Heidi Splete

Phototherapy remains a viable element of psoriasis care for many patients, used alone or in conjunction with other treatments, according to updated guidelines issued jointly by the American Academy of Dermatology and the National Psoriasis Foundation.

“Phototherapy serves as a reasonable and effective treatment option for patients requiring more than topical medications and/or those wishing to avoid systemic medications or simply seeking an adjunct to a failing regimen,” wrote working group cochair Craig A. Elmets, MD, professor of dermatology at the University of Alabama at Birmingham, and coauthors.

The guidelines, which focus on phototherapy for adults with psoriasis, join a multipart series on psoriasis being published this year in the Journal of the American Academy of Dermatology.

The working group used an evidence-based model to examine efficacy, effectiveness, and adverse effects of the following modalities: narrow-band ultraviolet B (NB-UVB); broadband ultraviolet B (BB-UVB); targeted phototherapy using excimer laser and excimer lamp; psoralen plus ultraviolet A (PUVA) therapy, including topical, oral, and bath PUVA; photodynamic therapy (PDT), grenz ray therapy, climatotherapy; visible light therapy; Goeckerman therapy; and pulsed dye laser/intense pulsed light.

NB-UVB, which can be used to treat generalized plaque psoriasis, refers to wavelengths of 311-313 nm. The recommended treatment is two or three times a week, with a starting dose based on skin phenotype or minimal erythema dose. Although oral PUVA has shown higher clearance rates, compared with NB-UVB, NB-UVB has demonstrated fewer side effects. NB-UVB also has shown effectiveness for psoriasis in combination with medications including oral retinoids, “particularly useful in patients at increased risk for skin cancer,” the working group wrote. Genital shielding and eye protection are recommended during all phototherapy sessions to reduce the risk of cancer and cataracts, they emphasized.

BB-UVB, an older version of NB-UVB, is still effective for generalized plaque psoriasis as monotherapy, but evidence does not support additional benefit in combination with other treatments, and overall BB-UVB is less effective than either NB-UVB or oral PUVA, the working group said.

For treatment of localized psoriatic lesions, some evidence supports the ability of targeted UVB therapy to improve lesions in fewer treatments and at a lower cumulative dose, compared with nontargeted phototherapy, for palmoplantar plaque psoriasis and palmoplantar pustulosis. Excimer lasers also have shown effectiveness against scalp psoriasis, the working group noted. However, “there is insufficient evidence to recommend the excimer laser rather than topical PUVA for treatment of localized plaque psoriasis,” they said.

PUVA treatments are available as topical creams, or they can be taken orally, or mixed with bath water. All forms of PUVA include psoralens, photosensitizing agents that prepare target cells for the effects of UVA light. Topical PUVA has demonstrated particular effectiveness for palmoplantar psoriasis, the working group noted, but there is a risk of phototoxicity, so it has become less popular, they added. Similarly, evidence supports effectiveness of oral and bath PUVA, but all forms are used less frequently because of the increased availability of NB-UVB phototherapy, they said.

PDT is primarily used to destroy premalignant or malignant cells, and in theory “PDT-induced apoptosis of T lymphocytes could lead to reductions in inflammatory cytokines and, in turn, to improvement of psoriasis,” the working group noted. However, “clinical studies have failed to find significant benefit” of PDT using either 5-aminolevulinic acid (ALA) or methyl aminolevulinic acid (MAL) for psoriasis, or any significant benefits of MAL-PDT for nail psoriasis.

The grenz ray is an effective, but rarely used treatment in which 75% of long-wavelength ionizing radiation is absorbed by the first 1 mm of skin and 95% is absorbed within the first 3 mm of skin to protect the deeper tissues from radiation. Although more alternatives are available, grenz rays can be used for psoriasis patients unable to tolerate UV therapy, according to the working group.

Climatotherapy involves temporary or permanent relocation of the patient to a part of the world with a climate that could be favorable for psoriasis because of the unique effects of environmental factors in those areas. The evidence to support climatotherapy is both subjective and objective, but considered safe.

Visible light has been associated with improvement in erythema in psoriasis, with hyperpigmentation as the only notable side effect based on the evidence reviewed. However, the working group found the current evidence insufficient to recommend the use of intense pulsed light for treating psoriasis.

Goeckerman therapy, a method that combines coal tar and UVB phototherapy, has shown safety and effectiveness for patients with recalcitrant or severe psoriasis, and remains a recommended treatment, according to the working group research. However, this method is underused, especially in the United States, because of the messiness of the application, challenge of insurance reimbursement, and investment of time for outpatient care, the work group noted.

Pulsed dye laser treatment is effective for nail psoriasis, and reported adverse effects have been mild, according to the working group.

Overall, the guidelines emphasize that quality of life and disease severity should be considered and discussed with patients along with efficacy and safety information so they can make informed decisions about adding phototherapy to a current regimen or switching among modalities.

The guidelines have no funding sources. Several coauthors disclosed relationships with multiple companies, including manufacturers of psoriasis products; however, a minimum of 51% of the work group had no relevant financial conflicts to disclose, in accordance with AAD policy. Work group members with potential conflicts recused themselves from discussion and drafting of recommendations in the relevant topic areas. Alan Menter, MD, chairman of the division of dermatology, Baylor University Medical Center, Dallas, is the other cochair of the work group.
 

SOURCE: Elmets CA et al. J Am Acad Dermatol. 2019 Jul 18. doi: 10.1016/j.jaad.2019.04.042.

Phototherapy remains a viable element of psoriasis care for many patients, used alone or in conjunction with other treatments, according to updated guidelines issued jointly by the American Academy of Dermatology and the National Psoriasis Foundation.

“Phototherapy serves as a reasonable and effective treatment option for patients requiring more than topical medications and/or those wishing to avoid systemic medications or simply seeking an adjunct to a failing regimen,” wrote working group cochair Craig A. Elmets, MD, professor of dermatology at the University of Alabama at Birmingham, and coauthors.

The guidelines, which focus on phototherapy for adults with psoriasis, join a multipart series on psoriasis being published this year in the Journal of the American Academy of Dermatology.

The working group used an evidence-based model to examine efficacy, effectiveness, and adverse effects of the following modalities: narrow-band ultraviolet B (NB-UVB); broadband ultraviolet B (BB-UVB); targeted phototherapy using excimer laser and excimer lamp; psoralen plus ultraviolet A (PUVA) therapy, including topical, oral, and bath PUVA; photodynamic therapy (PDT), grenz ray therapy, climatotherapy; visible light therapy; Goeckerman therapy; and pulsed dye laser/intense pulsed light.

NB-UVB, which can be used to treat generalized plaque psoriasis, refers to wavelengths of 311-313 nm. The recommended treatment is two or three times a week, with a starting dose based on skin phenotype or minimal erythema dose. Although oral PUVA has shown higher clearance rates, compared with NB-UVB, NB-UVB has demonstrated fewer side effects. NB-UVB also has shown effectiveness for psoriasis in combination with medications including oral retinoids, “particularly useful in patients at increased risk for skin cancer,” the working group wrote. Genital shielding and eye protection are recommended during all phototherapy sessions to reduce the risk of cancer and cataracts, they emphasized.

BB-UVB, an older version of NB-UVB, is still effective for generalized plaque psoriasis as monotherapy, but evidence does not support additional benefit in combination with other treatments, and overall BB-UVB is less effective than either NB-UVB or oral PUVA, the working group said.

For treatment of localized psoriatic lesions, some evidence supports the ability of targeted UVB therapy to improve lesions in fewer treatments and at a lower cumulative dose, compared with nontargeted phototherapy, for palmoplantar plaque psoriasis and palmoplantar pustulosis. Excimer lasers also have shown effectiveness against scalp psoriasis, the working group noted. However, “there is insufficient evidence to recommend the excimer laser rather than topical PUVA for treatment of localized plaque psoriasis,” they said.

PUVA treatments are available as topical creams, or they can be taken orally, or mixed with bath water. All forms of PUVA include psoralens, photosensitizing agents that prepare target cells for the effects of UVA light. Topical PUVA has demonstrated particular effectiveness for palmoplantar psoriasis, the working group noted, but there is a risk of phototoxicity, so it has become less popular, they added. Similarly, evidence supports effectiveness of oral and bath PUVA, but all forms are used less frequently because of the increased availability of NB-UVB phototherapy, they said.

PDT is primarily used to destroy premalignant or malignant cells, and in theory “PDT-induced apoptosis of T lymphocytes could lead to reductions in inflammatory cytokines and, in turn, to improvement of psoriasis,” the working group noted. However, “clinical studies have failed to find significant benefit” of PDT using either 5-aminolevulinic acid (ALA) or methyl aminolevulinic acid (MAL) for psoriasis, or any significant benefits of MAL-PDT for nail psoriasis.

The grenz ray is an effective, but rarely used treatment in which 75% of long-wavelength ionizing radiation is absorbed by the first 1 mm of skin and 95% is absorbed within the first 3 mm of skin to protect the deeper tissues from radiation. Although more alternatives are available, grenz rays can be used for psoriasis patients unable to tolerate UV therapy, according to the working group.

Climatotherapy involves temporary or permanent relocation of the patient to a part of the world with a climate that could be favorable for psoriasis because of the unique effects of environmental factors in those areas. The evidence to support climatotherapy is both subjective and objective, but considered safe.

Visible light has been associated with improvement in erythema in psoriasis, with hyperpigmentation as the only notable side effect based on the evidence reviewed. However, the working group found the current evidence insufficient to recommend the use of intense pulsed light for treating psoriasis.

Goeckerman therapy, a method that combines coal tar and UVB phototherapy, has shown safety and effectiveness for patients with recalcitrant or severe psoriasis, and remains a recommended treatment, according to the working group research. However, this method is underused, especially in the United States, because of the messiness of the application, challenge of insurance reimbursement, and investment of time for outpatient care, the work group noted.

Pulsed dye laser treatment is effective for nail psoriasis, and reported adverse effects have been mild, according to the working group.

Overall, the guidelines emphasize that quality of life and disease severity should be considered and discussed with patients along with efficacy and safety information so they can make informed decisions about adding phototherapy to a current regimen or switching among modalities.

The guidelines have no funding sources. Several coauthors disclosed relationships with multiple companies, including manufacturers of psoriasis products; however, a minimum of 51% of the work group had no relevant financial conflicts to disclose, in accordance with AAD policy. Work group members with potential conflicts recused themselves from discussion and drafting of recommendations in the relevant topic areas. Alan Menter, MD, chairman of the division of dermatology, Baylor University Medical Center, Dallas, is the other cochair of the work group.
 

SOURCE: Elmets CA et al. J Am Acad Dermatol. 2019 Jul 18. doi: 10.1016/j.jaad.2019.04.042.

Phototherapy remains a viable element of psoriasis care for many patients, used alone or in conjunction with other treatments, according to updated guidelines issued jointly by the American Academy of Dermatology and the National Psoriasis Foundation.

“Phototherapy serves as a reasonable and effective treatment option for patients requiring more than topical medications and/or those wishing to avoid systemic medications or simply seeking an adjunct to a failing regimen,” wrote working group cochair Craig A. Elmets, MD, professor of dermatology at the University of Alabama at Birmingham, and coauthors.

The guidelines, which focus on phototherapy for adults with psoriasis, join a multipart series on psoriasis being published this year in the Journal of the American Academy of Dermatology.

The working group used an evidence-based model to examine efficacy, effectiveness, and adverse effects of the following modalities: narrow-band ultraviolet B (NB-UVB); broadband ultraviolet B (BB-UVB); targeted phototherapy using excimer laser and excimer lamp; psoralen plus ultraviolet A (PUVA) therapy, including topical, oral, and bath PUVA; photodynamic therapy (PDT), grenz ray therapy, climatotherapy; visible light therapy; Goeckerman therapy; and pulsed dye laser/intense pulsed light.

