Migraines are associated with a significantly greater risk of Alzheimer’s disease and all forms of dementia except vascular dementia, according to research published online Sept. 4 in the International Journal of Geriatric Psychiatry.

In the Manitoba Study of Health and Aging, a population-based, prospective cohort study, 679 community-dwelling adults with a mean age of 75.9 years were followed for 5 years. Participants screened as cognitively intact at baseline had complete data on migraine history and all covariates at baseline and were assessed for cognitive outcomes 5 years later.

The study showed that a history of migraines was associated with a 2.97-fold greater likelihood of dementia, after adjustment for age, education, and a history of stroke, compared with individuals without a history of migraine. Individuals with Alzheimer’s disease were more than four times more likely to have a history of migraines (odds ratio 4.22).

However, researchers found no significant association between vascular dementia and a history of migraines, either before or after adjusting for confounders but particularly after incorporating a history of stroke into the model.

Lead investigator Suzanne L. Tyas, PhD, associate professor in the School of Public Health and Health Systems at the University of Waterloo, Ont., and coauthors suggested that the association between migraine and dementia was largely driven by the strong association between migraines and Alzheimer’s disease.

“This interpretation is supported by the weaker association for dementia than for Alzheimer’s disease, reflecting a dilution of the association with migraines across all types of dementia including vascular dementia, where a significant association was not found,” the researchers wrote.

The study population was 61.9% female, and no men reporting a history of migraine were diagnosed with dementia. While the study reflected a strong association between migraine and dementia in women, the researchers said they were unable to assess potential gender differences in this association.

Commenting on possible mechanisms behind the association, the authors wrote that there were overlaps underlying the biological mechanisms of migraine and dementia. Vascular risk factors such as diabetes, hypertension, heart attack, and stroke are associated with the development of dementia, and a relationship of these risk factors and migraine also has been seen.

“Many of the mechanisms involved in migraine neurophysiology, such as inflammation and reduced cerebral blood flow, are also underlying causes of dementia,” they wrote. “Repeated activation of these pathways in chronic migraineurs has been shown to cause permanent neurological and vascular damage.”

They also observed that the association could be influenced by genetic factors, as individuals with presenilin-1 mutations, which predispose them to Alzheimer’s disease, are more likely to experience migraines or recurrent headaches.

They suggested their findings could inform preventive strategies and treatments for Alzheimer’s disease, as well as interventions such as earlier screening for cognitive decline in individuals who experience migraines.

The study was funded by Manitoba Health and the National Health Research and Development Program of Health Canada. No conflicts of interest were declared.
 

SOURCE: Morton R et al. Int J Geriatr Psychiatry, 2019 Sep 4. doi: 10.1002/gps.5180.

Migraines are associated with a significantly greater risk of Alzheimer’s disease and all forms of dementia except vascular dementia, according to research published online Sept. 4 in the International Journal of Geriatric Psychiatry.

In the Manitoba Study of Health and Aging, a population-based, prospective cohort study, 679 community-dwelling adults with a mean age of 75.9 years were followed for 5 years. Participants screened as cognitively intact at baseline had complete data on migraine history and all covariates at baseline and were assessed for cognitive outcomes 5 years later.

The study showed that a history of migraines was associated with a 2.97-fold greater likelihood of dementia, after adjustment for age, education, and a history of stroke, compared with individuals without a history of migraine. Individuals with Alzheimer’s disease were more than four times more likely to have a history of migraines (odds ratio 4.22).

However, researchers found no significant association between vascular dementia and a history of migraines, either before or after adjusting for confounders but particularly after incorporating a history of stroke into the model.

Lead investigator Suzanne L. Tyas, PhD, associate professor in the School of Public Health and Health Systems at the University of Waterloo, Ont., and coauthors suggested that the association between migraine and dementia was largely driven by the strong association between migraines and Alzheimer’s disease.

“This interpretation is supported by the weaker association for dementia than for Alzheimer’s disease, reflecting a dilution of the association with migraines across all types of dementia including vascular dementia, where a significant association was not found,” the researchers wrote.

The study population was 61.9% female, and no men reporting a history of migraine were diagnosed with dementia. While the study reflected a strong association between migraine and dementia in women, the researchers said they were unable to assess potential gender differences in this association.

Commenting on possible mechanisms behind the association, the authors wrote that there were overlaps underlying the biological mechanisms of migraine and dementia. Vascular risk factors such as diabetes, hypertension, heart attack, and stroke are associated with the development of dementia, and a relationship of these risk factors and migraine also has been seen.

“Many of the mechanisms involved in migraine neurophysiology, such as inflammation and reduced cerebral blood flow, are also underlying causes of dementia,” they wrote. “Repeated activation of these pathways in chronic migraineurs has been shown to cause permanent neurological and vascular damage.”

They also observed that the association could be influenced by genetic factors, as individuals with presenilin-1 mutations, which predispose them to Alzheimer’s disease, are more likely to experience migraines or recurrent headaches.

They suggested their findings could inform preventive strategies and treatments for Alzheimer’s disease, as well as interventions such as earlier screening for cognitive decline in individuals who experience migraines.

The study was funded by Manitoba Health and the National Health Research and Development Program of Health Canada. No conflicts of interest were declared.
 

SOURCE: Morton R et al. Int J Geriatr Psychiatry, 2019 Sep 4. doi: 10.1002/gps.5180.

Migraines are associated with a significantly greater risk of Alzheimer’s disease and all forms of dementia except vascular dementia, according to research published online Sept. 4 in the International Journal of Geriatric Psychiatry.

In the Manitoba Study of Health and Aging, a population-based, prospective cohort study, 679 community-dwelling adults with a mean age of 75.9 years were followed for 5 years. Participants screened as cognitively intact at baseline had complete data on migraine history and all covariates at baseline and were assessed for cognitive outcomes 5 years later.

The study showed that a history of migraines was associated with a 2.97-fold greater likelihood of dementia, after adjustment for age, education, and a history of stroke, compared with individuals without a history of migraine. Individuals with Alzheimer’s disease were more than four times more likely to have a history of migraines (odds ratio 4.22).

However, researchers found no significant association between vascular dementia and a history of migraines, either before or after adjusting for confounders but particularly after incorporating a history of stroke into the model.

Lead investigator Suzanne L. Tyas, PhD, associate professor in the School of Public Health and Health Systems at the University of Waterloo, Ont., and coauthors suggested that the association between migraine and dementia was largely driven by the strong association between migraines and Alzheimer’s disease.

“This interpretation is supported by the weaker association for dementia than for Alzheimer’s disease, reflecting a dilution of the association with migraines across all types of dementia including vascular dementia, where a significant association was not found,” the researchers wrote.

The study population was 61.9% female, and no men reporting a history of migraine were diagnosed with dementia. While the study reflected a strong association between migraine and dementia in women, the researchers said they were unable to assess potential gender differences in this association.

Commenting on possible mechanisms behind the association, the authors wrote that there were overlaps underlying the biological mechanisms of migraine and dementia. Vascular risk factors such as diabetes, hypertension, heart attack, and stroke are associated with the development of dementia, and a relationship of these risk factors and migraine also has been seen.

“Many of the mechanisms involved in migraine neurophysiology, such as inflammation and reduced cerebral blood flow, are also underlying causes of dementia,” they wrote. “Repeated activation of these pathways in chronic migraineurs has been shown to cause permanent neurological and vascular damage.”

They also observed that the association could be influenced by genetic factors, as individuals with presenilin-1 mutations, which predispose them to Alzheimer’s disease, are more likely to experience migraines or recurrent headaches.

They suggested their findings could inform preventive strategies and treatments for Alzheimer’s disease, as well as interventions such as earlier screening for cognitive decline in individuals who experience migraines.

The study was funded by Manitoba Health and the National Health Research and Development Program of Health Canada. No conflicts of interest were declared.
 

SOURCE: Morton R et al. Int J Geriatr Psychiatry, 2019 Sep 4. doi: 10.1002/gps.5180.

SAN DIEGO – The use of threads to improve skin laxity is making a comeback, thanks largely to advances in absorbable sutures.

“Thread lifts were popularized in the 1990s, but I think they were misrepresented as an alternative to a surgical face-lift, which remains the gold standard,” Arisa E. Ortiz, MD, said at the annual Masters of Aesthetics Symposium. “A thread lift is certainly not like a traditional face-lift; it’s much more subtle.”

In the 1990s, clinicians used nonabsorbable sutures for thread lifts, including polypropylene-barbed threads, which caused adverse events ranging from extrusion and migration to thread expulsion, dimpling, granuloma formation, and prolonged pain. As a result, the Food and Drug Administration withdrew its approval of contour thread aesthetic procedures in 2009. Since then, the development of absorbable threads made from polydioxanone (PDO) and poly-l-lactic acid (PLLA) has led to renewed interest in thread-lift procedures, yet the long-term effects remain unclear.

“There are some nice benefits to thread lifts,” said Dr. Ortiz, who is director of laser and cosmetic dermatology at the University of California, San Diego. “You get immediate results, which is always nice for patients, but with tissue tightening using energy-based devices, results are unpredictable and it can take 6 months to see the results. With resorbable sutures, we’re seeing fewer complications, and the amount of lifting is more predictable because you’re physically lifting the tissue. In some cases, threads are able to lift tissue more than energy-based devices. There is minimal recovery, it requires local anesthesia, and it’s less expensive than a surgical face-lift, which can run $10,000-$15,000 or more.”

For skin lifting, clinicians implant threads subcutaneously. When tugged in the opposite direction, the barbs anchor in adipose tissue, increasing tensile strength while suspended in the dermis and overlying tissue. This produces a fibrous adhesion capsule that helps to solidify anchorage of the suture long term. Fibrosis has been shown to increase local collagen production. PDO and PLLA are known collagen stimulants and are postulated to stimulate a long-term benefit in rejuvenation, Dr. Ortiz said, but overall evidence regarding their use in thread lifts is weak.

“Existing studies have a very short follow-up period and there is really no standardized protocol, so we don’t know really know a lot about them yet,” she said. Lana Tong, MD, and Evan A. Rieder, MD, of New York University recently published a systematic review of the literature on the topic (Dermatol Surg. 2019 45[7]:931-40).

PDO is biodegradable by hydrolysis over 4-8 months and is used as absorbable suture material for prolonged tension–bearing areas. “It causes neocollagenesis with a foreign-body reaction,” Dr. Ortiz said. Meanwhile, PLLA is a collagen stimulator used for prolonged volume restoration. “It’s used an aesthetic filler, but a known complication with PLLA injections is the formation of subcutaneous nodules and late onset granulomas,” she said.

Early in 2019, Korean researchers published results of a study that set out to evaluate the collagen-producing effects of powdered PDO injection, compared with PLLA injection, in a murine model (J Cosmet Dermatol. 2019 Feb 27. doi: 10.1111/jocd.12894). “It showed both PDO and PLLA induced granulomatous reactions and collagen formation, but this decreased at 12 weeks,” said Dr. Ortiz, who was not involved with the work. “PDO had slightly more collagen formation than PLLA.”

Indications for thread lifts, she continued, are for jawline lift, cheek enhancement, brow lift, wrinkle reduction, body contouring, acne scarring, and texturing. “Choose patients with good skin quality: not too thick/heavy, and not too thin. Patients with moderate skin sagging are going to better candidates than those with severe skin sagging.”

One type of absorbable suspension suture, the Silhouette InstaLift, is made of polyglycolide/l-lactide and is FDA cleared for temporary midface suspension targeting the elevation of cheek laxity. “It is a bidirectional implant with four, six, or eight cones per side,” Dr. Ortiz said. “They provide immediate suspension of the tissue until collagen production ensues. These tend to last a year or 2, but there are no controlled studies to confirm that. I’ve found that if you’re able to lift tissue in an upward direction rather than posteriorly you get a better result, but you’re limited by the length of these sutures. They’re not as customizable as some of the shorter sutures.”

In terms of adverse events following thread lift procedures, patients usually feel tender for about a week or 2. “They can have some bruising, mostly from the anesthesia,” she said.

To prevent temporary dimpling, Dr. Ortiz undermines with an 18-gauge needle and inserts perpendicular to the skin surface. “Extrusions can still occur,” she said. To prevent this, she pulls on the end and makes sure it’s buried subcutaneously.

Dr. Ortiz reported having financial relationships with numerous pharmaceutical and device companies, though none related to the content of her presentation. She is also cochair of the Masters of Aesthetics symposium.

[email protected]

SAN DIEGO – The use of threads to improve skin laxity is making a comeback, thanks largely to advances in absorbable sutures.

“Thread lifts were popularized in the 1990s, but I think they were misrepresented as an alternative to a surgical face-lift, which remains the gold standard,” Arisa E. Ortiz, MD, said at the annual Masters of Aesthetics Symposium. “A thread lift is certainly not like a traditional face-lift; it’s much more subtle.”

In the 1990s, clinicians used nonabsorbable sutures for thread lifts, including polypropylene-barbed threads, which caused adverse events ranging from extrusion and migration to thread expulsion, dimpling, granuloma formation, and prolonged pain. As a result, the Food and Drug Administration withdrew its approval of contour thread aesthetic procedures in 2009. Since then, the development of absorbable threads made from polydioxanone (PDO) and poly-l-lactic acid (PLLA) has led to renewed interest in thread-lift procedures, yet the long-term effects remain unclear.

“There are some nice benefits to thread lifts,” said Dr. Ortiz, who is director of laser and cosmetic dermatology at the University of California, San Diego. “You get immediate results, which is always nice for patients, but with tissue tightening using energy-based devices, results are unpredictable and it can take 6 months to see the results. With resorbable sutures, we’re seeing fewer complications, and the amount of lifting is more predictable because you’re physically lifting the tissue. In some cases, threads are able to lift tissue more than energy-based devices. There is minimal recovery, it requires local anesthesia, and it’s less expensive than a surgical face-lift, which can run $10,000-$15,000 or more.”

For skin lifting, clinicians implant threads subcutaneously. When tugged in the opposite direction, the barbs anchor in adipose tissue, increasing tensile strength while suspended in the dermis and overlying tissue. This produces a fibrous adhesion capsule that helps to solidify anchorage of the suture long term. Fibrosis has been shown to increase local collagen production. PDO and PLLA are known collagen stimulants and are postulated to stimulate a long-term benefit in rejuvenation, Dr. Ortiz said, but overall evidence regarding their use in thread lifts is weak.

“Existing studies have a very short follow-up period and there is really no standardized protocol, so we don’t know really know a lot about them yet,” she said. Lana Tong, MD, and Evan A. Rieder, MD, of New York University recently published a systematic review of the literature on the topic (Dermatol Surg. 2019 45[7]:931-40).

PDO is biodegradable by hydrolysis over 4-8 months and is used as absorbable suture material for prolonged tension–bearing areas. “It causes neocollagenesis with a foreign-body reaction,” Dr. Ortiz said. Meanwhile, PLLA is a collagen stimulator used for prolonged volume restoration. “It’s used an aesthetic filler, but a known complication with PLLA injections is the formation of subcutaneous nodules and late onset granulomas,” she said.

Early in 2019, Korean researchers published results of a study that set out to evaluate the collagen-producing effects of powdered PDO injection, compared with PLLA injection, in a murine model (J Cosmet Dermatol. 2019 Feb 27. doi: 10.1111/jocd.12894). “It showed both PDO and PLLA induced granulomatous reactions and collagen formation, but this decreased at 12 weeks,” said Dr. Ortiz, who was not involved with the work. “PDO had slightly more collagen formation than PLLA.”

