Jim Kling

SEATTLE – Psoriasis is a complex condition, made more difficult by comorbidities. Psoriatic arthritis is the most common and is frequently discussed. But mental health issues and cardiovascular events also co-occur and can present major complications, according to Jashin Wu, MD, founder and CEO of the Dermatology Research and Education Foundation, who discussed psoriasis comorbidities at the annual Coastal Dermatology Symposium.

Mental health–related issues associated with psoriasis (Psychiatr Danub. 2017 Dec;29[4]:401-6) include sleep disorders (prevalence, 62%), sexual dysfunction (46%), personality disorder (35%), anxiety (30%), adjustment (29%), and depressive disorders (28%); 25% of patients have an accompanying substance abuse disorder. Suicidal ideation and suicidal depression are particularly concerning, and a meta-analysis (J Am Acad Dermatol. 2017 Sep;77[3]:425-40.e2) showed a 44% increased risk of suicidal ideation associated with psoriasis.

Such problems aren’t surprising, since psoriasis is a lifelong disease, and many patients’ symptoms aren’t adequately controlled. “A lot of these patients get topical therapies, which is probably not enough, especially if they have severe disease,” said Dr. Wu in an interview.

Dermatologists can sometimes be nervous about biologics because of concerns over increased risk of infection or cancer. That can lead to conservative, topical treatment. Dr. Wu feels that rare side effects shouldn’t deter from aggressive treatment, when appropriate. “It’s better to treat the patient to make sure they’re clear, which may improve their comorbidities as well. In general, if you’re worried, you can send them to other specialists to do monitoring,” Dr. Wu said in the interview.

Different treatment methods may influence mental health outcomes, according to the PSOLAR study (J Am Acad Dermatol. 2018 Jan;78[1]:70-80). It examined the issue prospectively with over 12,000 psoriasis patients, and found a depression incidence of 3.01 per 100-patient years when treated with biologics, compared with 5.85 for phototherapy and 5.70 for conventional therapy. Put another way, exposure to biologics was associated with a reduced risk of depression, compared with conventional therapies (hazard ratio, 0.76; P = .0367). “It seems to show that biologics have a better improvement of depression symptoms, compared to phototherapy or oral therapy,” said Dr. Wu.

Those results suggest that dermatologists should be on the lookout for mental health issues, though that is a challenge for someone not trained in the field. Dr. Wu takes a simple approach. “I like just asking open-ended questions, like how they’re doing, and if you get a sense that maybe they’re depressed, ask more specific questions about their mood, how they’re feeling, how things are at work, how things are at home.” When things aren’t right, “the key is to try to get them on something that’s going to clear them very quickly. If it’s severe disease, use a biologic that’s going to clear it very quickly,” he added.

Unfortunately, just being clear isn’t a complete guarantee of improved mental health. Dr. Wu had two patients who committed suicide despite significant skin improvement. Patients may have between-visit flare-ups, or regular injections may be a reminder that psoriasis is an ongoing health struggle. Or patients may have other psychological concerns. That underlines the importance of awareness of mental health issues. “You don’t need to refer everyone [to a mental health specialist], but you should have a rolodex where you have someone you can send a patient to if you’re worried,” said Dr. Wu.

As with mental health issues, psoriasis patients are also at elevated risk for a wide range of cardiovascular comorbidities, such as diabetes, dyslipidemia, and high blood pressure. “As a dermatologist, you may not want to screen for these things, but you can send them to their primary care doctor or a cardiologist,” Dr. Wu said in the interview.

Also like mental health issues, there is evidence that treatment with biologics may have an outsized protective effect. One study (J Eur Acad Dermatol Venereol. 2018 Mar 24. doi: 10.1111/jdv.14951) led by Dr. Wu showed that treatment with a tumor necrosis factor (TNF)–alpha inhibitor led to a significant reduction in major adverse cardiac events, compared with topical therapy (propensity score–adjusted HR, 0.80; 95% CI, 0.66-0.98), while phototherapy or oral therapy trended towards an increased risk (adjusted HR, 1.13; 95% CI, 1.00-1.28). Another analysis (J Am Acad Dermatol. 2017 Jan;76[1]:81-90) from Dr. Wu’s group that included about 380,000 psoriasis patients found that treatment with TNF-alpha inhibitors was associated with fewer major cardiovascular events, compared with treatment with methotrexate (adjusted HR, 0.55; P less than .0001). Individual analyses showed associated reductions in stroke or transient ischemic attack (aHR, 0.55; P less than .0001), unstable angina (aHR, 0.58; P = .0024), and MI (aHR, 0.49; P = .0002). TNF-alpha inhibitors also seem to beat out phototherapy with respect to major cardiovascular events (aHR, 0.77; P = .046. J Am Acad Dermatol. 2018 Jul;79[1]:60-6).