NB-UVB, which can be used to treat generalized plaque psoriasis, refers to wavelengths of 311-313 nm. The recommended treatment is two or three times a week, with a starting dose based on skin phenotype or minimal erythema dose. Although oral PUVA has shown higher clearance rates, compared with NB-UVB, NB-UVB has demonstrated fewer side effects. NB-UVB also has shown effectiveness for psoriasis in combination with medications including oral retinoids, “particularly useful in patients at increased risk for skin cancer,” the working group wrote. Genital shielding and eye protection are recommended during all phototherapy sessions to reduce the risk of cancer and cataracts, they emphasized.

BB-UVB, an older version of NB-UVB, is still effective for generalized plaque psoriasis as monotherapy, but evidence does not support additional benefit in combination with other treatments, and overall BB-UVB is less effective than either NB-UVB or oral PUVA, the working group said.

For treatment of localized psoriatic lesions, some evidence supports the ability of targeted UVB therapy to improve lesions in fewer treatments and at a lower cumulative dose, compared with nontargeted phototherapy, for palmoplantar plaque psoriasis and palmoplantar pustulosis. Excimer lasers also have shown effectiveness against scalp psoriasis, the working group noted. However, “there is insufficient evidence to recommend the excimer laser rather than topical PUVA for treatment of localized plaque psoriasis,” they said.

PUVA treatments are available as topical creams, or they can be taken orally, or mixed with bath water. All forms of PUVA include psoralens, photosensitizing agents that prepare target cells for the effects of UVA light. Topical PUVA has demonstrated particular effectiveness for palmoplantar psoriasis, the working group noted, but there is a risk of phototoxicity, so it has become less popular, they added. Similarly, evidence supports effectiveness of oral and bath PUVA, but all forms are used less frequently because of the increased availability of NB-UVB phototherapy, they said.

PDT is primarily used to destroy premalignant or malignant cells, and in theory “PDT-induced apoptosis of T lymphocytes could lead to reductions in inflammatory cytokines and, in turn, to improvement of psoriasis,” the working group noted. However, “clinical studies have failed to find significant benefit” of PDT using either 5-aminolevulinic acid (ALA) or methyl aminolevulinic acid (MAL) for psoriasis, or any significant benefits of MAL-PDT for nail psoriasis.

The grenz ray is an effective, but rarely used treatment in which 75% of long-wavelength ionizing radiation is absorbed by the first 1 mm of skin and 95% is absorbed within the first 3 mm of skin to protect the deeper tissues from radiation. Although more alternatives are available, grenz rays can be used for psoriasis patients unable to tolerate UV therapy, according to the working group.

Climatotherapy involves temporary or permanent relocation of the patient to a part of the world with a climate that could be favorable for psoriasis because of the unique effects of environmental factors in those areas. The evidence to support climatotherapy is both subjective and objective, but considered safe.

Visible light has been associated with improvement in erythema in psoriasis, with hyperpigmentation as the only notable side effect based on the evidence reviewed. However, the working group found the current evidence insufficient to recommend the use of intense pulsed light for treating psoriasis.

Goeckerman therapy, a method that combines coal tar and UVB phototherapy, has shown safety and effectiveness for patients with recalcitrant or severe psoriasis, and remains a recommended treatment, according to the working group research. However, this method is underused, especially in the United States, because of the messiness of the application, challenge of insurance reimbursement, and investment of time for outpatient care, the work group noted.

Pulsed dye laser treatment is effective for nail psoriasis, and reported adverse effects have been mild, according to the working group.

Overall, the guidelines emphasize that quality of life and disease severity should be considered and discussed with patients along with efficacy and safety information so they can make informed decisions about adding phototherapy to a current regimen or switching among modalities.

The guidelines have no funding sources. Several coauthors disclosed relationships with multiple companies, including manufacturers of psoriasis products; however, a minimum of 51% of the work group had no relevant financial conflicts to disclose, in accordance with AAD policy. Work group members with potential conflicts recused themselves from discussion and drafting of recommendations in the relevant topic areas. Alan Menter, MD, chairman of the division of dermatology, Baylor University Medical Center, Dallas, is the other cochair of the work group.
 

SOURCE: Elmets CA et al. J Am Acad Dermatol. 2019 Jul 18. doi: 10.1016/j.jaad.2019.04.042.

Adults with chronic stable angina who had acupuncture as an adjunct treatment had fewer angina attacks, compared with controls, based on data from a randomized trial of 398 patients in China.

“Acupuncture has been used as nonpharmacologic treatment for several decades, especially to relieve symptoms of myocardial ischemia, improve cardiac function, and prevent recurrence,” and several small studies have reported benefits in angina patients, wrote Ling Zhao, PhD, of Chengdu (China) University of Traditional Chinese Medicine and colleagues.

In a study published in JAMA Internal Medicine, the researchers randomized patients aged 35-80 years with chronic stable angina into four groups: treatment on the disease-affected meridian (DAM), treatment on the nonaffected meridian (NAM), sham acupuncture (SA), and no acupuncture (wait list, or WL).

Chronic stable angina is defined by the American College of Cardiology and the American Heart Association as angina at least twice a week. Patients with other serious conditions including a history of MI, severe heart failure, valvular heart disease, and poorly controlled blood pressure or diabetes were excluded.

Each treatment group received three acupuncture sessions for 30 minutes each week for 4 weeks. Patients kept diaries of angina attacks and were assessed every 4 weeks for 16 weeks. After 16 weeks, the DAM patients had a significantly greater reduction in angina attacks, compared with the NAM group (4.1 fewer attacks), the SA group (5.2 fewer attacks), and the WL group (5.6 fewer attacks).

Overall, 16 patients reported adverse events related to acupuncture, including 5 cases of subcutaneous hemorrhage at the insertion point, 3 reports of tingling at the insertion point, and 8 reports of sleeplessness during the study period, but no patients discontinued the study because of these events. One patient in the WL group died of an acute MI and received no acupuncture treatment.

“We found that acupuncture on the DAM had superior and clinically relevant benefits in reducing angina frequency and pain intensity to a greater degree than acupuncture on a NAM, SA, or no acupuncture,” the researchers wrote. They found improvements in DAM patients on most metrics, including the Seattle Angina Questionnaire, compared with the other groups.

In addition, “compared with SA and no acupuncture, acupuncture on the DAM resulted in better regulation of anxiety and depression within the 12 weeks after treatment than at the end of the treatment period,” they wrote. “Acupuncture on the DAM causes autonomic remodeling by improving the balance between the vagus nerve and sympathetic nervous system during treatment.”

The findings were limited by several factors including the small sample size, potential performance bias based on variation in the acupuncturists’ experience, lack of analysis of doses of rescue medication, and lack of subgroup analysis, the researchers noted. However, the results are consistent with previous studies and support acupuncture as a potential adjunct treatment for patients with mild to moderate chronic angina.

The researchers had no financial conflicts to disclose. The study was funded by the National Natural Science Foundation of China and the State Key Program for Basic Research of China.

SOURCE: Zhao L et al. JAMA Intern Med. 2019 Jul 29. doi: 10.1001/jamainternmed.2019.2407.

Adults with chronic stable angina who had acupuncture as an adjunct treatment had fewer angina attacks, compared with controls, based on data from a randomized trial of 398 patients in China.

“Acupuncture has been used as nonpharmacologic treatment for several decades, especially to relieve symptoms of myocardial ischemia, improve cardiac function, and prevent recurrence,” and several small studies have reported benefits in angina patients, wrote Ling Zhao, PhD, of Chengdu (China) University of Traditional Chinese Medicine and colleagues.

In a study published in JAMA Internal Medicine, the researchers randomized patients aged 35-80 years with chronic stable angina into four groups: treatment on the disease-affected meridian (DAM), treatment on the nonaffected meridian (NAM), sham acupuncture (SA), and no acupuncture (wait list, or WL).

Chronic stable angina is defined by the American College of Cardiology and the American Heart Association as angina at least twice a week. Patients with other serious conditions including a history of MI, severe heart failure, valvular heart disease, and poorly controlled blood pressure or diabetes were excluded.

Each treatment group received three acupuncture sessions for 30 minutes each week for 4 weeks. Patients kept diaries of angina attacks and were assessed every 4 weeks for 16 weeks. After 16 weeks, the DAM patients had a significantly greater reduction in angina attacks, compared with the NAM group (4.1 fewer attacks), the SA group (5.2 fewer attacks), and the WL group (5.6 fewer attacks).

Overall, 16 patients reported adverse events related to acupuncture, including 5 cases of subcutaneous hemorrhage at the insertion point, 3 reports of tingling at the insertion point, and 8 reports of sleeplessness during the study period, but no patients discontinued the study because of these events. One patient in the WL group died of an acute MI and received no acupuncture treatment.

“We found that acupuncture on the DAM had superior and clinically relevant benefits in reducing angina frequency and pain intensity to a greater degree than acupuncture on a NAM, SA, or no acupuncture,” the researchers wrote. They found improvements in DAM patients on most metrics, including the Seattle Angina Questionnaire, compared with the other groups.

In addition, “compared with SA and no acupuncture, acupuncture on the DAM resulted in better regulation of anxiety and depression within the 12 weeks after treatment than at the end of the treatment period,” they wrote. “Acupuncture on the DAM causes autonomic remodeling by improving the balance between the vagus nerve and sympathetic nervous system during treatment.”

The findings were limited by several factors including the small sample size, potential performance bias based on variation in the acupuncturists’ experience, lack of analysis of doses of rescue medication, and lack of subgroup analysis, the researchers noted. However, the results are consistent with previous studies and support acupuncture as a potential adjunct treatment for patients with mild to moderate chronic angina.

The researchers had no financial conflicts to disclose. The study was funded by the National Natural Science Foundation of China and the State Key Program for Basic Research of China.

SOURCE: Zhao L et al. JAMA Intern Med. 2019 Jul 29. doi: 10.1001/jamainternmed.2019.2407.

Adults with chronic stable angina who had acupuncture as an adjunct treatment had fewer angina attacks, compared with controls, based on data from a randomized trial of 398 patients in China.

“Acupuncture has been used as nonpharmacologic treatment for several decades, especially to relieve symptoms of myocardial ischemia, improve cardiac function, and prevent recurrence,” and several small studies have reported benefits in angina patients, wrote Ling Zhao, PhD, of Chengdu (China) University of Traditional Chinese Medicine and colleagues.

In a study published in JAMA Internal Medicine, the researchers randomized patients aged 35-80 years with chronic stable angina into four groups: treatment on the disease-affected meridian (DAM), treatment on the nonaffected meridian (NAM), sham acupuncture (SA), and no acupuncture (wait list, or WL).

Chronic stable angina is defined by the American College of Cardiology and the American Heart Association as angina at least twice a week. Patients with other serious conditions including a history of MI, severe heart failure, valvular heart disease, and poorly controlled blood pressure or diabetes were excluded.

Each treatment group received three acupuncture sessions for 30 minutes each week for 4 weeks. Patients kept diaries of angina attacks and were assessed every 4 weeks for 16 weeks. After 16 weeks, the DAM patients had a significantly greater reduction in angina attacks, compared with the NAM group (4.1 fewer attacks), the SA group (5.2 fewer attacks), and the WL group (5.6 fewer attacks).

Overall, 16 patients reported adverse events related to acupuncture, including 5 cases of subcutaneous hemorrhage at the insertion point, 3 reports of tingling at the insertion point, and 8 reports of sleeplessness during the study period, but no patients discontinued the study because of these events. One patient in the WL group died of an acute MI and received no acupuncture treatment.

“We found that acupuncture on the DAM had superior and clinically relevant benefits in reducing angina frequency and pain intensity to a greater degree than acupuncture on a NAM, SA, or no acupuncture,” the researchers wrote. They found improvements in DAM patients on most metrics, including the Seattle Angina Questionnaire, compared with the other groups.

In addition, “compared with SA and no acupuncture, acupuncture on the DAM resulted in better regulation of anxiety and depression within the 12 weeks after treatment than at the end of the treatment period,” they wrote. “Acupuncture on the DAM causes autonomic remodeling by improving the balance between the vagus nerve and sympathetic nervous system during treatment.”

