New york – Hidradenitis suppurativa (HS) might be more common and more of a clinical burden in the black population than the white population, but the opportunity for disease control and improvements in quality of life in the former are improving, according to an overview presented at the Skin of Color Update 2019.

Two studies published within the last 18 months that included large proportions of black patients have provided evidence that surgery is effective in those inadequately controlled on medical therapies, Theodore Rosen, MD, professor of dermatology at Baylor College of Medicine, Houston, Texas, said at the meeting.

The best results were observed in a study that evaluated the impact of surgery and adjunctive biologic therapy, according to Dr. Rosen. Of the 68 patients, 59 (72%) were black (Int J Dermatol. 2018;57[1]:62-9). For those patients who received both surgery and biologic therapy, there was a nearly three times greater likelihood of achieving a 75% reduction in the active nodule count (AN75) after adjusting for covariates, compared with those who received only surgery (hazard ratio, 2.88; P = .047).

“It did not appear to matter which came first,” said Dr. Rosen, who is also chief of the dermatology service at Michael E. DeBakey Veterans Affairs Medical Center, Houston. He added, “this is a lot of work, and it is a lot of cost. It requires dedicated people, but it probably is the best thing we possibly do in difficult cases.”

In the other study cited by Dr. Rosen, a review of surgical procedures used to treat HS, the authors concluded that en bloc excision of HS was a better approach than less aggressive surgical approaches, such as drainage, because it lowered the risk of recurrences. This evaluation also included a substantial number of black patients, he said.

It is appropriate to consider black patients separately when discussing HS for a number of reasons. One is the evidence that the disease is more common in this population. Although Dr. Rosen cautioned that prevalence studies do not show this consistently, he believes the preponderance of evidence supports this assertion.

In addition, HS appears to be more severe in black patients. Many of the risk factors that predict a difficult course, such as obesity and diabetes, are more prevalent in the black population, Dr. Rosen said. He also cited a study that concluded HS imposes a larger overall negative impact on quality of life in nonwhite than in white patients (Skin Appendage Disord 2015 Sep;1[2]:65-73).

Despite the evidence that surgery plus biologics is an effective strategy for control of severe disease, there remains no standard approach – even for initial therapy, according to Dr. Rosen. Lifestyle modifications, such as weight loss and smoking cessation, are a starting point, but the order of the next best steps are unclear.

At many centers, biologics have been moved forward in the algorithm on the basis of two placebo-controlled trials that associated adalimumab with higher clinical response rates activity in HS (N Engl J Med. 2016 Aug 4;375[5]:422-34). But Dr. Rosen cautioned that this trial did not include many patients with skin of color, and failure rates are not insignificant.

Promising activity has been reported in HS with both anti–interleukin-17 therapies and apremilast, a phosphodiesterase 4 (PDE4) inhibitor, according to Dr. Rosen but this experience is limited overall and more so in black patients. He listed other drugs associated with benefit in cases studies, such as metformin, which deserve consideration when more conventional options fail, but he reiterated that there is no established ladder of therapies to consider in HS patients regardless of skin type.

Overall, treatment strategies are not different in nonwhite patients relative to white patients, but Dr. Rosen believes that the greater severity of HS in black individuals warrants attention. He noted, for example, that the risk of squamous cell carcinoma, which is elevated in HS patients overall, appears to be even higher in black patients with HS.

Although he did not advocate metformin or any of the other off-label treatments associated with efficacy in case studies, he acknowledged that “this may be where you have to go” when the devastating symptoms of HS remain uncontrolled.
 

Dr. Rosen reports no relevant financial relationships to disclose.

New york – Hidradenitis suppurativa (HS) might be more common and more of a clinical burden in the black population than the white population, but the opportunity for disease control and improvements in quality of life in the former are improving, according to an overview presented at the Skin of Color Update 2019.

Two studies published within the last 18 months that included large proportions of black patients have provided evidence that surgery is effective in those inadequately controlled on medical therapies, Theodore Rosen, MD, professor of dermatology at Baylor College of Medicine, Houston, Texas, said at the meeting.

The best results were observed in a study that evaluated the impact of surgery and adjunctive biologic therapy, according to Dr. Rosen. Of the 68 patients, 59 (72%) were black (Int J Dermatol. 2018;57[1]:62-9). For those patients who received both surgery and biologic therapy, there was a nearly three times greater likelihood of achieving a 75% reduction in the active nodule count (AN75) after adjusting for covariates, compared with those who received only surgery (hazard ratio, 2.88; P = .047).

“It did not appear to matter which came first,” said Dr. Rosen, who is also chief of the dermatology service at Michael E. DeBakey Veterans Affairs Medical Center, Houston. He added, “this is a lot of work, and it is a lot of cost. It requires dedicated people, but it probably is the best thing we possibly do in difficult cases.”

In the other study cited by Dr. Rosen, a review of surgical procedures used to treat HS, the authors concluded that en bloc excision of HS was a better approach than less aggressive surgical approaches, such as drainage, because it lowered the risk of recurrences. This evaluation also included a substantial number of black patients, he said.

It is appropriate to consider black patients separately when discussing HS for a number of reasons. One is the evidence that the disease is more common in this population. Although Dr. Rosen cautioned that prevalence studies do not show this consistently, he believes the preponderance of evidence supports this assertion.

In addition, HS appears to be more severe in black patients. Many of the risk factors that predict a difficult course, such as obesity and diabetes, are more prevalent in the black population, Dr. Rosen said. He also cited a study that concluded HS imposes a larger overall negative impact on quality of life in nonwhite than in white patients (Skin Appendage Disord 2015 Sep;1[2]:65-73).

Despite the evidence that surgery plus biologics is an effective strategy for control of severe disease, there remains no standard approach – even for initial therapy, according to Dr. Rosen. Lifestyle modifications, such as weight loss and smoking cessation, are a starting point, but the order of the next best steps are unclear.

At many centers, biologics have been moved forward in the algorithm on the basis of two placebo-controlled trials that associated adalimumab with higher clinical response rates activity in HS (N Engl J Med. 2016 Aug 4;375[5]:422-34). But Dr. Rosen cautioned that this trial did not include many patients with skin of color, and failure rates are not insignificant.

Promising activity has been reported in HS with both anti–interleukin-17 therapies and apremilast, a phosphodiesterase 4 (PDE4) inhibitor, according to Dr. Rosen but this experience is limited overall and more so in black patients. He listed other drugs associated with benefit in cases studies, such as metformin, which deserve consideration when more conventional options fail, but he reiterated that there is no established ladder of therapies to consider in HS patients regardless of skin type.

Overall, treatment strategies are not different in nonwhite patients relative to white patients, but Dr. Rosen believes that the greater severity of HS in black individuals warrants attention. He noted, for example, that the risk of squamous cell carcinoma, which is elevated in HS patients overall, appears to be even higher in black patients with HS.

Although he did not advocate metformin or any of the other off-label treatments associated with efficacy in case studies, he acknowledged that “this may be where you have to go” when the devastating symptoms of HS remain uncontrolled.
 

Dr. Rosen reports no relevant financial relationships to disclose.

New york – Hidradenitis suppurativa (HS) might be more common and more of a clinical burden in the black population than the white population, but the opportunity for disease control and improvements in quality of life in the former are improving, according to an overview presented at the Skin of Color Update 2019.

Two studies published within the last 18 months that included large proportions of black patients have provided evidence that surgery is effective in those inadequately controlled on medical therapies, Theodore Rosen, MD, professor of dermatology at Baylor College of Medicine, Houston, Texas, said at the meeting.

The best results were observed in a study that evaluated the impact of surgery and adjunctive biologic therapy, according to Dr. Rosen. Of the 68 patients, 59 (72%) were black (Int J Dermatol. 2018;57[1]:62-9). For those patients who received both surgery and biologic therapy, there was a nearly three times greater likelihood of achieving a 75% reduction in the active nodule count (AN75) after adjusting for covariates, compared with those who received only surgery (hazard ratio, 2.88; P = .047).

“It did not appear to matter which came first,” said Dr. Rosen, who is also chief of the dermatology service at Michael E. DeBakey Veterans Affairs Medical Center, Houston. He added, “this is a lot of work, and it is a lot of cost. It requires dedicated people, but it probably is the best thing we possibly do in difficult cases.”

In the other study cited by Dr. Rosen, a review of surgical procedures used to treat HS, the authors concluded that en bloc excision of HS was a better approach than less aggressive surgical approaches, such as drainage, because it lowered the risk of recurrences. This evaluation also included a substantial number of black patients, he said.

It is appropriate to consider black patients separately when discussing HS for a number of reasons. One is the evidence that the disease is more common in this population. Although Dr. Rosen cautioned that prevalence studies do not show this consistently, he believes the preponderance of evidence supports this assertion.

In addition, HS appears to be more severe in black patients. Many of the risk factors that predict a difficult course, such as obesity and diabetes, are more prevalent in the black population, Dr. Rosen said. He also cited a study that concluded HS imposes a larger overall negative impact on quality of life in nonwhite than in white patients (Skin Appendage Disord 2015 Sep;1[2]:65-73).

Despite the evidence that surgery plus biologics is an effective strategy for control of severe disease, there remains no standard approach – even for initial therapy, according to Dr. Rosen. Lifestyle modifications, such as weight loss and smoking cessation, are a starting point, but the order of the next best steps are unclear.

At many centers, biologics have been moved forward in the algorithm on the basis of two placebo-controlled trials that associated adalimumab with higher clinical response rates activity in HS (N Engl J Med. 2016 Aug 4;375[5]:422-34). But Dr. Rosen cautioned that this trial did not include many patients with skin of color, and failure rates are not insignificant.

Promising activity has been reported in HS with both anti–interleukin-17 therapies and apremilast, a phosphodiesterase 4 (PDE4) inhibitor, according to Dr. Rosen but this experience is limited overall and more so in black patients. He listed other drugs associated with benefit in cases studies, such as metformin, which deserve consideration when more conventional options fail, but he reiterated that there is no established ladder of therapies to consider in HS patients regardless of skin type.

Overall, treatment strategies are not different in nonwhite patients relative to white patients, but Dr. Rosen believes that the greater severity of HS in black individuals warrants attention. He noted, for example, that the risk of squamous cell carcinoma, which is elevated in HS patients overall, appears to be even higher in black patients with HS.

Although he did not advocate metformin or any of the other off-label treatments associated with efficacy in case studies, he acknowledged that “this may be where you have to go” when the devastating symptoms of HS remain uncontrolled.
 

