the escalating phase of using phototherapy doesn’t work. Three times a week is better than twice a week during the escalating phase, but one time a week isn’t enough.”

Even for maintenance therapy, it remains a question whether limiting phototherapy to once every 2 or 4 weeks is sufficient for disease control. “I let the patient choose, but I like to go down to no less than once a week and hold people steady at that dose,” he said.

Purported risks of narrowband UVB phototherapy include photoaging, sunburn, herpes simplex virus reactivation, loss of the patient’s productive time, and development of skin cancer. “I don’t think we have good data about the effect of phototherapy on photoaging,” Dr. Gordon said. “Loss of productive time is my single biggest [complaint]. People are having trouble getting to work and having bosses who are not pleased with them [leaving work for treatment].”

As for the association between phototherapy and skin cancer, he noted that published studies that show statistical differences all incorporate psoralen-UVA photochemotherapy into their analyses. “There’s really no study that has demonstrated a significant impact on nonmelanoma skin cancers with the use of phototherapy [alone],” Dr. Gordon said. A British study of 3,867 psoriasis patients found no significant association between narrowband UVB treatment and basal cell cancer, squamous cell cancer, or melanoma (Br J Dermatol. 2008 Sep;159[4]:931-5). However, among those who also were treated with psoralen-UVA photochemotherapy, there was a small increase in basal cell cancer.

In a more recent Swedish study of 162 psoriasis patients who were treated with UVB phototherapy, researchers found that, after controlling for age, the risk of skin cancer was associated with the number of treatments, but not with the type of UVB lamp used (Acta Derm Venereol. 2014 Jul;94[4]:425-30). They reported that overall, the risk of malignancy in the UVB-treated patients did not exceed that in the general population.

Dr. Gordon concluded his presentation by noting that home-based UVB phototherapy is gaining in popularity and is comparable with in-office UVB in terms of accuracy and efficacy (BMJ. 2009;338:b1542). Because of convenience and decreased time away from work, he said, “it’s easier for patients ... and it’s probably cheaper in the long run.” The National Psoriasis Foundation web site includes a list of home UVB equipment.

Dr. Gordon disclosed that he is a consultant with AbbVie, Almirall, Amgen, Bristol-Meyers Squibb, Celgene, Dermavant, Eli Lilly, Janssen, Leo, Novartis, Ortho Dermatologics, Pfizer, Sun Pharma, and UCB. He has also received grant/research support from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, and Novartis.

SDEF and this news organization are owned by the same parent company.

[email protected]

ATLANTA – Methotrexate did not significantly improve pain scores in patients with symptomatic erosive osteoarthritis of the hand, but it may have a role in reducing joint damage and increasing bone remodeling, according to results from the small, prospective, double-blind, randomized, placebo-controlled ADEM trial.

Jeff Craven/MDedge News

“Our study failed to show the superiority of methotrexate over placebo on pain evolution, but our results on structural evolution and the presence of inflammatory parameters as predictors of erosive evolution in nonerosive diseases may lead us to discuss the place of methotrexate in early steps of the disease evolution, and underlines the importance of the part played by the interaction between synovitis and subchondral bone in erosive progression,” Christian Roux, MD, PhD, of the department of rheumatology at Côte d’Azur University, Nice, France, said in his presentation at the annual meeting of the American College of Rheumatology.

Dr. Roux and colleagues enrolled 64 patients in the ADEM trial, where patients with symptomatic erosive hand osteoarthritis (EHOA) were randomized to receive 10 mg of methotrexate (MTX) per week or placebo. At 3 months, researchers assessed patients for pain using the Visual Analog Scale (VAS) score for hand pain, and secondary outcome measures at 12 months included VAS score for hand pain, radiographic progression using Verbruggen-Veys Anatomical Phase Score and Gent University Scoring System, and MRI.

Patients were included in the study if they were between 45 and 85 years old with a VAS pain score greater than 40, had failed classic therapeutics (acetaminophen, topical NSAIDs, and symptomatic slow-acting drugs), and had at least one erosive lesion. At baseline, the MTX and placebo groups were not significantly different with regard to gender (91% vs. 97% female), mean body mass index (24.6 kg/m² vs. 24.2 kg/m²) and mean age (67.5 years vs. 64.9 years). Radiologic data showed joint loss, erosive, and erosive plus remodeling measurements were also similar between groups at baseline.

The mean VAS score for patients in the MTX group decreased from 65.7 at baseline to 48.2 at 3 months (–17.5; P = .07), compared with a decrease from 63.9 to 55.5 (–8.4; P = .002). At 12 months, VAS scores for patients in the MTX group decreased to 47.5, compared with a decrease in the placebo group to 48.2. However, the between-group differences for VAS scores were not significant at 3 months (P = .2) and at 12 months (P = .6).