The findings were limited by several factors including the small sample size, potential performance bias based on variation in the acupuncturists’ experience, lack of analysis of doses of rescue medication, and lack of subgroup analysis, the researchers noted. However, the results are consistent with previous studies and support acupuncture as a potential adjunct treatment for patients with mild to moderate chronic angina.

The researchers had no financial conflicts to disclose. The study was funded by the National Natural Science Foundation of China and the State Key Program for Basic Research of China.

SOURCE: Zhao L et al. JAMA Intern Med. 2019 Jul 29. doi: 10.1001/jamainternmed.2019.2407.

Individuals with undiagnosed autism spectrum disorders and those with a formal diagnosis employ similar compensation behaviors to manage social and cognitive difficulties, and undiagnosed individuals may go unrecognized, data from an online survey of 136 adults suggest.

Unlike other adaptive behaviors in psychiatry, “autistic compensators, despite apparent lack of observable autistic behavior, continue being autistic at the neurocognitive level,” wrote Lucy Anne Livingston of Kings College London, and colleagues. “Because autism spectrum disorder is diagnosed by behavior alone, compensators might not receive a diagnosis and support until later in life, if at all. “

The researchers compared compensation behaviors in adults with and without an autism diagnosis. They recruited adults aged 18 years and older through an online advertisement distributed through social media and the U.K. National Autistic Society. Participants completed an online survey during Oct. 19, 2017–Jan. 2, 2018. The study was published in the Lancet Psychiatry.

“Compensation involved using intellectual and executive functions to regulate social behavior, such as intellectually conceived patterns about social norms (e.g., making eye contact), preplanning social niceties (e.g., asking others questions about themselves), and switching between social rules,” the researchers wrote.

The study population included 58 individuals with a clinical diagnosis of autism, 19 of whom self-identified as autistic but were not formally diagnosed, and 59 of whom reported social difficulties but had no formal diagnosis and did not self-identify as autistic. The average age of the three groups was 36 years, 40 years, and 34 years, respectively, and the average age at diagnosis for the diagnosed group was 30 years. Most of the individuals in each group were women (64%, 47%, and 86%, respectively). Responses were examined using a thematic analysis and thematic map.

In general, participants reported that compensation was a cognitively taxing process that served as a secondary route for social interaction because the primary route was unavailable, but that compensation strategies fell short in certain situations, such as unexpected turns of conversation. Overall, 38% of the respondents said their compensation strategies were “extremely successful” and 56% reported “somewhat successful.” However, 12% also reported their strategies were “extremely tiring,” and 36% reported “somewhat tiring.”

Factors affecting the participants’ abilities to compensate included environmental and sensory factors such as bright lights, loud noise, and large groups with unstructured social settings, such as parties. Also, transition to living independently as an adult led to problems, because compensation had allowed individuals to grow up appearing normal but lacking in additional support and strategies, the researchers noted.

Factors that contributed to successful interactions included similar interests with an interaction partner, and motivation to develop meaningful relationships. Participants also said they viewed compensation as a way to avoid ostracism and bullying. In addition, “fitting neurotypical peoples’ interaction style (e.g., eye contact or small talk) was viewed as vital for achieving life goals (e.g., independence and employment),” the researchers wrote.

In an accompanying editorial, Julia Parish-Morris, PhD, suggested the observation made by Ms. Livingston, a researcher at the Institute of Psychiatry, Psychology and Neuroscience at the college, and associates that compensation also occurs in people who do not have autism suggests that compensation might be a “general social lubricant that facilitates community living and is therefore a potentially useful tool.”

“In other words, perhaps raising awareness about compensation in autism spectrum disorder is an important first step toward eliminating the need for it,” wrote Dr. Parish-Morris, of the Center for Autism Research at Children’s Hospital of Philadelphia (Lancet Psychiatry. 2019 Jul 23. doi: 10.1016/S2215-0366[19]30294-9).

The study data were limited by the prevalence of female, well-educated, late-diagnosed individuals in the study population, which might limit the generalizability of the findings, and the lack of data on subconscious compensation because of the use of self-reports, the researchers noted.

However, “Given the individual differences found in this study, we tentatively suggest that clinicians take an individualized approach when assessing and discussing compensatory strategies with people with autism,” they said. “It will be important to establish which compensatory strategies are most beneficial, and how their success might be maximized with changes to external environments irrespective of clinical intervention.”

The researchers had no financial interests to disclose.

SOURCE: Livingston LA et al. Lancet Psychiatry. 2019 Jul 23. doi. org/10.1016/S2215-0366(19)30224-X.

Individuals with undiagnosed autism spectrum disorders and those with a formal diagnosis employ similar compensation behaviors to manage social and cognitive difficulties, and undiagnosed individuals may go unrecognized, data from an online survey of 136 adults suggest.

Unlike other adaptive behaviors in psychiatry, “autistic compensators, despite apparent lack of observable autistic behavior, continue being autistic at the neurocognitive level,” wrote Lucy Anne Livingston of Kings College London, and colleagues. “Because autism spectrum disorder is diagnosed by behavior alone, compensators might not receive a diagnosis and support until later in life, if at all. “

The researchers compared compensation behaviors in adults with and without an autism diagnosis. They recruited adults aged 18 years and older through an online advertisement distributed through social media and the U.K. National Autistic Society. Participants completed an online survey during Oct. 19, 2017–Jan. 2, 2018. The study was published in the Lancet Psychiatry.

“Compensation involved using intellectual and executive functions to regulate social behavior, such as intellectually conceived patterns about social norms (e.g., making eye contact), preplanning social niceties (e.g., asking others questions about themselves), and switching between social rules,” the researchers wrote.

The study population included 58 individuals with a clinical diagnosis of autism, 19 of whom self-identified as autistic but were not formally diagnosed, and 59 of whom reported social difficulties but had no formal diagnosis and did not self-identify as autistic. The average age of the three groups was 36 years, 40 years, and 34 years, respectively, and the average age at diagnosis for the diagnosed group was 30 years. Most of the individuals in each group were women (64%, 47%, and 86%, respectively). Responses were examined using a thematic analysis and thematic map.

In general, participants reported that compensation was a cognitively taxing process that served as a secondary route for social interaction because the primary route was unavailable, but that compensation strategies fell short in certain situations, such as unexpected turns of conversation. Overall, 38% of the respondents said their compensation strategies were “extremely successful” and 56% reported “somewhat successful.” However, 12% also reported their strategies were “extremely tiring,” and 36% reported “somewhat tiring.”

Factors affecting the participants’ abilities to compensate included environmental and sensory factors such as bright lights, loud noise, and large groups with unstructured social settings, such as parties. Also, transition to living independently as an adult led to problems, because compensation had allowed individuals to grow up appearing normal but lacking in additional support and strategies, the researchers noted.

Factors that contributed to successful interactions included similar interests with an interaction partner, and motivation to develop meaningful relationships. Participants also said they viewed compensation as a way to avoid ostracism and bullying. In addition, “fitting neurotypical peoples’ interaction style (e.g., eye contact or small talk) was viewed as vital for achieving life goals (e.g., independence and employment),” the researchers wrote.

In an accompanying editorial, Julia Parish-Morris, PhD, suggested the observation made by Ms. Livingston, a researcher at the Institute of Psychiatry, Psychology and Neuroscience at the college, and associates that compensation also occurs in people who do not have autism suggests that compensation might be a “general social lubricant that facilitates community living and is therefore a potentially useful tool.”

“In other words, perhaps raising awareness about compensation in autism spectrum disorder is an important first step toward eliminating the need for it,” wrote Dr. Parish-Morris, of the Center for Autism Research at Children’s Hospital of Philadelphia (Lancet Psychiatry. 2019 Jul 23. doi: 10.1016/S2215-0366[19]30294-9).

The study data were limited by the prevalence of female, well-educated, late-diagnosed individuals in the study population, which might limit the generalizability of the findings, and the lack of data on subconscious compensation because of the use of self-reports, the researchers noted.

However, “Given the individual differences found in this study, we tentatively suggest that clinicians take an individualized approach when assessing and discussing compensatory strategies with people with autism,” they said. “It will be important to establish which compensatory strategies are most beneficial, and how their success might be maximized with changes to external environments irrespective of clinical intervention.”

The researchers had no financial interests to disclose.

SOURCE: Livingston LA et al. Lancet Psychiatry. 2019 Jul 23. doi. org/10.1016/S2215-0366(19)30224-X.

Individuals with undiagnosed autism spectrum disorders and those with a formal diagnosis employ similar compensation behaviors to manage social and cognitive difficulties, and undiagnosed individuals may go unrecognized, data from an online survey of 136 adults suggest.

Unlike other adaptive behaviors in psychiatry, “autistic compensators, despite apparent lack of observable autistic behavior, continue being autistic at the neurocognitive level,” wrote Lucy Anne Livingston of Kings College London, and colleagues. “Because autism spectrum disorder is diagnosed by behavior alone, compensators might not receive a diagnosis and support until later in life, if at all. “

The researchers compared compensation behaviors in adults with and without an autism diagnosis. They recruited adults aged 18 years and older through an online advertisement distributed through social media and the U.K. National Autistic Society. Participants completed an online survey during Oct. 19, 2017–Jan. 2, 2018. The study was published in the Lancet Psychiatry.

“Compensation involved using intellectual and executive functions to regulate social behavior, such as intellectually conceived patterns about social norms (e.g., making eye contact), preplanning social niceties (e.g., asking others questions about themselves), and switching between social rules,” the researchers wrote.

The study population included 58 individuals with a clinical diagnosis of autism, 19 of whom self-identified as autistic but were not formally diagnosed, and 59 of whom reported social difficulties but had no formal diagnosis and did not self-identify as autistic. The average age of the three groups was 36 years, 40 years, and 34 years, respectively, and the average age at diagnosis for the diagnosed group was 30 years. Most of the individuals in each group were women (64%, 47%, and 86%, respectively). Responses were examined using a thematic analysis and thematic map.

In general, participants reported that compensation was a cognitively taxing process that served as a secondary route for social interaction because the primary route was unavailable, but that compensation strategies fell short in certain situations, such as unexpected turns of conversation. Overall, 38% of the respondents said their compensation strategies were “extremely successful” and 56% reported “somewhat successful.” However, 12% also reported their strategies were “extremely tiring,” and 36% reported “somewhat tiring.”

Factors affecting the participants’ abilities to compensate included environmental and sensory factors such as bright lights, loud noise, and large groups with unstructured social settings, such as parties. Also, transition to living independently as an adult led to problems, because compensation had allowed individuals to grow up appearing normal but lacking in additional support and strategies, the researchers noted.

Factors that contributed to successful interactions included similar interests with an interaction partner, and motivation to develop meaningful relationships. Participants also said they viewed compensation as a way to avoid ostracism and bullying. In addition, “fitting neurotypical peoples’ interaction style (e.g., eye contact or small talk) was viewed as vital for achieving life goals (e.g., independence and employment),” the researchers wrote.

In an accompanying editorial, Julia Parish-Morris, PhD, suggested the observation made by Ms. Livingston, a researcher at the Institute of Psychiatry, Psychology and Neuroscience at the college, and associates that compensation also occurs in people who do not have autism suggests that compensation might be a “general social lubricant that facilitates community living and is therefore a potentially useful tool.”

“In other words, perhaps raising awareness about compensation in autism spectrum disorder is an important first step toward eliminating the need for it,” wrote Dr. Parish-Morris, of the Center for Autism Research at Children’s Hospital of Philadelphia (Lancet Psychiatry. 2019 Jul 23. doi: 10.1016/S2215-0366[19]30294-9).

The study data were limited by the prevalence of female, well-educated, late-diagnosed individuals in the study population, which might limit the generalizability of the findings, and the lack of data on subconscious compensation because of the use of self-reports, the researchers noted.