Dr. Rosen reports no relevant financial relationships to disclose.

Is your glass always half full? Is that because you’re so busy that you never have time to finish drinking it? Or is it because you are an optimist? Have you always been someone who could see a glimmer at the end of even the darkest, longest tunnels? Do you think your positive outlook is something you inherited? Or did you model it after continued exposure to an optimistic parent or medical school mentor?

Wavebreakmedia/Thinkstock

Are you aware that your optimism makes it more likely that you will live to a ripe old age? A recent study of 69,744 women and 1,429 men initiated by researchers at the Harvard School T.H. Chan School of Public Health in Boston, Boston University Medical School, and the National Center for PTSD at Veterans Affairs Boston Health Care System found that “individuals with greater optimism are more likely to live longer and to achieve ‘exceptional longevity,’ that is, living to 85 or older” (“New Evidence that optimists live longer.” Harvard T.C. Chan School of Public Health. August 27, 2019).

Do you think your optimism has been a positive contribution to your success as a physician? Or have there been times when it has been a liability?

Because I’m not going to wait for you to answer, I’ll share my own observations. I sense that optimism is something with a strong genetic component, just as is the vulnerability to anxiety and depression. My mother was an optimist. However, I suspect that being around an individual who exudes a high degree of optimism can have a positive influence on a person who already has a partly cloudy disposition.

On the other hand, I’ve found that it is very difficult for even the most optimistic people to induce a positive outlook in individuals born with a chronically half empty glass simply by radiating their own aura of optimism. In my own experience, I have found that being an optimist has definitely been an asset in my role as a physician. In most situations, sounding or just appearing hopeful can help ease the tension for a patient or family – tension that may be exacerbating their ability to cope with the presenting problem. However, I have had to learn to recognize more quickly that there are situations when my optimism isn’t going to be effective and not become frustrated by its inadequacy.

Are there downsides to being an optimistic physician? Of course; there can be a fine line between being an optimist and sounding like a Pollyanna. To avoid stepping over the line, optimists must choose their words carefully. And more importantly, they must be reading the patient’s and family’s response to attempts at injecting positivity into the situation. Optimism also can be mistaken for a nonchalant attitude that signals a lack of caring and concern.

However, the most dangerous liability of optimism occurs when it slips into the swift running and turbulent waters of denial. I have almost killed myself on a couple of occasions when my “optimistic” interpretation of my symptoms has prompted me to “tough out” a potentially fatal situation instead of seeking timely advice from my physician.

My optimism sometimes has made it difficult for me to be appropriately objective when assessing the seriousness of a patient’s condition. Given a list of positives and negatives, my tendency might be focus more on the positives. As far as I know, my overly positive attitude has never killed any of my patients, but I fear a few diagnoses and remedies may have been delayed when the Prince of Optimism became the Queen of Denial.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

Is your glass always half full? Is that because you’re so busy that you never have time to finish drinking it? Or is it because you are an optimist? Have you always been someone who could see a glimmer at the end of even the darkest, longest tunnels? Do you think your positive outlook is something you inherited? Or did you model it after continued exposure to an optimistic parent or medical school mentor?

Wavebreakmedia/Thinkstock

Are you aware that your optimism makes it more likely that you will live to a ripe old age? A recent study of 69,744 women and 1,429 men initiated by researchers at the Harvard School T.H. Chan School of Public Health in Boston, Boston University Medical School, and the National Center for PTSD at Veterans Affairs Boston Health Care System found that “individuals with greater optimism are more likely to live longer and to achieve ‘exceptional longevity,’ that is, living to 85 or older” (“New Evidence that optimists live longer.” Harvard T.C. Chan School of Public Health. August 27, 2019).

Do you think your optimism has been a positive contribution to your success as a physician? Or have there been times when it has been a liability?

Because I’m not going to wait for you to answer, I’ll share my own observations. I sense that optimism is something with a strong genetic component, just as is the vulnerability to anxiety and depression. My mother was an optimist. However, I suspect that being around an individual who exudes a high degree of optimism can have a positive influence on a person who already has a partly cloudy disposition.

On the other hand, I’ve found that it is very difficult for even the most optimistic people to induce a positive outlook in individuals born with a chronically half empty glass simply by radiating their own aura of optimism. In my own experience, I have found that being an optimist has definitely been an asset in my role as a physician. In most situations, sounding or just appearing hopeful can help ease the tension for a patient or family – tension that may be exacerbating their ability to cope with the presenting problem. However, I have had to learn to recognize more quickly that there are situations when my optimism isn’t going to be effective and not become frustrated by its inadequacy.

Are there downsides to being an optimistic physician? Of course; there can be a fine line between being an optimist and sounding like a Pollyanna. To avoid stepping over the line, optimists must choose their words carefully. And more importantly, they must be reading the patient’s and family’s response to attempts at injecting positivity into the situation. Optimism also can be mistaken for a nonchalant attitude that signals a lack of caring and concern.

However, the most dangerous liability of optimism occurs when it slips into the swift running and turbulent waters of denial. I have almost killed myself on a couple of occasions when my “optimistic” interpretation of my symptoms has prompted me to “tough out” a potentially fatal situation instead of seeking timely advice from my physician.

My optimism sometimes has made it difficult for me to be appropriately objective when assessing the seriousness of a patient’s condition. Given a list of positives and negatives, my tendency might be focus more on the positives. As far as I know, my overly positive attitude has never killed any of my patients, but I fear a few diagnoses and remedies may have been delayed when the Prince of Optimism became the Queen of Denial.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

Is your glass always half full? Is that because you’re so busy that you never have time to finish drinking it? Or is it because you are an optimist? Have you always been someone who could see a glimmer at the end of even the darkest, longest tunnels? Do you think your positive outlook is something you inherited? Or did you model it after continued exposure to an optimistic parent or medical school mentor?

Wavebreakmedia/Thinkstock

Are you aware that your optimism makes it more likely that you will live to a ripe old age? A recent study of 69,744 women and 1,429 men initiated by researchers at the Harvard School T.H. Chan School of Public Health in Boston, Boston University Medical School, and the National Center for PTSD at Veterans Affairs Boston Health Care System found that “individuals with greater optimism are more likely to live longer and to achieve ‘exceptional longevity,’ that is, living to 85 or older” (“New Evidence that optimists live longer.” Harvard T.C. Chan School of Public Health. August 27, 2019).

Do you think your optimism has been a positive contribution to your success as a physician? Or have there been times when it has been a liability?

Because I’m not going to wait for you to answer, I’ll share my own observations. I sense that optimism is something with a strong genetic component, just as is the vulnerability to anxiety and depression. My mother was an optimist. However, I suspect that being around an individual who exudes a high degree of optimism can have a positive influence on a person who already has a partly cloudy disposition.

On the other hand, I’ve found that it is very difficult for even the most optimistic people to induce a positive outlook in individuals born with a chronically half empty glass simply by radiating their own aura of optimism. In my own experience, I have found that being an optimist has definitely been an asset in my role as a physician. In most situations, sounding or just appearing hopeful can help ease the tension for a patient or family – tension that may be exacerbating their ability to cope with the presenting problem. However, I have had to learn to recognize more quickly that there are situations when my optimism isn’t going to be effective and not become frustrated by its inadequacy.

Are there downsides to being an optimistic physician? Of course; there can be a fine line between being an optimist and sounding like a Pollyanna. To avoid stepping over the line, optimists must choose their words carefully. And more importantly, they must be reading the patient’s and family’s response to attempts at injecting positivity into the situation. Optimism also can be mistaken for a nonchalant attitude that signals a lack of caring and concern.

However, the most dangerous liability of optimism occurs when it slips into the swift running and turbulent waters of denial. I have almost killed myself on a couple of occasions when my “optimistic” interpretation of my symptoms has prompted me to “tough out” a potentially fatal situation instead of seeking timely advice from my physician.

My optimism sometimes has made it difficult for me to be appropriately objective when assessing the seriousness of a patient’s condition. Given a list of positives and negatives, my tendency might be focus more on the positives. As far as I know, my overly positive attitude has never killed any of my patients, but I fear a few diagnoses and remedies may have been delayed when the Prince of Optimism became the Queen of Denial.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

NEW ORLEANS – In children, ambulatory systolic daytime blood pressure load – the amount of time spent above the 95^th blood pressure percentile for age and height – predicts cardiovascular target-organ damage, specifically diastolic dysfunction and arterial stiffness, according to an investigation from the American Heart Association Strategically Focused Research Network.

M. Alexander Otto/MDedge News

Blood pressure load is considered in the 2017 American Academy of Pediatrics BP guideline, but the new findings add granularity on how to use it in practice. It’s part of an effort “to supply data to guide future guidelines, rather than arbitrarily picking a number – the 95th percentile – out of the sky,” said lead investigator and pediatric cardiologist Elaine Urbina, MD, director of preventative cardiology at the Cincinnati Children’s Hospital Medical Center, and senior author on the 2017 guideline.

In the absence of data linking specific BP levels to hard cardiovascular outcomes, as in adults, “we feel that load is helpful in determining risk categories for kids as we make decisions about who should get lifestyle counseling and who should get medication. It gets a little bit at blood pressure variability” and supplements the arbitrary 95th-percentile threshold, she said.

“If I saw a child with only a mild elevation of mean ambulatory blood pressure but they had increased load, it would prompt me to order an echocardiogram to look for target organ damage, which may then change my therapy from lifestyle to medication,” Dr. Urbina said at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

These conclusions come from an investigation of 339 healthy adolescents with a mean age of 15.6 years at six sites across the United States. Office BP was averaged over six readings during two visits, and ambulatory pressure was taken every 20 minutes over 26 hours. BP load was correlated with measures of left ventricular mass index (LVMI), systolic and diastolic function (E/e’ ratio), and pulse wave velocity (PWV), a gauge of arterial stiffness.

Overall, 215 subjects spent less than 25% of their time above the 95th percentile and were classified as the low-load group, 62 were above that mark 25%-49% of the time (mid-load group), and 62 were over it at least half of the time (high-load group).

Both load category and load as a continuous variable were significant predictors of arterial stiffness and diastolic dysfunction even after adjustment for age, sex, body mass index, and mean daytime ambulatory systolic blood pressure (P less than 0.0001).

Subjects in the high-load group, for instance, had a PWV above 5.5 m/sec, versus about 5.2 m/sec and less than 5 m/sec in the mid- and low-load groups, respectively. The high-load group had an E/e’ ratio above 7, versus 6 or less in the other groups. There was a trend for higher LVMI and reduced strain as well in the low- versus high-load groups.