“We have different hypotheses on the failure of our study on our main outcome, which was pain,” he said. “The first is a low-dose of methotrexate, and the second may be ... a placebo effect, which is very, very important in osteoarthritis.”

SOURCE: Ferraro S et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 1759.

ATLANTA – Methotrexate did not significantly improve pain scores in patients with symptomatic erosive osteoarthritis of the hand, but it may have a role in reducing joint damage and increasing bone remodeling, according to results from the small, prospective, double-blind, randomized, placebo-controlled ADEM trial.

Jeff Craven/MDedge News

“Our study failed to show the superiority of methotrexate over placebo on pain evolution, but our results on structural evolution and the presence of inflammatory parameters as predictors of erosive evolution in nonerosive diseases may lead us to discuss the place of methotrexate in early steps of the disease evolution, and underlines the importance of the part played by the interaction between synovitis and subchondral bone in erosive progression,” Christian Roux, MD, PhD, of the department of rheumatology at Côte d’Azur University, Nice, France, said in his presentation at the annual meeting of the American College of Rheumatology.

Dr. Roux and colleagues enrolled 64 patients in the ADEM trial, where patients with symptomatic erosive hand osteoarthritis (EHOA) were randomized to receive 10 mg of methotrexate (MTX) per week or placebo. At 3 months, researchers assessed patients for pain using the Visual Analog Scale (VAS) score for hand pain, and secondary outcome measures at 12 months included VAS score for hand pain, radiographic progression using Verbruggen-Veys Anatomical Phase Score and Gent University Scoring System, and MRI.

Patients were included in the study if they were between 45 and 85 years old with a VAS pain score greater than 40, had failed classic therapeutics (acetaminophen, topical NSAIDs, and symptomatic slow-acting drugs), and had at least one erosive lesion. At baseline, the MTX and placebo groups were not significantly different with regard to gender (91% vs. 97% female), mean body mass index (24.6 kg/m² vs. 24.2 kg/m²) and mean age (67.5 years vs. 64.9 years). Radiologic data showed joint loss, erosive, and erosive plus remodeling measurements were also similar between groups at baseline.

The mean VAS score for patients in the MTX group decreased from 65.7 at baseline to 48.2 at 3 months (–17.5; P = .07), compared with a decrease from 63.9 to 55.5 (–8.4; P = .002). At 12 months, VAS scores for patients in the MTX group decreased to 47.5, compared with a decrease in the placebo group to 48.2. However, the between-group differences for VAS scores were not significant at 3 months (P = .2) and at 12 months (P = .6).

“We have different hypotheses on the failure of our study on our main outcome, which was pain,” he said. “The first is a low-dose of methotrexate, and the second may be ... a placebo effect, which is very, very important in osteoarthritis.”

SOURCE: Ferraro S et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 1759.

ATLANTA – Methotrexate did not significantly improve pain scores in patients with symptomatic erosive osteoarthritis of the hand, but it may have a role in reducing joint damage and increasing bone remodeling, according to results from the small, prospective, double-blind, randomized, placebo-controlled ADEM trial.

Jeff Craven/MDedge News

“Our study failed to show the superiority of methotrexate over placebo on pain evolution, but our results on structural evolution and the presence of inflammatory parameters as predictors of erosive evolution in nonerosive diseases may lead us to discuss the place of methotrexate in early steps of the disease evolution, and underlines the importance of the part played by the interaction between synovitis and subchondral bone in erosive progression,” Christian Roux, MD, PhD, of the department of rheumatology at Côte d’Azur University, Nice, France, said in his presentation at the annual meeting of the American College of Rheumatology.

Dr. Roux and colleagues enrolled 64 patients in the ADEM trial, where patients with symptomatic erosive hand osteoarthritis (EHOA) were randomized to receive 10 mg of methotrexate (MTX) per week or placebo. At 3 months, researchers assessed patients for pain using the Visual Analog Scale (VAS) score for hand pain, and secondary outcome measures at 12 months included VAS score for hand pain, radiographic progression using Verbruggen-Veys Anatomical Phase Score and Gent University Scoring System, and MRI.

Patients were included in the study if they were between 45 and 85 years old with a VAS pain score greater than 40, had failed classic therapeutics (acetaminophen, topical NSAIDs, and symptomatic slow-acting drugs), and had at least one erosive lesion. At baseline, the MTX and placebo groups were not significantly different with regard to gender (91% vs. 97% female), mean body mass index (24.6 kg/m² vs. 24.2 kg/m²) and mean age (67.5 years vs. 64.9 years). Radiologic data showed joint loss, erosive, and erosive plus remodeling measurements were also similar between groups at baseline.