Indications for thread lifts, she continued, are for jawline lift, cheek enhancement, brow lift, wrinkle reduction, body contouring, acne scarring, and texturing. “Choose patients with good skin quality: not too thick/heavy, and not too thin. Patients with moderate skin sagging are going to better candidates than those with severe skin sagging.”

One type of absorbable suspension suture, the Silhouette InstaLift, is made of polyglycolide/l-lactide and is FDA cleared for temporary midface suspension targeting the elevation of cheek laxity. “It is a bidirectional implant with four, six, or eight cones per side,” Dr. Ortiz said. “They provide immediate suspension of the tissue until collagen production ensues. These tend to last a year or 2, but there are no controlled studies to confirm that. I’ve found that if you’re able to lift tissue in an upward direction rather than posteriorly you get a better result, but you’re limited by the length of these sutures. They’re not as customizable as some of the shorter sutures.”

In terms of adverse events following thread lift procedures, patients usually feel tender for about a week or 2. “They can have some bruising, mostly from the anesthesia,” she said.

To prevent temporary dimpling, Dr. Ortiz undermines with an 18-gauge needle and inserts perpendicular to the skin surface. “Extrusions can still occur,” she said. To prevent this, she pulls on the end and makes sure it’s buried subcutaneously.

Dr. Ortiz reported having financial relationships with numerous pharmaceutical and device companies, though none related to the content of her presentation. She is also cochair of the Masters of Aesthetics symposium.

[email protected]

SAN DIEGO – The use of threads to improve skin laxity is making a comeback, thanks largely to advances in absorbable sutures.

“Thread lifts were popularized in the 1990s, but I think they were misrepresented as an alternative to a surgical face-lift, which remains the gold standard,” Arisa E. Ortiz, MD, said at the annual Masters of Aesthetics Symposium. “A thread lift is certainly not like a traditional face-lift; it’s much more subtle.”

In the 1990s, clinicians used nonabsorbable sutures for thread lifts, including polypropylene-barbed threads, which caused adverse events ranging from extrusion and migration to thread expulsion, dimpling, granuloma formation, and prolonged pain. As a result, the Food and Drug Administration withdrew its approval of contour thread aesthetic procedures in 2009. Since then, the development of absorbable threads made from polydioxanone (PDO) and poly-l-lactic acid (PLLA) has led to renewed interest in thread-lift procedures, yet the long-term effects remain unclear.

“There are some nice benefits to thread lifts,” said Dr. Ortiz, who is director of laser and cosmetic dermatology at the University of California, San Diego. “You get immediate results, which is always nice for patients, but with tissue tightening using energy-based devices, results are unpredictable and it can take 6 months to see the results. With resorbable sutures, we’re seeing fewer complications, and the amount of lifting is more predictable because you’re physically lifting the tissue. In some cases, threads are able to lift tissue more than energy-based devices. There is minimal recovery, it requires local anesthesia, and it’s less expensive than a surgical face-lift, which can run $10,000-$15,000 or more.”

For skin lifting, clinicians implant threads subcutaneously. When tugged in the opposite direction, the barbs anchor in adipose tissue, increasing tensile strength while suspended in the dermis and overlying tissue. This produces a fibrous adhesion capsule that helps to solidify anchorage of the suture long term. Fibrosis has been shown to increase local collagen production. PDO and PLLA are known collagen stimulants and are postulated to stimulate a long-term benefit in rejuvenation, Dr. Ortiz said, but overall evidence regarding their use in thread lifts is weak.

“Existing studies have a very short follow-up period and there is really no standardized protocol, so we don’t know really know a lot about them yet,” she said. Lana Tong, MD, and Evan A. Rieder, MD, of New York University recently published a systematic review of the literature on the topic (Dermatol Surg. 2019 45[7]:931-40).

PDO is biodegradable by hydrolysis over 4-8 months and is used as absorbable suture material for prolonged tension–bearing areas. “It causes neocollagenesis with a foreign-body reaction,” Dr. Ortiz said. Meanwhile, PLLA is a collagen stimulator used for prolonged volume restoration. “It’s used an aesthetic filler, but a known complication with PLLA injections is the formation of subcutaneous nodules and late onset granulomas,” she said.

Early in 2019, Korean researchers published results of a study that set out to evaluate the collagen-producing effects of powdered PDO injection, compared with PLLA injection, in a murine model (J Cosmet Dermatol. 2019 Feb 27. doi: 10.1111/jocd.12894). “It showed both PDO and PLLA induced granulomatous reactions and collagen formation, but this decreased at 12 weeks,” said Dr. Ortiz, who was not involved with the work. “PDO had slightly more collagen formation than PLLA.”

Indications for thread lifts, she continued, are for jawline lift, cheek enhancement, brow lift, wrinkle reduction, body contouring, acne scarring, and texturing. “Choose patients with good skin quality: not too thick/heavy, and not too thin. Patients with moderate skin sagging are going to better candidates than those with severe skin sagging.”

One type of absorbable suspension suture, the Silhouette InstaLift, is made of polyglycolide/l-lactide and is FDA cleared for temporary midface suspension targeting the elevation of cheek laxity. “It is a bidirectional implant with four, six, or eight cones per side,” Dr. Ortiz said. “They provide immediate suspension of the tissue until collagen production ensues. These tend to last a year or 2, but there are no controlled studies to confirm that. I’ve found that if you’re able to lift tissue in an upward direction rather than posteriorly you get a better result, but you’re limited by the length of these sutures. They’re not as customizable as some of the shorter sutures.”

In terms of adverse events following thread lift procedures, patients usually feel tender for about a week or 2. “They can have some bruising, mostly from the anesthesia,” she said.

To prevent temporary dimpling, Dr. Ortiz undermines with an 18-gauge needle and inserts perpendicular to the skin surface. “Extrusions can still occur,” she said. To prevent this, she pulls on the end and makes sure it’s buried subcutaneously.

Dr. Ortiz reported having financial relationships with numerous pharmaceutical and device companies, though none related to the content of her presentation. She is also cochair of the Masters of Aesthetics symposium.

[email protected]

Dermatologist Dr. Jeffrey Benabio quipped, “The phrase ‘dermatologist burnout’ may seem as oxymoronic as jumbo shrimp, yet both are real.”¹ Indeed, dermatologists often self-report as among the happiest specialists both at work and home, according to the annual Medscape Physician Lifestyle and Happiness Report.² Similarly, others in the medical field may perceive dermatologists as low-stress providers—well-groomed, well-rested rays of sunshine, getting out of work every day at 5:00 pm to catch happy hour and live the #dermlife. However, the reality is that the syndrome of burnout does not spare our specialty. In fact, the low-stress perception of dermatologists may instead make recognizing burnout within others and ourselves challenging. Awareness of the notable prevalence of burnout within dermatology may facilitate identification and modification of associated predictors.

Burnout in Dermatology Residents

Burnout is a syndrome of emotional exhaustion, depersonalization, and a sense of reduced personal accomplishment that affects residents of all specialties³; however, there is a paucity of literature on burnout as it relates to dermatology. Although long work hours and schedule volatility have captured the focus of resident burnout conversations, a less discussed set of factors may contribute to dermatology resident burnout, such as increasing patient load, intensifying regulations, and an unrelenting pace of clinic. A recent survey study by Shoimer et al³ found that 61% of 116 participating Canadian dermatology residents cited examinations (including the board certifying examination) as their top stressor, followed by work (27%). Other stressors included family, relationships, finances, pressure from staff, research, and moving. More than 50% of dermatology residents surveyed experienced high levels of emotional exhaustion and depersonalization, while 40% demonstrated a low sense of personal accomplishment, all of which are determinants of the burnout syndrome.³

Comparison to Residents in Other Specialties

Although dermatology residents experience lower burnout rates than colleagues in other specialties, the absolute prevalence warrants attention. A recent study published in the Journal of the American Medical Association of 3588 second-year medical residents in the United States found that rates of burnout symptoms across clinical specialties ranged from 29.6% to 63.8%. The highest rates of burnout were found in urology (63.8%), neurology (61.6%), and ophthalmology (55.8%), but the lowest reported rate of burnout was demonstrated in dermatology (29.6%).⁴ Although dermatology ranked the lowest, that is still nearly a whopping 1 in 3 dermatology residents with burnout symptoms. The absolute prevalence should not be obscured by the ranking among other specialties.

Preventing Burnout

Several burnout prevention and coping strategies across specialties have been suggested.

Mindfulness and Self-awareness
A study by Chaukos et al⁵ found that mindfulness and self-awareness are resilience factors associated with resident burnout. Counseling is one strategy demonstrated to increase self-awareness. Mindfulness may be practiced through meditation or yoga. Regular meditation has been shown to improve mood and emotional stress.⁶ Similarly, yoga has been shown to yield physical, emotional, and psychological benefits to resdients.⁷

Work Factors
A supportive clinical faculty and receiving constructive monthly performance feedback have been negatively correlated with dermatology resident burnout.³ Other workplace interventions demonstrating utility in decreasing resident burnout include increasing staff awareness about burnout, increasing support for health professionals treating challenging populations, and ensuring a reasonable workload.⁶

Sleep
It has been demonstrated that sleeping less than 7 hours per night also is associated with resident burnout,⁷ yet it has been reported that 72% of dermatology residents fall into this category.³ Poor sleep quality has been shown to be a predictor of lower academic performance. It has been proposed that to minimize sleep deprivation and poor sleep quality, institutions should focus on programs that promote regular exercise, sleep hygiene, mindfulness, and time-out activities such as meditation.⁷

Social Support
Focusing on peers may foster the inner strength to endure suffering.¹ Venting, laughing, and discussing care with colleagues has been demonstrated to decrease anxiety.⁶ Work-related social networks may be strengthened through attendance at conferences, lectures, and professional organizations.⁷ Additionally, social supports and spending quality time with family have been demonstrated as negative predictors of dermatology resident burnout.³

Physical Exercise
Exercise has been demonstrated to improve mood, anxiety, and depression, thereby decreasing resident burnout.⁶

Final Thoughts

Burnout among dermatology residents warrants awareness, as it does in other medical specialties. Awareness may facilitate identification and prevention, the latter of which is perhaps best summarized by the words of psychologist Dr. Christina Maslach: “If all of the knowledge and advice about how to beat burnout could be summed up in 1 word, that word would be balance—balance between giving and getting, balance between stress and calm, balance between work and home.”⁸

Dermatologist Dr. Jeffrey Benabio quipped, “The phrase ‘dermatologist burnout’ may seem as oxymoronic as jumbo shrimp, yet both are real.”¹ Indeed, dermatologists often self-report as among the happiest specialists both at work and home, according to the annual Medscape Physician Lifestyle and Happiness Report.² Similarly, others in the medical field may perceive dermatologists as low-stress providers—well-groomed, well-rested rays of sunshine, getting out of work every day at 5:00 pm to catch happy hour and live the #dermlife. However, the reality is that the syndrome of burnout does not spare our specialty. In fact, the low-stress perception of dermatologists may instead make recognizing burnout within others and ourselves challenging. Awareness of the notable prevalence of burnout within dermatology may facilitate identification and modification of associated predictors.

Burnout in Dermatology Residents

Burnout is a syndrome of emotional exhaustion, depersonalization, and a sense of reduced personal accomplishment that affects residents of all specialties³; however, there is a paucity of literature on burnout as it relates to dermatology. Although long work hours and schedule volatility have captured the focus of resident burnout conversations, a less discussed set of factors may contribute to dermatology resident burnout, such as increasing patient load, intensifying regulations, and an unrelenting pace of clinic. A recent survey study by Shoimer et al³ found that 61% of 116 participating Canadian dermatology residents cited examinations (including the board certifying examination) as their top stressor, followed by work (27%). Other stressors included family, relationships, finances, pressure from staff, research, and moving. More than 50% of dermatology residents surveyed experienced high levels of emotional exhaustion and depersonalization, while 40% demonstrated a low sense of personal accomplishment, all of which are determinants of the burnout syndrome.³

Comparison to Residents in Other Specialties

Although dermatology residents experience lower burnout rates than colleagues in other specialties, the absolute prevalence warrants attention. A recent study published in the Journal of the American Medical Association of 3588 second-year medical residents in the United States found that rates of burnout symptoms across clinical specialties ranged from 29.6% to 63.8%. The highest rates of burnout were found in urology (63.8%), neurology (61.6%), and ophthalmology (55.8%), but the lowest reported rate of burnout was demonstrated in dermatology (29.6%).⁴ Although dermatology ranked the lowest, that is still nearly a whopping 1 in 3 dermatology residents with burnout symptoms. The absolute prevalence should not be obscured by the ranking among other specialties.

Preventing Burnout

Several burnout prevention and coping strategies across specialties have been suggested.

Mindfulness and Self-awareness
A study by Chaukos et al⁵ found that mindfulness and self-awareness are resilience factors associated with resident burnout. Counseling is one strategy demonstrated to increase self-awareness. Mindfulness may be practiced through meditation or yoga. Regular meditation has been shown to improve mood and emotional stress.⁶ Similarly, yoga has been shown to yield physical, emotional, and psychological benefits to resdients.⁷

Work Factors
A supportive clinical faculty and receiving constructive monthly performance feedback have been negatively correlated with dermatology resident burnout.³ Other workplace interventions demonstrating utility in decreasing resident burnout include increasing staff awareness about burnout, increasing support for health professionals treating challenging populations, and ensuring a reasonable workload.⁶

Sleep
It has been demonstrated that sleeping less than 7 hours per night also is associated with resident burnout,⁷ yet it has been reported that 72% of dermatology residents fall into this category.³ Poor sleep quality has been shown to be a predictor of lower academic performance. It has been proposed that to minimize sleep deprivation and poor sleep quality, institutions should focus on programs that promote regular exercise, sleep hygiene, mindfulness, and time-out activities such as meditation.⁷

Social Support
Focusing on peers may foster the inner strength to endure suffering.¹ Venting, laughing, and discussing care with colleagues has been demonstrated to decrease anxiety.⁶ Work-related social networks may be strengthened through attendance at conferences, lectures, and professional organizations.⁷ Additionally, social supports and spending quality time with family have been demonstrated as negative predictors of dermatology resident burnout.³

Physical Exercise
Exercise has been demonstrated to improve mood, anxiety, and depression, thereby decreasing resident burnout.⁶

Final Thoughts

Burnout among dermatology residents warrants awareness, as it does in other medical specialties. Awareness may facilitate identification and prevention, the latter of which is perhaps best summarized by the words of psychologist Dr. Christina Maslach: “If all of the knowledge and advice about how to beat burnout could be summed up in 1 word, that word would be balance—balance between giving and getting, balance between stress and calm, balance between work and home.”⁸

Dermatologist Dr. Jeffrey Benabio quipped, “The phrase ‘dermatologist burnout’ may seem as oxymoronic as jumbo shrimp, yet both are real.”¹ Indeed, dermatologists often self-report as among the happiest specialists both at work and home, according to the annual Medscape Physician Lifestyle and Happiness Report.² Similarly, others in the medical field may perceive dermatologists as low-stress providers—well-groomed, well-rested rays of sunshine, getting out of work every day at 5:00 pm to catch happy hour and live the #dermlife. However, the reality is that the syndrome of burnout does not spare our specialty. In fact, the low-stress perception of dermatologists may instead make recognizing burnout within others and ourselves challenging. Awareness of the notable prevalence of burnout within dermatology may facilitate identification and modification of associated predictors.