Although the findings don’t indicate clinically relevant cardiovascular damage, children with higher loads seem to be “on the road to getting it,” Dr. Urbina said. Greater arterial stiffness means that high pulsatile pressures are transmitted to the microvasculature. Meanwhile, “the strength of the relationship with diastolic dysfunction worries me. It’s a precursor of heart failure with preserved ejection fraction, for which there are no effective therapies. We have to identify the precursors early and treat them so these kids don’t get heart failure later in life.”

Almost two-thirds of the subjects were white, most of the remainder were black, and 58% were boys. There were no statistically significant differences in age, race, sex, or body mass index across the groups, but overall, the children were overweight, and those with high BP load were more insulin resistant and had higher clinic and ambulatory BPs.

The team is assessing cognitive performance as a function of BP load.

Ambulatory pressures were taken by the Spacelabs OnTrak monitor.

The work was funded by the AHA and the National Institutes of Health. The investigators had no commercial disclosures.

[email protected]

SOURCE: Urbina E. Joint Hypertension 2019, Abstract P2056.

NEW ORLEANS – In children, ambulatory systolic daytime blood pressure load – the amount of time spent above the 95^th blood pressure percentile for age and height – predicts cardiovascular target-organ damage, specifically diastolic dysfunction and arterial stiffness, according to an investigation from the American Heart Association Strategically Focused Research Network.

M. Alexander Otto/MDedge News

Blood pressure load is considered in the 2017 American Academy of Pediatrics BP guideline, but the new findings add granularity on how to use it in practice. It’s part of an effort “to supply data to guide future guidelines, rather than arbitrarily picking a number – the 95th percentile – out of the sky,” said lead investigator and pediatric cardiologist Elaine Urbina, MD, director of preventative cardiology at the Cincinnati Children’s Hospital Medical Center, and senior author on the 2017 guideline.

In the absence of data linking specific BP levels to hard cardiovascular outcomes, as in adults, “we feel that load is helpful in determining risk categories for kids as we make decisions about who should get lifestyle counseling and who should get medication. It gets a little bit at blood pressure variability” and supplements the arbitrary 95th-percentile threshold, she said.

“If I saw a child with only a mild elevation of mean ambulatory blood pressure but they had increased load, it would prompt me to order an echocardiogram to look for target organ damage, which may then change my therapy from lifestyle to medication,” Dr. Urbina said at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

These conclusions come from an investigation of 339 healthy adolescents with a mean age of 15.6 years at six sites across the United States. Office BP was averaged over six readings during two visits, and ambulatory pressure was taken every 20 minutes over 26 hours. BP load was correlated with measures of left ventricular mass index (LVMI), systolic and diastolic function (E/e’ ratio), and pulse wave velocity (PWV), a gauge of arterial stiffness.

Overall, 215 subjects spent less than 25% of their time above the 95th percentile and were classified as the low-load group, 62 were above that mark 25%-49% of the time (mid-load group), and 62 were over it at least half of the time (high-load group).

Both load category and load as a continuous variable were significant predictors of arterial stiffness and diastolic dysfunction even after adjustment for age, sex, body mass index, and mean daytime ambulatory systolic blood pressure (P less than 0.0001).

Subjects in the high-load group, for instance, had a PWV above 5.5 m/sec, versus about 5.2 m/sec and less than 5 m/sec in the mid- and low-load groups, respectively. The high-load group had an E/e’ ratio above 7, versus 6 or less in the other groups. There was a trend for higher LVMI and reduced strain as well in the low- versus high-load groups.

Although the findings don’t indicate clinically relevant cardiovascular damage, children with higher loads seem to be “on the road to getting it,” Dr. Urbina said. Greater arterial stiffness means that high pulsatile pressures are transmitted to the microvasculature. Meanwhile, “the strength of the relationship with diastolic dysfunction worries me. It’s a precursor of heart failure with preserved ejection fraction, for which there are no effective therapies. We have to identify the precursors early and treat them so these kids don’t get heart failure later in life.”

Almost two-thirds of the subjects were white, most of the remainder were black, and 58% were boys. There were no statistically significant differences in age, race, sex, or body mass index across the groups, but overall, the children were overweight, and those with high BP load were more insulin resistant and had higher clinic and ambulatory BPs.

The team is assessing cognitive performance as a function of BP load.

Ambulatory pressures were taken by the Spacelabs OnTrak monitor.

The work was funded by the AHA and the National Institutes of Health. The investigators had no commercial disclosures.

[email protected]

SOURCE: Urbina E. Joint Hypertension 2019, Abstract P2056.

NEW ORLEANS – In children, ambulatory systolic daytime blood pressure load – the amount of time spent above the 95^th blood pressure percentile for age and height – predicts cardiovascular target-organ damage, specifically diastolic dysfunction and arterial stiffness, according to an investigation from the American Heart Association Strategically Focused Research Network.

M. Alexander Otto/MDedge News

Blood pressure load is considered in the 2017 American Academy of Pediatrics BP guideline, but the new findings add granularity on how to use it in practice. It’s part of an effort “to supply data to guide future guidelines, rather than arbitrarily picking a number – the 95th percentile – out of the sky,” said lead investigator and pediatric cardiologist Elaine Urbina, MD, director of preventative cardiology at the Cincinnati Children’s Hospital Medical Center, and senior author on the 2017 guideline.

In the absence of data linking specific BP levels to hard cardiovascular outcomes, as in adults, “we feel that load is helpful in determining risk categories for kids as we make decisions about who should get lifestyle counseling and who should get medication. It gets a little bit at blood pressure variability” and supplements the arbitrary 95th-percentile threshold, she said.

“If I saw a child with only a mild elevation of mean ambulatory blood pressure but they had increased load, it would prompt me to order an echocardiogram to look for target organ damage, which may then change my therapy from lifestyle to medication,” Dr. Urbina said at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

These conclusions come from an investigation of 339 healthy adolescents with a mean age of 15.6 years at six sites across the United States. Office BP was averaged over six readings during two visits, and ambulatory pressure was taken every 20 minutes over 26 hours. BP load was correlated with measures of left ventricular mass index (LVMI), systolic and diastolic function (E/e’ ratio), and pulse wave velocity (PWV), a gauge of arterial stiffness.

Overall, 215 subjects spent less than 25% of their time above the 95th percentile and were classified as the low-load group, 62 were above that mark 25%-49% of the time (mid-load group), and 62 were over it at least half of the time (high-load group).

Both load category and load as a continuous variable were significant predictors of arterial stiffness and diastolic dysfunction even after adjustment for age, sex, body mass index, and mean daytime ambulatory systolic blood pressure (P less than 0.0001).

Subjects in the high-load group, for instance, had a PWV above 5.5 m/sec, versus about 5.2 m/sec and less than 5 m/sec in the mid- and low-load groups, respectively. The high-load group had an E/e’ ratio above 7, versus 6 or less in the other groups. There was a trend for higher LVMI and reduced strain as well in the low- versus high-load groups.

Although the findings don’t indicate clinically relevant cardiovascular damage, children with higher loads seem to be “on the road to getting it,” Dr. Urbina said. Greater arterial stiffness means that high pulsatile pressures are transmitted to the microvasculature. Meanwhile, “the strength of the relationship with diastolic dysfunction worries me. It’s a precursor of heart failure with preserved ejection fraction, for which there are no effective therapies. We have to identify the precursors early and treat them so these kids don’t get heart failure later in life.”

Almost two-thirds of the subjects were white, most of the remainder were black, and 58% were boys. There were no statistically significant differences in age, race, sex, or body mass index across the groups, but overall, the children were overweight, and those with high BP load were more insulin resistant and had higher clinic and ambulatory BPs.

The team is assessing cognitive performance as a function of BP load.

Ambulatory pressures were taken by the Spacelabs OnTrak monitor.

The work was funded by the AHA and the National Institutes of Health. The investigators had no commercial disclosures.

[email protected]

SOURCE: Urbina E. Joint Hypertension 2019, Abstract P2056.

Add-on benralizumab is not associated with a significantly lower annualized rate of exacerbations in patients with moderate to severe chronic obstructive pulmonary disease (COPD) and eosinophilic inflammation, according to results from two phase 3 trials. The data were published in the New England Journal of Medicine.

Benralizumab, an interleukin-5 receptor alpha–directed cytolytic monoclonal antibody, is approved for the treatment of patients with severe eosinophilic asthma. To assess whether the treatment may prevent COPD exacerbations, Gerard J. Criner, MD, chair and professor of thoracic medicine and surgery at Temple University in Philadelphia and colleagues conducted two randomized, double-blind, parallel-group studies: GALATHEA and TERRANOVA. Researchers enrolled patients with frequent moderate or severe COPD exacerbations and blood eosinophil counts of at least 220 per mm³.

A 56-week treatment period

“An eosinophil threshold of 220 per mm³ was selected on the basis of the phase 2 trial of benralizumab in patients with COPD, in which modeling of annual exacerbations according to baseline blood eosinophil count indicated that patients with eosinophil counts above a similar threshold were more likely to have a response to benralizumab,” the authors wrote. “The doses selected were 30 mg, the approved dose for asthma treatment; 100 mg, to inform the safety margin; and 10 mg (in TERRANOVA), to evaluate the dose-efficacy relationship.”

Patients received placebo or benralizumab via subcutaneous injection every 4 weeks for the first three doses, then every 8 weeks for the rest of the 56-week treatment period. The primary end point was the annualized COPD exacerbation rate ratio (benralizumab vs. placebo) at week 56.

The primary analysis populations included 1,120 patients in GALATHEA and 1,545 patients in TERRANOVA. Most patients were white men, and the average age was 65 years. The percentages of patients with current asthma (5.4% in GALATHEA and 3.3% in TERRANOVA) or past asthma (8.3% in GALATHEA and 6.1% in TERRANOVA) were low.

In GALATHEA, the estimated annualized exacerbation rates were 1.19 per year in the 30-mg benralizumab group, 1.03 per year in the 100-mg benralizumab group, and 1.24 per year in the placebo group. Compared with placebo, the rate ratio was 0.96 for 30 mg of benralizumab and 0.83 for 100 mg of benralizumab.

In TERRANOVA, the estimated annualized exacerbation rates for 10 mg, 30 mg, and 100 mg of benralizumab and for placebo were 0.99 per year, 1.21 per year, 1.09 per year, and 1.17 per year, respectively. The corresponding rate ratios were 0.85, 1.04, and 0.93. “At 56 weeks, none of the annualized COPD exacerbation rate ratios for any dose of benralizumab as compared with placebo reached significance in either trial,” the researchers said. “Types and frequencies of adverse events were similar with benralizumab and placebo.”