The mean VAS score for patients in the MTX group decreased from 65.7 at baseline to 48.2 at 3 months (–17.5; P = .07), compared with a decrease from 63.9 to 55.5 (–8.4; P = .002). At 12 months, VAS scores for patients in the MTX group decreased to 47.5, compared with a decrease in the placebo group to 48.2. However, the between-group differences for VAS scores were not significant at 3 months (P = .2) and at 12 months (P = .6).

“We have different hypotheses on the failure of our study on our main outcome, which was pain,” he said. “The first is a low-dose of methotrexate, and the second may be ... a placebo effect, which is very, very important in osteoarthritis.”

SOURCE: Ferraro S et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 1759.

The Diagnosis: Mosaic Tuberous Sclerosis 

A punch biopsy of the facial lesion was stained with hematoxylin and eosin, which demonstrated spindled and stellate fibroblasts with dilated blood vessels (Figure), consistent with an angiofibroma. Given the clinical presentation and histologic findings, there was concern for a diagnosis of tuberous sclerosis (TSC). The patient was referred for genetic workup but tested negative for mutations of the TSC genes in the blood. Because the patient had only unilateral facial lesions, a possible cortical tuber, no other symptoms, and tested negative for TSC gene mutations, mosaic TSC was considered a likely diagnosis. Her facial lesions were treated with pulsed dye vascular laser therapy. 

Tuberous sclerosis is an autosomal-dominant neurocutaneous disorder caused by inactivation of the genes TSC1 (encoding hamartin) and TSC2 (encoding tuberin). Mutation results in overactivation of the downstream mTOR (mammalian target of rapamycin) pathway, resulting in abnormal cellular proliferation and hamartomas. These benign tumors can be found in nearly every organ, most often in the central nervous system and skin, and they provide for a highly variable presentation of the disease.¹ 

Tuberous sclerosis affects 1 in 6000 to 10,000 live births and has a prevalence of 1 in 20,000 individuals. Of these individuals, 75% carry sporadic mutations, and 75% to 90% eventually test positive for a TSC gene mutation.² Genetic mosaicism has been reported in 28% of cases affected by large deletions¹ and as few as 1% of cases involving small mutations.³ 

The dermatologic manifestation of mosaic TSC most often includes unilateral angiofibromas, whereas in nonmosaic cases, angiofibromas cover both cheeks, the forehead, and the eyelids. The other skin lesions of TSC--shagreen patches, forehead plaques, hypomelanotic macules, and ungual fibromas--are seen less frequently.^4-6 Additionally, neurologic disease in mosaic patients is notably milder, with 57% of mosaic patients found to have epilepsy compared to 91% of nonmosaic patients.⁷ Our patient had both unilateral facial angiofibromas and a cortical lesion suspicious for a tuber, prompting a suspected diagnosis of mosaic TSC. 

The methods of diagnosis outlined by the International Tuberous Sclerosis Complex Consensus Group pose a challenge in diagnosing mosaic TSC. The clinical criteria require 2 major (eg, multiple angiofibromas, angiomyolipomas, a shagreen patch) and 1 minor feature (eg, dental enamel pit, renal cyst).² However, case reports detailing unilateral facial angiofibromas have described patients with isolated dermatologic findings.^5,6 Further, it has been demonstrated that genetic studies in mosaic TSC can be unreliable depending on the tissue sampled.⁸ Thus, for patients who have mosaic TSC, establishing a definitive diagnosis is not always possible and may rely solely on the clinical picture. 

Considering the differential diagnosis, benign cephalic histiocytosis usually would present with small red-brown macules and papules symmetrically located on the head and neck. The lesions occur at a younger age, usually in the first year or two of life. Fibrofolliculomas present as multiple whitish, slightly larger papules found on the central face. They are a marker for Birt-Hogg-Dubé syndrome, which also is associated with spontaneous pneumothorax.  

Agminated means clustering or grouping of lesions. Agminated melanocytic nevi and agminated Spitz nevi are clusters of nevi. These lesions can vary in size and color. They may be elevated or flat. Melanocytic nevi usually are tan-brown or black. Spitz nevi may be pink or pigmented brown or black. To definitively differentiate between these 2 diagnoses and this patient's diagnosis of angiofibroma, a biopsy is needed.