More direct evidence of the benefit of biologics comes from the CANTOS trial (N Engl J Med. 2017 Sep 21;377[12]:1119-31), which randomized more than 10,000 patients with cryopyrin-associated periodic syndromes to receive the IL-1 beta-blocker canakinumab or placebo. Canakinumab was associated with significant reductions in nonfatal MI, nonfatal stroke, or cardiovascular death at 150 mg (HR, 0.85; P = .021) and 300 mg (HR, 0.86; P = .031), but not at 50 mg.

The bottom line, said Dr. Wu, is that psoriasis and psoriatic arthritis should be treated early with TNF-alpha inhibitors or IL-17 inhibitors in an effort to improve mental health, cardiovascular, and psoriatic arthritis outcomes.

Dr. Wu has been a consultant or speaker for, or done research on behalf of, AbbVie, Almirall, Amgen, Bristol-Myers Squibb, Celgene, Dermira, Dr. Reddy’s Laboratories, Eli Lilly, Janssen, LEO Pharma, Novartis, Regeneron, Sun Pharmaceutical, UCB, and Valeant Pharmaceuticals North America.

The meeting is jointly presented by the University of Louisville and Global Academy for Medical Education. This publication and Global Academy for Medical Education are owned by the same parent company.

SEATTLE – Psoriasis is a complex condition, made more difficult by comorbidities. Psoriatic arthritis is the most common and is frequently discussed. But mental health issues and cardiovascular events also co-occur and can present major complications, according to Jashin Wu, MD, founder and CEO of the Dermatology Research and Education Foundation, who discussed psoriasis comorbidities at the annual Coastal Dermatology Symposium.

Mental health–related issues associated with psoriasis (Psychiatr Danub. 2017 Dec;29[4]:401-6) include sleep disorders (prevalence, 62%), sexual dysfunction (46%), personality disorder (35%), anxiety (30%), adjustment (29%), and depressive disorders (28%); 25% of patients have an accompanying substance abuse disorder. Suicidal ideation and suicidal depression are particularly concerning, and a meta-analysis (J Am Acad Dermatol. 2017 Sep;77[3]:425-40.e2) showed a 44% increased risk of suicidal ideation associated with psoriasis.

Such problems aren’t surprising, since psoriasis is a lifelong disease, and many patients’ symptoms aren’t adequately controlled. “A lot of these patients get topical therapies, which is probably not enough, especially if they have severe disease,” said Dr. Wu in an interview.

Dermatologists can sometimes be nervous about biologics because of concerns over increased risk of infection or cancer. That can lead to conservative, topical treatment. Dr. Wu feels that rare side effects shouldn’t deter from aggressive treatment, when appropriate. “It’s better to treat the patient to make sure they’re clear, which may improve their comorbidities as well. In general, if you’re worried, you can send them to other specialists to do monitoring,” Dr. Wu said in the interview.

Different treatment methods may influence mental health outcomes, according to the PSOLAR study (J Am Acad Dermatol. 2018 Jan;78[1]:70-80). It examined the issue prospectively with over 12,000 psoriasis patients, and found a depression incidence of 3.01 per 100-patient years when treated with biologics, compared with 5.85 for phototherapy and 5.70 for conventional therapy. Put another way, exposure to biologics was associated with a reduced risk of depression, compared with conventional therapies (hazard ratio, 0.76; P = .0367). “It seems to show that biologics have a better improvement of depression symptoms, compared to phototherapy or oral therapy,” said Dr. Wu.

Those results suggest that dermatologists should be on the lookout for mental health issues, though that is a challenge for someone not trained in the field. Dr. Wu takes a simple approach. “I like just asking open-ended questions, like how they’re doing, and if you get a sense that maybe they’re depressed, ask more specific questions about their mood, how they’re feeling, how things are at work, how things are at home.” When things aren’t right, “the key is to try to get them on something that’s going to clear them very quickly. If it’s severe disease, use a biologic that’s going to clear it very quickly,” he added.

Unfortunately, just being clear isn’t a complete guarantee of improved mental health. Dr. Wu had two patients who committed suicide despite significant skin improvement. Patients may have between-visit flare-ups, or regular injections may be a reminder that psoriasis is an ongoing health struggle. Or patients may have other psychological concerns. That underlines the importance of awareness of mental health issues. “You don’t need to refer everyone [to a mental health specialist], but you should have a rolodex where you have someone you can send a patient to if you’re worried,” said Dr. Wu.