Depletion of eosinophils in blood and sputum

By week 4, benralizumab substantially depleted blood eosinophils. In addition, treatment substantially depleted sputum eosinophils by week 24. “However, in contrast to the results in benralizumab-treated patients with severe eosinophilic asthma, this eosinophil depletion did not correspond to a significant difference in the rate of exacerbations. This finding, together with the effect on eosinophils – with minimal effect on the COPD exacerbation rate – that was observed in the mepolizumab trials, suggests that eosinophil depletion is unlikely to ameliorate exacerbation outcomes for the majority of patients with COPD,” Dr. Criner and his coauthors concluded. “Future investigation is required to identify additional clinical factors or biomarkers that may characterize the patients with COPD who are most likely to benefit from anti–interleukin-5 receptor antibody therapy.”

The trials were sponsored by AstraZeneca, which manufactures benralizumab (Fasenra), and by Kyowa Hakko Kirin. One author is supported by the National Institute for Health Research Manchester Biomedical Research Centre. The authors’ disclosures included grants and personal fees from AstraZeneca and other pharmaceutical companies.

[email protected]

SOURCE: Criner GJ et al. N Engl J Med. 2019;382(11):1023-34. doi: 10.1056/NEJMoa1905248.

Add-on benralizumab is not associated with a significantly lower annualized rate of exacerbations in patients with moderate to severe chronic obstructive pulmonary disease (COPD) and eosinophilic inflammation, according to results from two phase 3 trials. The data were published in the New England Journal of Medicine.

Benralizumab, an interleukin-5 receptor alpha–directed cytolytic monoclonal antibody, is approved for the treatment of patients with severe eosinophilic asthma. To assess whether the treatment may prevent COPD exacerbations, Gerard J. Criner, MD, chair and professor of thoracic medicine and surgery at Temple University in Philadelphia and colleagues conducted two randomized, double-blind, parallel-group studies: GALATHEA and TERRANOVA. Researchers enrolled patients with frequent moderate or severe COPD exacerbations and blood eosinophil counts of at least 220 per mm³.

A 56-week treatment period

“An eosinophil threshold of 220 per mm³ was selected on the basis of the phase 2 trial of benralizumab in patients with COPD, in which modeling of annual exacerbations according to baseline blood eosinophil count indicated that patients with eosinophil counts above a similar threshold were more likely to have a response to benralizumab,” the authors wrote. “The doses selected were 30 mg, the approved dose for asthma treatment; 100 mg, to inform the safety margin; and 10 mg (in TERRANOVA), to evaluate the dose-efficacy relationship.”

Patients received placebo or benralizumab via subcutaneous injection every 4 weeks for the first three doses, then every 8 weeks for the rest of the 56-week treatment period. The primary end point was the annualized COPD exacerbation rate ratio (benralizumab vs. placebo) at week 56.

The primary analysis populations included 1,120 patients in GALATHEA and 1,545 patients in TERRANOVA. Most patients were white men, and the average age was 65 years. The percentages of patients with current asthma (5.4% in GALATHEA and 3.3% in TERRANOVA) or past asthma (8.3% in GALATHEA and 6.1% in TERRANOVA) were low.

In GALATHEA, the estimated annualized exacerbation rates were 1.19 per year in the 30-mg benralizumab group, 1.03 per year in the 100-mg benralizumab group, and 1.24 per year in the placebo group. Compared with placebo, the rate ratio was 0.96 for 30 mg of benralizumab and 0.83 for 100 mg of benralizumab.

In TERRANOVA, the estimated annualized exacerbation rates for 10 mg, 30 mg, and 100 mg of benralizumab and for placebo were 0.99 per year, 1.21 per year, 1.09 per year, and 1.17 per year, respectively. The corresponding rate ratios were 0.85, 1.04, and 0.93. “At 56 weeks, none of the annualized COPD exacerbation rate ratios for any dose of benralizumab as compared with placebo reached significance in either trial,” the researchers said. “Types and frequencies of adverse events were similar with benralizumab and placebo.”

Depletion of eosinophils in blood and sputum

By week 4, benralizumab substantially depleted blood eosinophils. In addition, treatment substantially depleted sputum eosinophils by week 24. “However, in contrast to the results in benralizumab-treated patients with severe eosinophilic asthma, this eosinophil depletion did not correspond to a significant difference in the rate of exacerbations. This finding, together with the effect on eosinophils – with minimal effect on the COPD exacerbation rate – that was observed in the mepolizumab trials, suggests that eosinophil depletion is unlikely to ameliorate exacerbation outcomes for the majority of patients with COPD,” Dr. Criner and his coauthors concluded. “Future investigation is required to identify additional clinical factors or biomarkers that may characterize the patients with COPD who are most likely to benefit from anti–interleukin-5 receptor antibody therapy.”

The trials were sponsored by AstraZeneca, which manufactures benralizumab (Fasenra), and by Kyowa Hakko Kirin. One author is supported by the National Institute for Health Research Manchester Biomedical Research Centre. The authors’ disclosures included grants and personal fees from AstraZeneca and other pharmaceutical companies.

[email protected]

SOURCE: Criner GJ et al. N Engl J Med. 2019;382(11):1023-34. doi: 10.1056/NEJMoa1905248.

Add-on benralizumab is not associated with a significantly lower annualized rate of exacerbations in patients with moderate to severe chronic obstructive pulmonary disease (COPD) and eosinophilic inflammation, according to results from two phase 3 trials. The data were published in the New England Journal of Medicine.

Benralizumab, an interleukin-5 receptor alpha–directed cytolytic monoclonal antibody, is approved for the treatment of patients with severe eosinophilic asthma. To assess whether the treatment may prevent COPD exacerbations, Gerard J. Criner, MD, chair and professor of thoracic medicine and surgery at Temple University in Philadelphia and colleagues conducted two randomized, double-blind, parallel-group studies: GALATHEA and TERRANOVA. Researchers enrolled patients with frequent moderate or severe COPD exacerbations and blood eosinophil counts of at least 220 per mm³.

A 56-week treatment period

“An eosinophil threshold of 220 per mm³ was selected on the basis of the phase 2 trial of benralizumab in patients with COPD, in which modeling of annual exacerbations according to baseline blood eosinophil count indicated that patients with eosinophil counts above a similar threshold were more likely to have a response to benralizumab,” the authors wrote. “The doses selected were 30 mg, the approved dose for asthma treatment; 100 mg, to inform the safety margin; and 10 mg (in TERRANOVA), to evaluate the dose-efficacy relationship.”

Patients received placebo or benralizumab via subcutaneous injection every 4 weeks for the first three doses, then every 8 weeks for the rest of the 56-week treatment period. The primary end point was the annualized COPD exacerbation rate ratio (benralizumab vs. placebo) at week 56.

The primary analysis populations included 1,120 patients in GALATHEA and 1,545 patients in TERRANOVA. Most patients were white men, and the average age was 65 years. The percentages of patients with current asthma (5.4% in GALATHEA and 3.3% in TERRANOVA) or past asthma (8.3% in GALATHEA and 6.1% in TERRANOVA) were low.

In GALATHEA, the estimated annualized exacerbation rates were 1.19 per year in the 30-mg benralizumab group, 1.03 per year in the 100-mg benralizumab group, and 1.24 per year in the placebo group. Compared with placebo, the rate ratio was 0.96 for 30 mg of benralizumab and 0.83 for 100 mg of benralizumab.

In TERRANOVA, the estimated annualized exacerbation rates for 10 mg, 30 mg, and 100 mg of benralizumab and for placebo were 0.99 per year, 1.21 per year, 1.09 per year, and 1.17 per year, respectively. The corresponding rate ratios were 0.85, 1.04, and 0.93. “At 56 weeks, none of the annualized COPD exacerbation rate ratios for any dose of benralizumab as compared with placebo reached significance in either trial,” the researchers said. “Types and frequencies of adverse events were similar with benralizumab and placebo.”

Depletion of eosinophils in blood and sputum

By week 4, benralizumab substantially depleted blood eosinophils. In addition, treatment substantially depleted sputum eosinophils by week 24. “However, in contrast to the results in benralizumab-treated patients with severe eosinophilic asthma, this eosinophil depletion did not correspond to a significant difference in the rate of exacerbations. This finding, together with the effect on eosinophils – with minimal effect on the COPD exacerbation rate – that was observed in the mepolizumab trials, suggests that eosinophil depletion is unlikely to ameliorate exacerbation outcomes for the majority of patients with COPD,” Dr. Criner and his coauthors concluded. “Future investigation is required to identify additional clinical factors or biomarkers that may characterize the patients with COPD who are most likely to benefit from anti–interleukin-5 receptor antibody therapy.”

The trials were sponsored by AstraZeneca, which manufactures benralizumab (Fasenra), and by Kyowa Hakko Kirin. One author is supported by the National Institute for Health Research Manchester Biomedical Research Centre. The authors’ disclosures included grants and personal fees from AstraZeneca and other pharmaceutical companies.

[email protected]

SOURCE: Criner GJ et al. N Engl J Med. 2019;382(11):1023-34. doi: 10.1056/NEJMoa1905248.

Grace is a 15-year-old girl in the 10th grade whom you have been treating for anxiety. Family history also is notable for her father having an anxiety disorder. She has been taking an SSRI and is engaged in therapy, which has resulted in some improvement in symptoms. She can become overwhelmed when taking tests, and she has breakthrough anxiety in social situations and occasional difficulties with sleep. She denies using any substances. Her parents, who have come to her appointment with her, noted that while they see some progress, they would like to try more natural interventions. They had done some research on cannabidiol (CBD), and Grace’s father said that using it has tremendously helped his sleep. They inquired about Grace using it as well.

Bhupi/Getty Images

Discussion

CBD use has dramatically increased over the past few years, and in many places can be found in gummies, chocolate, tinctures, and other forms at grocery and convenience stores, in addition to being widely available online. It is a nonpsychoactive compound (versus tetrahydrocannabinol or THC) found in the Cannabis sativa plant. The Farm Bill, which was passed in 2018, legalized production of hemp or the cannabis plant with a THC concentration less than 0.3%. This bill additionally maintained the Food and Drug Administration’s oversight with CBD. States may have laws that are more restrictive about use. CBD was approved in 2018 by the FDA for treatment of Lennox-Gastaut syndrome and Dravet syndrome in individuals 2 years of age and older, and is categorized as a schedule I substance due to its being derived from the cannabis plant.