However, “Given the individual differences found in this study, we tentatively suggest that clinicians take an individualized approach when assessing and discussing compensatory strategies with people with autism,” they said. “It will be important to establish which compensatory strategies are most beneficial, and how their success might be maximized with changes to external environments irrespective of clinical intervention.”

The researchers had no financial interests to disclose.

SOURCE: Livingston LA et al. Lancet Psychiatry. 2019 Jul 23. doi. org/10.1016/S2215-0366(19)30224-X.

Adults who quit smoking reduced their risk for peripheral artery disease in the short term, but remained at increased risk for up to 30 years, compared with never-smokers, based on data from more than 13,000 adults in a community-based study.

Courtesy Journal of the American College of Cardiology

Most reports on the impact of smoking cessation on cardiovascular disease have focused on coronary heart disease (CHD), and stroke, while data on the effects of smoking cessation on peripheral artery disease (PAD) are limited, wrote Ning Ding, MBBS, SCM, of the Johns Hopkins Bloomberg School of Public Health, Baltimore, Md., and colleagues.

To compare the impact of smoking on PAD, CHD, and stroke, the researchers used data from the Atherosclerosis Risk in Communities (ARIC) study, which included 15,792 adults aged 45-64 years in four communities. The findings were published in the Journal of the American College of Cardiology.

The study population of 13,355 individuals had no baseline history of PAD, CHD, or stroke. Over a median 26 years of follow-up, the researchers identified 492 cases of PAD, 1,798 cases of CHD, and 1,106 cases of stroke.

The risk of all three conditions began to decline within 5 years of smoking cessation, which could be encouraging to smokers who wish to quit, the researchers noted. In addition, the longer the duration of smoking cessation, the lower the risk for all three conditions (See central illustration).

However, a significantly elevated risk remained for PAD for up to 30 years after smoking cessation and for CHD for up to 20 years after smoking cessation, compared with never-smokers.

The researchers also found a roughly fourfold increased risk for PAD for smokers who smoked for 40 or more pack-years, compared with never-smokers, which was greater than the 2.1 hazard ratio for CHD and 1.8 HR for stroke. In addition, current smokers of at least one pack per day had a significantly greater risk of PAD, compared with never-smokers (HR, 5.36) that was higher than the risk for CHD or stroke (HR, 2.38 and HR, 1.88, respectively).

The study findings were limited by several factors including the reliance on self-reports, potential misclassification of data, and the potential exclusion of mild PAD cases that did not require hospitalization, the researchers noted. However, the results support the value of encouraging smokers to quit and support the need to include PAD risk in public health information, they said. “Although public statements about smoking and [cardiovascular disease] have been focusing on CHD and stroke, our results indicate the need to take account of PAD as well for comprehensively acknowledging the effect of smoking on overall cardiovascular health,” they added.

The ARIC study was funded by the National Heart, Lung, and Blood Institute, National Institutes of Health. Lead author Dr. Ding had no financial conflicts to disclose; coauthors disclosed relationships with Bristol-Myers Squibb and Fukuda Denshi.

SOURCE: Ding N et al. J Am Coll Cardiol. 2019 Jul 22;74:498-507. doi: 10.1016/j.jacc.2019.06.003.

Adults who quit smoking reduced their risk for peripheral artery disease in the short term, but remained at increased risk for up to 30 years, compared with never-smokers, based on data from more than 13,000 adults in a community-based study.

Courtesy Journal of the American College of Cardiology

Most reports on the impact of smoking cessation on cardiovascular disease have focused on coronary heart disease (CHD), and stroke, while data on the effects of smoking cessation on peripheral artery disease (PAD) are limited, wrote Ning Ding, MBBS, SCM, of the Johns Hopkins Bloomberg School of Public Health, Baltimore, Md., and colleagues.

To compare the impact of smoking on PAD, CHD, and stroke, the researchers used data from the Atherosclerosis Risk in Communities (ARIC) study, which included 15,792 adults aged 45-64 years in four communities. The findings were published in the Journal of the American College of Cardiology.

The study population of 13,355 individuals had no baseline history of PAD, CHD, or stroke. Over a median 26 years of follow-up, the researchers identified 492 cases of PAD, 1,798 cases of CHD, and 1,106 cases of stroke.

The risk of all three conditions began to decline within 5 years of smoking cessation, which could be encouraging to smokers who wish to quit, the researchers noted. In addition, the longer the duration of smoking cessation, the lower the risk for all three conditions (See central illustration).

However, a significantly elevated risk remained for PAD for up to 30 years after smoking cessation and for CHD for up to 20 years after smoking cessation, compared with never-smokers.

The researchers also found a roughly fourfold increased risk for PAD for smokers who smoked for 40 or more pack-years, compared with never-smokers, which was greater than the 2.1 hazard ratio for CHD and 1.8 HR for stroke. In addition, current smokers of at least one pack per day had a significantly greater risk of PAD, compared with never-smokers (HR, 5.36) that was higher than the risk for CHD or stroke (HR, 2.38 and HR, 1.88, respectively).

The study findings were limited by several factors including the reliance on self-reports, potential misclassification of data, and the potential exclusion of mild PAD cases that did not require hospitalization, the researchers noted. However, the results support the value of encouraging smokers to quit and support the need to include PAD risk in public health information, they said. “Although public statements about smoking and [cardiovascular disease] have been focusing on CHD and stroke, our results indicate the need to take account of PAD as well for comprehensively acknowledging the effect of smoking on overall cardiovascular health,” they added.

The ARIC study was funded by the National Heart, Lung, and Blood Institute, National Institutes of Health. Lead author Dr. Ding had no financial conflicts to disclose; coauthors disclosed relationships with Bristol-Myers Squibb and Fukuda Denshi.

SOURCE: Ding N et al. J Am Coll Cardiol. 2019 Jul 22;74:498-507. doi: 10.1016/j.jacc.2019.06.003.

Adults who quit smoking reduced their risk for peripheral artery disease in the short term, but remained at increased risk for up to 30 years, compared with never-smokers, based on data from more than 13,000 adults in a community-based study.

Courtesy Journal of the American College of Cardiology

Most reports on the impact of smoking cessation on cardiovascular disease have focused on coronary heart disease (CHD), and stroke, while data on the effects of smoking cessation on peripheral artery disease (PAD) are limited, wrote Ning Ding, MBBS, SCM, of the Johns Hopkins Bloomberg School of Public Health, Baltimore, Md., and colleagues.

To compare the impact of smoking on PAD, CHD, and stroke, the researchers used data from the Atherosclerosis Risk in Communities (ARIC) study, which included 15,792 adults aged 45-64 years in four communities. The findings were published in the Journal of the American College of Cardiology.

The study population of 13,355 individuals had no baseline history of PAD, CHD, or stroke. Over a median 26 years of follow-up, the researchers identified 492 cases of PAD, 1,798 cases of CHD, and 1,106 cases of stroke.

The risk of all three conditions began to decline within 5 years of smoking cessation, which could be encouraging to smokers who wish to quit, the researchers noted. In addition, the longer the duration of smoking cessation, the lower the risk for all three conditions (See central illustration).

However, a significantly elevated risk remained for PAD for up to 30 years after smoking cessation and for CHD for up to 20 years after smoking cessation, compared with never-smokers.

The researchers also found a roughly fourfold increased risk for PAD for smokers who smoked for 40 or more pack-years, compared with never-smokers, which was greater than the 2.1 hazard ratio for CHD and 1.8 HR for stroke. In addition, current smokers of at least one pack per day had a significantly greater risk of PAD, compared with never-smokers (HR, 5.36) that was higher than the risk for CHD or stroke (HR, 2.38 and HR, 1.88, respectively).

The study findings were limited by several factors including the reliance on self-reports, potential misclassification of data, and the potential exclusion of mild PAD cases that did not require hospitalization, the researchers noted. However, the results support the value of encouraging smokers to quit and support the need to include PAD risk in public health information, they said. “Although public statements about smoking and [cardiovascular disease] have been focusing on CHD and stroke, our results indicate the need to take account of PAD as well for comprehensively acknowledging the effect of smoking on overall cardiovascular health,” they added.

The ARIC study was funded by the National Heart, Lung, and Blood Institute, National Institutes of Health. Lead author Dr. Ding had no financial conflicts to disclose; coauthors disclosed relationships with Bristol-Myers Squibb and Fukuda Denshi.

SOURCE: Ding N et al. J Am Coll Cardiol. 2019 Jul 22;74:498-507. doi: 10.1016/j.jacc.2019.06.003.

Adults with asthma–chronic obstructive pulmonary disease overlap syndrome who took statins had lower rates of anxiety and depression than did those not on statins, based on data from approximately 9,000 patients.

Although asthma–COPD overlap syndrome (ACOS) has been associated with depression, the effects of oral and inhaled corticosteroids on anxiety and depression in these patients have not been well investigated, wrote Jun-Jun Yeh, MD, of Ditmanson Medical Foundation Chia-Yi (Taiwan) Christian Hospital, and colleagues.

In a study published in the Journal of Affective Disorders, the researchers analyzed 9,139 ACOS patients including 1,252 statin users and 7,887 nonstatin users; 62% were male.

The statin users had significantly lower risk of both anxiety and depression than did the nonstatin users (adjusted hazard ratio 0.34 for anxiety and 0.36 for depression) after researchers controlled for factors including age, sex, comorbidities, and medications. Statin users experienced a total of 109 anxiety or depression events over an average of 8 years’ follow-up, while nonstatin users experienced a total of 1,333 anxiety or depression events over an average of 5 years’ follow-up.

The incidence density rate of anxiety was 11/1,000 person-years for statin users and 33/1,000 person-years for nonstatin users. The incidence density rate of depression was 3/1,000 person-years for statin users and 9/1,000 person-years for nonstatin users.

Significantly lower risk of anxiety and depression also were observed in statin users, compared with nonstatin users, in subgroups of men, women, patients younger than 50 years, and patients aged 50 years and older. The risks of anxiety and depression were lower in statin users versus nonstatin users across all subgroups with or without inhaled or oral corticosteroids.

Overall, the statin users were significantly younger, had more comorbidities, and were more likely to use inhaled or oral corticosteroids than were the nonstatin users.

The findings were limited by several factors including the retrospective nature of the study and a lack of information on prescribed daily doses of medication, the researchers noted. However, the results support those from previous studies and suggest that “the anti-inflammatory effect of statins may attenuate anxiety and depression in ACOS patients, even in the late stages of the disease,” although the exact mechanism of action remains unknown and larger, randomized, controlled trials are needed, they said.

The study was supported by grants from a variety of organizations in Taiwan, China, and Japan. The researchers had no financial conflicts to disclose.

SOURCE: Yeh JJ et al. J Affect Disord. 2019 Jun 15; 253:277-84.

Adults with asthma–chronic obstructive pulmonary disease overlap syndrome who took statins had lower rates of anxiety and depression than did those not on statins, based on data from approximately 9,000 patients.

Although asthma–COPD overlap syndrome (ACOS) has been associated with depression, the effects of oral and inhaled corticosteroids on anxiety and depression in these patients have not been well investigated, wrote Jun-Jun Yeh, MD, of Ditmanson Medical Foundation Chia-Yi (Taiwan) Christian Hospital, and colleagues.

In a study published in the Journal of Affective Disorders, the researchers analyzed 9,139 ACOS patients including 1,252 statin users and 7,887 nonstatin users; 62% were male.

The statin users had significantly lower risk of both anxiety and depression than did the nonstatin users (adjusted hazard ratio 0.34 for anxiety and 0.36 for depression) after researchers controlled for factors including age, sex, comorbidities, and medications. Statin users experienced a total of 109 anxiety or depression events over an average of 8 years’ follow-up, while nonstatin users experienced a total of 1,333 anxiety or depression events over an average of 5 years’ follow-up.

The incidence density rate of anxiety was 11/1,000 person-years for statin users and 33/1,000 person-years for nonstatin users. The incidence density rate of depression was 3/1,000 person-years for statin users and 9/1,000 person-years for nonstatin users.