As with mental health issues, psoriasis patients are also at elevated risk for a wide range of cardiovascular comorbidities, such as diabetes, dyslipidemia, and high blood pressure. “As a dermatologist, you may not want to screen for these things, but you can send them to their primary care doctor or a cardiologist,” Dr. Wu said in the interview.

Also like mental health issues, there is evidence that treatment with biologics may have an outsized protective effect. One study (J Eur Acad Dermatol Venereol. 2018 Mar 24. doi: 10.1111/jdv.14951) led by Dr. Wu showed that treatment with a tumor necrosis factor (TNF)–alpha inhibitor led to a significant reduction in major adverse cardiac events, compared with topical therapy (propensity score–adjusted HR, 0.80; 95% CI, 0.66-0.98), while phototherapy or oral therapy trended towards an increased risk (adjusted HR, 1.13; 95% CI, 1.00-1.28). Another analysis (J Am Acad Dermatol. 2017 Jan;76[1]:81-90) from Dr. Wu’s group that included about 380,000 psoriasis patients found that treatment with TNF-alpha inhibitors was associated with fewer major cardiovascular events, compared with treatment with methotrexate (adjusted HR, 0.55; P less than .0001). Individual analyses showed associated reductions in stroke or transient ischemic attack (aHR, 0.55; P less than .0001), unstable angina (aHR, 0.58; P = .0024), and MI (aHR, 0.49; P = .0002). TNF-alpha inhibitors also seem to beat out phototherapy with respect to major cardiovascular events (aHR, 0.77; P = .046. J Am Acad Dermatol. 2018 Jul;79[1]:60-6).

More direct evidence of the benefit of biologics comes from the CANTOS trial (N Engl J Med. 2017 Sep 21;377[12]:1119-31), which randomized more than 10,000 patients with cryopyrin-associated periodic syndromes to receive the IL-1 beta-blocker canakinumab or placebo. Canakinumab was associated with significant reductions in nonfatal MI, nonfatal stroke, or cardiovascular death at 150 mg (HR, 0.85; P = .021) and 300 mg (HR, 0.86; P = .031), but not at 50 mg.

The bottom line, said Dr. Wu, is that psoriasis and psoriatic arthritis should be treated early with TNF-alpha inhibitors or IL-17 inhibitors in an effort to improve mental health, cardiovascular, and psoriatic arthritis outcomes.

Dr. Wu has been a consultant or speaker for, or done research on behalf of, AbbVie, Almirall, Amgen, Bristol-Myers Squibb, Celgene, Dermira, Dr. Reddy’s Laboratories, Eli Lilly, Janssen, LEO Pharma, Novartis, Regeneron, Sun Pharmaceutical, UCB, and Valeant Pharmaceuticals North America.

The meeting is jointly presented by the University of Louisville and Global Academy for Medical Education. This publication and Global Academy for Medical Education are owned by the same parent company.

SEATTLE – Psoriasis is a complex condition, made more difficult by comorbidities. Psoriatic arthritis is the most common and is frequently discussed. But mental health issues and cardiovascular events also co-occur and can present major complications, according to Jashin Wu, MD, founder and CEO of the Dermatology Research and Education Foundation, who discussed psoriasis comorbidities at the annual Coastal Dermatology Symposium.

Mental health–related issues associated with psoriasis (Psychiatr Danub. 2017 Dec;29[4]:401-6) include sleep disorders (prevalence, 62%), sexual dysfunction (46%), personality disorder (35%), anxiety (30%), adjustment (29%), and depressive disorders (28%); 25% of patients have an accompanying substance abuse disorder. Suicidal ideation and suicidal depression are particularly concerning, and a meta-analysis (J Am Acad Dermatol. 2017 Sep;77[3]:425-40.e2) showed a 44% increased risk of suicidal ideation associated with psoriasis.

Such problems aren’t surprising, since psoriasis is a lifelong disease, and many patients’ symptoms aren’t adequately controlled. “A lot of these patients get topical therapies, which is probably not enough, especially if they have severe disease,” said Dr. Wu in an interview.

Dermatologists can sometimes be nervous about biologics because of concerns over increased risk of infection or cancer. That can lead to conservative, topical treatment. Dr. Wu feels that rare side effects shouldn’t deter from aggressive treatment, when appropriate. “It’s better to treat the patient to make sure they’re clear, which may improve their comorbidities as well. In general, if you’re worried, you can send them to other specialists to do monitoring,” Dr. Wu said in the interview.