In randomized, double-blind, placebo-controlled trials leading to CBD’s approval, the most common side effects were drowsiness, insomnia, disrupted sleep, sedation, malaise, weakness, decreased appetite, diarrhea, elevated liver enzymes, rash, and infections. CBD also carries a warning about the potential for suicidal ideation, agitation, new or worsening depression, aggression, and panic attacks.¹ In in vitro and animal studies, CBD has been found to affect growth of tumor cell lines, to have no effects on embryonic development, and to potentially cause some drug-drug interactions through inhibition of CYP2C9, CYP2C19, and CYP3A4. However, the clinical relevance currently is unknown. Animal studies also indicate potential efficacy in decreasing anxiety.²

CBD has been promoted as being effective in treating a number of ailments including migraines, chronic pain, insomnia, ADHD, and anxiety. Multiple anecdotal reports tout the benefits. In a study exploring abuse potential, there were no significant findings, and CBD was generally well tolerated in open trials exploring potential clinical benefits. A retrospective feasibility study – conducted in Israel – exploring use of CBD to decrease problematic behaviors in youth with autism spectrum disorder demonstrated improvement in communication, anxiety, disruptive behaviors, and parental stress.³

• There is potential lack of clarity regarding legality of use in some states. Based on federal law, it is legal to possess CBD derived from hemp, but state laws may differ.
• There is lack of oversight regarding monitoring what is in each supplement. Lab testing for CBD to determine contents is not mandatory in every state. The amount of active compound as well as other ingredients may not be consistent or accurate. According to the FDA, CBD-containing products cannot claim to have health benefits, treat disease, or be sold as dietary supplements without its approval.
• Clear information about appropriate dosing for children is limited.
• Varying delivery systems could affect absorption and bioavailability of CBD.
• Information is lacking regarding potential drug-drug interactions.
• There is a lack of information regarding effects of long-term use.

Use of CBD is an area with significant interest and potential for growth. Although risks are thought to be low overall, there likely is insufficient evidence at this time to actively recommend its use. Additional research in human subjects exploring effective and safe dosing, tolerability, as well as use in special populations (including children, pregnant women, elderly) is needed.
 

Dr. Strange is an assistant professor in the department of psychiatry at the University of Vermont Medical Center and University of Vermont Robert Larner College of Medicine, both in Burlington. She works with children and adolescents. She has no relevant financial disclosures. Email her at [email protected].

References

1. “FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy,” FDA news release, June 25, 2018.

2. Cannabidiol (CBD) Critical Review Report. Expert Committee on Drug Dependence Fortieth Meeting. World Health Organization. Geneva June 4-7, 2018.

3. J Autism Dev Disord. 2019 Mar;49(3):1284-8.

Grace is a 15-year-old girl in the 10th grade whom you have been treating for anxiety. Family history also is notable for her father having an anxiety disorder. She has been taking an SSRI and is engaged in therapy, which has resulted in some improvement in symptoms. She can become overwhelmed when taking tests, and she has breakthrough anxiety in social situations and occasional difficulties with sleep. She denies using any substances. Her parents, who have come to her appointment with her, noted that while they see some progress, they would like to try more natural interventions. They had done some research on cannabidiol (CBD), and Grace’s father said that using it has tremendously helped his sleep. They inquired about Grace using it as well.

Bhupi/Getty Images

Discussion

CBD use has dramatically increased over the past few years, and in many places can be found in gummies, chocolate, tinctures, and other forms at grocery and convenience stores, in addition to being widely available online. It is a nonpsychoactive compound (versus tetrahydrocannabinol or THC) found in the Cannabis sativa plant. The Farm Bill, which was passed in 2018, legalized production of hemp or the cannabis plant with a THC concentration less than 0.3%. This bill additionally maintained the Food and Drug Administration’s oversight with CBD. States may have laws that are more restrictive about use. CBD was approved in 2018 by the FDA for treatment of Lennox-Gastaut syndrome and Dravet syndrome in individuals 2 years of age and older, and is categorized as a schedule I substance due to its being derived from the cannabis plant.

In randomized, double-blind, placebo-controlled trials leading to CBD’s approval, the most common side effects were drowsiness, insomnia, disrupted sleep, sedation, malaise, weakness, decreased appetite, diarrhea, elevated liver enzymes, rash, and infections. CBD also carries a warning about the potential for suicidal ideation, agitation, new or worsening depression, aggression, and panic attacks.¹ In in vitro and animal studies, CBD has been found to affect growth of tumor cell lines, to have no effects on embryonic development, and to potentially cause some drug-drug interactions through inhibition of CYP2C9, CYP2C19, and CYP3A4. However, the clinical relevance currently is unknown. Animal studies also indicate potential efficacy in decreasing anxiety.²

CBD has been promoted as being effective in treating a number of ailments including migraines, chronic pain, insomnia, ADHD, and anxiety. Multiple anecdotal reports tout the benefits. In a study exploring abuse potential, there were no significant findings, and CBD was generally well tolerated in open trials exploring potential clinical benefits. A retrospective feasibility study – conducted in Israel – exploring use of CBD to decrease problematic behaviors in youth with autism spectrum disorder demonstrated improvement in communication, anxiety, disruptive behaviors, and parental stress.³

• There is potential lack of clarity regarding legality of use in some states. Based on federal law, it is legal to possess CBD derived from hemp, but state laws may differ.
• There is lack of oversight regarding monitoring what is in each supplement. Lab testing for CBD to determine contents is not mandatory in every state. The amount of active compound as well as other ingredients may not be consistent or accurate. According to the FDA, CBD-containing products cannot claim to have health benefits, treat disease, or be sold as dietary supplements without its approval.
• Clear information about appropriate dosing for children is limited.
• Varying delivery systems could affect absorption and bioavailability of CBD.
• Information is lacking regarding potential drug-drug interactions.
• There is a lack of information regarding effects of long-term use.

Use of CBD is an area with significant interest and potential for growth. Although risks are thought to be low overall, there likely is insufficient evidence at this time to actively recommend its use. Additional research in human subjects exploring effective and safe dosing, tolerability, as well as use in special populations (including children, pregnant women, elderly) is needed.
 

Dr. Strange is an assistant professor in the department of psychiatry at the University of Vermont Medical Center and University of Vermont Robert Larner College of Medicine, both in Burlington. She works with children and adolescents. She has no relevant financial disclosures. Email her at [email protected].

References

1. “FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy,” FDA news release, June 25, 2018.

2. Cannabidiol (CBD) Critical Review Report. Expert Committee on Drug Dependence Fortieth Meeting. World Health Organization. Geneva June 4-7, 2018.

3. J Autism Dev Disord. 2019 Mar;49(3):1284-8.

Grace is a 15-year-old girl in the 10th grade whom you have been treating for anxiety. Family history also is notable for her father having an anxiety disorder. She has been taking an SSRI and is engaged in therapy, which has resulted in some improvement in symptoms. She can become overwhelmed when taking tests, and she has breakthrough anxiety in social situations and occasional difficulties with sleep. She denies using any substances. Her parents, who have come to her appointment with her, noted that while they see some progress, they would like to try more natural interventions. They had done some research on cannabidiol (CBD), and Grace’s father said that using it has tremendously helped his sleep. They inquired about Grace using it as well.

Bhupi/Getty Images

Discussion

CBD use has dramatically increased over the past few years, and in many places can be found in gummies, chocolate, tinctures, and other forms at grocery and convenience stores, in addition to being widely available online. It is a nonpsychoactive compound (versus tetrahydrocannabinol or THC) found in the Cannabis sativa plant. The Farm Bill, which was passed in 2018, legalized production of hemp or the cannabis plant with a THC concentration less than 0.3%. This bill additionally maintained the Food and Drug Administration’s oversight with CBD. States may have laws that are more restrictive about use. CBD was approved in 2018 by the FDA for treatment of Lennox-Gastaut syndrome and Dravet syndrome in individuals 2 years of age and older, and is categorized as a schedule I substance due to its being derived from the cannabis plant.

In randomized, double-blind, placebo-controlled trials leading to CBD’s approval, the most common side effects were drowsiness, insomnia, disrupted sleep, sedation, malaise, weakness, decreased appetite, diarrhea, elevated liver enzymes, rash, and infections. CBD also carries a warning about the potential for suicidal ideation, agitation, new or worsening depression, aggression, and panic attacks.¹ In in vitro and animal studies, CBD has been found to affect growth of tumor cell lines, to have no effects on embryonic development, and to potentially cause some drug-drug interactions through inhibition of CYP2C9, CYP2C19, and CYP3A4. However, the clinical relevance currently is unknown. Animal studies also indicate potential efficacy in decreasing anxiety.²

CBD has been promoted as being effective in treating a number of ailments including migraines, chronic pain, insomnia, ADHD, and anxiety. Multiple anecdotal reports tout the benefits. In a study exploring abuse potential, there were no significant findings, and CBD was generally well tolerated in open trials exploring potential clinical benefits. A retrospective feasibility study – conducted in Israel – exploring use of CBD to decrease problematic behaviors in youth with autism spectrum disorder demonstrated improvement in communication, anxiety, disruptive behaviors, and parental stress.³

• There is potential lack of clarity regarding legality of use in some states. Based on federal law, it is legal to possess CBD derived from hemp, but state laws may differ.
• There is lack of oversight regarding monitoring what is in each supplement. Lab testing for CBD to determine contents is not mandatory in every state. The amount of active compound as well as other ingredients may not be consistent or accurate. According to the FDA, CBD-containing products cannot claim to have health benefits, treat disease, or be sold as dietary supplements without its approval.
• Clear information about appropriate dosing for children is limited.
• Varying delivery systems could affect absorption and bioavailability of CBD.
• Information is lacking regarding potential drug-drug interactions.
• There is a lack of information regarding effects of long-term use.

Use of CBD is an area with significant interest and potential for growth. Although risks are thought to be low overall, there likely is insufficient evidence at this time to actively recommend its use. Additional research in human subjects exploring effective and safe dosing, tolerability, as well as use in special populations (including children, pregnant women, elderly) is needed.
 

Dr. Strange is an assistant professor in the department of psychiatry at the University of Vermont Medical Center and University of Vermont Robert Larner College of Medicine, both in Burlington. She works with children and adolescents. She has no relevant financial disclosures. Email her at [email protected].

References

1. “FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy,” FDA news release, June 25, 2018.