The Diagnosis: Mosaic Tuberous Sclerosis 

A punch biopsy of the facial lesion was stained with hematoxylin and eosin, which demonstrated spindled and stellate fibroblasts with dilated blood vessels (Figure), consistent with an angiofibroma. Given the clinical presentation and histologic findings, there was concern for a diagnosis of tuberous sclerosis (TSC). The patient was referred for genetic workup but tested negative for mutations of the TSC genes in the blood. Because the patient had only unilateral facial lesions, a possible cortical tuber, no other symptoms, and tested negative for TSC gene mutations, mosaic TSC was considered a likely diagnosis. Her facial lesions were treated with pulsed dye vascular laser therapy. 

Tuberous sclerosis is an autosomal-dominant neurocutaneous disorder caused by inactivation of the genes TSC1 (encoding hamartin) and TSC2 (encoding tuberin). Mutation results in overactivation of the downstream mTOR (mammalian target of rapamycin) pathway, resulting in abnormal cellular proliferation and hamartomas. These benign tumors can be found in nearly every organ, most often in the central nervous system and skin, and they provide for a highly variable presentation of the disease.¹ 

Tuberous sclerosis affects 1 in 6000 to 10,000 live births and has a prevalence of 1 in 20,000 individuals. Of these individuals, 75% carry sporadic mutations, and 75% to 90% eventually test positive for a TSC gene mutation.² Genetic mosaicism has been reported in 28% of cases affected by large deletions¹ and as few as 1% of cases involving small mutations.³ 

The dermatologic manifestation of mosaic TSC most often includes unilateral angiofibromas, whereas in nonmosaic cases, angiofibromas cover both cheeks, the forehead, and the eyelids. The other skin lesions of TSC--shagreen patches, forehead plaques, hypomelanotic macules, and ungual fibromas--are seen less frequently.^4-6 Additionally, neurologic disease in mosaic patients is notably milder, with 57% of mosaic patients found to have epilepsy compared to 91% of nonmosaic patients.⁷ Our patient had both unilateral facial angiofibromas and a cortical lesion suspicious for a tuber, prompting a suspected diagnosis of mosaic TSC. 

The methods of diagnosis outlined by the International Tuberous Sclerosis Complex Consensus Group pose a challenge in diagnosing mosaic TSC. The clinical criteria require 2 major (eg, multiple angiofibromas, angiomyolipomas, a shagreen patch) and 1 minor feature (eg, dental enamel pit, renal cyst).² However, case reports detailing unilateral facial angiofibromas have described patients with isolated dermatologic findings.^5,6 Further, it has been demonstrated that genetic studies in mosaic TSC can be unreliable depending on the tissue sampled.⁸ Thus, for patients who have mosaic TSC, establishing a definitive diagnosis is not always possible and may rely solely on the clinical picture. 

Considering the differential diagnosis, benign cephalic histiocytosis usually would present with small red-brown macules and papules symmetrically located on the head and neck. The lesions occur at a younger age, usually in the first year or two of life. Fibrofolliculomas present as multiple whitish, slightly larger papules found on the central face. They are a marker for Birt-Hogg-Dubé syndrome, which also is associated with spontaneous pneumothorax.  

Agminated means clustering or grouping of lesions. Agminated melanocytic nevi and agminated Spitz nevi are clusters of nevi. These lesions can vary in size and color. They may be elevated or flat. Melanocytic nevi usually are tan-brown or black. Spitz nevi may be pink or pigmented brown or black. To definitively differentiate between these 2 diagnoses and this patient's diagnosis of angiofibroma, a biopsy is needed.

The Diagnosis: Mosaic Tuberous Sclerosis 

A punch biopsy of the facial lesion was stained with hematoxylin and eosin, which demonstrated spindled and stellate fibroblasts with dilated blood vessels (Figure), consistent with an angiofibroma. Given the clinical presentation and histologic findings, there was concern for a diagnosis of tuberous sclerosis (TSC). The patient was referred for genetic workup but tested negative for mutations of the TSC genes in the blood. Because the patient had only unilateral facial lesions, a possible cortical tuber, no other symptoms, and tested negative for TSC gene mutations, mosaic TSC was considered a likely diagnosis. Her facial lesions were treated with pulsed dye vascular laser therapy. 

Tuberous sclerosis is an autosomal-dominant neurocutaneous disorder caused by inactivation of the genes TSC1 (encoding hamartin) and TSC2 (encoding tuberin). Mutation results in overactivation of the downstream mTOR (mammalian target of rapamycin) pathway, resulting in abnormal cellular proliferation and hamartomas. These benign tumors can be found in nearly every organ, most often in the central nervous system and skin, and they provide for a highly variable presentation of the disease.¹ 

Tuberous sclerosis affects 1 in 6000 to 10,000 live births and has a prevalence of 1 in 20,000 individuals. Of these individuals, 75% carry sporadic mutations, and 75% to 90% eventually test positive for a TSC gene mutation.² Genetic mosaicism has been reported in 28% of cases affected by large deletions¹ and as few as 1% of cases involving small mutations.³ 