Different treatment methods may influence mental health outcomes, according to the PSOLAR study (J Am Acad Dermatol. 2018 Jan;78[1]:70-80). It examined the issue prospectively with over 12,000 psoriasis patients, and found a depression incidence of 3.01 per 100-patient years when treated with biologics, compared with 5.85 for phototherapy and 5.70 for conventional therapy. Put another way, exposure to biologics was associated with a reduced risk of depression, compared with conventional therapies (hazard ratio, 0.76; P = .0367). “It seems to show that biologics have a better improvement of depression symptoms, compared to phototherapy or oral therapy,” said Dr. Wu.

Those results suggest that dermatologists should be on the lookout for mental health issues, though that is a challenge for someone not trained in the field. Dr. Wu takes a simple approach. “I like just asking open-ended questions, like how they’re doing, and if you get a sense that maybe they’re depressed, ask more specific questions about their mood, how they’re feeling, how things are at work, how things are at home.” When things aren’t right, “the key is to try to get them on something that’s going to clear them very quickly. If it’s severe disease, use a biologic that’s going to clear it very quickly,” he added.

Unfortunately, just being clear isn’t a complete guarantee of improved mental health. Dr. Wu had two patients who committed suicide despite significant skin improvement. Patients may have between-visit flare-ups, or regular injections may be a reminder that psoriasis is an ongoing health struggle. Or patients may have other psychological concerns. That underlines the importance of awareness of mental health issues. “You don’t need to refer everyone [to a mental health specialist], but you should have a rolodex where you have someone you can send a patient to if you’re worried,” said Dr. Wu.

As with mental health issues, psoriasis patients are also at elevated risk for a wide range of cardiovascular comorbidities, such as diabetes, dyslipidemia, and high blood pressure. “As a dermatologist, you may not want to screen for these things, but you can send them to their primary care doctor or a cardiologist,” Dr. Wu said in the interview.

Also like mental health issues, there is evidence that treatment with biologics may have an outsized protective effect. One study (J Eur Acad Dermatol Venereol. 2018 Mar 24. doi: 10.1111/jdv.14951) led by Dr. Wu showed that treatment with a tumor necrosis factor (TNF)–alpha inhibitor led to a significant reduction in major adverse cardiac events, compared with topical therapy (propensity score–adjusted HR, 0.80; 95% CI, 0.66-0.98), while phototherapy or oral therapy trended towards an increased risk (adjusted HR, 1.13; 95% CI, 1.00-1.28). Another analysis (J Am Acad Dermatol. 2017 Jan;76[1]:81-90) from Dr. Wu’s group that included about 380,000 psoriasis patients found that treatment with TNF-alpha inhibitors was associated with fewer major cardiovascular events, compared with treatment with methotrexate (adjusted HR, 0.55; P less than .0001). Individual analyses showed associated reductions in stroke or transient ischemic attack (aHR, 0.55; P less than .0001), unstable angina (aHR, 0.58; P = .0024), and MI (aHR, 0.49; P = .0002). TNF-alpha inhibitors also seem to beat out phototherapy with respect to major cardiovascular events (aHR, 0.77; P = .046. J Am Acad Dermatol. 2018 Jul;79[1]:60-6).

More direct evidence of the benefit of biologics comes from the CANTOS trial (N Engl J Med. 2017 Sep 21;377[12]:1119-31), which randomized more than 10,000 patients with cryopyrin-associated periodic syndromes to receive the IL-1 beta-blocker canakinumab or placebo. Canakinumab was associated with significant reductions in nonfatal MI, nonfatal stroke, or cardiovascular death at 150 mg (HR, 0.85; P = .021) and 300 mg (HR, 0.86; P = .031), but not at 50 mg.

The bottom line, said Dr. Wu, is that psoriasis and psoriatic arthritis should be treated early with TNF-alpha inhibitors or IL-17 inhibitors in an effort to improve mental health, cardiovascular, and psoriatic arthritis outcomes.

Dr. Wu has been a consultant or speaker for, or done research on behalf of, AbbVie, Almirall, Amgen, Bristol-Myers Squibb, Celgene, Dermira, Dr. Reddy’s Laboratories, Eli Lilly, Janssen, LEO Pharma, Novartis, Regeneron, Sun Pharmaceutical, UCB, and Valeant Pharmaceuticals North America.

The meeting is jointly presented by the University of Louisville and Global Academy for Medical Education. This publication and Global Academy for Medical Education are owned by the same parent company.