Significantly lower risk of anxiety and depression also were observed in statin users, compared with nonstatin users, in subgroups of men, women, patients younger than 50 years, and patients aged 50 years and older. The risks of anxiety and depression were lower in statin users versus nonstatin users across all subgroups with or without inhaled or oral corticosteroids.

Overall, the statin users were significantly younger, had more comorbidities, and were more likely to use inhaled or oral corticosteroids than were the nonstatin users.

The findings were limited by several factors including the retrospective nature of the study and a lack of information on prescribed daily doses of medication, the researchers noted. However, the results support those from previous studies and suggest that “the anti-inflammatory effect of statins may attenuate anxiety and depression in ACOS patients, even in the late stages of the disease,” although the exact mechanism of action remains unknown and larger, randomized, controlled trials are needed, they said.

The study was supported by grants from a variety of organizations in Taiwan, China, and Japan. The researchers had no financial conflicts to disclose.

SOURCE: Yeh JJ et al. J Affect Disord. 2019 Jun 15; 253:277-84.

Adults with asthma–chronic obstructive pulmonary disease overlap syndrome who took statins had lower rates of anxiety and depression than did those not on statins, based on data from approximately 9,000 patients.

Although asthma–COPD overlap syndrome (ACOS) has been associated with depression, the effects of oral and inhaled corticosteroids on anxiety and depression in these patients have not been well investigated, wrote Jun-Jun Yeh, MD, of Ditmanson Medical Foundation Chia-Yi (Taiwan) Christian Hospital, and colleagues.

In a study published in the Journal of Affective Disorders, the researchers analyzed 9,139 ACOS patients including 1,252 statin users and 7,887 nonstatin users; 62% were male.

The statin users had significantly lower risk of both anxiety and depression than did the nonstatin users (adjusted hazard ratio 0.34 for anxiety and 0.36 for depression) after researchers controlled for factors including age, sex, comorbidities, and medications. Statin users experienced a total of 109 anxiety or depression events over an average of 8 years’ follow-up, while nonstatin users experienced a total of 1,333 anxiety or depression events over an average of 5 years’ follow-up.

The incidence density rate of anxiety was 11/1,000 person-years for statin users and 33/1,000 person-years for nonstatin users. The incidence density rate of depression was 3/1,000 person-years for statin users and 9/1,000 person-years for nonstatin users.

Significantly lower risk of anxiety and depression also were observed in statin users, compared with nonstatin users, in subgroups of men, women, patients younger than 50 years, and patients aged 50 years and older. The risks of anxiety and depression were lower in statin users versus nonstatin users across all subgroups with or without inhaled or oral corticosteroids.

Overall, the statin users were significantly younger, had more comorbidities, and were more likely to use inhaled or oral corticosteroids than were the nonstatin users.

The findings were limited by several factors including the retrospective nature of the study and a lack of information on prescribed daily doses of medication, the researchers noted. However, the results support those from previous studies and suggest that “the anti-inflammatory effect of statins may attenuate anxiety and depression in ACOS patients, even in the late stages of the disease,” although the exact mechanism of action remains unknown and larger, randomized, controlled trials are needed, they said.

The study was supported by grants from a variety of organizations in Taiwan, China, and Japan. The researchers had no financial conflicts to disclose.

SOURCE: Yeh JJ et al. J Affect Disord. 2019 Jun 15; 253:277-84.

Non–vitamin K oral anticoagulants (NOACs) significantly reduced the risk of stroke or systemic embolism compared to vitamin K antagonists (VKAs) for patients in the early stages of chronic kidney disease and comorbid atrial fibrillation, based on data from a meta-analysis of roughly 34,000 patients.

Chronic kidney disease increases the risk of complications including stroke, congestive heart failure, and death in patients who also have atrial fibrillation, but most trials of anticoagulant therapy to reduce the risk of such events have excluded these patients, wrote Jeffrey T. Ha, MBBS, of the George Institute for Global Health, Newtown, Australia, and colleagues.

To assess the benefits and harms of oral anticoagulants for multiple indications in chronic kidney disease patients, the researchers conducted a meta-analysis of 45 studies including 34,082 individuals. The findings were published in the Annals of Internal Medicine. The analysis included 8 trials of end stage kidney disease patients on dialysis; the remaining trials excluded patients with creatinine clearance less than 20 mL/min or an estimated glomerular filtration rate less than 15 mL/min per 1.73 m². The interventional agents were rivaroxaban, dabigatran, apixaban, edoxaban, betrixaban, warfarin, and acenocoumarol.

A notable finding was the significant reduction in relative risk of stroke or systemic embolism (21%), hemorrhagic stroke (52%), and intracranial hemorrhage (51%) for early-stage chronic kidney disease patients with atrial fibrillation given NOACs, compared with those given VKAs.

The evidence for the superiority of NOACs over VKAs for reducing risk of venous thromboembolism (VTE) or VTE-related death was uncertain, as was the evidence to draw any conclusions about benefits and harms of either NOACs or VKAs for patients with advanced or end-stage kidney disease.

Across all trials, NOACs appeared to reduce the relative risk of major bleeding, compared with VKAs by roughly 25%, but the difference was not statistically significant, the researchers noted.

The findings were limited by the lack of evidence for oral anticoagulant use in patients with advanced chronic or end-stage kidney disease, as well as inability to assess differences among NOACs, the researchers noted. However, the results suggest that NOACs may be recommended over VKAs for the subgroup of early-stage chronic kidney disease patients with atrial fibrillation, they said.

Several additional trials are in progress, and future trials “should include not only participants with dialysis-dependent ESKD [end-stage kidney disease] but also those with CrCl [creatinine clearance of] less than 25 mL/min,” and compare NOACs with placebo as well, they noted.

Lead author Dr. Ha is supported by a University Postgraduate Award from University of New South Wales, Sydney, but had no financial conflicts to disclose; coauthors disclosed support from various organizations as well as pharmaceutical companies including Baxter, Amgen, Eli Lilly, Boehringer Ingelheim, Vifor Pharma, Janssen, Pfizer, Bristol-Myers Squibb, and GlaxoSmithKline.
 

SOURCE: Ha JT et al. Ann Intern Med. 2019 July 15. doi: 10.7326/M19-0087

Non–vitamin K oral anticoagulants (NOACs) significantly reduced the risk of stroke or systemic embolism compared to vitamin K antagonists (VKAs) for patients in the early stages of chronic kidney disease and comorbid atrial fibrillation, based on data from a meta-analysis of roughly 34,000 patients.

Chronic kidney disease increases the risk of complications including stroke, congestive heart failure, and death in patients who also have atrial fibrillation, but most trials of anticoagulant therapy to reduce the risk of such events have excluded these patients, wrote Jeffrey T. Ha, MBBS, of the George Institute for Global Health, Newtown, Australia, and colleagues.

To assess the benefits and harms of oral anticoagulants for multiple indications in chronic kidney disease patients, the researchers conducted a meta-analysis of 45 studies including 34,082 individuals. The findings were published in the Annals of Internal Medicine. The analysis included 8 trials of end stage kidney disease patients on dialysis; the remaining trials excluded patients with creatinine clearance less than 20 mL/min or an estimated glomerular filtration rate less than 15 mL/min per 1.73 m². The interventional agents were rivaroxaban, dabigatran, apixaban, edoxaban, betrixaban, warfarin, and acenocoumarol.

A notable finding was the significant reduction in relative risk of stroke or systemic embolism (21%), hemorrhagic stroke (52%), and intracranial hemorrhage (51%) for early-stage chronic kidney disease patients with atrial fibrillation given NOACs, compared with those given VKAs.

The evidence for the superiority of NOACs over VKAs for reducing risk of venous thromboembolism (VTE) or VTE-related death was uncertain, as was the evidence to draw any conclusions about benefits and harms of either NOACs or VKAs for patients with advanced or end-stage kidney disease.

Across all trials, NOACs appeared to reduce the relative risk of major bleeding, compared with VKAs by roughly 25%, but the difference was not statistically significant, the researchers noted.

The findings were limited by the lack of evidence for oral anticoagulant use in patients with advanced chronic or end-stage kidney disease, as well as inability to assess differences among NOACs, the researchers noted. However, the results suggest that NOACs may be recommended over VKAs for the subgroup of early-stage chronic kidney disease patients with atrial fibrillation, they said.

Several additional trials are in progress, and future trials “should include not only participants with dialysis-dependent ESKD [end-stage kidney disease] but also those with CrCl [creatinine clearance of] less than 25 mL/min,” and compare NOACs with placebo as well, they noted.

Lead author Dr. Ha is supported by a University Postgraduate Award from University of New South Wales, Sydney, but had no financial conflicts to disclose; coauthors disclosed support from various organizations as well as pharmaceutical companies including Baxter, Amgen, Eli Lilly, Boehringer Ingelheim, Vifor Pharma, Janssen, Pfizer, Bristol-Myers Squibb, and GlaxoSmithKline.
 

SOURCE: Ha JT et al. Ann Intern Med. 2019 July 15. doi: 10.7326/M19-0087

Non–vitamin K oral anticoagulants (NOACs) significantly reduced the risk of stroke or systemic embolism compared to vitamin K antagonists (VKAs) for patients in the early stages of chronic kidney disease and comorbid atrial fibrillation, based on data from a meta-analysis of roughly 34,000 patients.

Chronic kidney disease increases the risk of complications including stroke, congestive heart failure, and death in patients who also have atrial fibrillation, but most trials of anticoagulant therapy to reduce the risk of such events have excluded these patients, wrote Jeffrey T. Ha, MBBS, of the George Institute for Global Health, Newtown, Australia, and colleagues.

To assess the benefits and harms of oral anticoagulants for multiple indications in chronic kidney disease patients, the researchers conducted a meta-analysis of 45 studies including 34,082 individuals. The findings were published in the Annals of Internal Medicine. The analysis included 8 trials of end stage kidney disease patients on dialysis; the remaining trials excluded patients with creatinine clearance less than 20 mL/min or an estimated glomerular filtration rate less than 15 mL/min per 1.73 m². The interventional agents were rivaroxaban, dabigatran, apixaban, edoxaban, betrixaban, warfarin, and acenocoumarol.

A notable finding was the significant reduction in relative risk of stroke or systemic embolism (21%), hemorrhagic stroke (52%), and intracranial hemorrhage (51%) for early-stage chronic kidney disease patients with atrial fibrillation given NOACs, compared with those given VKAs.

The evidence for the superiority of NOACs over VKAs for reducing risk of venous thromboembolism (VTE) or VTE-related death was uncertain, as was the evidence to draw any conclusions about benefits and harms of either NOACs or VKAs for patients with advanced or end-stage kidney disease.

Across all trials, NOACs appeared to reduce the relative risk of major bleeding, compared with VKAs by roughly 25%, but the difference was not statistically significant, the researchers noted.

The findings were limited by the lack of evidence for oral anticoagulant use in patients with advanced chronic or end-stage kidney disease, as well as inability to assess differences among NOACs, the researchers noted. However, the results suggest that NOACs may be recommended over VKAs for the subgroup of early-stage chronic kidney disease patients with atrial fibrillation, they said.

Several additional trials are in progress, and future trials “should include not only participants with dialysis-dependent ESKD [end-stage kidney disease] but also those with CrCl [creatinine clearance of] less than 25 mL/min,” and compare NOACs with placebo as well, they noted.

Lead author Dr. Ha is supported by a University Postgraduate Award from University of New South Wales, Sydney, but had no financial conflicts to disclose; coauthors disclosed support from various organizations as well as pharmaceutical companies including Baxter, Amgen, Eli Lilly, Boehringer Ingelheim, Vifor Pharma, Janssen, Pfizer, Bristol-Myers Squibb, and GlaxoSmithKline.
 

SOURCE: Ha JT et al. Ann Intern Med. 2019 July 15. doi: 10.7326/M19-0087

Primary cutaneous melanomas more than 2 mm thick can be excised with 2-cm margins with outcomes similar to excision with 4-cm margins, based on data from a randomized, multicenter trial of 936 patients.