The dermatologic manifestation of mosaic TSC most often includes unilateral angiofibromas, whereas in nonmosaic cases, angiofibromas cover both cheeks, the forehead, and the eyelids. The other skin lesions of TSC--shagreen patches, forehead plaques, hypomelanotic macules, and ungual fibromas--are seen less frequently.^4-6 Additionally, neurologic disease in mosaic patients is notably milder, with 57% of mosaic patients found to have epilepsy compared to 91% of nonmosaic patients.⁷ Our patient had both unilateral facial angiofibromas and a cortical lesion suspicious for a tuber, prompting a suspected diagnosis of mosaic TSC. 

The methods of diagnosis outlined by the International Tuberous Sclerosis Complex Consensus Group pose a challenge in diagnosing mosaic TSC. The clinical criteria require 2 major (eg, multiple angiofibromas, angiomyolipomas, a shagreen patch) and 1 minor feature (eg, dental enamel pit, renal cyst).² However, case reports detailing unilateral facial angiofibromas have described patients with isolated dermatologic findings.^5,6 Further, it has been demonstrated that genetic studies in mosaic TSC can be unreliable depending on the tissue sampled.⁸ Thus, for patients who have mosaic TSC, establishing a definitive diagnosis is not always possible and may rely solely on the clinical picture. 

Considering the differential diagnosis, benign cephalic histiocytosis usually would present with small red-brown macules and papules symmetrically located on the head and neck. The lesions occur at a younger age, usually in the first year or two of life. Fibrofolliculomas present as multiple whitish, slightly larger papules found on the central face. They are a marker for Birt-Hogg-Dubé syndrome, which also is associated with spontaneous pneumothorax.  

Agminated means clustering or grouping of lesions. Agminated melanocytic nevi and agminated Spitz nevi are clusters of nevi. These lesions can vary in size and color. They may be elevated or flat. Melanocytic nevi usually are tan-brown or black. Spitz nevi may be pink or pigmented brown or black. To definitively differentiate between these 2 diagnoses and this patient's diagnosis of angiofibroma, a biopsy is needed.

According to the Centers for Disease Control and Prevention, a foodborne disease occurs in one in six persons (48 million), resulting in 128,000 hospitalizations and 3,000 deaths annually in the United States. The Foodborne Active Surveillance Network (FoodNet) of the CDC’s Emerging Infections Program monitors cases of eight laboratory diagnosed infections from 10 U.S. sites (covering 15% of the U.S. population). Monitored organisms include Campylobacter, Cyclospora, Listeria, Salmonella, Shiga toxin–producing Escherichia coli (STEC), Shigella, Vibrio, and Yersinia. In 2018, FoodNet identified 25,606 cases of infection, 5,893 hospitalizations, and 120 deaths. The incidence of infection (cases/100,000) was highest for Campylobacter (20), Salmonella (18), STEC (6), Shigella (5), Vibrio (1), Yersinia (0.9), Cyclospora (0.7), and Listeria (0.3). How might these pathogens affect your patients? First, a quick review about the four more common infections. Treatment is beyond the scope of our discussion and you are referred to the 2018-2021 Red Book for assistance. The goal of this column is to prevent your patients from becoming a statistic this holiday season.

Campylobacter

It has been the most common infection reported in FoodNet since 2013. Clinically, patients present with fever, abdominal pain, and nonbloody diarrhea. However, bloody diarrhea maybe the only symptom in neonates and young infants. Abdominal pain can mimic acute appendicitis or intussusception. Bacteremia is rare but has been reported in the elderly and in some patients with underlying conditions. During convalescence, immunoreactive complications including Guillain-Barré syndrome, reactive arthritis, and erythema nodosum may occur. In patients with diarrhea, Campylobacter jejuni and C. coli are the most frequently isolated species.

Campylobacter is present in the intestinal tract of both domestic and wild birds and animals. Transmission is via consumption of contaminated food or water. Undercooked poultry, untreated water, and unpasteurized milk are the three main vehicles of transmission. Campylobacter can be isolated in stool and blood, however isolation from stool requires special media. Rehydration is the primary therapy. Use of azithromycin or erythromycin can shorten both the duration of symptoms and bacterial shedding.

Salmonella

Nontyphoidal salmonella (NTS) are responsible for a variety of infections including asymptomatic carriage, gastroenteritis, bacteremia, and serious focal infections. Gastroenteritis is the most common illness and is manifested as diarrhea, abdominal pain, and fever. If bacteremia occurs, up to 10% of patients will develop focal infections. Invasive disease occurs most frequently in infants, persons with hemoglobinopathies, immunosuppressive disorders, and malignancies. The genus Salmonella is divided into two species, S. enterica and S. bongori with S. enterica subspecies accounting for about half of culture-confirmed Salmonella isolates reported by public health laboratories.