Burnout in Dermatology Residents

Burnout is a syndrome of emotional exhaustion, depersonalization, and a sense of reduced personal accomplishment that affects residents of all specialties³; however, there is a paucity of literature on burnout as it relates to dermatology. Although long work hours and schedule volatility have captured the focus of resident burnout conversations, a less discussed set of factors may contribute to dermatology resident burnout, such as increasing patient load, intensifying regulations, and an unrelenting pace of clinic. A recent survey study by Shoimer et al³ found that 61% of 116 participating Canadian dermatology residents cited examinations (including the board certifying examination) as their top stressor, followed by work (27%). Other stressors included family, relationships, finances, pressure from staff, research, and moving. More than 50% of dermatology residents surveyed experienced high levels of emotional exhaustion and depersonalization, while 40% demonstrated a low sense of personal accomplishment, all of which are determinants of the burnout syndrome.³

Comparison to Residents in Other Specialties

Although dermatology residents experience lower burnout rates than colleagues in other specialties, the absolute prevalence warrants attention. A recent study published in the Journal of the American Medical Association of 3588 second-year medical residents in the United States found that rates of burnout symptoms across clinical specialties ranged from 29.6% to 63.8%. The highest rates of burnout were found in urology (63.8%), neurology (61.6%), and ophthalmology (55.8%), but the lowest reported rate of burnout was demonstrated in dermatology (29.6%).⁴ Although dermatology ranked the lowest, that is still nearly a whopping 1 in 3 dermatology residents with burnout symptoms. The absolute prevalence should not be obscured by the ranking among other specialties.

Preventing Burnout

Several burnout prevention and coping strategies across specialties have been suggested.

Mindfulness and Self-awareness
A study by Chaukos et al⁵ found that mindfulness and self-awareness are resilience factors associated with resident burnout. Counseling is one strategy demonstrated to increase self-awareness. Mindfulness may be practiced through meditation or yoga. Regular meditation has been shown to improve mood and emotional stress.⁶ Similarly, yoga has been shown to yield physical, emotional, and psychological benefits to resdients.⁷

Work Factors
A supportive clinical faculty and receiving constructive monthly performance feedback have been negatively correlated with dermatology resident burnout.³ Other workplace interventions demonstrating utility in decreasing resident burnout include increasing staff awareness about burnout, increasing support for health professionals treating challenging populations, and ensuring a reasonable workload.⁶

Sleep
It has been demonstrated that sleeping less than 7 hours per night also is associated with resident burnout,⁷ yet it has been reported that 72% of dermatology residents fall into this category.³ Poor sleep quality has been shown to be a predictor of lower academic performance. It has been proposed that to minimize sleep deprivation and poor sleep quality, institutions should focus on programs that promote regular exercise, sleep hygiene, mindfulness, and time-out activities such as meditation.⁷

Social Support
Focusing on peers may foster the inner strength to endure suffering.¹ Venting, laughing, and discussing care with colleagues has been demonstrated to decrease anxiety.⁶ Work-related social networks may be strengthened through attendance at conferences, lectures, and professional organizations.⁷ Additionally, social supports and spending quality time with family have been demonstrated as negative predictors of dermatology resident burnout.³

Physical Exercise
Exercise has been demonstrated to improve mood, anxiety, and depression, thereby decreasing resident burnout.⁶

Final Thoughts

Burnout among dermatology residents warrants awareness, as it does in other medical specialties. Awareness may facilitate identification and prevention, the latter of which is perhaps best summarized by the words of psychologist Dr. Christina Maslach: “If all of the knowledge and advice about how to beat burnout could be summed up in 1 word, that word would be balance—balance between giving and getting, balance between stress and calm, balance between work and home.”⁸

CHICAGO – Evidence suggests that diet may cause incident inflammatory bowel disease (IBD) and induce associated symptoms, according to a lecture delivered at Freston Conference 2019, sponsored by the American Gastroenterological Association.

Although the literature is highly consistent, it contains discordant findings, and many questions remain unanswered. “We need more rigorous studies, and particularly more interventions, to truly understand the role diet may play in patients with IBD,” said Ashwin N. Ananthakrishnan, MD, MPH, associate professor of medicine at Massachusetts General Hospital in Boston.
 

Food can cause symptoms in IBD

Many patients with IBD are convinced that their diet caused their disease. A relevant point for physicians to consider is that these patients are at least as likely as is the general population to have intolerance or sensitivity to food components such as lactose and gluten. In a prospective questionnaire of 400 consecutive patients with IBD in the United Kingdom, 48% expressed the belief that diet could initiate IBD, and 57% said that diet could trigger a flare-up. In addition, 60% of respondents reported worsening of symptoms after eating certain foods, and about two-thirds deprived themselves of their favorite foods to prevent relapses (Inflamm Bowel Dis. 2016;22[1]:164-70). A French study found similar results. “Clearly there’s something there,” said Dr. Ananthakrishnan. Patients’ beliefs about the relationship between food and their symptoms are not simply misconceptions, he added.

A Canadian study published in 2016 found that almost one-third of patients with IBD avoid many food groups. “But there is significant heterogeneity in the foods that are avoided, and sometimes we mistake this heterogeneity for a lack of association between diet and symptoms in IBD,” said Dr. Ananthakrishnan. A larger number of patients avoid certain foods during periods of active disease, which suggests that food exacerbates their symptoms, he added. The same study showed that patients with IBD have more restrictive diets than do community controls. Patients eat fewer fruits and vegetables and generally consume less iron-rich food and less protein-rich food than healthy controls. GI intolerance, rather than professional advice, is the most common reason that patients with IBD restrict their diets (JPEN J Parenter Enteral Nutr. 2016;40[3]:405-11.).

A cross-sectional survey of 130 patients with IBD and 70 controls yielded similar results. Among patients, GI symptoms that resulted from consuming foods were not related to disease activity, disease location, or prior surgery. Patients with IBD tended to have greater frequency of GI intolerance to foods than did controls (Scand J Gastroenterol. 1997;32[6]:569-71.).

Diet may cause intestinal inflammation

International research has recorded increases in the consumption of sugar and fat (particularly saturated fat) and concomitant decreases in fiber consumption during the past several decades. The incidence of IBD has increased in parallel with these dietary changes with a remarkably similar trajectory, said Dr. Ananthakrishnan. The correlation between dietary changes and IBD incidence “holds true even more strikingly in countries that are now experiencing Westernization,” he added. These countries have undergone more rapid dietary changes, and their IBD incidence has doubled or tripled. The transition to “less traditional diets” appears to promote intestinal inflammation, said Dr. Ananthakrishnan.

An analysis of data from the European Prospective Investigation into Cancer (EPIC) study found an association between high consumption of sugar and soft drinks, together with low consumption of vegetables, and risk of ulcerative colitis (Inflamm Bowel Dis. 2016;22[2]:345-54.). A subsequent analysis of data from two prospective Swedish cohorts, however, found no association between consumption of sugary beverages and risk of Crohn’s disease or ulcerative colitis (Clin Gastroenterol Hepatol. 2019;17[1]:123-9.).

Although the data on sugar are mixed, data on the association between other macronutrient groups and risk of IBD are more consistent. When Dr. Ananthakrishnan and colleagues examined data from the Nurses’ Health Study, they found that the highest quintile of dietary fiber intake was associated with a 40% reduction in risk of Crohn’s disease, compared with the lowest quintile. The observed reduction of risk seemed to be greatest for fiber derived from fruits. Fiber from cereals, whole grains, or legumes, however, did not affect risk of Crohn’s disease (Gastroenterology. 2013;145[5]:970-7.).

A separate analysis of the Nurses’ Health Study suggested that high intake of n-3 polyunsaturated fatty acids (PUFAs) and low intake of n-6 PUFAs was associated with a 31% reduction in risk of ulcerative colitis and a 15% reduction in the risk of Crohn’s disease. These data were consistent with a previous analysis of EPIC data that found that high intake of n-6 PUFAs was associated with increased risk of ulcerative colitis (Gut. 2009;58[12]:1606-11.). Other analyses indicate that genetic polymorphisms likely modify the association between PUFAs and risk of ulcerative colitis, said Dr. Ananthakrishnan. “There may be an additional layer of complexity beyond just measuring your dietary intake.”

In addition to macronutrients, micronutrients can modify a patient’s risk of ulcerative colitis or Crohn’s disease. When Dr. Ananthakrishnan and colleagues examined the Nurses’ Health Study, they found an inverse association between vitamin D intake and risk of Crohn’s disease (Gastroenterology. 2012;142[3]:482-9.). In a separate study, they found that a zinc intake greater than 16 mg/day was associated with reduced risk of Crohn’s disease (Int J Epidemiol. 2015;44[6]:1995-2005.).

Patients aged older than 40 years and patients of European ancestry tend to be overrepresented in cohort studies, which reduces the generalizability of their conclusions, said Dr. Ananthakrishnan. Furthermore, cohort studies have not produced consistent findings regarding the relationship between various dietary components and risk of IBD. Nevertheless, the data suggest that dietary patterns may be associated with incident Crohn’s disease or ulcerative colitis.
 

An influence of diet on IBD risk is plausible

One mechanism through which diet may exercise a causal influence on the risk of IBD is by affecting the microbiome. In 2011, investigators studied 98 healthy volunteers who answered questionnaires about their diet. The researchers also used 16s rDNA sequencing to characterize the population’s stool samples. A diet high in animal protein, amino acids, and saturated fats was associated with large populations of Bacteroides. A diet low in fat and in animal protein, but high in carbohydrates and simple sugars was associated with large populations of Prevotella. When the investigators conducted a controlled-feeding study of 10 patients, microbiome composition changed within 1 day of initiating a high-fat-and-low-fiber or a low-fat-and-high-fiber diet (Science. 2011;334[6052]:105-8.). A more recent study showed that the diversity of the microbiome increased with the adoption of an animal-based diet (Nature. 2014;505[7484]:559-63.).

Diet also may exert a causal influence on IBD risk by altering the intestinal barrier. In an experimental model, 5-mg/mL concentrations of fiber from plantain and broccoli significantly reduced the translocation of Escherichia coli through a human intestinal epithelial barrier (Gut. 2010;59[10]:1331-9.). Increased fiber intake may thus result in reduced intestinal inflammation, said Dr. Ananthakrishnan.

Observational and experimental evidence thus support an effect of diet on the risk of IBD, and experimental evidence indicates that this effect is biologically plausible. Nevertheless, “there are many missing links,” and further study will clarify the role of diet in IBD incidence, said Dr. Ananthakrishnan.

[email protected]

CHICAGO – Evidence suggests that diet may cause incident inflammatory bowel disease (IBD) and induce associated symptoms, according to a lecture delivered at Freston Conference 2019, sponsored by the American Gastroenterological Association.

Although the literature is highly consistent, it contains discordant findings, and many questions remain unanswered. “We need more rigorous studies, and particularly more interventions, to truly understand the role diet may play in patients with IBD,” said Ashwin N. Ananthakrishnan, MD, MPH, associate professor of medicine at Massachusetts General Hospital in Boston.
 

Food can cause symptoms in IBD

Many patients with IBD are convinced that their diet caused their disease. A relevant point for physicians to consider is that these patients are at least as likely as is the general population to have intolerance or sensitivity to food components such as lactose and gluten. In a prospective questionnaire of 400 consecutive patients with IBD in the United Kingdom, 48% expressed the belief that diet could initiate IBD, and 57% said that diet could trigger a flare-up. In addition, 60% of respondents reported worsening of symptoms after eating certain foods, and about two-thirds deprived themselves of their favorite foods to prevent relapses (Inflamm Bowel Dis. 2016;22[1]:164-70). A French study found similar results. “Clearly there’s something there,” said Dr. Ananthakrishnan. Patients’ beliefs about the relationship between food and their symptoms are not simply misconceptions, he added.

A Canadian study published in 2016 found that almost one-third of patients with IBD avoid many food groups. “But there is significant heterogeneity in the foods that are avoided, and sometimes we mistake this heterogeneity for a lack of association between diet and symptoms in IBD,” said Dr. Ananthakrishnan. A larger number of patients avoid certain foods during periods of active disease, which suggests that food exacerbates their symptoms, he added. The same study showed that patients with IBD have more restrictive diets than do community controls. Patients eat fewer fruits and vegetables and generally consume less iron-rich food and less protein-rich food than healthy controls. GI intolerance, rather than professional advice, is the most common reason that patients with IBD restrict their diets (JPEN J Parenter Enteral Nutr. 2016;40[3]:405-11.).

A cross-sectional survey of 130 patients with IBD and 70 controls yielded similar results. Among patients, GI symptoms that resulted from consuming foods were not related to disease activity, disease location, or prior surgery. Patients with IBD tended to have greater frequency of GI intolerance to foods than did controls (Scand J Gastroenterol. 1997;32[6]:569-71.).

Diet may cause intestinal inflammation

International research has recorded increases in the consumption of sugar and fat (particularly saturated fat) and concomitant decreases in fiber consumption during the past several decades. The incidence of IBD has increased in parallel with these dietary changes with a remarkably similar trajectory, said Dr. Ananthakrishnan. The correlation between dietary changes and IBD incidence “holds true even more strikingly in countries that are now experiencing Westernization,” he added. These countries have undergone more rapid dietary changes, and their IBD incidence has doubled or tripled. The transition to “less traditional diets” appears to promote intestinal inflammation, said Dr. Ananthakrishnan.

An analysis of data from the European Prospective Investigation into Cancer (EPIC) study found an association between high consumption of sugar and soft drinks, together with low consumption of vegetables, and risk of ulcerative colitis (Inflamm Bowel Dis. 2016;22[2]:345-54.). A subsequent analysis of data from two prospective Swedish cohorts, however, found no association between consumption of sugary beverages and risk of Crohn’s disease or ulcerative colitis (Clin Gastroenterol Hepatol. 2019;17[1]:123-9.).

Although the data on sugar are mixed, data on the association between other macronutrient groups and risk of IBD are more consistent. When Dr. Ananthakrishnan and colleagues examined data from the Nurses’ Health Study, they found that the highest quintile of dietary fiber intake was associated with a 40% reduction in risk of Crohn’s disease, compared with the lowest quintile. The observed reduction of risk seemed to be greatest for fiber derived from fruits. Fiber from cereals, whole grains, or legumes, however, did not affect risk of Crohn’s disease (Gastroenterology. 2013;145[5]:970-7.).

A separate analysis of the Nurses’ Health Study suggested that high intake of n-3 polyunsaturated fatty acids (PUFAs) and low intake of n-6 PUFAs was associated with a 31% reduction in risk of ulcerative colitis and a 15% reduction in the risk of Crohn’s disease. These data were consistent with a previous analysis of EPIC data that found that high intake of n-6 PUFAs was associated with increased risk of ulcerative colitis (Gut. 2009;58[12]:1606-11.). Other analyses indicate that genetic polymorphisms likely modify the association between PUFAs and risk of ulcerative colitis, said Dr. Ananthakrishnan. “There may be an additional layer of complexity beyond just measuring your dietary intake.”

In addition to macronutrients, micronutrients can modify a patient’s risk of ulcerative colitis or Crohn’s disease. When Dr. Ananthakrishnan and colleagues examined the Nurses’ Health Study, they found an inverse association between vitamin D intake and risk of Crohn’s disease (Gastroenterology. 2012;142[3]:482-9.). In a separate study, they found that a zinc intake greater than 16 mg/day was associated with reduced risk of Crohn’s disease (Int J Epidemiol. 2015;44[6]:1995-2005.).