“Over time, and in light of the findings of several randomized studies, less extensive surgery for primary melanoma with tumor thickness greater than 2 mm has become more established,” and most recent guidelines recommend a 2-cm margin for these tumors, wrote Deborah Utjés, MD, of the Karolinska Institute in Stockholm and colleagues.

To reinforce the safety and effectiveness of the 2-cm margin, the researchers conducted an open-label, randomized trial of clinically staged melanoma patients aged 75 years and younger with localized cutaneous melanomas thicker than 2 mm, from January 1992 to May 2004. Patients were treated in Denmark, Estonia, Norway, and Sweden. The findings were published in the Lancet.

Patients were randomized to treatment with a 2-cm (471) or 4-cm excision margin (465). The melanomas were located on the trunk, upper extremities, or lower extremities.

The primary outcome of overall survival was similar between the groups. Over a median 20-year follow-up period, the death rate was approximately 50% in each group (49% in the 2-cm group and 51% in the 4-cm group). Disease-specific survival rates were similar as well. Of the 621 reported deaths, 397 were attributed to melanoma: 192 (48%) in the 2-cm group and 205 (52%) in the 4-cm group.

The study findings were limited by several factors, including a lower-than-expected number of patients, lack of nodal staging during the study period, and a focus only on the surgical margin without recording data on pathological excision margins.

However, the extended follow-up supports the safe use of the 2-cm margin for the treatment of melanomas thicker than 2 mm, the investigators wrote. In addition, results from an ongoing trial comparing 1-cm and 2-cm margins for melanomas at least 1 mm thick may yield more evidence to support still narrower surgical margins for some cutaneous melanomas.

The study notes that guidelines from organizations that include the American National Comprehensive Cancer Network and the American Academy of Dermatology recommend the 2-cm margin for tumors that are thicker than 2 mm.

The study was supported by the Swedish Cancer Society, Stockholm Cancer Society, Swedish Society for Medical Research, and the Stockholm County Council, and by funds from Radiumhemmet Research and Wallström. The authors reported no disclosures.

SOURCE: Utjés D et al. Lancet. 2019 Jul 4. doi: 10.1016/S0140-6736(19)31132-8.

Primary cutaneous melanomas more than 2 mm thick can be excised with 2-cm margins with outcomes similar to excision with 4-cm margins, based on data from a randomized, multicenter trial of 936 patients.

“Over time, and in light of the findings of several randomized studies, less extensive surgery for primary melanoma with tumor thickness greater than 2 mm has become more established,” and most recent guidelines recommend a 2-cm margin for these tumors, wrote Deborah Utjés, MD, of the Karolinska Institute in Stockholm and colleagues.

To reinforce the safety and effectiveness of the 2-cm margin, the researchers conducted an open-label, randomized trial of clinically staged melanoma patients aged 75 years and younger with localized cutaneous melanomas thicker than 2 mm, from January 1992 to May 2004. Patients were treated in Denmark, Estonia, Norway, and Sweden. The findings were published in the Lancet.

Patients were randomized to treatment with a 2-cm (471) or 4-cm excision margin (465). The melanomas were located on the trunk, upper extremities, or lower extremities.

The primary outcome of overall survival was similar between the groups. Over a median 20-year follow-up period, the death rate was approximately 50% in each group (49% in the 2-cm group and 51% in the 4-cm group). Disease-specific survival rates were similar as well. Of the 621 reported deaths, 397 were attributed to melanoma: 192 (48%) in the 2-cm group and 205 (52%) in the 4-cm group.

The study findings were limited by several factors, including a lower-than-expected number of patients, lack of nodal staging during the study period, and a focus only on the surgical margin without recording data on pathological excision margins.

However, the extended follow-up supports the safe use of the 2-cm margin for the treatment of melanomas thicker than 2 mm, the investigators wrote. In addition, results from an ongoing trial comparing 1-cm and 2-cm margins for melanomas at least 1 mm thick may yield more evidence to support still narrower surgical margins for some cutaneous melanomas.

The study notes that guidelines from organizations that include the American National Comprehensive Cancer Network and the American Academy of Dermatology recommend the 2-cm margin for tumors that are thicker than 2 mm.

The study was supported by the Swedish Cancer Society, Stockholm Cancer Society, Swedish Society for Medical Research, and the Stockholm County Council, and by funds from Radiumhemmet Research and Wallström. The authors reported no disclosures.

SOURCE: Utjés D et al. Lancet. 2019 Jul 4. doi: 10.1016/S0140-6736(19)31132-8.

Primary cutaneous melanomas more than 2 mm thick can be excised with 2-cm margins with outcomes similar to excision with 4-cm margins, based on data from a randomized, multicenter trial of 936 patients.

“Over time, and in light of the findings of several randomized studies, less extensive surgery for primary melanoma with tumor thickness greater than 2 mm has become more established,” and most recent guidelines recommend a 2-cm margin for these tumors, wrote Deborah Utjés, MD, of the Karolinska Institute in Stockholm and colleagues.

To reinforce the safety and effectiveness of the 2-cm margin, the researchers conducted an open-label, randomized trial of clinically staged melanoma patients aged 75 years and younger with localized cutaneous melanomas thicker than 2 mm, from January 1992 to May 2004. Patients were treated in Denmark, Estonia, Norway, and Sweden. The findings were published in the Lancet.

Patients were randomized to treatment with a 2-cm (471) or 4-cm excision margin (465). The melanomas were located on the trunk, upper extremities, or lower extremities.

The primary outcome of overall survival was similar between the groups. Over a median 20-year follow-up period, the death rate was approximately 50% in each group (49% in the 2-cm group and 51% in the 4-cm group). Disease-specific survival rates were similar as well. Of the 621 reported deaths, 397 were attributed to melanoma: 192 (48%) in the 2-cm group and 205 (52%) in the 4-cm group.

The study findings were limited by several factors, including a lower-than-expected number of patients, lack of nodal staging during the study period, and a focus only on the surgical margin without recording data on pathological excision margins.

However, the extended follow-up supports the safe use of the 2-cm margin for the treatment of melanomas thicker than 2 mm, the investigators wrote. In addition, results from an ongoing trial comparing 1-cm and 2-cm margins for melanomas at least 1 mm thick may yield more evidence to support still narrower surgical margins for some cutaneous melanomas.

The study notes that guidelines from organizations that include the American National Comprehensive Cancer Network and the American Academy of Dermatology recommend the 2-cm margin for tumors that are thicker than 2 mm.

The study was supported by the Swedish Cancer Society, Stockholm Cancer Society, Swedish Society for Medical Research, and the Stockholm County Council, and by funds from Radiumhemmet Research and Wallström. The authors reported no disclosures.

SOURCE: Utjés D et al. Lancet. 2019 Jul 4. doi: 10.1016/S0140-6736(19)31132-8.

Children exposed to opioids via maternal use during pregnancy were at increased risk of perinatal and postnatal physical and neurodevelopmental disabilities, according to data from more than 8,000 children.

Antonio_Diaz/Thinkstock

Previous studies have shown the increased risk of a range of health problems associated with maternal opioid use, including neonatal abstinence syndrome (NAS), but data on the long-term consequences of in utero opioid exposure are limited, wrote Romuladus E. Azuine, DrPH, MPH, of the U.S. Department of Health and Human Services, Rockville, Md., and colleagues.

In a study published in JAMA Network Open, the researchers reviewed data from 8,509 mother/newborn pairs in the Boston Birth Cohort, a database that included a large urban, low-income, multiethnic population of women who had singleton births at the Boston Medical Center starting in 1998.

A total of 454 infants (5%) experienced prenatal opioid exposure. Mothers were interviewed 48-72 hours after delivery about sociodemographic factors, drug use, smoking, and alcohol use.

The risk of small for gestational age and preterm birth were significantly higher in babies exposed to opioids (OR 1.87 and OR 1.49, respectively), compared with unexposed newborns.

Children’s developmental outcomes were collected starting in 2003 based on electronic medical records. A total of 3,153 mother-newborn pairs were enrolled in a postnatal follow-up study. For preschoolers, prenatal opioid exposure was associated with increased risk of lack of expected physiological development and conduct disorder/emotional disturbance (OR 1.80 and OR 2.13, respectively), compared with unexposed children. School-aged children with prenatal opioid exposure had an increased risk of ADHD (OR 2.55).

The incidence of NAS in the study population was at least 24 per 1,000 hospital births starting in 2004, and peaked at 61 per 1,000 hospital births in 2008, but remained higher than 32 per 1,000 through 2016.

The study findings were limited by several factors including potential misclassification of opioid exposure, confounding from other pregnancy exposures, loss of many participants to follow-up, and a lack of generalizability, but the results support the need for additional research, and show that the prevalence of NAS was approximately 10 times the national average in a subset of low-income, urban, minority women, the researchers said.

“However, the effect of opioids is still difficult to disentangle from effects of other childhood exposures. Policy and programmatic efforts to prevent NAS and mitigate its health consequences require more comprehensive longitudinal and intergenerational research,” they concluded.

The study findings contribute to and support the evidence of poor neurodevelopmental and emotional/behavioral outcomes for children with prenatal exposure to opioids or a history of NAS, Susan Brogly, PhD, MSc, noted in an accompanying editorial. Other studies have shown increased risks for visual impairments including strabismus, reduced visual acuity, and delayed visual maturation.

Dr. Brogly, of Queen’s University, Kingston Health Science Center, Ontario, nonetheless noted that a child’s home environment may modify the impact of prenatal opioid exposure or NAS, as evidence has shown that children with in utero heroin exposure have improved outcomes in healthy home environments.

Although the mechanism for how opioid exposure affects development remains uncertain, she suggested that future research should address “interventions to improve health outcomes in this rapidly growing population of children, regardless of the causal mechanism of impairment.”

Dr. Brogly noted that most of the opioid-using mothers in the study by Azuine et al. were unmarried, non-Hispanic white, and multiparous, and had histories of other substance abuse. She emphasized the need for supportive communities for women at risk of opioid use, who also are more likely to have unstable housing situations and histories of sexual and physical abuse.

“The risks of poor pregnancy and child outcomes in cases of maternal opioid exposure are not because of prenatal opioid exposure alone; ongoing difficult social and environmental circumstances have an important role,” and future interventions should address these circumstances to improve long-term health of high-risk women and their children, she emphasized.

The Boston Birth Cohort study is supported in part by grants from the National Institutes of Health and the U.S. Department of Health and Human Services. None of the authors had financial conflicts to disclose.

Dr. Brogly disclosed grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development outside the submitted work.

SOURCE: Azuine RE et al. JAMA Network Open. 2019 Jun 28. doi: 10.1001/jamanetworkopen.2019.6405; Brogly S. JAMA Network Open. 2019 Jun 28. doi:10.1001/jamanetworkopen.2019.6428.

Children exposed to opioids via maternal use during pregnancy were at increased risk of perinatal and postnatal physical and neurodevelopmental disabilities, according to data from more than 8,000 children.

Antonio_Diaz/Thinkstock

Previous studies have shown the increased risk of a range of health problems associated with maternal opioid use, including neonatal abstinence syndrome (NAS), but data on the long-term consequences of in utero opioid exposure are limited, wrote Romuladus E. Azuine, DrPH, MPH, of the U.S. Department of Health and Human Services, Rockville, Md., and colleagues.

In a study published in JAMA Network Open, the researchers reviewed data from 8,509 mother/newborn pairs in the Boston Birth Cohort, a database that included a large urban, low-income, multiethnic population of women who had singleton births at the Boston Medical Center starting in 1998.

A total of 454 infants (5%) experienced prenatal opioid exposure. Mothers were interviewed 48-72 hours after delivery about sociodemographic factors, drug use, smoking, and alcohol use.

The risk of small for gestational age and preterm birth were significantly higher in babies exposed to opioids (OR 1.87 and OR 1.49, respectively), compared with unexposed newborns.