Although infections are more common in the summer, infections can occur year-round. In 2018, the CDC investigated at least 15 food-related NTS outbreaks and 6 have been investigated so far in 2019. In industrialized countries, acquisition usually occurs from ingestion of poultry, eggs, and milk products. Infection also has been reported after animal contact and consumption of fresh produce, meats, and contaminated water. Ground beef is the source of the November 2019 outbreak of S. dublin. Diarrhea develops within 12-72 hours. Salmonella can be isolated from stool, blood, and urine. Treatment usually is not indicated for uncomplicated gastroenteritis. While benefit has not been proven, it is recommended for those at increased risk for developing invasive disease.
 

Shigella

Shigella is the classic cause of colonic or dysenteric diarrhea. Humans are the primary hosts but other primates can be infected. Transmission occurs through direct person-to-person spread, from ingestion of contaminated food and water, and contact with contaminated inanimate objects. Bacteria can survive up to 6 months in food and 30 days in water. As few as 10 organisms can initiate disease. Typically mucoid or bloody diarrhea with abdominal cramps and fever occurs 1-7 days following exposure. Isolation is from stool. Bacteremia is unusual. Therapy is recommended for severe disease.

Shiga toxin–producing Escherichia coli (STEC)

STEC causes hemorrhagic colitis, which can be complicated by hemolytic uremic syndrome. While E. coli O157:H7 is the serotype most often implicated, other serotypes can cause disease. STEC is shed in feces of cattle and other animals. Infection most often is associated with ingestion of undercooked ground beef, but outbreaks also have confirmed that contaminated leafy vegetables, drinking water, peanut butter, and unpasteurized milk have been the source. Symptoms usually develop 3 to 4 days after exposure. Stools initially may be nonbloody. Abdominal pain and bloody diarrhea occur over the next 2-3 days. Fever often is absent or low grade. Stools should be sent for culture and Shiga toxin for diagnosis. Antimicrobial treatment generally is not warranted if STEC is suspected or diagnosed.

Prevention

It seems so simple. Here are the basic guidelines:

• Clean. Wash hands and surfaces frequently.
• Separate. Separate raw meats and eggs from other foods.
• Cook. Cook all meats to the right temperature.
• Chill. Refrigerate food properly.

Finally, two comments about food poisoning:

This article was updated on 11/12/19.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Email her at [email protected].

Information sources

1. foodsafety.gov

2. cdc.gov/foodsafety

3. The United States Department of Agriculture Meat and Poultry Hotline: 888-674-6854

4. Appendix VII: Clinical syndromes associated with foodborne diseases, Red Book online, 31st ed. (Washington DC: Red Book online, 2018, pp. 1086-92).

5. Foodkeeper App available at the App store. Provides appropriate food storage information; food recalls also are available.

According to the Centers for Disease Control and Prevention, a foodborne disease occurs in one in six persons (48 million), resulting in 128,000 hospitalizations and 3,000 deaths annually in the United States. The Foodborne Active Surveillance Network (FoodNet) of the CDC’s Emerging Infections Program monitors cases of eight laboratory diagnosed infections from 10 U.S. sites (covering 15% of the U.S. population). Monitored organisms include Campylobacter, Cyclospora, Listeria, Salmonella, Shiga toxin–producing Escherichia coli (STEC), Shigella, Vibrio, and Yersinia. In 2018, FoodNet identified 25,606 cases of infection, 5,893 hospitalizations, and 120 deaths. The incidence of infection (cases/100,000) was highest for Campylobacter (20), Salmonella (18), STEC (6), Shigella (5), Vibrio (1), Yersinia (0.9), Cyclospora (0.7), and Listeria (0.3). How might these pathogens affect your patients? First, a quick review about the four more common infections. Treatment is beyond the scope of our discussion and you are referred to the 2018-2021 Red Book for assistance. The goal of this column is to prevent your patients from becoming a statistic this holiday season.

Campylobacter

It has been the most common infection reported in FoodNet since 2013. Clinically, patients present with fever, abdominal pain, and nonbloody diarrhea. However, bloody diarrhea maybe the only symptom in neonates and young infants. Abdominal pain can mimic acute appendicitis or intussusception. Bacteremia is rare but has been reported in the elderly and in some patients with underlying conditions. During convalescence, immunoreactive complications including Guillain-Barré syndrome, reactive arthritis, and erythema nodosum may occur. In patients with diarrhea, Campylobacter jejuni and C. coli are the most frequently isolated species.