Patients aged older than 40 years and patients of European ancestry tend to be overrepresented in cohort studies, which reduces the generalizability of their conclusions, said Dr. Ananthakrishnan. Furthermore, cohort studies have not produced consistent findings regarding the relationship between various dietary components and risk of IBD. Nevertheless, the data suggest that dietary patterns may be associated with incident Crohn’s disease or ulcerative colitis.
 

An influence of diet on IBD risk is plausible

One mechanism through which diet may exercise a causal influence on the risk of IBD is by affecting the microbiome. In 2011, investigators studied 98 healthy volunteers who answered questionnaires about their diet. The researchers also used 16s rDNA sequencing to characterize the population’s stool samples. A diet high in animal protein, amino acids, and saturated fats was associated with large populations of Bacteroides. A diet low in fat and in animal protein, but high in carbohydrates and simple sugars was associated with large populations of Prevotella. When the investigators conducted a controlled-feeding study of 10 patients, microbiome composition changed within 1 day of initiating a high-fat-and-low-fiber or a low-fat-and-high-fiber diet (Science. 2011;334[6052]:105-8.). A more recent study showed that the diversity of the microbiome increased with the adoption of an animal-based diet (Nature. 2014;505[7484]:559-63.).

Diet also may exert a causal influence on IBD risk by altering the intestinal barrier. In an experimental model, 5-mg/mL concentrations of fiber from plantain and broccoli significantly reduced the translocation of Escherichia coli through a human intestinal epithelial barrier (Gut. 2010;59[10]:1331-9.). Increased fiber intake may thus result in reduced intestinal inflammation, said Dr. Ananthakrishnan.

Observational and experimental evidence thus support an effect of diet on the risk of IBD, and experimental evidence indicates that this effect is biologically plausible. Nevertheless, “there are many missing links,” and further study will clarify the role of diet in IBD incidence, said Dr. Ananthakrishnan.

[email protected]

CHICAGO – Evidence suggests that diet may cause incident inflammatory bowel disease (IBD) and induce associated symptoms, according to a lecture delivered at Freston Conference 2019, sponsored by the American Gastroenterological Association.

Although the literature is highly consistent, it contains discordant findings, and many questions remain unanswered. “We need more rigorous studies, and particularly more interventions, to truly understand the role diet may play in patients with IBD,” said Ashwin N. Ananthakrishnan, MD, MPH, associate professor of medicine at Massachusetts General Hospital in Boston.
 

Food can cause symptoms in IBD

Many patients with IBD are convinced that their diet caused their disease. A relevant point for physicians to consider is that these patients are at least as likely as is the general population to have intolerance or sensitivity to food components such as lactose and gluten. In a prospective questionnaire of 400 consecutive patients with IBD in the United Kingdom, 48% expressed the belief that diet could initiate IBD, and 57% said that diet could trigger a flare-up. In addition, 60% of respondents reported worsening of symptoms after eating certain foods, and about two-thirds deprived themselves of their favorite foods to prevent relapses (Inflamm Bowel Dis. 2016;22[1]:164-70). A French study found similar results. “Clearly there’s something there,” said Dr. Ananthakrishnan. Patients’ beliefs about the relationship between food and their symptoms are not simply misconceptions, he added.

A Canadian study published in 2016 found that almost one-third of patients with IBD avoid many food groups. “But there is significant heterogeneity in the foods that are avoided, and sometimes we mistake this heterogeneity for a lack of association between diet and symptoms in IBD,” said Dr. Ananthakrishnan. A larger number of patients avoid certain foods during periods of active disease, which suggests that food exacerbates their symptoms, he added. The same study showed that patients with IBD have more restrictive diets than do community controls. Patients eat fewer fruits and vegetables and generally consume less iron-rich food and less protein-rich food than healthy controls. GI intolerance, rather than professional advice, is the most common reason that patients with IBD restrict their diets (JPEN J Parenter Enteral Nutr. 2016;40[3]:405-11.).

A cross-sectional survey of 130 patients with IBD and 70 controls yielded similar results. Among patients, GI symptoms that resulted from consuming foods were not related to disease activity, disease location, or prior surgery. Patients with IBD tended to have greater frequency of GI intolerance to foods than did controls (Scand J Gastroenterol. 1997;32[6]:569-71.).

Diet may cause intestinal inflammation

International research has recorded increases in the consumption of sugar and fat (particularly saturated fat) and concomitant decreases in fiber consumption during the past several decades. The incidence of IBD has increased in parallel with these dietary changes with a remarkably similar trajectory, said Dr. Ananthakrishnan. The correlation between dietary changes and IBD incidence “holds true even more strikingly in countries that are now experiencing Westernization,” he added. These countries have undergone more rapid dietary changes, and their IBD incidence has doubled or tripled. The transition to “less traditional diets” appears to promote intestinal inflammation, said Dr. Ananthakrishnan.

An analysis of data from the European Prospective Investigation into Cancer (EPIC) study found an association between high consumption of sugar and soft drinks, together with low consumption of vegetables, and risk of ulcerative colitis (Inflamm Bowel Dis. 2016;22[2]:345-54.). A subsequent analysis of data from two prospective Swedish cohorts, however, found no association between consumption of sugary beverages and risk of Crohn’s disease or ulcerative colitis (Clin Gastroenterol Hepatol. 2019;17[1]:123-9.).

Although the data on sugar are mixed, data on the association between other macronutrient groups and risk of IBD are more consistent. When Dr. Ananthakrishnan and colleagues examined data from the Nurses’ Health Study, they found that the highest quintile of dietary fiber intake was associated with a 40% reduction in risk of Crohn’s disease, compared with the lowest quintile. The observed reduction of risk seemed to be greatest for fiber derived from fruits. Fiber from cereals, whole grains, or legumes, however, did not affect risk of Crohn’s disease (Gastroenterology. 2013;145[5]:970-7.).

A separate analysis of the Nurses’ Health Study suggested that high intake of n-3 polyunsaturated fatty acids (PUFAs) and low intake of n-6 PUFAs was associated with a 31% reduction in risk of ulcerative colitis and a 15% reduction in the risk of Crohn’s disease. These data were consistent with a previous analysis of EPIC data that found that high intake of n-6 PUFAs was associated with increased risk of ulcerative colitis (Gut. 2009;58[12]:1606-11.). Other analyses indicate that genetic polymorphisms likely modify the association between PUFAs and risk of ulcerative colitis, said Dr. Ananthakrishnan. “There may be an additional layer of complexity beyond just measuring your dietary intake.”

In addition to macronutrients, micronutrients can modify a patient’s risk of ulcerative colitis or Crohn’s disease. When Dr. Ananthakrishnan and colleagues examined the Nurses’ Health Study, they found an inverse association between vitamin D intake and risk of Crohn’s disease (Gastroenterology. 2012;142[3]:482-9.). In a separate study, they found that a zinc intake greater than 16 mg/day was associated with reduced risk of Crohn’s disease (Int J Epidemiol. 2015;44[6]:1995-2005.).

Patients aged older than 40 years and patients of European ancestry tend to be overrepresented in cohort studies, which reduces the generalizability of their conclusions, said Dr. Ananthakrishnan. Furthermore, cohort studies have not produced consistent findings regarding the relationship between various dietary components and risk of IBD. Nevertheless, the data suggest that dietary patterns may be associated with incident Crohn’s disease or ulcerative colitis.
 

An influence of diet on IBD risk is plausible

One mechanism through which diet may exercise a causal influence on the risk of IBD is by affecting the microbiome. In 2011, investigators studied 98 healthy volunteers who answered questionnaires about their diet. The researchers also used 16s rDNA sequencing to characterize the population’s stool samples. A diet high in animal protein, amino acids, and saturated fats was associated with large populations of Bacteroides. A diet low in fat and in animal protein, but high in carbohydrates and simple sugars was associated with large populations of Prevotella. When the investigators conducted a controlled-feeding study of 10 patients, microbiome composition changed within 1 day of initiating a high-fat-and-low-fiber or a low-fat-and-high-fiber diet (Science. 2011;334[6052]:105-8.). A more recent study showed that the diversity of the microbiome increased with the adoption of an animal-based diet (Nature. 2014;505[7484]:559-63.).

Diet also may exert a causal influence on IBD risk by altering the intestinal barrier. In an experimental model, 5-mg/mL concentrations of fiber from plantain and broccoli significantly reduced the translocation of Escherichia coli through a human intestinal epithelial barrier (Gut. 2010;59[10]:1331-9.). Increased fiber intake may thus result in reduced intestinal inflammation, said Dr. Ananthakrishnan.

Observational and experimental evidence thus support an effect of diet on the risk of IBD, and experimental evidence indicates that this effect is biologically plausible. Nevertheless, “there are many missing links,” and further study will clarify the role of diet in IBD incidence, said Dr. Ananthakrishnan.

[email protected]

Background: HAIs are key drivers of morbidity and mortality for hospitalized patients. In 2011, the Centers for Disease Control and Prevention (CDC) conducted a point-prevalence survey that revealed an HAI in 4% of hospitalized patients. The most common infections included pneumonia, gastrointestinal infections, and surgical-site infections. Over time, efforts in patient safety and quality have expanded to reduce the rate of HAIs. This same survey was repeated in 2015 to assess for improvements.

The reduction in HAIs was primarily driven by a reduction in surgical-site infections and urinary tract infections. There was no reduction in the prevalence of health care–associated pneumonia, Clostridium difficile infection, or mortality. Consequently, this emphasizes the necessity of further work in these domains.

Bottom line: The overall prevalence of HAIs has decreased, but further quality improvement work is needed in order to expand this reduction to health care–associated pneumonia, C. difficile infection, and mortality from HAIs.

Citation: Magill SS et al. Changes in prevalence of heath care–associated infections in U.S. hospitals. N Engl J Med. 2018;379(18):1732-44.

Dr. McIntyre is an associate physician in the division of hospital medicine at the University of California, San Diego.

Background: HAIs are key drivers of morbidity and mortality for hospitalized patients. In 2011, the Centers for Disease Control and Prevention (CDC) conducted a point-prevalence survey that revealed an HAI in 4% of hospitalized patients. The most common infections included pneumonia, gastrointestinal infections, and surgical-site infections. Over time, efforts in patient safety and quality have expanded to reduce the rate of HAIs. This same survey was repeated in 2015 to assess for improvements.

The reduction in HAIs was primarily driven by a reduction in surgical-site infections and urinary tract infections. There was no reduction in the prevalence of health care–associated pneumonia, Clostridium difficile infection, or mortality. Consequently, this emphasizes the necessity of further work in these domains.

Bottom line: The overall prevalence of HAIs has decreased, but further quality improvement work is needed in order to expand this reduction to health care–associated pneumonia, C. difficile infection, and mortality from HAIs.

Citation: Magill SS et al. Changes in prevalence of heath care–associated infections in U.S. hospitals. N Engl J Med. 2018;379(18):1732-44.

Dr. McIntyre is an associate physician in the division of hospital medicine at the University of California, San Diego.

Background: HAIs are key drivers of morbidity and mortality for hospitalized patients. In 2011, the Centers for Disease Control and Prevention (CDC) conducted a point-prevalence survey that revealed an HAI in 4% of hospitalized patients. The most common infections included pneumonia, gastrointestinal infections, and surgical-site infections. Over time, efforts in patient safety and quality have expanded to reduce the rate of HAIs. This same survey was repeated in 2015 to assess for improvements.

The reduction in HAIs was primarily driven by a reduction in surgical-site infections and urinary tract infections. There was no reduction in the prevalence of health care–associated pneumonia, Clostridium difficile infection, or mortality. Consequently, this emphasizes the necessity of further work in these domains.

Bottom line: The overall prevalence of HAIs has decreased, but further quality improvement work is needed in order to expand this reduction to health care–associated pneumonia, C. difficile infection, and mortality from HAIs.

Citation: Magill SS et al. Changes in prevalence of heath care–associated infections in U.S. hospitals. N Engl J Med. 2018;379(18):1732-44.

Dr. McIntyre is an associate physician in the division of hospital medicine at the University of California, San Diego.

Some people are civil; others are not. Some patients are polite, grateful, and courteous to a fault; others are angry, truculent, and aggressive. There may be reasons why such people are uncivil. Knowing those reasons does not make them any more civil than they aren’t, or any easier to take.

********

Charlie is 18. His mother is with him.

“I see my colleague prescribed an antibiotic for your acne.”

“No. I stopped the medicine after 2 weeks. It’s not acne.”

“Then what do you think it is?”

“Some sort of allergic reaction. I have a dog. I’ve taken two courses of prednisone.”

“Prednisone? That is not a good treatment for acne.”

“It’s not acne.”

“If that’s how you feel, then I think you will need to get another opinion.”

“My son can be difficult,” says his mother. “But just tell me – why do you think it’s acne?”

(Because I have been a skin doctor forever? Because Charlie is 18 and has pimples on his face?)

“If this were acne,” his mother goes on, “wouldn’t the pimples come in one place and go away in another?”

“Actually, no.”

“I don’t think I’ve ever been so offended,” says Charlie, who gets up and leaves.

“This is the most useless medical visit I have ever had,” says his mother. On the way out, she berates my secretary for working for such a worthless doctor.

Later that day Charlie calls back. He asks my secretary where he can post a bad review.

“Try our website,” suggests my staffer.

********

Gwen has many moles. Two were severely dysplastic and required re-excision.

“There is one mole on your back that I think needs to be tested.”

“Why?”

“Because it shows irregularity at the border.”

“I really hate surgery.”

“You may not need more surgery. We should find out, though.”

“I’m not saying you’re doing this just to get more money.”

“Well, thank you for that.”

“I’m not trying to be difficult.”

(But you are succeeding, aren’t you?)

“I also have warts on my finger.”

“I can freeze those for you.”

“Wait. Before you do, let me show you where to freeze. Put the nitrogen over here, where the wart is.”

“Thank you. I will try to do it correctly.”

“I just want to advocate for myself.”

********

“The emergency patient you worked in this morning is coming at 1:30,” says my secretary. “I couldn’t find his name in the system, so I called back.”

“Sorry sir, but I wanted to confirm your last name. It’s Jones, correct?”

“Are all of you incompetent there? I told you my name, didn’t I?”

“Just once more, if you wouldn’t mind.”

“It’s Jomes, J-O-M-E-S. Have you got that?”

“Why, yes, and thank you for your patience. Your appointment is at 1:30.”

“It may rain.”

“Yes, so they say.”

“Well?”

“I’m sorry?”

“I asked you a question.”

“What question?”

“I asked you if it is going to rain.”

“I’m sorry Mr. Jomes. I just book appointments.”

Amor Towles named his recent novel “Rules of Civility” after a note George Washington penned for his youthful self as a guide for getting along with people. Most of us intuit such rules just by noticing what works and what doesn’t, what pleases other people, or what makes them embarrassed or angry.

But there are people who don’t notice such things, or don’t care. They see nothing wrong with asking an old-time skin doctor how he knows that pimples are acne or demanding that he justify his opinion. (Or asking his staffer the best way to attack her boss.) They think it’s fine to suggest that a biopsy has been proposed for profit – after two prior biopsies arguably prevented severe disease – or making sure that a geezer with a spray can knows to put the nitrogen on the wart, not near it. Or berating a clerk for misspelling a last name of which he must have spent his life correcting other people’s misspellings.

I always taught students: “When people ask you how you know something, never invoke your experience or authority. If they don’t already think you have them, telling them you do won’t change their minds.”