2. Cannabidiol (CBD) Critical Review Report. Expert Committee on Drug Dependence Fortieth Meeting. World Health Organization. Geneva June 4-7, 2018.

3. J Autism Dev Disord. 2019 Mar;49(3):1284-8.

Bariatric surgery prior to arthroplasty reduces the likelihood of multiple complications but some risks increase, a large study has found.

KatarzynaBialasiewicz/Thinkstock

The study, led by Yicun Wang, PhD, of Nanjing (China) University was published in the Journal of Arthroplasty. “Generally speaking, bariatric surgery decreases some postoperative complications, decreases length of stay, and lowers mortality,” the study investigators wrote, [but] anemia and blood transfusion seem to be more common in patients with prior bariatric surgery.

They analyzed the effect of bariatric surgery on subsequent arthroplasty in morbidly obese patients in the United States using Nationwide Inpatient Sample 2006-2014 data on total hip arthroplasty (THA) and total knee arthroplasty (TKA). The researchers defined morbid obese patients as those with a body mass index higher than 40 kg/m².

Among patients who underwent TKA, the researchers compared a group of 9,803 morbidly obese patients with the same number of patients who had undergone bariatric surgery. The two groups were matched by age, sex, income, primary insurance payer, and race.

There were large differences between the bariatric surgery group vs. morbidly obese group: Pulmonary embolism was much more common in the morbid obesity group (odds ratio, 0.22; 95% confidence interval, 0.05-1.03; P = .0346) while blood transfusion was more common in the bariatric surgery group (OR, 1.76; 95% CI, 1.52-2.03; P less than .0001).

For TKA, the researchers used the same approach to analyze 2,540 matched pairs of patients. In the bariatric surgery vs. morbidly obese comparison, pulmonary embolism was more common in the morbidly obese group (OR, 0.34; 95% CI, 0.20-0.57; P less than .0001), as were respiratory complications (OR, 0.45; 95% CI, 0.26-0.78; P = .0032) and death (OR, 0.07; 95% CI, 0.01-0.50; P = .0005). But the bariatric surgery group had higher levels of blood transfusion (OR, 1.87; 95% CI, 1.71-2.04; P less than .0001) and anemia (OR, 1.16; 95% CI, 1.09-1.24; P less than .0001).

Going forward, the researchers write, “future studies on these patients should attempt to evaluate the impact of bariatric surgery on the long-term outcomes of arthroplasty.”

The study was supported by various funders including the National Natural Science Foundation of China, the Natural Science Foundation of Guangdong Province, the Project of Administration of Traditional Chinese Medicine of Guangdong Province and others. No author disclosures are reported.

SOURCE: Wang Y et al. J Arthroplasty. 2019;S0883-5403(19)30667-9.

Bariatric surgery prior to arthroplasty reduces the likelihood of multiple complications but some risks increase, a large study has found.

KatarzynaBialasiewicz/Thinkstock

The study, led by Yicun Wang, PhD, of Nanjing (China) University was published in the Journal of Arthroplasty. “Generally speaking, bariatric surgery decreases some postoperative complications, decreases length of stay, and lowers mortality,” the study investigators wrote, [but] anemia and blood transfusion seem to be more common in patients with prior bariatric surgery.

They analyzed the effect of bariatric surgery on subsequent arthroplasty in morbidly obese patients in the United States using Nationwide Inpatient Sample 2006-2014 data on total hip arthroplasty (THA) and total knee arthroplasty (TKA). The researchers defined morbid obese patients as those with a body mass index higher than 40 kg/m².

Among patients who underwent TKA, the researchers compared a group of 9,803 morbidly obese patients with the same number of patients who had undergone bariatric surgery. The two groups were matched by age, sex, income, primary insurance payer, and race.

There were large differences between the bariatric surgery group vs. morbidly obese group: Pulmonary embolism was much more common in the morbid obesity group (odds ratio, 0.22; 95% confidence interval, 0.05-1.03; P = .0346) while blood transfusion was more common in the bariatric surgery group (OR, 1.76; 95% CI, 1.52-2.03; P less than .0001).

For TKA, the researchers used the same approach to analyze 2,540 matched pairs of patients. In the bariatric surgery vs. morbidly obese comparison, pulmonary embolism was more common in the morbidly obese group (OR, 0.34; 95% CI, 0.20-0.57; P less than .0001), as were respiratory complications (OR, 0.45; 95% CI, 0.26-0.78; P = .0032) and death (OR, 0.07; 95% CI, 0.01-0.50; P = .0005). But the bariatric surgery group had higher levels of blood transfusion (OR, 1.87; 95% CI, 1.71-2.04; P less than .0001) and anemia (OR, 1.16; 95% CI, 1.09-1.24; P less than .0001).

Going forward, the researchers write, “future studies on these patients should attempt to evaluate the impact of bariatric surgery on the long-term outcomes of arthroplasty.”

The study was supported by various funders including the National Natural Science Foundation of China, the Natural Science Foundation of Guangdong Province, the Project of Administration of Traditional Chinese Medicine of Guangdong Province and others. No author disclosures are reported.

SOURCE: Wang Y et al. J Arthroplasty. 2019;S0883-5403(19)30667-9.

Bariatric surgery prior to arthroplasty reduces the likelihood of multiple complications but some risks increase, a large study has found.

KatarzynaBialasiewicz/Thinkstock

The study, led by Yicun Wang, PhD, of Nanjing (China) University was published in the Journal of Arthroplasty. “Generally speaking, bariatric surgery decreases some postoperative complications, decreases length of stay, and lowers mortality,” the study investigators wrote, [but] anemia and blood transfusion seem to be more common in patients with prior bariatric surgery.

They analyzed the effect of bariatric surgery on subsequent arthroplasty in morbidly obese patients in the United States using Nationwide Inpatient Sample 2006-2014 data on total hip arthroplasty (THA) and total knee arthroplasty (TKA). The researchers defined morbid obese patients as those with a body mass index higher than 40 kg/m².

Among patients who underwent TKA, the researchers compared a group of 9,803 morbidly obese patients with the same number of patients who had undergone bariatric surgery. The two groups were matched by age, sex, income, primary insurance payer, and race.

There were large differences between the bariatric surgery group vs. morbidly obese group: Pulmonary embolism was much more common in the morbid obesity group (odds ratio, 0.22; 95% confidence interval, 0.05-1.03; P = .0346) while blood transfusion was more common in the bariatric surgery group (OR, 1.76; 95% CI, 1.52-2.03; P less than .0001).

For TKA, the researchers used the same approach to analyze 2,540 matched pairs of patients. In the bariatric surgery vs. morbidly obese comparison, pulmonary embolism was more common in the morbidly obese group (OR, 0.34; 95% CI, 0.20-0.57; P less than .0001), as were respiratory complications (OR, 0.45; 95% CI, 0.26-0.78; P = .0032) and death (OR, 0.07; 95% CI, 0.01-0.50; P = .0005). But the bariatric surgery group had higher levels of blood transfusion (OR, 1.87; 95% CI, 1.71-2.04; P less than .0001) and anemia (OR, 1.16; 95% CI, 1.09-1.24; P less than .0001).

Going forward, the researchers write, “future studies on these patients should attempt to evaluate the impact of bariatric surgery on the long-term outcomes of arthroplasty.”

The study was supported by various funders including the National Natural Science Foundation of China, the Natural Science Foundation of Guangdong Province, the Project of Administration of Traditional Chinese Medicine of Guangdong Province and others. No author disclosures are reported.

SOURCE: Wang Y et al. J Arthroplasty. 2019;S0883-5403(19)30667-9.

As immunotherapy has become more widely available, cancer patients have been referred to subacute rehabilitation (SAR) facilities at an increasing rate, to become well enough to tolerate treatment, investigators report.

However, “many patients never receive additional therapy and are readmitted or deceased within a short time, marking this population as one with strong needs for concurrent palliative and usual oncology care,” wrote Jonathan C. Yeh, MD, of Johns Hopkins University, Baltimore, and coauthors. Their report is in Journal of Oncology Practice.

To determine if the advent of immunotherapy contributed to an increase in referrals to SAR facilities – and which patients survived long enough to benefit – the researchers reviewed the electronic charts of 358 patients who were referred to such facilities. The number of referrals increased gradually over the 8-year period of the study.

Of these 358 patients, 174 (49%) were seen again in the oncology clinic before readmission or death and 117 (33%) ever received additional cancer-directed treatment. The patients most likely to receive additional treatment were those with leukemia, lymphoma, or localized solid disease.

Of the 413 total discharges, 116 (28%) resulted in hospital readmission within 30 days of discharge. Seventy-four (21%) of the patients were deceased within 30 days; 212 (59%) were deceased within 180 days. Only 123 (30%) of the initial admissions involved a palliative care specialist; this involvement was associated with increases in documented goals of care, completion of advance directives, and election of do-not-resuscitate status.

The authors noted their study’s limitations, including all of the data coming from a single tertiary cancer center. In addition, the data are observational, which made the researchers “unable to control for key patient characteristics such as performance status, patient goals, insurance coverage of trials, and the like.”

Dr. Smith reported being employed by UpToDate and receiving royalties as coeditor of the Oxford Textbook of Cancer Communication. No other conflicts of interest were reported.

SOURCE: Yeh JC et al. J Oncol Pract. 2019 Aug 29. doi: 10.1200/JOP.19.00044.

As immunotherapy has become more widely available, cancer patients have been referred to subacute rehabilitation (SAR) facilities at an increasing rate, to become well enough to tolerate treatment, investigators report.

However, “many patients never receive additional therapy and are readmitted or deceased within a short time, marking this population as one with strong needs for concurrent palliative and usual oncology care,” wrote Jonathan C. Yeh, MD, of Johns Hopkins University, Baltimore, and coauthors. Their report is in Journal of Oncology Practice.

To determine if the advent of immunotherapy contributed to an increase in referrals to SAR facilities – and which patients survived long enough to benefit – the researchers reviewed the electronic charts of 358 patients who were referred to such facilities. The number of referrals increased gradually over the 8-year period of the study.

Of these 358 patients, 174 (49%) were seen again in the oncology clinic before readmission or death and 117 (33%) ever received additional cancer-directed treatment. The patients most likely to receive additional treatment were those with leukemia, lymphoma, or localized solid disease.

Of the 413 total discharges, 116 (28%) resulted in hospital readmission within 30 days of discharge. Seventy-four (21%) of the patients were deceased within 30 days; 212 (59%) were deceased within 180 days. Only 123 (30%) of the initial admissions involved a palliative care specialist; this involvement was associated with increases in documented goals of care, completion of advance directives, and election of do-not-resuscitate status.