Campylobacter is present in the intestinal tract of both domestic and wild birds and animals. Transmission is via consumption of contaminated food or water. Undercooked poultry, untreated water, and unpasteurized milk are the three main vehicles of transmission. Campylobacter can be isolated in stool and blood, however isolation from stool requires special media. Rehydration is the primary therapy. Use of azithromycin or erythromycin can shorten both the duration of symptoms and bacterial shedding.

Salmonella

Nontyphoidal salmonella (NTS) are responsible for a variety of infections including asymptomatic carriage, gastroenteritis, bacteremia, and serious focal infections. Gastroenteritis is the most common illness and is manifested as diarrhea, abdominal pain, and fever. If bacteremia occurs, up to 10% of patients will develop focal infections. Invasive disease occurs most frequently in infants, persons with hemoglobinopathies, immunosuppressive disorders, and malignancies. The genus Salmonella is divided into two species, S. enterica and S. bongori with S. enterica subspecies accounting for about half of culture-confirmed Salmonella isolates reported by public health laboratories.

Although infections are more common in the summer, infections can occur year-round. In 2018, the CDC investigated at least 15 food-related NTS outbreaks and 6 have been investigated so far in 2019. In industrialized countries, acquisition usually occurs from ingestion of poultry, eggs, and milk products. Infection also has been reported after animal contact and consumption of fresh produce, meats, and contaminated water. Ground beef is the source of the November 2019 outbreak of S. dublin. Diarrhea develops within 12-72 hours. Salmonella can be isolated from stool, blood, and urine. Treatment usually is not indicated for uncomplicated gastroenteritis. While benefit has not been proven, it is recommended for those at increased risk for developing invasive disease.
 

Shigella

Shigella is the classic cause of colonic or dysenteric diarrhea. Humans are the primary hosts but other primates can be infected. Transmission occurs through direct person-to-person spread, from ingestion of contaminated food and water, and contact with contaminated inanimate objects. Bacteria can survive up to 6 months in food and 30 days in water. As few as 10 organisms can initiate disease. Typically mucoid or bloody diarrhea with abdominal cramps and fever occurs 1-7 days following exposure. Isolation is from stool. Bacteremia is unusual. Therapy is recommended for severe disease.

Shiga toxin–producing Escherichia coli (STEC)

STEC causes hemorrhagic colitis, which can be complicated by hemolytic uremic syndrome. While E. coli O157:H7 is the serotype most often implicated, other serotypes can cause disease. STEC is shed in feces of cattle and other animals. Infection most often is associated with ingestion of undercooked ground beef, but outbreaks also have confirmed that contaminated leafy vegetables, drinking water, peanut butter, and unpasteurized milk have been the source. Symptoms usually develop 3 to 4 days after exposure. Stools initially may be nonbloody. Abdominal pain and bloody diarrhea occur over the next 2-3 days. Fever often is absent or low grade. Stools should be sent for culture and Shiga toxin for diagnosis. Antimicrobial treatment generally is not warranted if STEC is suspected or diagnosed.

Prevention

It seems so simple. Here are the basic guidelines:

• Clean. Wash hands and surfaces frequently.
• Separate. Separate raw meats and eggs from other foods.
• Cook. Cook all meats to the right temperature.
• Chill. Refrigerate food properly.

Finally, two comments about food poisoning:

This article was updated on 11/12/19.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Email her at [email protected].

Information sources

1. foodsafety.gov

2. cdc.gov/foodsafety

3. The United States Department of Agriculture Meat and Poultry Hotline: 888-674-6854

4. Appendix VII: Clinical syndromes associated with foodborne diseases, Red Book online, 31st ed. (Washington DC: Red Book online, 2018, pp. 1086-92).

5. Foodkeeper App available at the App store. Provides appropriate food storage information; food recalls also are available.

According to the Centers for Disease Control and Prevention, a foodborne disease occurs in one in six persons (48 million), resulting in 128,000 hospitalizations and 3,000 deaths annually in the United States. The Foodborne Active Surveillance Network (FoodNet) of the CDC’s Emerging Infections Program monitors cases of eight laboratory diagnosed infections from 10 U.S. sites (covering 15% of the U.S. population). Monitored organisms include Campylobacter, Cyclospora, Listeria, Salmonella, Shiga toxin–producing Escherichia coli (STEC), Shigella, Vibrio, and Yersinia. In 2018, FoodNet identified 25,606 cases of infection, 5,893 hospitalizations, and 120 deaths. The incidence of infection (cases/100,000) was highest for Campylobacter (20), Salmonella (18), STEC (6), Shigella (5), Vibrio (1), Yersinia (0.9), Cyclospora (0.7), and Listeria (0.3). How might these pathogens affect your patients? First, a quick review about the four more common infections. Treatment is beyond the scope of our discussion and you are referred to the 2018-2021 Red Book for assistance. The goal of this column is to prevent your patients from becoming a statistic this holiday season.