Children’s developmental outcomes were collected starting in 2003 based on electronic medical records. A total of 3,153 mother-newborn pairs were enrolled in a postnatal follow-up study. For preschoolers, prenatal opioid exposure was associated with increased risk of lack of expected physiological development and conduct disorder/emotional disturbance (OR 1.80 and OR 2.13, respectively), compared with unexposed children. School-aged children with prenatal opioid exposure had an increased risk of ADHD (OR 2.55).

The incidence of NAS in the study population was at least 24 per 1,000 hospital births starting in 2004, and peaked at 61 per 1,000 hospital births in 2008, but remained higher than 32 per 1,000 through 2016.

The study findings were limited by several factors including potential misclassification of opioid exposure, confounding from other pregnancy exposures, loss of many participants to follow-up, and a lack of generalizability, but the results support the need for additional research, and show that the prevalence of NAS was approximately 10 times the national average in a subset of low-income, urban, minority women, the researchers said.

“However, the effect of opioids is still difficult to disentangle from effects of other childhood exposures. Policy and programmatic efforts to prevent NAS and mitigate its health consequences require more comprehensive longitudinal and intergenerational research,” they concluded.

The study findings contribute to and support the evidence of poor neurodevelopmental and emotional/behavioral outcomes for children with prenatal exposure to opioids or a history of NAS, Susan Brogly, PhD, MSc, noted in an accompanying editorial. Other studies have shown increased risks for visual impairments including strabismus, reduced visual acuity, and delayed visual maturation.

Dr. Brogly, of Queen’s University, Kingston Health Science Center, Ontario, nonetheless noted that a child’s home environment may modify the impact of prenatal opioid exposure or NAS, as evidence has shown that children with in utero heroin exposure have improved outcomes in healthy home environments.

Although the mechanism for how opioid exposure affects development remains uncertain, she suggested that future research should address “interventions to improve health outcomes in this rapidly growing population of children, regardless of the causal mechanism of impairment.”

Dr. Brogly noted that most of the opioid-using mothers in the study by Azuine et al. were unmarried, non-Hispanic white, and multiparous, and had histories of other substance abuse. She emphasized the need for supportive communities for women at risk of opioid use, who also are more likely to have unstable housing situations and histories of sexual and physical abuse.

“The risks of poor pregnancy and child outcomes in cases of maternal opioid exposure are not because of prenatal opioid exposure alone; ongoing difficult social and environmental circumstances have an important role,” and future interventions should address these circumstances to improve long-term health of high-risk women and their children, she emphasized.

The Boston Birth Cohort study is supported in part by grants from the National Institutes of Health and the U.S. Department of Health and Human Services. None of the authors had financial conflicts to disclose.

Dr. Brogly disclosed grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development outside the submitted work.

SOURCE: Azuine RE et al. JAMA Network Open. 2019 Jun 28. doi: 10.1001/jamanetworkopen.2019.6405; Brogly S. JAMA Network Open. 2019 Jun 28. doi:10.1001/jamanetworkopen.2019.6428.

Children exposed to opioids via maternal use during pregnancy were at increased risk of perinatal and postnatal physical and neurodevelopmental disabilities, according to data from more than 8,000 children.

Antonio_Diaz/Thinkstock

Previous studies have shown the increased risk of a range of health problems associated with maternal opioid use, including neonatal abstinence syndrome (NAS), but data on the long-term consequences of in utero opioid exposure are limited, wrote Romuladus E. Azuine, DrPH, MPH, of the U.S. Department of Health and Human Services, Rockville, Md., and colleagues.

In a study published in JAMA Network Open, the researchers reviewed data from 8,509 mother/newborn pairs in the Boston Birth Cohort, a database that included a large urban, low-income, multiethnic population of women who had singleton births at the Boston Medical Center starting in 1998.

A total of 454 infants (5%) experienced prenatal opioid exposure. Mothers were interviewed 48-72 hours after delivery about sociodemographic factors, drug use, smoking, and alcohol use.

The risk of small for gestational age and preterm birth were significantly higher in babies exposed to opioids (OR 1.87 and OR 1.49, respectively), compared with unexposed newborns.

Children’s developmental outcomes were collected starting in 2003 based on electronic medical records. A total of 3,153 mother-newborn pairs were enrolled in a postnatal follow-up study. For preschoolers, prenatal opioid exposure was associated with increased risk of lack of expected physiological development and conduct disorder/emotional disturbance (OR 1.80 and OR 2.13, respectively), compared with unexposed children. School-aged children with prenatal opioid exposure had an increased risk of ADHD (OR 2.55).

The incidence of NAS in the study population was at least 24 per 1,000 hospital births starting in 2004, and peaked at 61 per 1,000 hospital births in 2008, but remained higher than 32 per 1,000 through 2016.

The study findings were limited by several factors including potential misclassification of opioid exposure, confounding from other pregnancy exposures, loss of many participants to follow-up, and a lack of generalizability, but the results support the need for additional research, and show that the prevalence of NAS was approximately 10 times the national average in a subset of low-income, urban, minority women, the researchers said.

“However, the effect of opioids is still difficult to disentangle from effects of other childhood exposures. Policy and programmatic efforts to prevent NAS and mitigate its health consequences require more comprehensive longitudinal and intergenerational research,” they concluded.

The study findings contribute to and support the evidence of poor neurodevelopmental and emotional/behavioral outcomes for children with prenatal exposure to opioids or a history of NAS, Susan Brogly, PhD, MSc, noted in an accompanying editorial. Other studies have shown increased risks for visual impairments including strabismus, reduced visual acuity, and delayed visual maturation.

Dr. Brogly, of Queen’s University, Kingston Health Science Center, Ontario, nonetheless noted that a child’s home environment may modify the impact of prenatal opioid exposure or NAS, as evidence has shown that children with in utero heroin exposure have improved outcomes in healthy home environments.

Although the mechanism for how opioid exposure affects development remains uncertain, she suggested that future research should address “interventions to improve health outcomes in this rapidly growing population of children, regardless of the causal mechanism of impairment.”

Dr. Brogly noted that most of the opioid-using mothers in the study by Azuine et al. were unmarried, non-Hispanic white, and multiparous, and had histories of other substance abuse. She emphasized the need for supportive communities for women at risk of opioid use, who also are more likely to have unstable housing situations and histories of sexual and physical abuse.

“The risks of poor pregnancy and child outcomes in cases of maternal opioid exposure are not because of prenatal opioid exposure alone; ongoing difficult social and environmental circumstances have an important role,” and future interventions should address these circumstances to improve long-term health of high-risk women and their children, she emphasized.

The Boston Birth Cohort study is supported in part by grants from the National Institutes of Health and the U.S. Department of Health and Human Services. None of the authors had financial conflicts to disclose.

Dr. Brogly disclosed grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development outside the submitted work.

SOURCE: Azuine RE et al. JAMA Network Open. 2019 Jun 28. doi: 10.1001/jamanetworkopen.2019.6405; Brogly S. JAMA Network Open. 2019 Jun 28. doi:10.1001/jamanetworkopen.2019.6428.

Higher levels of eicosapentaenoic acid, a type of omega-3 polyunsaturated fatty acid, were associated with a significantly reduced risk of heart failure in a large, multi-ethnic cohort of adults in the United States.

Despite the potential benefits of omega-3s eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for heart health, their use has been controversial, although data in a mouse model showed that dietary EPA was protective against heart failure, wrote Robert C. Block, MD, of the University of Rochester (N.Y.), and colleagues. Their report is in the Journal of the American College of Cardiology.

To examine the impact of EPA on heart failure in humans, the researchers used data from the Multi-Ethnic Study of Atherosclerosis (MESA), a longitudinal cohort study of U.S. adults, including those who are African American, Hispanic, Asian, and white.

The researchers included 6,562 MESA participants aged 45-84 years from six communities. Participants underwent a baseline exam between July 2000 and July 2002 that included phospholipid measurements used to identify plasma EPA percentage, and they completed study visits approximately every other year for a median follow-up of 13 years.

A total of 292 heart failure events occurred during the follow-up period: 128 with reduced ejection fraction (EF less than 45%), 110 with preserved ejection fraction (EF at least 45%), and 54 with unknown EF status.

The percent EPA for individuals without heart failure was significantly higher compared with those with heart failure (0.76% vs. 0.69%, P =.005). The association remained significant after the researchers controlled for age, sex, race, body mass index, smoking, diabetes, blood pressure, lipids and lipid-lowering drugs, albuminuria, and the lead fatty acid (defined as the fatty acid with the largest in-cluster correlation).


An EPA level greater than 2.5% was considered sufficient to prevent heart failure based on prior definitions. A total of 73% of the participants had insufficient EPA (less than 1.0%), 2.4% had marginal levels (1.0%-2.5%), and 4.5% had sufficient levels. However, given that EPA levels can be easily and safely increased with the consumption of seafood or fish oil capsules, increasing EPA is a feasible heart failure prevention strategy, the researchers said.

The study included 2,532 white, 1,794 black, 1,442 Hispanic, and 794 Chinese participants. Overall, the fewest Hispanic participants met the criteria for sufficient EPA (1.4%), followed by black (4.4%), white (4.9%), and Chinese participants (9.8%).

The study findings were limited by several factors, including relatively few participants with preserved ejection fractions and sufficient EPA levels, as well as the inability to account for changes in omega-3 levels and other risk factors over time, the researchers noted.

“We consider this study to strongly determine a benefit of EPA exists, but insufficient to determine whether a threshold for %EPA exists near 3%,” they said. They proposed a follow-up study including individuals with higher levels of EPA to better detect a protective effect.

Lead author Dr. Block had no financial conflicts to disclose. Several coauthors received honoraria from Amarin Pharmaceuticals. The study was funded in part by the National Heart, Lung, and Blood Institute.

Higher levels of eicosapentaenoic acid, a type of omega-3 polyunsaturated fatty acid, were associated with a significantly reduced risk of heart failure in a large, multi-ethnic cohort of adults in the United States.

Despite the potential benefits of omega-3s eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for heart health, their use has been controversial, although data in a mouse model showed that dietary EPA was protective against heart failure, wrote Robert C. Block, MD, of the University of Rochester (N.Y.), and colleagues. Their report is in the Journal of the American College of Cardiology.

To examine the impact of EPA on heart failure in humans, the researchers used data from the Multi-Ethnic Study of Atherosclerosis (MESA), a longitudinal cohort study of U.S. adults, including those who are African American, Hispanic, Asian, and white.

The researchers included 6,562 MESA participants aged 45-84 years from six communities. Participants underwent a baseline exam between July 2000 and July 2002 that included phospholipid measurements used to identify plasma EPA percentage, and they completed study visits approximately every other year for a median follow-up of 13 years.

A total of 292 heart failure events occurred during the follow-up period: 128 with reduced ejection fraction (EF less than 45%), 110 with preserved ejection fraction (EF at least 45%), and 54 with unknown EF status.

The percent EPA for individuals without heart failure was significantly higher compared with those with heart failure (0.76% vs. 0.69%, P =.005). The association remained significant after the researchers controlled for age, sex, race, body mass index, smoking, diabetes, blood pressure, lipids and lipid-lowering drugs, albuminuria, and the lead fatty acid (defined as the fatty acid with the largest in-cluster correlation).


An EPA level greater than 2.5% was considered sufficient to prevent heart failure based on prior definitions. A total of 73% of the participants had insufficient EPA (less than 1.0%), 2.4% had marginal levels (1.0%-2.5%), and 4.5% had sufficient levels. However, given that EPA levels can be easily and safely increased with the consumption of seafood or fish oil capsules, increasing EPA is a feasible heart failure prevention strategy, the researchers said.

The study included 2,532 white, 1,794 black, 1,442 Hispanic, and 794 Chinese participants. Overall, the fewest Hispanic participants met the criteria for sufficient EPA (1.4%), followed by black (4.4%), white (4.9%), and Chinese participants (9.8%).