Our job, often hard, is to always be civil. Society has zero tolerance for our ever being anything else. We know the rules. Uncivil people play by their own.

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at [email protected].

Some people are civil; others are not. Some patients are polite, grateful, and courteous to a fault; others are angry, truculent, and aggressive. There may be reasons why such people are uncivil. Knowing those reasons does not make them any more civil than they aren’t, or any easier to take.

********

Charlie is 18. His mother is with him.

“I see my colleague prescribed an antibiotic for your acne.”

“No. I stopped the medicine after 2 weeks. It’s not acne.”

“Then what do you think it is?”

“Some sort of allergic reaction. I have a dog. I’ve taken two courses of prednisone.”

“Prednisone? That is not a good treatment for acne.”

“It’s not acne.”

“If that’s how you feel, then I think you will need to get another opinion.”

“My son can be difficult,” says his mother. “But just tell me – why do you think it’s acne?”

(Because I have been a skin doctor forever? Because Charlie is 18 and has pimples on his face?)

“If this were acne,” his mother goes on, “wouldn’t the pimples come in one place and go away in another?”

“Actually, no.”

“I don’t think I’ve ever been so offended,” says Charlie, who gets up and leaves.

“This is the most useless medical visit I have ever had,” says his mother. On the way out, she berates my secretary for working for such a worthless doctor.

Later that day Charlie calls back. He asks my secretary where he can post a bad review.

“Try our website,” suggests my staffer.

********

Gwen has many moles. Two were severely dysplastic and required re-excision.

“There is one mole on your back that I think needs to be tested.”

“Why?”

“Because it shows irregularity at the border.”

“I really hate surgery.”

“You may not need more surgery. We should find out, though.”

“I’m not saying you’re doing this just to get more money.”

“Well, thank you for that.”

“I’m not trying to be difficult.”

(But you are succeeding, aren’t you?)

“I also have warts on my finger.”

“I can freeze those for you.”

“Wait. Before you do, let me show you where to freeze. Put the nitrogen over here, where the wart is.”

“Thank you. I will try to do it correctly.”

“I just want to advocate for myself.”

********

“The emergency patient you worked in this morning is coming at 1:30,” says my secretary. “I couldn’t find his name in the system, so I called back.”

“Sorry sir, but I wanted to confirm your last name. It’s Jones, correct?”

“Are all of you incompetent there? I told you my name, didn’t I?”

“Just once more, if you wouldn’t mind.”

“It’s Jomes, J-O-M-E-S. Have you got that?”

“Why, yes, and thank you for your patience. Your appointment is at 1:30.”

“It may rain.”

“Yes, so they say.”

“Well?”

“I’m sorry?”

“I asked you a question.”

“What question?”

“I asked you if it is going to rain.”

“I’m sorry Mr. Jomes. I just book appointments.”

Amor Towles named his recent novel “Rules of Civility” after a note George Washington penned for his youthful self as a guide for getting along with people. Most of us intuit such rules just by noticing what works and what doesn’t, what pleases other people, or what makes them embarrassed or angry.

But there are people who don’t notice such things, or don’t care. They see nothing wrong with asking an old-time skin doctor how he knows that pimples are acne or demanding that he justify his opinion. (Or asking his staffer the best way to attack her boss.) They think it’s fine to suggest that a biopsy has been proposed for profit – after two prior biopsies arguably prevented severe disease – or making sure that a geezer with a spray can knows to put the nitrogen on the wart, not near it. Or berating a clerk for misspelling a last name of which he must have spent his life correcting other people’s misspellings.

I always taught students: “When people ask you how you know something, never invoke your experience or authority. If they don’t already think you have them, telling them you do won’t change their minds.”

Our job, often hard, is to always be civil. Society has zero tolerance for our ever being anything else. We know the rules. Uncivil people play by their own.

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at [email protected].

Some people are civil; others are not. Some patients are polite, grateful, and courteous to a fault; others are angry, truculent, and aggressive. There may be reasons why such people are uncivil. Knowing those reasons does not make them any more civil than they aren’t, or any easier to take.

********

Charlie is 18. His mother is with him.

“I see my colleague prescribed an antibiotic for your acne.”

“No. I stopped the medicine after 2 weeks. It’s not acne.”

“Then what do you think it is?”

“Some sort of allergic reaction. I have a dog. I’ve taken two courses of prednisone.”

“Prednisone? That is not a good treatment for acne.”

“It’s not acne.”

“If that’s how you feel, then I think you will need to get another opinion.”

“My son can be difficult,” says his mother. “But just tell me – why do you think it’s acne?”

(Because I have been a skin doctor forever? Because Charlie is 18 and has pimples on his face?)

“If this were acne,” his mother goes on, “wouldn’t the pimples come in one place and go away in another?”

“Actually, no.”

“I don’t think I’ve ever been so offended,” says Charlie, who gets up and leaves.

“This is the most useless medical visit I have ever had,” says his mother. On the way out, she berates my secretary for working for such a worthless doctor.

Later that day Charlie calls back. He asks my secretary where he can post a bad review.

“Try our website,” suggests my staffer.

********

Gwen has many moles. Two were severely dysplastic and required re-excision.

“There is one mole on your back that I think needs to be tested.”

“Why?”

“Because it shows irregularity at the border.”

“I really hate surgery.”

“You may not need more surgery. We should find out, though.”

“I’m not saying you’re doing this just to get more money.”

“Well, thank you for that.”

“I’m not trying to be difficult.”

(But you are succeeding, aren’t you?)

“I also have warts on my finger.”

“I can freeze those for you.”

“Wait. Before you do, let me show you where to freeze. Put the nitrogen over here, where the wart is.”

“Thank you. I will try to do it correctly.”

“I just want to advocate for myself.”

********

“The emergency patient you worked in this morning is coming at 1:30,” says my secretary. “I couldn’t find his name in the system, so I called back.”

“Sorry sir, but I wanted to confirm your last name. It’s Jones, correct?”

“Are all of you incompetent there? I told you my name, didn’t I?”

“Just once more, if you wouldn’t mind.”

“It’s Jomes, J-O-M-E-S. Have you got that?”

“Why, yes, and thank you for your patience. Your appointment is at 1:30.”

“It may rain.”

“Yes, so they say.”

“Well?”

“I’m sorry?”

“I asked you a question.”

“What question?”

“I asked you if it is going to rain.”

“I’m sorry Mr. Jomes. I just book appointments.”

Amor Towles named his recent novel “Rules of Civility” after a note George Washington penned for his youthful self as a guide for getting along with people. Most of us intuit such rules just by noticing what works and what doesn’t, what pleases other people, or what makes them embarrassed or angry.

But there are people who don’t notice such things, or don’t care. They see nothing wrong with asking an old-time skin doctor how he knows that pimples are acne or demanding that he justify his opinion. (Or asking his staffer the best way to attack her boss.) They think it’s fine to suggest that a biopsy has been proposed for profit – after two prior biopsies arguably prevented severe disease – or making sure that a geezer with a spray can knows to put the nitrogen on the wart, not near it. Or berating a clerk for misspelling a last name of which he must have spent his life correcting other people’s misspellings.

I always taught students: “When people ask you how you know something, never invoke your experience or authority. If they don’t already think you have them, telling them you do won’t change their minds.”

Our job, often hard, is to always be civil. Society has zero tolerance for our ever being anything else. We know the rules. Uncivil people play by their own.

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at [email protected].

Patients with multiple myeloma who don’t respond to induction therapy may be better off advancing straight to autologous stem cell therapy, rather than undergoing salvage therapy before transplant, according to findings of an analysis that included both real-world and clinical trial patients.

Wikimedia Commons/KGH/Creative Commons License

Joanna Blocka, MD, of the University Hospital of Heidelberg (Germany) and colleagues found similar progression-free and overall survival rates for patients who had progressive disease and underwent autologous stem cell therapy (ASCT), compared with patients who underwent salvage therapy and improved to at least stable disease before proceeding to transplant. The findings were published in Leukemia & Lymphoma.

The real-world analysis included 1,599 patients with multiple myeloma who had undergone ASCT between 1991 and 2016. More than half of the patients (58%) were not enrolled in clinical trials. The remainder were split between the German-Speaking Myeloma Multicenter Group (GMMG)-HD3 and GMMG-HD4 trials, which compared various induction regimens.

Just 23 patients in the analysis received salvage therapy because of progressive disease and deepened their response before ASCT. Of these patients, 12 received novel agents in induction therapy and 11 received older medications.

Looking across all 1,599 patients, 5.3% achieved complete remission before first ASCT. Most patients (71.8%) achieved partial remission, 9.7% had a minimal response, and 5.7% had stable disease. A group of 120 patients (7.5%) progressed between the last course of induction and ASCT.

The researchers compared the progression-free and overall survival rates of patients with progressive disease versus those who had stable disease or better before their first transplant. Both univariable and multivariable analysis showed no statistically significant differences in either survival outcome between the two groups.

In the multivariable analysis, there was a hazard ratio of 1.23 (95% confidence interval, 0.98-1.56) for progression-free survival for patients with progressive disease versus those who responded to induction therapy. Similarly, the HR for overall survival between the two groups was 1.24 (95% CI, 0.93-1.65).

The researchers also analyzed the groups based on whether they received novel or older agents during induction.

Patients with progressive disease who received novel agents had significantly worse progression-free survival (22.2 months), compared with patients who responded to treatment with novel agents (22.2 months vs. 29.1 months; P = .03). The same trend was seen with overall survival in these groups (54.4 months vs. 97.5 months; P less than .001).

Rates of survival were similar for patients with progressive disease and responders who had received older medications at induction.

“This might be explained by a prognostically disadvantageous disease biology in patients nonresponsive to novel agents,” the researchers wrote.

The researchers also compared survival outcomes for the 120 patients who underwent ASCT with progressive disease versus the 23 patients who received salvage therapy and improved their response to at least stable disease before transplant. Univariable analysis showed that salvage patients actually did worse than those with progressive disease who proceeded straight to transplant – 12.1 months versus 22.9 months of progression-free survival (P = .04) and 33.1 versus 69.5 months of overall survival (P = .08). But on multivariable analysis, there was no significant difference between the two groups for progression-free survival (HR, 0.71; 95% CI, 0.28-1.80; P = .5) or overall survival (HR, 0.77; 95% CI, 0.30-1.95; P = .6). The use of novel agents did not appear to affect the survival outcomes in these patients.

The worse outcomes seen among salvage patients observed in univariable analysis “might be due to a cumulative toxic effect of salvage therapy,” the researchers suggested. “An alternative explanation could be that the patients who were offered salvage therapy might have had more aggressive disease than those who did not undergo salvage therapy.”

Dr. Blocka reported having no relevant financial disclosures. Other coauthors reported relationships with Janssen, Amgen, Bristol-Myers Squibb, Celgene, and others.

[email protected]

SOURCE: Blocka J et al. Leuk Lymphoma. 2019 Aug 19. doi: 10.1080/10428194.2019.1646905.

Patients with multiple myeloma who don’t respond to induction therapy may be better off advancing straight to autologous stem cell therapy, rather than undergoing salvage therapy before transplant, according to findings of an analysis that included both real-world and clinical trial patients.

Wikimedia Commons/KGH/Creative Commons License

Joanna Blocka, MD, of the University Hospital of Heidelberg (Germany) and colleagues found similar progression-free and overall survival rates for patients who had progressive disease and underwent autologous stem cell therapy (ASCT), compared with patients who underwent salvage therapy and improved to at least stable disease before proceeding to transplant. The findings were published in Leukemia & Lymphoma.

The real-world analysis included 1,599 patients with multiple myeloma who had undergone ASCT between 1991 and 2016. More than half of the patients (58%) were not enrolled in clinical trials. The remainder were split between the German-Speaking Myeloma Multicenter Group (GMMG)-HD3 and GMMG-HD4 trials, which compared various induction regimens.

Just 23 patients in the analysis received salvage therapy because of progressive disease and deepened their response before ASCT. Of these patients, 12 received novel agents in induction therapy and 11 received older medications.

Looking across all 1,599 patients, 5.3% achieved complete remission before first ASCT. Most patients (71.8%) achieved partial remission, 9.7% had a minimal response, and 5.7% had stable disease. A group of 120 patients (7.5%) progressed between the last course of induction and ASCT.

The researchers compared the progression-free and overall survival rates of patients with progressive disease versus those who had stable disease or better before their first transplant. Both univariable and multivariable analysis showed no statistically significant differences in either survival outcome between the two groups.

In the multivariable analysis, there was a hazard ratio of 1.23 (95% confidence interval, 0.98-1.56) for progression-free survival for patients with progressive disease versus those who responded to induction therapy. Similarly, the HR for overall survival between the two groups was 1.24 (95% CI, 0.93-1.65).

The researchers also analyzed the groups based on whether they received novel or older agents during induction.

Patients with progressive disease who received novel agents had significantly worse progression-free survival (22.2 months), compared with patients who responded to treatment with novel agents (22.2 months vs. 29.1 months; P = .03). The same trend was seen with overall survival in these groups (54.4 months vs. 97.5 months; P less than .001).

Rates of survival were similar for patients with progressive disease and responders who had received older medications at induction.

“This might be explained by a prognostically disadvantageous disease biology in patients nonresponsive to novel agents,” the researchers wrote.

The researchers also compared survival outcomes for the 120 patients who underwent ASCT with progressive disease versus the 23 patients who received salvage therapy and improved their response to at least stable disease before transplant. Univariable analysis showed that salvage patients actually did worse than those with progressive disease who proceeded straight to transplant – 12.1 months versus 22.9 months of progression-free survival (P = .04) and 33.1 versus 69.5 months of overall survival (P = .08). But on multivariable analysis, there was no significant difference between the two groups for progression-free survival (HR, 0.71; 95% CI, 0.28-1.80; P = .5) or overall survival (HR, 0.77; 95% CI, 0.30-1.95; P = .6). The use of novel agents did not appear to affect the survival outcomes in these patients.

The worse outcomes seen among salvage patients observed in univariable analysis “might be due to a cumulative toxic effect of salvage therapy,” the researchers suggested. “An alternative explanation could be that the patients who were offered salvage therapy might have had more aggressive disease than those who did not undergo salvage therapy.”

Dr. Blocka reported having no relevant financial disclosures. Other coauthors reported relationships with Janssen, Amgen, Bristol-Myers Squibb, Celgene, and others.

[email protected]

SOURCE: Blocka J et al. Leuk Lymphoma. 2019 Aug 19. doi: 10.1080/10428194.2019.1646905.

Patients with multiple myeloma who don’t respond to induction therapy may be better off advancing straight to autologous stem cell therapy, rather than undergoing salvage therapy before transplant, according to findings of an analysis that included both real-world and clinical trial patients.

Wikimedia Commons/KGH/Creative Commons License

Joanna Blocka, MD, of the University Hospital of Heidelberg (Germany) and colleagues found similar progression-free and overall survival rates for patients who had progressive disease and underwent autologous stem cell therapy (ASCT), compared with patients who underwent salvage therapy and improved to at least stable disease before proceeding to transplant. The findings were published in Leukemia & Lymphoma.

The real-world analysis included 1,599 patients with multiple myeloma who had undergone ASCT between 1991 and 2016. More than half of the patients (58%) were not enrolled in clinical trials. The remainder were split between the German-Speaking Myeloma Multicenter Group (GMMG)-HD3 and GMMG-HD4 trials, which compared various induction regimens.