Campylobacter

It has been the most common infection reported in FoodNet since 2013. Clinically, patients present with fever, abdominal pain, and nonbloody diarrhea. However, bloody diarrhea maybe the only symptom in neonates and young infants. Abdominal pain can mimic acute appendicitis or intussusception. Bacteremia is rare but has been reported in the elderly and in some patients with underlying conditions. During convalescence, immunoreactive complications including Guillain-Barré syndrome, reactive arthritis, and erythema nodosum may occur. In patients with diarrhea, Campylobacter jejuni and C. coli are the most frequently isolated species.

Campylobacter is present in the intestinal tract of both domestic and wild birds and animals. Transmission is via consumption of contaminated food or water. Undercooked poultry, untreated water, and unpasteurized milk are the three main vehicles of transmission. Campylobacter can be isolated in stool and blood, however isolation from stool requires special media. Rehydration is the primary therapy. Use of azithromycin or erythromycin can shorten both the duration of symptoms and bacterial shedding.

Salmonella

Nontyphoidal salmonella (NTS) are responsible for a variety of infections including asymptomatic carriage, gastroenteritis, bacteremia, and serious focal infections. Gastroenteritis is the most common illness and is manifested as diarrhea, abdominal pain, and fever. If bacteremia occurs, up to 10% of patients will develop focal infections. Invasive disease occurs most frequently in infants, persons with hemoglobinopathies, immunosuppressive disorders, and malignancies. The genus Salmonella is divided into two species, S. enterica and S. bongori with S. enterica subspecies accounting for about half of culture-confirmed Salmonella isolates reported by public health laboratories.

Although infections are more common in the summer, infections can occur year-round. In 2018, the CDC investigated at least 15 food-related NTS outbreaks and 6 have been investigated so far in 2019. In industrialized countries, acquisition usually occurs from ingestion of poultry, eggs, and milk products. Infection also has been reported after animal contact and consumption of fresh produce, meats, and contaminated water. Ground beef is the source of the November 2019 outbreak of S. dublin. Diarrhea develops within 12-72 hours. Salmonella can be isolated from stool, blood, and urine. Treatment usually is not indicated for uncomplicated gastroenteritis. While benefit has not been proven, it is recommended for those at increased risk for developing invasive disease.
 

Shigella

Shigella is the classic cause of colonic or dysenteric diarrhea. Humans are the primary hosts but other primates can be infected. Transmission occurs through direct person-to-person spread, from ingestion of contaminated food and water, and contact with contaminated inanimate objects. Bacteria can survive up to 6 months in food and 30 days in water. As few as 10 organisms can initiate disease. Typically mucoid or bloody diarrhea with abdominal cramps and fever occurs 1-7 days following exposure. Isolation is from stool. Bacteremia is unusual. Therapy is recommended for severe disease.

Shiga toxin–producing Escherichia coli (STEC)

STEC causes hemorrhagic colitis, which can be complicated by hemolytic uremic syndrome. While E. coli O157:H7 is the serotype most often implicated, other serotypes can cause disease. STEC is shed in feces of cattle and other animals. Infection most often is associated with ingestion of undercooked ground beef, but outbreaks also have confirmed that contaminated leafy vegetables, drinking water, peanut butter, and unpasteurized milk have been the source. Symptoms usually develop 3 to 4 days after exposure. Stools initially may be nonbloody. Abdominal pain and bloody diarrhea occur over the next 2-3 days. Fever often is absent or low grade. Stools should be sent for culture and Shiga toxin for diagnosis. Antimicrobial treatment generally is not warranted if STEC is suspected or diagnosed.

Prevention

It seems so simple. Here are the basic guidelines:

• Clean. Wash hands and surfaces frequently.
• Separate. Separate raw meats and eggs from other foods.
• Cook. Cook all meats to the right temperature.
• Chill. Refrigerate food properly.

Finally, two comments about food poisoning:

This article was updated on 11/12/19.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Email her at [email protected].

Information sources

1. foodsafety.gov

2. cdc.gov/foodsafety

3. The United States Department of Agriculture Meat and Poultry Hotline: 888-674-6854

4. Appendix VII: Clinical syndromes associated with foodborne diseases, Red Book online, 31st ed. (Washington DC: Red Book online, 2018, pp. 1086-92).

5. Foodkeeper App available at the App store. Provides appropriate food storage information; food recalls also are available.