The study findings were limited by several factors, including relatively few participants with preserved ejection fractions and sufficient EPA levels, as well as the inability to account for changes in omega-3 levels and other risk factors over time, the researchers noted.

“We consider this study to strongly determine a benefit of EPA exists, but insufficient to determine whether a threshold for %EPA exists near 3%,” they said. They proposed a follow-up study including individuals with higher levels of EPA to better detect a protective effect.

Lead author Dr. Block had no financial conflicts to disclose. Several coauthors received honoraria from Amarin Pharmaceuticals. The study was funded in part by the National Heart, Lung, and Blood Institute.

Higher levels of eicosapentaenoic acid, a type of omega-3 polyunsaturated fatty acid, were associated with a significantly reduced risk of heart failure in a large, multi-ethnic cohort of adults in the United States.

Despite the potential benefits of omega-3s eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for heart health, their use has been controversial, although data in a mouse model showed that dietary EPA was protective against heart failure, wrote Robert C. Block, MD, of the University of Rochester (N.Y.), and colleagues. Their report is in the Journal of the American College of Cardiology.

To examine the impact of EPA on heart failure in humans, the researchers used data from the Multi-Ethnic Study of Atherosclerosis (MESA), a longitudinal cohort study of U.S. adults, including those who are African American, Hispanic, Asian, and white.

The researchers included 6,562 MESA participants aged 45-84 years from six communities. Participants underwent a baseline exam between July 2000 and July 2002 that included phospholipid measurements used to identify plasma EPA percentage, and they completed study visits approximately every other year for a median follow-up of 13 years.

A total of 292 heart failure events occurred during the follow-up period: 128 with reduced ejection fraction (EF less than 45%), 110 with preserved ejection fraction (EF at least 45%), and 54 with unknown EF status.

The percent EPA for individuals without heart failure was significantly higher compared with those with heart failure (0.76% vs. 0.69%, P =.005). The association remained significant after the researchers controlled for age, sex, race, body mass index, smoking, diabetes, blood pressure, lipids and lipid-lowering drugs, albuminuria, and the lead fatty acid (defined as the fatty acid with the largest in-cluster correlation).


An EPA level greater than 2.5% was considered sufficient to prevent heart failure based on prior definitions. A total of 73% of the participants had insufficient EPA (less than 1.0%), 2.4% had marginal levels (1.0%-2.5%), and 4.5% had sufficient levels. However, given that EPA levels can be easily and safely increased with the consumption of seafood or fish oil capsules, increasing EPA is a feasible heart failure prevention strategy, the researchers said.

The study included 2,532 white, 1,794 black, 1,442 Hispanic, and 794 Chinese participants. Overall, the fewest Hispanic participants met the criteria for sufficient EPA (1.4%), followed by black (4.4%), white (4.9%), and Chinese participants (9.8%).

The study findings were limited by several factors, including relatively few participants with preserved ejection fractions and sufficient EPA levels, as well as the inability to account for changes in omega-3 levels and other risk factors over time, the researchers noted.

“We consider this study to strongly determine a benefit of EPA exists, but insufficient to determine whether a threshold for %EPA exists near 3%,” they said. They proposed a follow-up study including individuals with higher levels of EPA to better detect a protective effect.

Lead author Dr. Block had no financial conflicts to disclose. Several coauthors received honoraria from Amarin Pharmaceuticals. The study was funded in part by the National Heart, Lung, and Blood Institute.

Isotretinoin use may increase vulnerability to psychiatric conditions, but available evidence does not support a causal relationship, on the basis of data from a retrospective study of 17,829 psychiatric adverse events reported to the Food and Drug Administration over 2 decades.

“Although one study highlighted consistent reporting of depression and suicide in patients taking isotretinoin in the United States from 1982 to 2000, few studies have examined reports of psychiatric adverse events at the national level since 2000,” wrote Sean Singer of Harvard University, Boston, and his colleagues.

In a study published in JAMA Dermatology, the researchers reviewed data from the FDA’s Adverse Event Reporting System between 1997 and 2017.

A total of 17,829 psychiatric adverse events in which isotretinoin was the primary suspect drug were reported during the study period. The researchers classified the events into 12 categories; the most common were depressive disorders (42%), emotional lability (17%), and anxiety (14%). The number of reported psychiatric adverse events was similar between men and women (8,936 and 8,362 events, respectively).

The researchers also identified 2,278 reports of suicidal ideation, 602 reports of attempted suicide, and 368 reports of completed suicide.

In addition, the researchers examined data from the iPLEDGE program and found completed suicide rates of 8.4 per 100,000 patients in 2009 and 5.6 per 100,000 patients in 2010. However, these rates were lower than national suicide rates in the general population of 11.8 per 100,000 people in 2009 and 12.1 per 100,000 people in 2010.

Patient age was available for 13,553 adverse event reports, and patients aged 10-19 years accounted for 53% of the reports overall and 58% of completed suicides for which age was reported.

The high number of psychiatric adverse events in the youngest age group “could reflect more isotretinoin prescriptions in this age group or may suggest that teenagers are particularly vulnerable to psychiatric adverse events while taking isotretinoin,” the researchers said.

The findings were limited by several factors, including the reliance on proper clinician reports to the Adverse Event Reporting System database and the separation of some psychiatric terms into categories that may reflect symptoms of other psychiatric diagnoses, the researchers said.

However, “Our data showed high numbers of reports of emotional lability, anxiety disorders, insomnia, self-injurious behavior, and psychotic disorders with isotretinoin as the primary suspect drug,” they noted.

“Although no causal link has been established between isotretinoin and psychiatric adverse events, it is important to recognize that there are data that suggest patients using this drug may be vulnerable to a number of psychiatric conditions” and that monthly iPLEDGE visits are an opportunity to screen patients for these conditions, they said.

They also stressed that “the risk of psychiatric adverse events in patients taking isotretinoin must be considered in the context of a known increased risk of suicidal ideation in patients with acne independent of isotretinoin therapy.”

Mr. Singer had no financial conflicts to disclose. Study coauthor John S. Barbieri, MD, disclosed partial salary support from Pfizer and grand support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and Arash Mostaghimi, MD, disclosed personal fees from Pfizer.

SOURCE: Singer S et al. JAMA Dermatol. 2019. Jul 3. doi: 10.1001/jamadermatol.2019.1416.

Isotretinoin use may increase vulnerability to psychiatric conditions, but available evidence does not support a causal relationship, on the basis of data from a retrospective study of 17,829 psychiatric adverse events reported to the Food and Drug Administration over 2 decades.

“Although one study highlighted consistent reporting of depression and suicide in patients taking isotretinoin in the United States from 1982 to 2000, few studies have examined reports of psychiatric adverse events at the national level since 2000,” wrote Sean Singer of Harvard University, Boston, and his colleagues.

In a study published in JAMA Dermatology, the researchers reviewed data from the FDA’s Adverse Event Reporting System between 1997 and 2017.

A total of 17,829 psychiatric adverse events in which isotretinoin was the primary suspect drug were reported during the study period. The researchers classified the events into 12 categories; the most common were depressive disorders (42%), emotional lability (17%), and anxiety (14%). The number of reported psychiatric adverse events was similar between men and women (8,936 and 8,362 events, respectively).

The researchers also identified 2,278 reports of suicidal ideation, 602 reports of attempted suicide, and 368 reports of completed suicide.

In addition, the researchers examined data from the iPLEDGE program and found completed suicide rates of 8.4 per 100,000 patients in 2009 and 5.6 per 100,000 patients in 2010. However, these rates were lower than national suicide rates in the general population of 11.8 per 100,000 people in 2009 and 12.1 per 100,000 people in 2010.

Patient age was available for 13,553 adverse event reports, and patients aged 10-19 years accounted for 53% of the reports overall and 58% of completed suicides for which age was reported.

The high number of psychiatric adverse events in the youngest age group “could reflect more isotretinoin prescriptions in this age group or may suggest that teenagers are particularly vulnerable to psychiatric adverse events while taking isotretinoin,” the researchers said.

The findings were limited by several factors, including the reliance on proper clinician reports to the Adverse Event Reporting System database and the separation of some psychiatric terms into categories that may reflect symptoms of other psychiatric diagnoses, the researchers said.

However, “Our data showed high numbers of reports of emotional lability, anxiety disorders, insomnia, self-injurious behavior, and psychotic disorders with isotretinoin as the primary suspect drug,” they noted.

“Although no causal link has been established between isotretinoin and psychiatric adverse events, it is important to recognize that there are data that suggest patients using this drug may be vulnerable to a number of psychiatric conditions” and that monthly iPLEDGE visits are an opportunity to screen patients for these conditions, they said.

They also stressed that “the risk of psychiatric adverse events in patients taking isotretinoin must be considered in the context of a known increased risk of suicidal ideation in patients with acne independent of isotretinoin therapy.”

Mr. Singer had no financial conflicts to disclose. Study coauthor John S. Barbieri, MD, disclosed partial salary support from Pfizer and grand support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and Arash Mostaghimi, MD, disclosed personal fees from Pfizer.

SOURCE: Singer S et al. JAMA Dermatol. 2019. Jul 3. doi: 10.1001/jamadermatol.2019.1416.

Isotretinoin use may increase vulnerability to psychiatric conditions, but available evidence does not support a causal relationship, on the basis of data from a retrospective study of 17,829 psychiatric adverse events reported to the Food and Drug Administration over 2 decades.

“Although one study highlighted consistent reporting of depression and suicide in patients taking isotretinoin in the United States from 1982 to 2000, few studies have examined reports of psychiatric adverse events at the national level since 2000,” wrote Sean Singer of Harvard University, Boston, and his colleagues.

In a study published in JAMA Dermatology, the researchers reviewed data from the FDA’s Adverse Event Reporting System between 1997 and 2017.

A total of 17,829 psychiatric adverse events in which isotretinoin was the primary suspect drug were reported during the study period. The researchers classified the events into 12 categories; the most common were depressive disorders (42%), emotional lability (17%), and anxiety (14%). The number of reported psychiatric adverse events was similar between men and women (8,936 and 8,362 events, respectively).

The researchers also identified 2,278 reports of suicidal ideation, 602 reports of attempted suicide, and 368 reports of completed suicide.

In addition, the researchers examined data from the iPLEDGE program and found completed suicide rates of 8.4 per 100,000 patients in 2009 and 5.6 per 100,000 patients in 2010. However, these rates were lower than national suicide rates in the general population of 11.8 per 100,000 people in 2009 and 12.1 per 100,000 people in 2010.

Patient age was available for 13,553 adverse event reports, and patients aged 10-19 years accounted for 53% of the reports overall and 58% of completed suicides for which age was reported.

The high number of psychiatric adverse events in the youngest age group “could reflect more isotretinoin prescriptions in this age group or may suggest that teenagers are particularly vulnerable to psychiatric adverse events while taking isotretinoin,” the researchers said.

The findings were limited by several factors, including the reliance on proper clinician reports to the Adverse Event Reporting System database and the separation of some psychiatric terms into categories that may reflect symptoms of other psychiatric diagnoses, the researchers said.

However, “Our data showed high numbers of reports of emotional lability, anxiety disorders, insomnia, self-injurious behavior, and psychotic disorders with isotretinoin as the primary suspect drug,” they noted.

“Although no causal link has been established between isotretinoin and psychiatric adverse events, it is important to recognize that there are data that suggest patients using this drug may be vulnerable to a number of psychiatric conditions” and that monthly iPLEDGE visits are an opportunity to screen patients for these conditions, they said.

They also stressed that “the risk of psychiatric adverse events in patients taking isotretinoin must be considered in the context of a known increased risk of suicidal ideation in patients with acne independent of isotretinoin therapy.”

Mr. Singer had no financial conflicts to disclose. Study coauthor John S. Barbieri, MD, disclosed partial salary support from Pfizer and grand support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and Arash Mostaghimi, MD, disclosed personal fees from Pfizer.

SOURCE: Singer S et al. JAMA Dermatol. 2019. Jul 3. doi: 10.1001/jamadermatol.2019.1416.