Just 23 patients in the analysis received salvage therapy because of progressive disease and deepened their response before ASCT. Of these patients, 12 received novel agents in induction therapy and 11 received older medications.

Looking across all 1,599 patients, 5.3% achieved complete remission before first ASCT. Most patients (71.8%) achieved partial remission, 9.7% had a minimal response, and 5.7% had stable disease. A group of 120 patients (7.5%) progressed between the last course of induction and ASCT.

The researchers compared the progression-free and overall survival rates of patients with progressive disease versus those who had stable disease or better before their first transplant. Both univariable and multivariable analysis showed no statistically significant differences in either survival outcome between the two groups.

In the multivariable analysis, there was a hazard ratio of 1.23 (95% confidence interval, 0.98-1.56) for progression-free survival for patients with progressive disease versus those who responded to induction therapy. Similarly, the HR for overall survival between the two groups was 1.24 (95% CI, 0.93-1.65).

The researchers also analyzed the groups based on whether they received novel or older agents during induction.

Patients with progressive disease who received novel agents had significantly worse progression-free survival (22.2 months), compared with patients who responded to treatment with novel agents (22.2 months vs. 29.1 months; P = .03). The same trend was seen with overall survival in these groups (54.4 months vs. 97.5 months; P less than .001).

Rates of survival were similar for patients with progressive disease and responders who had received older medications at induction.

“This might be explained by a prognostically disadvantageous disease biology in patients nonresponsive to novel agents,” the researchers wrote.

The researchers also compared survival outcomes for the 120 patients who underwent ASCT with progressive disease versus the 23 patients who received salvage therapy and improved their response to at least stable disease before transplant. Univariable analysis showed that salvage patients actually did worse than those with progressive disease who proceeded straight to transplant – 12.1 months versus 22.9 months of progression-free survival (P = .04) and 33.1 versus 69.5 months of overall survival (P = .08). But on multivariable analysis, there was no significant difference between the two groups for progression-free survival (HR, 0.71; 95% CI, 0.28-1.80; P = .5) or overall survival (HR, 0.77; 95% CI, 0.30-1.95; P = .6). The use of novel agents did not appear to affect the survival outcomes in these patients.

The worse outcomes seen among salvage patients observed in univariable analysis “might be due to a cumulative toxic effect of salvage therapy,” the researchers suggested. “An alternative explanation could be that the patients who were offered salvage therapy might have had more aggressive disease than those who did not undergo salvage therapy.”

Dr. Blocka reported having no relevant financial disclosures. Other coauthors reported relationships with Janssen, Amgen, Bristol-Myers Squibb, Celgene, and others.

[email protected]

SOURCE: Blocka J et al. Leuk Lymphoma. 2019 Aug 19. doi: 10.1080/10428194.2019.1646905.

Women who have tested positive for Chlamydia trachomatis have an increased risk for pelvic inflammatory disease (PID), ectopic pregnancy, and infertility, compared with women who have tested negative for C. trachomatis or who have not been tested for the bacterium, according to a retrospective cohort study.

CDC/Dr. E. Arum; Dr. N. Jacobs

The risk of PID increases with repeat chlamydial infections, and the use of antibiotics that are effective against C. trachomatis does not decrease the risk of subsequent PID, the researchers reported in Clinical Infectious Diseases.

Prior studies have yielded different estimates of the risk of reproductive complications after chlamydia infection, said Casper den Heijer, MD, PhD, a researcher at Utrecht Institute of Pharmaceutical Sciences in Heerlen, the Netherlands, and colleagues. To assess the risk of PID, ectopic pregnancy, and infertility in women with a previous C. trachomatis diagnosis, Dr. den Heijer and coauthors conducted a retrospective study of women aged 12-25 years at baseline in the Clinical Practice Research Datalink GOLD database. Their analysis included data from women living in England between 2000 and 2013. The investigators used Cox proportional hazard models to evaluate the risk of adverse outcomes.

The researchers analyzed data from 857,324 women with a mean follow-up of 7.5 years. Patients’ mean age at baseline was 15 years. In all, the participants had 8,346 occurrences of PID, 2,484 occurrences of ectopic pregnancy, and 2,066 occurrences of female infertility.

For PID, incidence rates per 1,000 person-years were 1.1 among women untested for C. trachomatis, 1.4 among women who tested negative, and 5.4 among women who tested positive. For ectopic pregnancy, the incidence rates were 0.3 for untested women, 0.4 for negatively tested women, and 1.2 for positively tested women. Infertility incidence rates were 0.3 for untested women, 0.3 for negatively tested women, and 0.9 for positively tested women.

Compared with women who tested negative for C. trachomatis, women who tested positive had an increased risk of PID (adjusted hazard ratio, 2.36), ectopic pregnancy (aHR, 1.87), and female infertility (aHR, 1.85). Untested women had a lower risk for PID, compared with women who tested negative (aHR, 0.57).

C. trachomatis–effective antibiotic use was associated with higher PID risk, and that risk increased as the women used more of the antibiotic prescriptions, Dr. den Heijer and associates said. This occurred in all three groups of women. A possible explanation for this association between the antibiotics and higher PID risk could be that PID can be caused by other infectious diseases that could be treated with C. trachomatis–effective antibiotics.

While the study relied on primary care data, genitourinary medicine clinics diagnose and treat “a sizable proportion” of sexually transmitted infections in the United Kingdom, the authors noted. This limitation means that the study underestimates the number of C. trachomatis diagnoses in the cohort, they said.

Nonetheless, “Our results confirm the reproductive health burden of [C. trachomatis] and show the need for adequate public health interventions,” Dr. den Heijer and associates concluded.

[email protected]

SOURCE: den Heijer CDJ et al. Clin Infect Dis. 2019 Aug 24. doi: 10.1093/cid/ciz429.

Women who have tested positive for Chlamydia trachomatis have an increased risk for pelvic inflammatory disease (PID), ectopic pregnancy, and infertility, compared with women who have tested negative for C. trachomatis or who have not been tested for the bacterium, according to a retrospective cohort study.

CDC/Dr. E. Arum; Dr. N. Jacobs

The risk of PID increases with repeat chlamydial infections, and the use of antibiotics that are effective against C. trachomatis does not decrease the risk of subsequent PID, the researchers reported in Clinical Infectious Diseases.

Prior studies have yielded different estimates of the risk of reproductive complications after chlamydia infection, said Casper den Heijer, MD, PhD, a researcher at Utrecht Institute of Pharmaceutical Sciences in Heerlen, the Netherlands, and colleagues. To assess the risk of PID, ectopic pregnancy, and infertility in women with a previous C. trachomatis diagnosis, Dr. den Heijer and coauthors conducted a retrospective study of women aged 12-25 years at baseline in the Clinical Practice Research Datalink GOLD database. Their analysis included data from women living in England between 2000 and 2013. The investigators used Cox proportional hazard models to evaluate the risk of adverse outcomes.

The researchers analyzed data from 857,324 women with a mean follow-up of 7.5 years. Patients’ mean age at baseline was 15 years. In all, the participants had 8,346 occurrences of PID, 2,484 occurrences of ectopic pregnancy, and 2,066 occurrences of female infertility.

For PID, incidence rates per 1,000 person-years were 1.1 among women untested for C. trachomatis, 1.4 among women who tested negative, and 5.4 among women who tested positive. For ectopic pregnancy, the incidence rates were 0.3 for untested women, 0.4 for negatively tested women, and 1.2 for positively tested women. Infertility incidence rates were 0.3 for untested women, 0.3 for negatively tested women, and 0.9 for positively tested women.

Compared with women who tested negative for C. trachomatis, women who tested positive had an increased risk of PID (adjusted hazard ratio, 2.36), ectopic pregnancy (aHR, 1.87), and female infertility (aHR, 1.85). Untested women had a lower risk for PID, compared with women who tested negative (aHR, 0.57).

C. trachomatis–effective antibiotic use was associated with higher PID risk, and that risk increased as the women used more of the antibiotic prescriptions, Dr. den Heijer and associates said. This occurred in all three groups of women. A possible explanation for this association between the antibiotics and higher PID risk could be that PID can be caused by other infectious diseases that could be treated with C. trachomatis–effective antibiotics.

While the study relied on primary care data, genitourinary medicine clinics diagnose and treat “a sizable proportion” of sexually transmitted infections in the United Kingdom, the authors noted. This limitation means that the study underestimates the number of C. trachomatis diagnoses in the cohort, they said.

Nonetheless, “Our results confirm the reproductive health burden of [C. trachomatis] and show the need for adequate public health interventions,” Dr. den Heijer and associates concluded.

[email protected]

SOURCE: den Heijer CDJ et al. Clin Infect Dis. 2019 Aug 24. doi: 10.1093/cid/ciz429.

Women who have tested positive for Chlamydia trachomatis have an increased risk for pelvic inflammatory disease (PID), ectopic pregnancy, and infertility, compared with women who have tested negative for C. trachomatis or who have not been tested for the bacterium, according to a retrospective cohort study.

CDC/Dr. E. Arum; Dr. N. Jacobs

The risk of PID increases with repeat chlamydial infections, and the use of antibiotics that are effective against C. trachomatis does not decrease the risk of subsequent PID, the researchers reported in Clinical Infectious Diseases.

Prior studies have yielded different estimates of the risk of reproductive complications after chlamydia infection, said Casper den Heijer, MD, PhD, a researcher at Utrecht Institute of Pharmaceutical Sciences in Heerlen, the Netherlands, and colleagues. To assess the risk of PID, ectopic pregnancy, and infertility in women with a previous C. trachomatis diagnosis, Dr. den Heijer and coauthors conducted a retrospective study of women aged 12-25 years at baseline in the Clinical Practice Research Datalink GOLD database. Their analysis included data from women living in England between 2000 and 2013. The investigators used Cox proportional hazard models to evaluate the risk of adverse outcomes.

The researchers analyzed data from 857,324 women with a mean follow-up of 7.5 years. Patients’ mean age at baseline was 15 years. In all, the participants had 8,346 occurrences of PID, 2,484 occurrences of ectopic pregnancy, and 2,066 occurrences of female infertility.

For PID, incidence rates per 1,000 person-years were 1.1 among women untested for C. trachomatis, 1.4 among women who tested negative, and 5.4 among women who tested positive. For ectopic pregnancy, the incidence rates were 0.3 for untested women, 0.4 for negatively tested women, and 1.2 for positively tested women. Infertility incidence rates were 0.3 for untested women, 0.3 for negatively tested women, and 0.9 for positively tested women.

Compared with women who tested negative for C. trachomatis, women who tested positive had an increased risk of PID (adjusted hazard ratio, 2.36), ectopic pregnancy (aHR, 1.87), and female infertility (aHR, 1.85). Untested women had a lower risk for PID, compared with women who tested negative (aHR, 0.57).

C. trachomatis–effective antibiotic use was associated with higher PID risk, and that risk increased as the women used more of the antibiotic prescriptions, Dr. den Heijer and associates said. This occurred in all three groups of women. A possible explanation for this association between the antibiotics and higher PID risk could be that PID can be caused by other infectious diseases that could be treated with C. trachomatis–effective antibiotics.

While the study relied on primary care data, genitourinary medicine clinics diagnose and treat “a sizable proportion” of sexually transmitted infections in the United Kingdom, the authors noted. This limitation means that the study underestimates the number of C. trachomatis diagnoses in the cohort, they said.

Nonetheless, “Our results confirm the reproductive health burden of [C. trachomatis] and show the need for adequate public health interventions,” Dr. den Heijer and associates concluded.

[email protected]

SOURCE: den Heijer CDJ et al. Clin Infect Dis. 2019 Aug 24. doi: 10.1093/cid/ciz429.

EVIDENCE SUMMARY

Efficacy. A 2014 double-blind RCT compared ondansetron with pyridoxine plus doxylamine (standard care) for outpatient treatment of nausea and vomiting in pregnancy.¹ The 36 patients had an average gestational age of 8 weeks and received either 4 mg oral ondansetron plus placebo or 25 mg pyridoxine plus 12.5 mg doxylamine 3 times daily for 5 days. Nausea and vomiting severity was measured using 2 separate 10-cm visual analog scales (VAS) with scores ranging from 0 to 10 (worst nausea or vomiting imaginable). Researchers determined that a VAS score reduction of 2.5 cm was clinically significant.

Patients treated with ondansetron described greater improvements in nausea (mean VAS change −5.1 cm vs −2 cm; P = .019) and vomiting (mean VAS change −4.1 cm vs −1.7 cm; P = .049). No patient required hospitalization. The researchers didn’t report on adverse effects or birth outcomes. The study was limited by the small sample size and a high rate (17%) of patients with missing data or who were lost to follow-up.

IV ondansetron vs metoclopramide: Similar efficacy, fewer adverse effects

A 2014 double-blind RCT compared IV ondansetron with IV metoclopramide (standard care) for treating hyperemesis gravidarum.² The 160 patients had an average gestational age of 9.5 weeks and intractable nausea and vomiting severe enough to cause dehydration, metabolic disturbance, and hospitalization. Patients received either 4 mg ondansetron or 10 mg metoclopramide IV every 8 hours for 24 hours. The primary outcomes were number of episodes of vomiting over 24 hours and self-reported sense of well-being rated on a 10-point scale.

No differences were found between the ondansetron- and metoclopramide-treated groups in terms of vomiting over 24 hours (median episodes 1 and 1; P = .38) or sense of well-being (mean scores 8.7 vs 8.3; P = .13). Patients treated with ondansetron were less likely to have persistent ketonuria at 24 hours (relative risk [RR] = 0.3; 95% confidence interval [CI], 0.1-0.8; number needed to treat [NNT] = 6). They also were less likely to feel drowsy (RR = 0.3; 95% CI, 0.1–0.8; NNT = 6) or complain of dry mouth (RR = 0.4; 95% CI, 0.1-0.9; NNT = 8). The study didn’t report birth outcomes or adverse fetal effects.

Oral ondansetron outperforms oral metoclopramide in small study

A 2013 double-blind RCT compared ondansetron with metoclopramide (standard care) for controlling severe nausea and vomiting.³ The 83 patients, with an average gestational age of 8.7 weeks, had more than 3 vomiting episodes daily, weight loss, and ketonuria. They received either 4 mg oral ondansetron or 10 mg oral metoclopramide for 2 weeks as follows: 3 times daily for 1 week, then twice daily for 3 days, then once daily for 4 days. Patients rated nausea severity using a 10-cm VAS from 0 to 10 (severe nausea) and recorded the number of vomiting episodes.

Women treated with ondansetron had significantly lower VAS scores on Days 3 and 4 of treatment (5.4 vs 6, P = .024 on Day­ 3; 4.1 vs 5.7, P = .023 on Day 4). They also had fewer episodes of vomiting on Days 2, 3, and 4 (3.7 vs 6, P = .006 on Day 2; 3.2 vs 5.3, P = .006 on Day 3; and 3.3 vs 5, P = .013 on Day 4). The study was limited by the small sample size.

Safety. A 2016 systematic review examining the risk of birth defects associated with ondansetron exposure in pregnancy found 8 reports: 5 birth registries, 2 case-control studies, and 1 prospective cohort study.⁴ Investigators compared rates of major malformations—cleft lips, cleft palates, neural tube defects, cardiac defects, and hypospadias—in 5101 women exposed to ondansetron in the first trimester with birth defect rates in more than 3.1 million nonexposed women.

Continue to: No study demonstrated...