The authors noted their study’s limitations, including all of the data coming from a single tertiary cancer center. In addition, the data are observational, which made the researchers “unable to control for key patient characteristics such as performance status, patient goals, insurance coverage of trials, and the like.”

Dr. Smith reported being employed by UpToDate and receiving royalties as coeditor of the Oxford Textbook of Cancer Communication. No other conflicts of interest were reported.

SOURCE: Yeh JC et al. J Oncol Pract. 2019 Aug 29. doi: 10.1200/JOP.19.00044.

As immunotherapy has become more widely available, cancer patients have been referred to subacute rehabilitation (SAR) facilities at an increasing rate, to become well enough to tolerate treatment, investigators report.

However, “many patients never receive additional therapy and are readmitted or deceased within a short time, marking this population as one with strong needs for concurrent palliative and usual oncology care,” wrote Jonathan C. Yeh, MD, of Johns Hopkins University, Baltimore, and coauthors. Their report is in Journal of Oncology Practice.

To determine if the advent of immunotherapy contributed to an increase in referrals to SAR facilities – and which patients survived long enough to benefit – the researchers reviewed the electronic charts of 358 patients who were referred to such facilities. The number of referrals increased gradually over the 8-year period of the study.

Of these 358 patients, 174 (49%) were seen again in the oncology clinic before readmission or death and 117 (33%) ever received additional cancer-directed treatment. The patients most likely to receive additional treatment were those with leukemia, lymphoma, or localized solid disease.

Of the 413 total discharges, 116 (28%) resulted in hospital readmission within 30 days of discharge. Seventy-four (21%) of the patients were deceased within 30 days; 212 (59%) were deceased within 180 days. Only 123 (30%) of the initial admissions involved a palliative care specialist; this involvement was associated with increases in documented goals of care, completion of advance directives, and election of do-not-resuscitate status.

The authors noted their study’s limitations, including all of the data coming from a single tertiary cancer center. In addition, the data are observational, which made the researchers “unable to control for key patient characteristics such as performance status, patient goals, insurance coverage of trials, and the like.”

Dr. Smith reported being employed by UpToDate and receiving royalties as coeditor of the Oxford Textbook of Cancer Communication. No other conflicts of interest were reported.

SOURCE: Yeh JC et al. J Oncol Pract. 2019 Aug 29. doi: 10.1200/JOP.19.00044.

A high dose of teriparatide in combination with denosumab increases bone mineral density (BMD) in postmenopausal women with osteoporosis to a greater extent than a lower-dose regimen.

The latest findings suggest that high-dose teriparatide “stimulates even greater separation between bone resorption and formation than that of standard-dose teriparatide,” wrote Joy N. Tsai, MD, of Harvard Medical School, Boston, and her coauthors in Lancet Diabetes & Endocrinology.

Previously, findings from the Denosumab and Teriparatide Administration (DATA) study showed that a combination of teriparatide and denosumab increased both BMD and estimated bone strength more than either drug alone. To determine if a higher dose of teriparatide plus denosumab would result in larger increases in BMD, investigators in the DATA-HD study randomly assigned 76 postmenopausal women with osteoporosis to receive either 40 μg of teriparatide daily (higher dose; n = 37) or 20 μg of teriparatide daily (standard dose; n = 39). At 3 months, patients in both groups were also started on 60 mg of denosumab every 6 months. Of the initial participants, 69 completed at least one postbaseline visit and were included in the analysis.

At the 15-month follow-up, areal BMD (aBMD) had increased in both groups in all measured sites – lumbar spine, femoral neck, total hip, and distal radius. Patients in the 40-μg group had a significantly higher increase in mean lumbar spine aBMD (17.5%), compared with those in the 20-μg or standard-dose group (9.5%; 95% confidence interval, 5.5-10.6; P less than .0001).

There was also a greater increase in mean femoral neck aBMD in patients in the 40-μg group (6.8%), compared with those in the 20-μg group (4.3; 95% CI, 0.5-4.5; P = .04) and in mean total hip aBMD (6.1% vs. 3.9%, 95% CI; 0.6-3.8, P less than .0001).

In all, 29 participants in the 40-μg group (78%) and 30 participants in the 20-μg group (77%) had adverse events, but with the exceptions of headache and rash, all serious adverse events were considered unrelated to treatment.

The authors noted the limitations of their study, including that it was conducted at a single site with a predominantly white population. In addition, the authors acknowledged that the small sample size did not allow for “direct assessment of fracture benefit [or] for rigorous evaluation of the tolerability and safety of this treatment.”

In an accompanying editorial, Sundeep Khosla, MD, of the Mayo Clinic, Rochester, Minn., wrote that the benefits of personalizing treatment for osteoporosis patients at high risk of fracture seemed to be coming into focus (Lancet Diabetes Endocrinol. 2019 Aug 22. doi: 10.1016/S2213-8587(19)30266-9).

Although the DATA and DATA-HD studies of teriparatide and denosumab reported by Dr. Tsai and colleagues have their limitations – including a small sample size for DATA-HD – they indicate the “possibility of refining treatment for patients with osteoporosis at high risk of fracture and personalizing treatment for these patients beyond the one-size-fits-all approach currently used,” Dr. Khosla wrote. Rather than offer bisphosphonates at standardized doses, patients at high risk could now be considered for the newly recommended high-dose teriparatide and denosumab combination, he said.

Dr. Khosla also noted that price remains an issue, given the estimated cost of $76,000 for 15 months of this proposed combination. However, the benefits in regard to at least bone mineral density are clear, he added, and that might prove sufficient enough for high-risk patients in need of an alternative therapy.

The study was supported by the Dart Family Foundation, the National Institutes of Health, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Eli Lilly and Amgen supplied the drugs. The authors reported numerous conflicts of interest, including receiving grants, reimbursements, and personal fees from various pharmaceutical companies, committees, and research institutes. Dr. Khosla reported no conflicts of interest.

SOURCE: Tsai JN et al. Lancet Diabetes Endocrinol. 2019 Aug 22. doi: 10.1016/S2213-8587(19)30255-4.

A high dose of teriparatide in combination with denosumab increases bone mineral density (BMD) in postmenopausal women with osteoporosis to a greater extent than a lower-dose regimen.

The latest findings suggest that high-dose teriparatide “stimulates even greater separation between bone resorption and formation than that of standard-dose teriparatide,” wrote Joy N. Tsai, MD, of Harvard Medical School, Boston, and her coauthors in Lancet Diabetes & Endocrinology.

Previously, findings from the Denosumab and Teriparatide Administration (DATA) study showed that a combination of teriparatide and denosumab increased both BMD and estimated bone strength more than either drug alone. To determine if a higher dose of teriparatide plus denosumab would result in larger increases in BMD, investigators in the DATA-HD study randomly assigned 76 postmenopausal women with osteoporosis to receive either 40 μg of teriparatide daily (higher dose; n = 37) or 20 μg of teriparatide daily (standard dose; n = 39). At 3 months, patients in both groups were also started on 60 mg of denosumab every 6 months. Of the initial participants, 69 completed at least one postbaseline visit and were included in the analysis.

At the 15-month follow-up, areal BMD (aBMD) had increased in both groups in all measured sites – lumbar spine, femoral neck, total hip, and distal radius. Patients in the 40-μg group had a significantly higher increase in mean lumbar spine aBMD (17.5%), compared with those in the 20-μg or standard-dose group (9.5%; 95% confidence interval, 5.5-10.6; P less than .0001).

There was also a greater increase in mean femoral neck aBMD in patients in the 40-μg group (6.8%), compared with those in the 20-μg group (4.3; 95% CI, 0.5-4.5; P = .04) and in mean total hip aBMD (6.1% vs. 3.9%, 95% CI; 0.6-3.8, P less than .0001).

In all, 29 participants in the 40-μg group (78%) and 30 participants in the 20-μg group (77%) had adverse events, but with the exceptions of headache and rash, all serious adverse events were considered unrelated to treatment.

The authors noted the limitations of their study, including that it was conducted at a single site with a predominantly white population. In addition, the authors acknowledged that the small sample size did not allow for “direct assessment of fracture benefit [or] for rigorous evaluation of the tolerability and safety of this treatment.”

In an accompanying editorial, Sundeep Khosla, MD, of the Mayo Clinic, Rochester, Minn., wrote that the benefits of personalizing treatment for osteoporosis patients at high risk of fracture seemed to be coming into focus (Lancet Diabetes Endocrinol. 2019 Aug 22. doi: 10.1016/S2213-8587(19)30266-9).

Although the DATA and DATA-HD studies of teriparatide and denosumab reported by Dr. Tsai and colleagues have their limitations – including a small sample size for DATA-HD – they indicate the “possibility of refining treatment for patients with osteoporosis at high risk of fracture and personalizing treatment for these patients beyond the one-size-fits-all approach currently used,” Dr. Khosla wrote. Rather than offer bisphosphonates at standardized doses, patients at high risk could now be considered for the newly recommended high-dose teriparatide and denosumab combination, he said.

Dr. Khosla also noted that price remains an issue, given the estimated cost of $76,000 for 15 months of this proposed combination. However, the benefits in regard to at least bone mineral density are clear, he added, and that might prove sufficient enough for high-risk patients in need of an alternative therapy.

The study was supported by the Dart Family Foundation, the National Institutes of Health, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Eli Lilly and Amgen supplied the drugs. The authors reported numerous conflicts of interest, including receiving grants, reimbursements, and personal fees from various pharmaceutical companies, committees, and research institutes. Dr. Khosla reported no conflicts of interest.

SOURCE: Tsai JN et al. Lancet Diabetes Endocrinol. 2019 Aug 22. doi: 10.1016/S2213-8587(19)30255-4.

A high dose of teriparatide in combination with denosumab increases bone mineral density (BMD) in postmenopausal women with osteoporosis to a greater extent than a lower-dose regimen.

The latest findings suggest that high-dose teriparatide “stimulates even greater separation between bone resorption and formation than that of standard-dose teriparatide,” wrote Joy N. Tsai, MD, of Harvard Medical School, Boston, and her coauthors in Lancet Diabetes & Endocrinology.

Previously, findings from the Denosumab and Teriparatide Administration (DATA) study showed that a combination of teriparatide and denosumab increased both BMD and estimated bone strength more than either drug alone. To determine if a higher dose of teriparatide plus denosumab would result in larger increases in BMD, investigators in the DATA-HD study randomly assigned 76 postmenopausal women with osteoporosis to receive either 40 μg of teriparatide daily (higher dose; n = 37) or 20 μg of teriparatide daily (standard dose; n = 39). At 3 months, patients in both groups were also started on 60 mg of denosumab every 6 months. Of the initial participants, 69 completed at least one postbaseline visit and were included in the analysis.