SEATTLE – The availability of biologics for treating psoriasis and psoriatic arthritis has exploded in recent years, with 11 biologics now approved by the Food and Drug Administration. Targets include four separate mechanisms: inhibition of tumor necrosis factor (TNF), interleukin (IL) 23, IL-12/23, and IL-17. The surfeit of treatment options can be a little overwhelming.

“It can be confusing. We have a lot of choices, but the good news is that most of our choices are excellent, and they treat both psoriasis and psoriatic arthritis. That’s very important because, when we think of our psoriasis patients, we need to think not only about their skin but also their joint involvement. Assessment of psoriatic arthritis will drive some of our therapeutic [decisions],” April Armstrong, MD, professor of dermatology at the University of Southern California, Los Angeles, said at the annual Coastal Dermatology Symposium.

In April, the American Academy of Dermatology came to the rescue with comprehensive guidelines. Aside from general advice, the guidelines “provide tips for monitoring as well as dose escalation, which will be very helpful in daily practice,” Dr. Armstrong said in an interview.

The best studied of the biologics with respect to psoriasis and psoriatic arthritis are the IL-17 inhibitors and TNF inhibitors, she said. While TNF inhibitors have traditionally been the treatment of choice for both conditions, “I think these days, people realize that IL-17 inhibitors can be just as good.”

A head-to-head study of the IL-17 inhibitor ixekizumab and the TNF inhibitor adalimumab, presented at the EULAR Congress, looked at a combined outcome of skin and joints and found ixekizumab to be superior, though the study design’s inclusion of a skin outcome may have favored ixekizumab (Ann Rheum Dis. 2019 Jun. doi: 10.1136/annrheumdis-2019-eular.8709).

A few other head-to-head studies have been performed, but properly ranking all 11 biologics would require dozens of clinical trials. At the American Academy of Dermatology meeting last March, Dr. Armstrong presented the results of a network meta-analysis of anti-TNF agents, anti-interleukin agents, anti–phosphodiesterase 4 agents, and fumaric acid esters (J Am Acad Dermatol. doi: 10.1016/j.jaad.2019.06.488). That study, funded by AbbVie, compared the individual agents to a collective placebo group and concluded that anti-interleukin agents generate the highest level of PASI 90/100 response rate. Risankizumab, ixekizumab, brodalumab, and guselkumab, all IL inhibitors, achieved the best marks over the primary response period.

The AAD guidelines include recommendations for tests to be done upon initiation of a biologic, including a tuberculosis test, complete blood count, comprehensive metabolic panel, and tests for hepatitis B and C. TB testing should be performed annually during treatment.

The guidelines also include recommendations for dose escalation, which can provide leverage for getting coverage approved. “One can use those guidelines to show payers how dose escalation can be done, so that [physicians] can potentially get more access to medications for their patients,” Dr. Armstrong said at the meeting jointly presented by the University of Louisville and Global Academy for Medical Education.

The guideline also ranks the existing evidence supporting individual biologics for the treatment of psoriasis subtypes. For example, for the treatment of moderate to severe scalp psoriasis, etanercept and guselkumab have consistent and good-quality patient-oriented evidence supporting them; infliximab, adalimumab, secukinumab, and ixekizumab are recommended based on inconsistent or limited quality patient-oriented evidence; and ustekinumab is supported only by consensus opinion, case studies, or disease-oriented evidence. The guidelines provide similar categorization of biologics for the treatment of moderate to severe plaque type palmoplantar psoriasis, moderate to severe psoriasis affecting the nails, adults with pustular or erythrodermic psoriasis, and adults with psoriatic arthritis.

Dr. Armstrong is a research investigator and/or advisor to AbbVie, Janssen, Lily, LEO Pharma, Novartis, UCB, Ortho Dermatologics, Dermera, Regeneron, BMS, Dermavant, and KHK. This publication and Global Academy for Medical Education are owned by the same parent company.

SEATTLE – The availability of biologics for treating psoriasis and psoriatic arthritis has exploded in recent years, with 11 biologics now approved by the Food and Drug Administration. Targets include four separate mechanisms: inhibition of tumor necrosis factor (TNF), interleukin (IL) 23, IL-12/23, and IL-17. The surfeit of treatment options can be a little overwhelming.

“It can be confusing. We have a lot of choices, but the good news is that most of our choices are excellent, and they treat both psoriasis and psoriatic arthritis. That’s very important because, when we think of our psoriasis patients, we need to think not only about their skin but also their joint involvement. Assessment of psoriatic arthritis will drive some of our therapeutic [decisions],” April Armstrong, MD, professor of dermatology at the University of Southern California, Los Angeles, said at the annual Coastal Dermatology Symposium.