No study demonstrated an increased rate of major malformations associated with ondansetron exposure except for 2 disease registry studies with nearly 2.4 million patients that reported a slight increase in the risk of cardiac defects (odds ratio [OR] = 2; 95% CI, 1.3-3.1; OR = 1.6, 95% CI, 1-2.1). Comparisons of other birth defect rates associated with ondansetron exposure were inconsistent, with studies showing small increases, decreases, or no difference in rates between exposed and nonexposed women.

Exposure vs nonexposure: No difference in adverse outcomes

A 2013 retrospective cohort study looked at 608,385 pregnancies among women in Denmark, of whom 1970 (0.3%) had been exposed to ondansetron.⁵ The study found that exposure to ondansetron compared with nonexposure was associated with a lower risk for spontaneous abortion between 7 and 12 weeks’ gestation (1.1% vs 3.7%; hazard ratio [HR] = 0.5; 95% CI, 0.3-0.9).

Oral ondansetron is more effective than pyridoxine plus doxylamine for outpatient treatment of nausea and vomiting in pregnancy.

No significant differences between ­ondansetron exposure and nonexposure were found for the following adverse outcomes: spontaneous abortion between 13 and 22 weeks’ gestation (1% vs 2.1%; HR = 0.6; 95% CI, 0.3-1.2); stillbirth (0.3% vs 0.4%;  HR = 0.4; 95% CI, 0.1-1.7); any major birth defect (2.9% in both exposed and nonexposed women; OR = 1.12; 95% CI, 0.69-1.82); preterm delivery (6.2% vs 5.2%; OR = 0.9; 95% CI, 0.7-1.3), low birth weight infant (4.1% vs 3.7%; OR = 0.8; 95% CI, 0.5-1.1); and small-for-­gestational-age infant (10.4% vs 9.2%; OR = 1.1; 95% CI, 0.9-1.4).

RECOMMENDATIONS

The American College of Obstetricians and Gynecologists (ACOG) states that insufficient data exist regarding the safety of ondansetron for the fetus.⁶ ACOG recommends individualizing the use of ondansetron before 10 weeks of pregnancy after weighing the risks and benefits. ACOG also recommends adding ondansetron as third-line treatment for nausea and vomiting unresponsive to first- and second-line treatments.

EDITOR'S TAKEAWAY

Higher-quality studies showed ondansetron to be an effective treatment for hyperemesis gravidarum. Lower-quality studies raised some concerns about adverse fetal effects. Although the adverse effects were rare and the quality of the evidence was lower, the cautionary principle suggests that ondansetron should be a second-line option.

EVIDENCE SUMMARY

Efficacy. A 2014 double-blind RCT compared ondansetron with pyridoxine plus doxylamine (standard care) for outpatient treatment of nausea and vomiting in pregnancy.¹ The 36 patients had an average gestational age of 8 weeks and received either 4 mg oral ondansetron plus placebo or 25 mg pyridoxine plus 12.5 mg doxylamine 3 times daily for 5 days. Nausea and vomiting severity was measured using 2 separate 10-cm visual analog scales (VAS) with scores ranging from 0 to 10 (worst nausea or vomiting imaginable). Researchers determined that a VAS score reduction of 2.5 cm was clinically significant.

Patients treated with ondansetron described greater improvements in nausea (mean VAS change −5.1 cm vs −2 cm; P = .019) and vomiting (mean VAS change −4.1 cm vs −1.7 cm; P = .049). No patient required hospitalization. The researchers didn’t report on adverse effects or birth outcomes. The study was limited by the small sample size and a high rate (17%) of patients with missing data or who were lost to follow-up.

IV ondansetron vs metoclopramide: Similar efficacy, fewer adverse effects

A 2014 double-blind RCT compared IV ondansetron with IV metoclopramide (standard care) for treating hyperemesis gravidarum.² The 160 patients had an average gestational age of 9.5 weeks and intractable nausea and vomiting severe enough to cause dehydration, metabolic disturbance, and hospitalization. Patients received either 4 mg ondansetron or 10 mg metoclopramide IV every 8 hours for 24 hours. The primary outcomes were number of episodes of vomiting over 24 hours and self-reported sense of well-being rated on a 10-point scale.

No differences were found between the ondansetron- and metoclopramide-treated groups in terms of vomiting over 24 hours (median episodes 1 and 1; P = .38) or sense of well-being (mean scores 8.7 vs 8.3; P = .13). Patients treated with ondansetron were less likely to have persistent ketonuria at 24 hours (relative risk [RR] = 0.3; 95% confidence interval [CI], 0.1-0.8; number needed to treat [NNT] = 6). They also were less likely to feel drowsy (RR = 0.3; 95% CI, 0.1–0.8; NNT = 6) or complain of dry mouth (RR = 0.4; 95% CI, 0.1-0.9; NNT = 8). The study didn’t report birth outcomes or adverse fetal effects.

Oral ondansetron outperforms oral metoclopramide in small study

A 2013 double-blind RCT compared ondansetron with metoclopramide (standard care) for controlling severe nausea and vomiting.³ The 83 patients, with an average gestational age of 8.7 weeks, had more than 3 vomiting episodes daily, weight loss, and ketonuria. They received either 4 mg oral ondansetron or 10 mg oral metoclopramide for 2 weeks as follows: 3 times daily for 1 week, then twice daily for 3 days, then once daily for 4 days. Patients rated nausea severity using a 10-cm VAS from 0 to 10 (severe nausea) and recorded the number of vomiting episodes.

Women treated with ondansetron had significantly lower VAS scores on Days 3 and 4 of treatment (5.4 vs 6, P = .024 on Day­ 3; 4.1 vs 5.7, P = .023 on Day 4). They also had fewer episodes of vomiting on Days 2, 3, and 4 (3.7 vs 6, P = .006 on Day 2; 3.2 vs 5.3, P = .006 on Day 3; and 3.3 vs 5, P = .013 on Day 4). The study was limited by the small sample size.

Safety. A 2016 systematic review examining the risk of birth defects associated with ondansetron exposure in pregnancy found 8 reports: 5 birth registries, 2 case-control studies, and 1 prospective cohort study.⁴ Investigators compared rates of major malformations—cleft lips, cleft palates, neural tube defects, cardiac defects, and hypospadias—in 5101 women exposed to ondansetron in the first trimester with birth defect rates in more than 3.1 million nonexposed women.

Continue to: No study demonstrated...

No study demonstrated an increased rate of major malformations associated with ondansetron exposure except for 2 disease registry studies with nearly 2.4 million patients that reported a slight increase in the risk of cardiac defects (odds ratio [OR] = 2; 95% CI, 1.3-3.1; OR = 1.6, 95% CI, 1-2.1). Comparisons of other birth defect rates associated with ondansetron exposure were inconsistent, with studies showing small increases, decreases, or no difference in rates between exposed and nonexposed women.

Exposure vs nonexposure: No difference in adverse outcomes

A 2013 retrospective cohort study looked at 608,385 pregnancies among women in Denmark, of whom 1970 (0.3%) had been exposed to ondansetron.⁵ The study found that exposure to ondansetron compared with nonexposure was associated with a lower risk for spontaneous abortion between 7 and 12 weeks’ gestation (1.1% vs 3.7%; hazard ratio [HR] = 0.5; 95% CI, 0.3-0.9).

Oral ondansetron is more effective than pyridoxine plus doxylamine for outpatient treatment of nausea and vomiting in pregnancy.

No significant differences between ­ondansetron exposure and nonexposure were found for the following adverse outcomes: spontaneous abortion between 13 and 22 weeks’ gestation (1% vs 2.1%; HR = 0.6; 95% CI, 0.3-1.2); stillbirth (0.3% vs 0.4%;  HR = 0.4; 95% CI, 0.1-1.7); any major birth defect (2.9% in both exposed and nonexposed women; OR = 1.12; 95% CI, 0.69-1.82); preterm delivery (6.2% vs 5.2%; OR = 0.9; 95% CI, 0.7-1.3), low birth weight infant (4.1% vs 3.7%; OR = 0.8; 95% CI, 0.5-1.1); and small-for-­gestational-age infant (10.4% vs 9.2%; OR = 1.1; 95% CI, 0.9-1.4).

RECOMMENDATIONS

The American College of Obstetricians and Gynecologists (ACOG) states that insufficient data exist regarding the safety of ondansetron for the fetus.⁶ ACOG recommends individualizing the use of ondansetron before 10 weeks of pregnancy after weighing the risks and benefits. ACOG also recommends adding ondansetron as third-line treatment for nausea and vomiting unresponsive to first- and second-line treatments.

EDITOR'S TAKEAWAY

Higher-quality studies showed ondansetron to be an effective treatment for hyperemesis gravidarum. Lower-quality studies raised some concerns about adverse fetal effects. Although the adverse effects were rare and the quality of the evidence was lower, the cautionary principle suggests that ondansetron should be a second-line option.

EVIDENCE SUMMARY

Efficacy. A 2014 double-blind RCT compared ondansetron with pyridoxine plus doxylamine (standard care) for outpatient treatment of nausea and vomiting in pregnancy.¹ The 36 patients had an average gestational age of 8 weeks and received either 4 mg oral ondansetron plus placebo or 25 mg pyridoxine plus 12.5 mg doxylamine 3 times daily for 5 days. Nausea and vomiting severity was measured using 2 separate 10-cm visual analog scales (VAS) with scores ranging from 0 to 10 (worst nausea or vomiting imaginable). Researchers determined that a VAS score reduction of 2.5 cm was clinically significant.

Patients treated with ondansetron described greater improvements in nausea (mean VAS change −5.1 cm vs −2 cm; P = .019) and vomiting (mean VAS change −4.1 cm vs −1.7 cm; P = .049). No patient required hospitalization. The researchers didn’t report on adverse effects or birth outcomes. The study was limited by the small sample size and a high rate (17%) of patients with missing data or who were lost to follow-up.

IV ondansetron vs metoclopramide: Similar efficacy, fewer adverse effects

A 2014 double-blind RCT compared IV ondansetron with IV metoclopramide (standard care) for treating hyperemesis gravidarum.² The 160 patients had an average gestational age of 9.5 weeks and intractable nausea and vomiting severe enough to cause dehydration, metabolic disturbance, and hospitalization. Patients received either 4 mg ondansetron or 10 mg metoclopramide IV every 8 hours for 24 hours. The primary outcomes were number of episodes of vomiting over 24 hours and self-reported sense of well-being rated on a 10-point scale.

No differences were found between the ondansetron- and metoclopramide-treated groups in terms of vomiting over 24 hours (median episodes 1 and 1; P = .38) or sense of well-being (mean scores 8.7 vs 8.3; P = .13). Patients treated with ondansetron were less likely to have persistent ketonuria at 24 hours (relative risk [RR] = 0.3; 95% confidence interval [CI], 0.1-0.8; number needed to treat [NNT] = 6). They also were less likely to feel drowsy (RR = 0.3; 95% CI, 0.1–0.8; NNT = 6) or complain of dry mouth (RR = 0.4; 95% CI, 0.1-0.9; NNT = 8). The study didn’t report birth outcomes or adverse fetal effects.

Oral ondansetron outperforms oral metoclopramide in small study

A 2013 double-blind RCT compared ondansetron with metoclopramide (standard care) for controlling severe nausea and vomiting.³ The 83 patients, with an average gestational age of 8.7 weeks, had more than 3 vomiting episodes daily, weight loss, and ketonuria. They received either 4 mg oral ondansetron or 10 mg oral metoclopramide for 2 weeks as follows: 3 times daily for 1 week, then twice daily for 3 days, then once daily for 4 days. Patients rated nausea severity using a 10-cm VAS from 0 to 10 (severe nausea) and recorded the number of vomiting episodes.

Women treated with ondansetron had significantly lower VAS scores on Days 3 and 4 of treatment (5.4 vs 6, P = .024 on Day­ 3; 4.1 vs 5.7, P = .023 on Day 4). They also had fewer episodes of vomiting on Days 2, 3, and 4 (3.7 vs 6, P = .006 on Day 2; 3.2 vs 5.3, P = .006 on Day 3; and 3.3 vs 5, P = .013 on Day 4). The study was limited by the small sample size.

Safety. A 2016 systematic review examining the risk of birth defects associated with ondansetron exposure in pregnancy found 8 reports: 5 birth registries, 2 case-control studies, and 1 prospective cohort study.⁴ Investigators compared rates of major malformations—cleft lips, cleft palates, neural tube defects, cardiac defects, and hypospadias—in 5101 women exposed to ondansetron in the first trimester with birth defect rates in more than 3.1 million nonexposed women.

Continue to: No study demonstrated...

No study demonstrated an increased rate of major malformations associated with ondansetron exposure except for 2 disease registry studies with nearly 2.4 million patients that reported a slight increase in the risk of cardiac defects (odds ratio [OR] = 2; 95% CI, 1.3-3.1; OR = 1.6, 95% CI, 1-2.1). Comparisons of other birth defect rates associated with ondansetron exposure were inconsistent, with studies showing small increases, decreases, or no difference in rates between exposed and nonexposed women.

Exposure vs nonexposure: No difference in adverse outcomes

A 2013 retrospective cohort study looked at 608,385 pregnancies among women in Denmark, of whom 1970 (0.3%) had been exposed to ondansetron.⁵ The study found that exposure to ondansetron compared with nonexposure was associated with a lower risk for spontaneous abortion between 7 and 12 weeks’ gestation (1.1% vs 3.7%; hazard ratio [HR] = 0.5; 95% CI, 0.3-0.9).

Oral ondansetron is more effective than pyridoxine plus doxylamine for outpatient treatment of nausea and vomiting in pregnancy.

No significant differences between ­ondansetron exposure and nonexposure were found for the following adverse outcomes: spontaneous abortion between 13 and 22 weeks’ gestation (1% vs 2.1%; HR = 0.6; 95% CI, 0.3-1.2); stillbirth (0.3% vs 0.4%;  HR = 0.4; 95% CI, 0.1-1.7); any major birth defect (2.9% in both exposed and nonexposed women; OR = 1.12; 95% CI, 0.69-1.82); preterm delivery (6.2% vs 5.2%; OR = 0.9; 95% CI, 0.7-1.3), low birth weight infant (4.1% vs 3.7%; OR = 0.8; 95% CI, 0.5-1.1); and small-for-­gestational-age infant (10.4% vs 9.2%; OR = 1.1; 95% CI, 0.9-1.4).

RECOMMENDATIONS

The American College of Obstetricians and Gynecologists (ACOG) states that insufficient data exist regarding the safety of ondansetron for the fetus.⁶ ACOG recommends individualizing the use of ondansetron before 10 weeks of pregnancy after weighing the risks and benefits. ACOG also recommends adding ondansetron as third-line treatment for nausea and vomiting unresponsive to first- and second-line treatments.

EDITOR'S TAKEAWAY

Higher-quality studies showed ondansetron to be an effective treatment for hyperemesis gravidarum. Lower-quality studies raised some concerns about adverse fetal effects. Although the adverse effects were rare and the quality of the evidence was lower, the cautionary principle suggests that ondansetron should be a second-line option.

THE CASE

A 49-year-old woman presented to our clinic with concerns about the changing appearance of her tongue over the past 2 to 3 weeks. She had been given a diagnosis of celiac disease by her gastroenterologist approximately 5 years earlier. At the time of that diagnosis, she had smooth patches on the surface of her tongue with missing papillae and slightly raised borders. (This gave her tongue a map-like appearance, consistent with geographic tongue [GT].) The patient’s symptoms improved after she started a gluten-free diet, but she reported occasional noncompliance over the past year.