At the 15-month follow-up, areal BMD (aBMD) had increased in both groups in all measured sites – lumbar spine, femoral neck, total hip, and distal radius. Patients in the 40-μg group had a significantly higher increase in mean lumbar spine aBMD (17.5%), compared with those in the 20-μg or standard-dose group (9.5%; 95% confidence interval, 5.5-10.6; P less than .0001).

There was also a greater increase in mean femoral neck aBMD in patients in the 40-μg group (6.8%), compared with those in the 20-μg group (4.3; 95% CI, 0.5-4.5; P = .04) and in mean total hip aBMD (6.1% vs. 3.9%, 95% CI; 0.6-3.8, P less than .0001).

In all, 29 participants in the 40-μg group (78%) and 30 participants in the 20-μg group (77%) had adverse events, but with the exceptions of headache and rash, all serious adverse events were considered unrelated to treatment.

The authors noted the limitations of their study, including that it was conducted at a single site with a predominantly white population. In addition, the authors acknowledged that the small sample size did not allow for “direct assessment of fracture benefit [or] for rigorous evaluation of the tolerability and safety of this treatment.”

In an accompanying editorial, Sundeep Khosla, MD, of the Mayo Clinic, Rochester, Minn., wrote that the benefits of personalizing treatment for osteoporosis patients at high risk of fracture seemed to be coming into focus (Lancet Diabetes Endocrinol. 2019 Aug 22. doi: 10.1016/S2213-8587(19)30266-9).

Although the DATA and DATA-HD studies of teriparatide and denosumab reported by Dr. Tsai and colleagues have their limitations – including a small sample size for DATA-HD – they indicate the “possibility of refining treatment for patients with osteoporosis at high risk of fracture and personalizing treatment for these patients beyond the one-size-fits-all approach currently used,” Dr. Khosla wrote. Rather than offer bisphosphonates at standardized doses, patients at high risk could now be considered for the newly recommended high-dose teriparatide and denosumab combination, he said.

Dr. Khosla also noted that price remains an issue, given the estimated cost of $76,000 for 15 months of this proposed combination. However, the benefits in regard to at least bone mineral density are clear, he added, and that might prove sufficient enough for high-risk patients in need of an alternative therapy.

The study was supported by the Dart Family Foundation, the National Institutes of Health, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Eli Lilly and Amgen supplied the drugs. The authors reported numerous conflicts of interest, including receiving grants, reimbursements, and personal fees from various pharmaceutical companies, committees, and research institutes. Dr. Khosla reported no conflicts of interest.

SOURCE: Tsai JN et al. Lancet Diabetes Endocrinol. 2019 Aug 22. doi: 10.1016/S2213-8587(19)30255-4.

Pharmacist-led intervention reduced inappropriate medication prescriptions

An outpatient pharmacy-led intervention of notifying prescribing physicians to discontinue inappropriate Beers Criteria medications resulted in a greater discontinuation of inappropriate medications for older adults at 6 months, compared with the control group (43% vs. 12% discontinuation).

Citation: Martin P et al. Effect of a pharmacist-led educational intervention on inappropriate medication prescriptions in older adults: The D-PRESCRIBE randomized clinical trial. JAMA. 2018;320(18):1889-98.

Omadacycline noninferior for community-acquired pneumonia and acute bacterial soft tissue skin infections

Randomized, double-blind, double-dummy trials showed omadacycline is a noninferior alternative to moxifloxacin for the treatment of community-acquired pneumonia and to linezolid for acute bacterial soft-tissue skin infections.

Citation: Nuzyra (omadacycline) [package insert]. Boston, MA: Paratek Pharmaceuticals. 2018.

Lack of evidence to support low-salt diet in adult heart failure patients

Systematic review of multiple databases demonstrated there is limited high-quality evidence to support current guidelines that recommend a low-salt diet to heart failure patients.

Citation: Mahtani KR et al. Reduced salt intake for heart failure: A systematic review. JAMA Int Med. 2018;178(12):1693-700.

Magnesium for rate control in rapid atrial fibrillation

Randomized, controlled trial demonstrated that intravenous magnesium sulfate in combination with atrioventricular (AV) nodal blocking agents resulted in better rate control for atrial fibrillation with rapid ventricular response than did placebo given in combination with AV nodal blocking agents.

Citation: Bouida W et al. Low-dose magnesium sulfate versus high-dose in the early management of rapid atrial fibrillation: Randomized controlled double-blind study (LOMAGHI Study). Acad Emerg Med. 2019 Feb;26(2):183-91.

Low versus intermediate tidal volume strategy on ventilator-free days in ICU patients without ARDS

Randomized, clinical trial of low tidal volume versus intermediate tidal volume strategies in invasively ventilated patients without accute respiratory distress syndrome (ARDS) demonstrated no difference in number of ventilator-free days, ICU length of stay, hospital length of stay, incidence of ventilator-associated adverse events (ARDS, pneumonia, severe atelectasis, pneumothorax), or 28-day mortality.

Citation: Writing Group for the PReVENT Investigators, Simonis FD, Serpa Neto A. Effect of a low vs intermediate tidal volume strategy on ventilator-free days in intensive care unit patients without ARDS: A randomized clinical trial. JAMA. 2018;320(18):1872-80.

Pharmacist-led intervention reduced inappropriate medication prescriptions

An outpatient pharmacy-led intervention of notifying prescribing physicians to discontinue inappropriate Beers Criteria medications resulted in a greater discontinuation of inappropriate medications for older adults at 6 months, compared with the control group (43% vs. 12% discontinuation).

Citation: Martin P et al. Effect of a pharmacist-led educational intervention on inappropriate medication prescriptions in older adults: The D-PRESCRIBE randomized clinical trial. JAMA. 2018;320(18):1889-98.

Omadacycline noninferior for community-acquired pneumonia and acute bacterial soft tissue skin infections

Randomized, double-blind, double-dummy trials showed omadacycline is a noninferior alternative to moxifloxacin for the treatment of community-acquired pneumonia and to linezolid for acute bacterial soft-tissue skin infections.

Citation: Nuzyra (omadacycline) [package insert]. Boston, MA: Paratek Pharmaceuticals. 2018.

Lack of evidence to support low-salt diet in adult heart failure patients

Systematic review of multiple databases demonstrated there is limited high-quality evidence to support current guidelines that recommend a low-salt diet to heart failure patients.

Citation: Mahtani KR et al. Reduced salt intake for heart failure: A systematic review. JAMA Int Med. 2018;178(12):1693-700.

Magnesium for rate control in rapid atrial fibrillation

Randomized, controlled trial demonstrated that intravenous magnesium sulfate in combination with atrioventricular (AV) nodal blocking agents resulted in better rate control for atrial fibrillation with rapid ventricular response than did placebo given in combination with AV nodal blocking agents.

Citation: Bouida W et al. Low-dose magnesium sulfate versus high-dose in the early management of rapid atrial fibrillation: Randomized controlled double-blind study (LOMAGHI Study). Acad Emerg Med. 2019 Feb;26(2):183-91.

Low versus intermediate tidal volume strategy on ventilator-free days in ICU patients without ARDS

Randomized, clinical trial of low tidal volume versus intermediate tidal volume strategies in invasively ventilated patients without accute respiratory distress syndrome (ARDS) demonstrated no difference in number of ventilator-free days, ICU length of stay, hospital length of stay, incidence of ventilator-associated adverse events (ARDS, pneumonia, severe atelectasis, pneumothorax), or 28-day mortality.

Citation: Writing Group for the PReVENT Investigators, Simonis FD, Serpa Neto A. Effect of a low vs intermediate tidal volume strategy on ventilator-free days in intensive care unit patients without ARDS: A randomized clinical trial. JAMA. 2018;320(18):1872-80.

Pharmacist-led intervention reduced inappropriate medication prescriptions

An outpatient pharmacy-led intervention of notifying prescribing physicians to discontinue inappropriate Beers Criteria medications resulted in a greater discontinuation of inappropriate medications for older adults at 6 months, compared with the control group (43% vs. 12% discontinuation).

Citation: Martin P et al. Effect of a pharmacist-led educational intervention on inappropriate medication prescriptions in older adults: The D-PRESCRIBE randomized clinical trial. JAMA. 2018;320(18):1889-98.

Omadacycline noninferior for community-acquired pneumonia and acute bacterial soft tissue skin infections

Randomized, double-blind, double-dummy trials showed omadacycline is a noninferior alternative to moxifloxacin for the treatment of community-acquired pneumonia and to linezolid for acute bacterial soft-tissue skin infections.

Citation: Nuzyra (omadacycline) [package insert]. Boston, MA: Paratek Pharmaceuticals. 2018.

Lack of evidence to support low-salt diet in adult heart failure patients

Systematic review of multiple databases demonstrated there is limited high-quality evidence to support current guidelines that recommend a low-salt diet to heart failure patients.

Citation: Mahtani KR et al. Reduced salt intake for heart failure: A systematic review. JAMA Int Med. 2018;178(12):1693-700.

Magnesium for rate control in rapid atrial fibrillation

Randomized, controlled trial demonstrated that intravenous magnesium sulfate in combination with atrioventricular (AV) nodal blocking agents resulted in better rate control for atrial fibrillation with rapid ventricular response than did placebo given in combination with AV nodal blocking agents.

Citation: Bouida W et al. Low-dose magnesium sulfate versus high-dose in the early management of rapid atrial fibrillation: Randomized controlled double-blind study (LOMAGHI Study). Acad Emerg Med. 2019 Feb;26(2):183-91.

Low versus intermediate tidal volume strategy on ventilator-free days in ICU patients without ARDS

Randomized, clinical trial of low tidal volume versus intermediate tidal volume strategies in invasively ventilated patients without accute respiratory distress syndrome (ARDS) demonstrated no difference in number of ventilator-free days, ICU length of stay, hospital length of stay, incidence of ventilator-associated adverse events (ARDS, pneumonia, severe atelectasis, pneumothorax), or 28-day mortality.

Citation: Writing Group for the PReVENT Investigators, Simonis FD, Serpa Neto A. Effect of a low vs intermediate tidal volume strategy on ventilator-free days in intensive care unit patients without ARDS: A randomized clinical trial. JAMA. 2018;320(18):1872-80.