In April, the American Academy of Dermatology came to the rescue with comprehensive guidelines. Aside from general advice, the guidelines “provide tips for monitoring as well as dose escalation, which will be very helpful in daily practice,” Dr. Armstrong said in an interview.

The best studied of the biologics with respect to psoriasis and psoriatic arthritis are the IL-17 inhibitors and TNF inhibitors, she said. While TNF inhibitors have traditionally been the treatment of choice for both conditions, “I think these days, people realize that IL-17 inhibitors can be just as good.”

A head-to-head study of the IL-17 inhibitor ixekizumab and the TNF inhibitor adalimumab, presented at the EULAR Congress, looked at a combined outcome of skin and joints and found ixekizumab to be superior, though the study design’s inclusion of a skin outcome may have favored ixekizumab (Ann Rheum Dis. 2019 Jun. doi: 10.1136/annrheumdis-2019-eular.8709).

A few other head-to-head studies have been performed, but properly ranking all 11 biologics would require dozens of clinical trials. At the American Academy of Dermatology meeting last March, Dr. Armstrong presented the results of a network meta-analysis of anti-TNF agents, anti-interleukin agents, anti–phosphodiesterase 4 agents, and fumaric acid esters (J Am Acad Dermatol. doi: 10.1016/j.jaad.2019.06.488). That study, funded by AbbVie, compared the individual agents to a collective placebo group and concluded that anti-interleukin agents generate the highest level of PASI 90/100 response rate. Risankizumab, ixekizumab, brodalumab, and guselkumab, all IL inhibitors, achieved the best marks over the primary response period.

The AAD guidelines include recommendations for tests to be done upon initiation of a biologic, including a tuberculosis test, complete blood count, comprehensive metabolic panel, and tests for hepatitis B and C. TB testing should be performed annually during treatment.

The guidelines also include recommendations for dose escalation, which can provide leverage for getting coverage approved. “One can use those guidelines to show payers how dose escalation can be done, so that [physicians] can potentially get more access to medications for their patients,” Dr. Armstrong said at the meeting jointly presented by the University of Louisville and Global Academy for Medical Education.

The guideline also ranks the existing evidence supporting individual biologics for the treatment of psoriasis subtypes. For example, for the treatment of moderate to severe scalp psoriasis, etanercept and guselkumab have consistent and good-quality patient-oriented evidence supporting them; infliximab, adalimumab, secukinumab, and ixekizumab are recommended based on inconsistent or limited quality patient-oriented evidence; and ustekinumab is supported only by consensus opinion, case studies, or disease-oriented evidence. The guidelines provide similar categorization of biologics for the treatment of moderate to severe plaque type palmoplantar psoriasis, moderate to severe psoriasis affecting the nails, adults with pustular or erythrodermic psoriasis, and adults with psoriatic arthritis.

Dr. Armstrong is a research investigator and/or advisor to AbbVie, Janssen, Lily, LEO Pharma, Novartis, UCB, Ortho Dermatologics, Dermera, Regeneron, BMS, Dermavant, and KHK. This publication and Global Academy for Medical Education are owned by the same parent company.

SEATTLE – The availability of biologics for treating psoriasis and psoriatic arthritis has exploded in recent years, with 11 biologics now approved by the Food and Drug Administration. Targets include four separate mechanisms: inhibition of tumor necrosis factor (TNF), interleukin (IL) 23, IL-12/23, and IL-17. The surfeit of treatment options can be a little overwhelming.

“It can be confusing. We have a lot of choices, but the good news is that most of our choices are excellent, and they treat both psoriasis and psoriatic arthritis. That’s very important because, when we think of our psoriasis patients, we need to think not only about their skin but also their joint involvement. Assessment of psoriatic arthritis will drive some of our therapeutic [decisions],” April Armstrong, MD, professor of dermatology at the University of Southern California, Los Angeles, said at the annual Coastal Dermatology Symposium.

In April, the American Academy of Dermatology came to the rescue with comprehensive guidelines. Aside from general advice, the guidelines “provide tips for monitoring as well as dose escalation, which will be very helpful in daily practice,” Dr. Armstrong said in an interview.

The best studied of the biologics with respect to psoriasis and psoriatic arthritis are the IL-17 inhibitors and TNF inhibitors, she said. While TNF inhibitors have traditionally been the treatment of choice for both conditions, “I think these days, people realize that IL-17 inhibitors can be just as good.”