At the current presentation, the patient noted that new lesions on the tongue had started as diffuse shiny red patches surrounded by clearly delineated white borders, ultimately progressing to structural changes. She denied any burning of the tongue or other oral symptoms but reported feelings of anxiety, a “foggy mind,” and diffuse arthralgia for the past several weeks. The patient’s list of medications included vitamin D and magnesium supplements, a multivitamin, and probiotics.

On physical examination, her tongue showed areas of shiny erythematous mucosa and deep central grooves with small radiating furrows giving a wrinkled appearance ­(FIGURE). A review of systems revealed nonspecific abdominal pain including bloating, cramping, and gas for the previous few months. An examination of her throat and oral cavity was unremarkable, and the remainder of the physical examination was normal.

THE DIAGNOSIS

A diagnosis of fissured tongue (FT) was suspected based on the clinical appearance of the patient’s tongue. Laboratory studies including a complete blood count; antinuclear antibody test; rheumatoid factor test; anticyclic citrullinated peptide test; a comprehensive metabolic panel; and thyroid-stimulating hormone, 25-hydroxyvitamin D, and vitamin B₁₂ level tests were performed based on her symptoms and current medications to rule out any other potential diagnoses. All laboratory results were normal, and a tissue transglutaminase IgA test was not repeated because it was positive when previously tested by the gastroenterologist at the time of her celiac disease diagnosis. A diagnosis of FT due to incompletely treated celiac disease was confirmed.

DISCUSSION

Clinical presentation. FT commonly presents in association with GT,^1,2 with some cases of GT naturally progressing to FT.^3,4 In most cases, FT is asymptomatic unless debris becomes entrapped in the fissures. Rarely, patients may complain of a burning sensation on the tongue. The clinical appearance of the tongue includes deep grooves with possible malodor or halitosis along with discoloration if trapping of debris and subsequent inflammation occurs.¹

Etiology. FT has been linked to celiac disease; systemic conditions such as arthritis, iron deficiency, depression, anxiety, and neuropathy; and poor oral hygiene. Genetics also may play a role, as some cases of FT may be inherited. Getting to the source requires a careful history to uncover signs and symptoms (that may not have been reported until now) and to determine if other family members also have FT. A careful examination of the oral cavity, with an eye toward the patient’s oral hygiene, is also instructive (TABLE).^5-8 In general, FT is believed to be a normal tongue variant in less than 10% of the general population.^5,6 Additionally, local factors such as ill-fitting prosthesis, infection, parafunctional habits, allergic reaction, xerostomia, and galvanism have been implicated in the etiology of FT.⁵

In most cases, fissured tongue is asymptomatic unless debris becomes entrapped in the fissures.

In our patient, progression of GT to FT was caused by incompletely treated celiac disease. Both FT and GT may represent different reaction patterns caused by the same hematologic and immunologic diseases.³ In fact, the appearance of the tongue may aid in the diagnosis of celiac disease, which has been observed in 15% of patients with GT.⁷ Fissured tongue also may indicate an inability of the gastrointestinal mucosa to absorb nutrients; therefore, close nutrition monitoring is recommended.⁹

Continue to: Other oral and dental manifestations...

Other oral and dental manifestations of celiac disease include enamel defects, delayed tooth eruption, recurrent aphthous ulcers, cheilosis, oral lichen planus, and atrophic glossitis.¹⁰ Our patient also reported anxiety, “foggy mind,” diffuse arthralgia, and abdominal pain, which are symptoms of uncontrolled celiac disease. There is no known etiology of tongue manifestations in patients with incompletely treated celiac disease.

Treatment. FT generally does not require specific therapy other than the treatment of the underlying inflammatory condition. It is important to maintain proper oral and dental care, such as brushing the top surface of the tongue to clean and remove food debris. Bacteria and plaque can collect in the fissures, leading to bad breath and an increased potential for tooth decay.

Our patient was referred to a dietitian to assist with adherence to the gluten-free diet. At follow-up 3 months later, the appearance of her tongue had improved and fewer fissures were visible. The majority of her other symptoms also had resolved.

THE TAKEAWAY

FT may be a normal variant of the tongue in some patients or may be associated with poor oral hygiene. Additionally, FT often is associated with an underlying medical or inherited condition and may serve as a marker for an untreated or partially treated condition such as celiac disease, as was the case with our patient. When other signs or symptoms of systemic disease are present, further laboratory and endoscopic workup is necessary to rule out other causes and to diagnose celiac disease, if present.

As FT has been reported to be a natural progression from GT, the appearance of FT may indicate partial treatment of the underlying disease process and therefore more intensive therapy and follow-up would be needed. In this case, more intensive dietary guidance was provided with subsequent improvement of symptoms.

CORRESPONDENCE
Peter J. Carek, MD, MS, Department of Community Health and Family Medicine, College of Medicine, University of Florida, P.O. Box 100237, Gainesville, FL 32610-0237; [email protected]

THE CASE

A 49-year-old woman presented to our clinic with concerns about the changing appearance of her tongue over the past 2 to 3 weeks. She had been given a diagnosis of celiac disease by her gastroenterologist approximately 5 years earlier. At the time of that diagnosis, she had smooth patches on the surface of her tongue with missing papillae and slightly raised borders. (This gave her tongue a map-like appearance, consistent with geographic tongue [GT].) The patient’s symptoms improved after she started a gluten-free diet, but she reported occasional noncompliance over the past year.

At the current presentation, the patient noted that new lesions on the tongue had started as diffuse shiny red patches surrounded by clearly delineated white borders, ultimately progressing to structural changes. She denied any burning of the tongue or other oral symptoms but reported feelings of anxiety, a “foggy mind,” and diffuse arthralgia for the past several weeks. The patient’s list of medications included vitamin D and magnesium supplements, a multivitamin, and probiotics.

On physical examination, her tongue showed areas of shiny erythematous mucosa and deep central grooves with small radiating furrows giving a wrinkled appearance ­(FIGURE). A review of systems revealed nonspecific abdominal pain including bloating, cramping, and gas for the previous few months. An examination of her throat and oral cavity was unremarkable, and the remainder of the physical examination was normal.

THE DIAGNOSIS

A diagnosis of fissured tongue (FT) was suspected based on the clinical appearance of the patient’s tongue. Laboratory studies including a complete blood count; antinuclear antibody test; rheumatoid factor test; anticyclic citrullinated peptide test; a comprehensive metabolic panel; and thyroid-stimulating hormone, 25-hydroxyvitamin D, and vitamin B₁₂ level tests were performed based on her symptoms and current medications to rule out any other potential diagnoses. All laboratory results were normal, and a tissue transglutaminase IgA test was not repeated because it was positive when previously tested by the gastroenterologist at the time of her celiac disease diagnosis. A diagnosis of FT due to incompletely treated celiac disease was confirmed.

DISCUSSION

Clinical presentation. FT commonly presents in association with GT,^1,2 with some cases of GT naturally progressing to FT.^3,4 In most cases, FT is asymptomatic unless debris becomes entrapped in the fissures. Rarely, patients may complain of a burning sensation on the tongue. The clinical appearance of the tongue includes deep grooves with possible malodor or halitosis along with discoloration if trapping of debris and subsequent inflammation occurs.¹

Etiology. FT has been linked to celiac disease; systemic conditions such as arthritis, iron deficiency, depression, anxiety, and neuropathy; and poor oral hygiene. Genetics also may play a role, as some cases of FT may be inherited. Getting to the source requires a careful history to uncover signs and symptoms (that may not have been reported until now) and to determine if other family members also have FT. A careful examination of the oral cavity, with an eye toward the patient’s oral hygiene, is also instructive (TABLE).^5-8 In general, FT is believed to be a normal tongue variant in less than 10% of the general population.^5,6 Additionally, local factors such as ill-fitting prosthesis, infection, parafunctional habits, allergic reaction, xerostomia, and galvanism have been implicated in the etiology of FT.⁵

In most cases, fissured tongue is asymptomatic unless debris becomes entrapped in the fissures.

In our patient, progression of GT to FT was caused by incompletely treated celiac disease. Both FT and GT may represent different reaction patterns caused by the same hematologic and immunologic diseases.³ In fact, the appearance of the tongue may aid in the diagnosis of celiac disease, which has been observed in 15% of patients with GT.⁷ Fissured tongue also may indicate an inability of the gastrointestinal mucosa to absorb nutrients; therefore, close nutrition monitoring is recommended.⁹

Continue to: Other oral and dental manifestations...

Other oral and dental manifestations of celiac disease include enamel defects, delayed tooth eruption, recurrent aphthous ulcers, cheilosis, oral lichen planus, and atrophic glossitis.¹⁰ Our patient also reported anxiety, “foggy mind,” diffuse arthralgia, and abdominal pain, which are symptoms of uncontrolled celiac disease. There is no known etiology of tongue manifestations in patients with incompletely treated celiac disease.

Treatment. FT generally does not require specific therapy other than the treatment of the underlying inflammatory condition. It is important to maintain proper oral and dental care, such as brushing the top surface of the tongue to clean and remove food debris. Bacteria and plaque can collect in the fissures, leading to bad breath and an increased potential for tooth decay.

Our patient was referred to a dietitian to assist with adherence to the gluten-free diet. At follow-up 3 months later, the appearance of her tongue had improved and fewer fissures were visible. The majority of her other symptoms also had resolved.

THE TAKEAWAY

FT may be a normal variant of the tongue in some patients or may be associated with poor oral hygiene. Additionally, FT often is associated with an underlying medical or inherited condition and may serve as a marker for an untreated or partially treated condition such as celiac disease, as was the case with our patient. When other signs or symptoms of systemic disease are present, further laboratory and endoscopic workup is necessary to rule out other causes and to diagnose celiac disease, if present.

As FT has been reported to be a natural progression from GT, the appearance of FT may indicate partial treatment of the underlying disease process and therefore more intensive therapy and follow-up would be needed. In this case, more intensive dietary guidance was provided with subsequent improvement of symptoms.

CORRESPONDENCE
Peter J. Carek, MD, MS, Department of Community Health and Family Medicine, College of Medicine, University of Florida, P.O. Box 100237, Gainesville, FL 32610-0237; [email protected]

THE CASE

A 49-year-old woman presented to our clinic with concerns about the changing appearance of her tongue over the past 2 to 3 weeks. She had been given a diagnosis of celiac disease by her gastroenterologist approximately 5 years earlier. At the time of that diagnosis, she had smooth patches on the surface of her tongue with missing papillae and slightly raised borders. (This gave her tongue a map-like appearance, consistent with geographic tongue [GT].) The patient’s symptoms improved after she started a gluten-free diet, but she reported occasional noncompliance over the past year.

At the current presentation, the patient noted that new lesions on the tongue had started as diffuse shiny red patches surrounded by clearly delineated white borders, ultimately progressing to structural changes. She denied any burning of the tongue or other oral symptoms but reported feelings of anxiety, a “foggy mind,” and diffuse arthralgia for the past several weeks. The patient’s list of medications included vitamin D and magnesium supplements, a multivitamin, and probiotics.

On physical examination, her tongue showed areas of shiny erythematous mucosa and deep central grooves with small radiating furrows giving a wrinkled appearance ­(FIGURE). A review of systems revealed nonspecific abdominal pain including bloating, cramping, and gas for the previous few months. An examination of her throat and oral cavity was unremarkable, and the remainder of the physical examination was normal.

THE DIAGNOSIS

A diagnosis of fissured tongue (FT) was suspected based on the clinical appearance of the patient’s tongue. Laboratory studies including a complete blood count; antinuclear antibody test; rheumatoid factor test; anticyclic citrullinated peptide test; a comprehensive metabolic panel; and thyroid-stimulating hormone, 25-hydroxyvitamin D, and vitamin B₁₂ level tests were performed based on her symptoms and current medications to rule out any other potential diagnoses. All laboratory results were normal, and a tissue transglutaminase IgA test was not repeated because it was positive when previously tested by the gastroenterologist at the time of her celiac disease diagnosis. A diagnosis of FT due to incompletely treated celiac disease was confirmed.

DISCUSSION

Clinical presentation. FT commonly presents in association with GT,^1,2 with some cases of GT naturally progressing to FT.^3,4 In most cases, FT is asymptomatic unless debris becomes entrapped in the fissures. Rarely, patients may complain of a burning sensation on the tongue. The clinical appearance of the tongue includes deep grooves with possible malodor or halitosis along with discoloration if trapping of debris and subsequent inflammation occurs.¹

Etiology. FT has been linked to celiac disease; systemic conditions such as arthritis, iron deficiency, depression, anxiety, and neuropathy; and poor oral hygiene. Genetics also may play a role, as some cases of FT may be inherited. Getting to the source requires a careful history to uncover signs and symptoms (that may not have been reported until now) and to determine if other family members also have FT. A careful examination of the oral cavity, with an eye toward the patient’s oral hygiene, is also instructive (TABLE).^5-8 In general, FT is believed to be a normal tongue variant in less than 10% of the general population.^5,6 Additionally, local factors such as ill-fitting prosthesis, infection, parafunctional habits, allergic reaction, xerostomia, and galvanism have been implicated in the etiology of FT.⁵

In most cases, fissured tongue is asymptomatic unless debris becomes entrapped in the fissures.

In our patient, progression of GT to FT was caused by incompletely treated celiac disease. Both FT and GT may represent different reaction patterns caused by the same hematologic and immunologic diseases.³ In fact, the appearance of the tongue may aid in the diagnosis of celiac disease, which has been observed in 15% of patients with GT.⁷ Fissured tongue also may indicate an inability of the gastrointestinal mucosa to absorb nutrients; therefore, close nutrition monitoring is recommended.⁹

Continue to: Other oral and dental manifestations...

Other oral and dental manifestations of celiac disease include enamel defects, delayed tooth eruption, recurrent aphthous ulcers, cheilosis, oral lichen planus, and atrophic glossitis.¹⁰ Our patient also reported anxiety, “foggy mind,” diffuse arthralgia, and abdominal pain, which are symptoms of uncontrolled celiac disease. There is no known etiology of tongue manifestations in patients with incompletely treated celiac disease.

Treatment. FT generally does not require specific therapy other than the treatment of the underlying inflammatory condition. It is important to maintain proper oral and dental care, such as brushing the top surface of the tongue to clean and remove food debris. Bacteria and plaque can collect in the fissures, leading to bad breath and an increased potential for tooth decay.

Our patient was referred to a dietitian to assist with adherence to the gluten-free diet. At follow-up 3 months later, the appearance of her tongue had improved and fewer fissures were visible. The majority of her other symptoms also had resolved.

THE TAKEAWAY

FT may be a normal variant of the tongue in some patients or may be associated with poor oral hygiene. Additionally, FT often is associated with an underlying medical or inherited condition and may serve as a marker for an untreated or partially treated condition such as celiac disease, as was the case with our patient. When other signs or symptoms of systemic disease are present, further laboratory and endoscopic workup is necessary to rule out other causes and to diagnose celiac disease, if present.

As FT has been reported to be a natural progression from GT, the appearance of FT may indicate partial treatment of the underlying disease process and therefore more intensive therapy and follow-up would be needed. In this case, more intensive dietary guidance was provided with subsequent improvement of symptoms.

CORRESPONDENCE
Peter J. Carek, MD, MS, Department of Community Health and Family Medicine, College of Medicine, University of Florida, P.O. Box 100237, Gainesville, FL 32610-0237; [email protected]