A head-to-head study of the IL-17 inhibitor ixekizumab and the TNF inhibitor adalimumab, presented at the EULAR Congress, looked at a combined outcome of skin and joints and found ixekizumab to be superior, though the study design’s inclusion of a skin outcome may have favored ixekizumab (Ann Rheum Dis. 2019 Jun. doi: 10.1136/annrheumdis-2019-eular.8709).

A few other head-to-head studies have been performed, but properly ranking all 11 biologics would require dozens of clinical trials. At the American Academy of Dermatology meeting last March, Dr. Armstrong presented the results of a network meta-analysis of anti-TNF agents, anti-interleukin agents, anti–phosphodiesterase 4 agents, and fumaric acid esters (J Am Acad Dermatol. doi: 10.1016/j.jaad.2019.06.488). That study, funded by AbbVie, compared the individual agents to a collective placebo group and concluded that anti-interleukin agents generate the highest level of PASI 90/100 response rate. Risankizumab, ixekizumab, brodalumab, and guselkumab, all IL inhibitors, achieved the best marks over the primary response period.

The AAD guidelines include recommendations for tests to be done upon initiation of a biologic, including a tuberculosis test, complete blood count, comprehensive metabolic panel, and tests for hepatitis B and C. TB testing should be performed annually during treatment.

The guidelines also include recommendations for dose escalation, which can provide leverage for getting coverage approved. “One can use those guidelines to show payers how dose escalation can be done, so that [physicians] can potentially get more access to medications for their patients,” Dr. Armstrong said at the meeting jointly presented by the University of Louisville and Global Academy for Medical Education.

The guideline also ranks the existing evidence supporting individual biologics for the treatment of psoriasis subtypes. For example, for the treatment of moderate to severe scalp psoriasis, etanercept and guselkumab have consistent and good-quality patient-oriented evidence supporting them; infliximab, adalimumab, secukinumab, and ixekizumab are recommended based on inconsistent or limited quality patient-oriented evidence; and ustekinumab is supported only by consensus opinion, case studies, or disease-oriented evidence. The guidelines provide similar categorization of biologics for the treatment of moderate to severe plaque type palmoplantar psoriasis, moderate to severe psoriasis affecting the nails, adults with pustular or erythrodermic psoriasis, and adults with psoriatic arthritis.

Dr. Armstrong is a research investigator and/or advisor to AbbVie, Janssen, Lily, LEO Pharma, Novartis, UCB, Ortho Dermatologics, Dermera, Regeneron, BMS, Dermavant, and KHK. This publication and Global Academy for Medical Education are owned by the same parent company.

SEATTLE – Photodermatoses are comparatively rare, and dermatologists may sometimes be reluctant to tackle them, according to Vincent DeLeo, MD, of the department of dermatology at the University of Southern California, Los Angeles, who discussed common diagnoses at the annual Coastal Dermatology Symposium.

“They’re not common bread-and-butter dermatitis, like acne rosacea. Many people feel uncomfortable trying to work out the differential diagnosis when they see someone who comes in with what either the patient or the physician thinks is a reaction to the sun,” Dr. DeLeo said in an interview at the meeting.

“Usually, the best clue is the distribution of the rash or lesion,” which often are on the backs of the hands or on the arms from the sleeves down, he added. “When you see that, you should think of a photosensitive eruption,” and consider a differential diagnosis, using “certain tests, asking questions, and looking at the morphology and distribution of the reaction.”

The most common of the photodermatoses is polymorphous light eruption, which typically occurs in people on vacation, often among those who live in temperate climates and react violently to sun overexposure. “You usually have to rule out things like connective tissue disease by getting serology,” Dr. DeLeo noted in the interview.

In general, these patients either present with a reaction or describe a rash that has since cleared up. When a patient is describing a problem that has disappeared, he or she may have a photo of the reaction on their phone, which can be helpful, he said at the meeting jointly presented by the University of Louisville and Global Academy for Medical Education.

Some photodermatoses are characterized by tell-tale rashes indicative of a connective tissue disease like lupus or dermatomyositis, which can be followed up with biopsy and serology to confirm a diagnosis, said Dr. DeLeo, who is also professor emeritus of dermatology at the Icahn School of Medicine at Mount Sinai, New York. Other patterns, such as blisters on the hands, should prompt tests for porphyria cutanea tarda, which requires a 24-hour urine test to confirm.

But reactions in sun-exposed areas can also be caused by drug-induced photosensitivity and drugs such as NSAIDs, antibiotics, and diuretics, among others, Dr. DeLeo said.

Another common reaction can occur with exposure to photosensitizing plant materials, resulting in blisters combined with altered pigmentation. Most frequently, these reactions are caused by exposure to limes, which contain psoralens that absorb light and produce the reaction. “That is a clinical diagnosis and we can recognize that because, like poison ivy, it is usually a streaky kind of reaction in a distinct pattern. You don’t need [additional] tests for that,” he said. This can occur, for example, after making cocktails, he said, describing an example of parents who had been mixing drinks and then picked up their child. Later, they brought the child to the ED with a hand-shaped rash, and treating physicians contacted social services out of fears of child abuse.

In some cases, patients who present with no rash can elicit the problem. Solar urticaria can produce hives on demand – ask a patient to go out in the sun and return after a few minutes, and a rash will generally appear, Dr. DeLeo advised.

Patients might want to take steps to avoid such problems and there are several options available to do so, Dr. DeLeo noted. There is some evidence of efficacy for photoprotection for an extract from a fern plant found in Central and South America, a product called Heliocare, in a study sponsored by the manufacturer, Ferndale Healthcare (J Clin Aesthet Dermatol. 2015 Feb;8[2]:19-23). Patients can also undergo two or three treatments of phototherapy for 3-4 weeks in advance of a trip in order to “harden” the skin and reduce the chances of an overreaction.

Dr. DeLeo presented a simplified guide to use when considering differential diagnoses in patients with photodermatoses.

• Solar urticaria occurs quickly upon exposure and is short lived.
• Polymorphous light eruption usually occurs during a vacation and does not affect the face.
• A sun-related eczematous rash affecting the face, which recurs, is typically photoallergy to sunscreen.
• A chronic, severe dermatitis seen in a photodistribution pattern could be chronic actinic dermatitis. The patient should undergo phototesting. A biopsy of a severe case may resemble lymphoma.
• In photosensitive individuals with an uncertain diagnosis, serology testing for connective tissue disease should be performed to rule out lupus or dermatomyositis.
• When the patient has a rash in only sun-exposed areas, as well as a history of exposure to photosensitizing drugs, the drug should be discontinued to see if the rash disappears.
• Porphyria cutanea tarda is diagnosed with a 24-hour urine test that reveals at least five times normal uroporphyrin levels, along with hemochromatosis polymorphisms. Levels of uroporphyrin that are elevated but not five times normal are suggestive of pseudoporphyria.
• Phototoxic contact dermatitis caused by plants often results in unusual distributions.
• Hispanic individuals with a photodistributed rash, especially in the presence of cheilitis, may have actinic prurigo.

Dr. DeLeo is a consultant for Estee Lauder. The annual Coastal Dermatology Symposium is jointly presented by the University of Louisville and Global Academy for Medical Education. This publication and Global Academy for Medical Education are owned by the same parent company.

SEATTLE – Photodermatoses are comparatively rare, and dermatologists may sometimes be reluctant to tackle them, according to Vincent DeLeo, MD, of the department of dermatology at the University of Southern California, Los Angeles, who discussed common diagnoses at the annual Coastal Dermatology Symposium.

“They’re not common bread-and-butter dermatitis, like acne rosacea. Many people feel uncomfortable trying to work out the differential diagnosis when they see someone who comes in with what either the patient or the physician thinks is a reaction to the sun,” Dr. DeLeo said in an interview at the meeting.

“Usually, the best clue is the distribution of the rash or lesion,” which often are on the backs of the hands or on the arms from the sleeves down, he added. “When you see that, you should think of a photosensitive eruption,” and consider a differential diagnosis, using “certain tests, asking questions, and looking at the morphology and distribution of the reaction.”

The most common of the photodermatoses is polymorphous light eruption, which typically occurs in people on vacation, often among those who live in temperate climates and react violently to sun overexposure. “You usually have to rule out things like connective tissue disease by getting serology,” Dr. DeLeo noted in the interview.

In general, these patients either present with a reaction or describe a rash that has since cleared up. When a patient is describing a problem that has disappeared, he or she may have a photo of the reaction on their phone, which can be helpful, he said at the meeting jointly presented by the University of Louisville and Global Academy for Medical Education.

Some photodermatoses are characterized by tell-tale rashes indicative of a connective tissue disease like lupus or dermatomyositis, which can be followed up with biopsy and serology to confirm a diagnosis, said Dr. DeLeo, who is also professor emeritus of dermatology at the Icahn School of Medicine at Mount Sinai, New York. Other patterns, such as blisters on the hands, should prompt tests for porphyria cutanea tarda, which requires a 24-hour urine test to confirm.

But reactions in sun-exposed areas can also be caused by drug-induced photosensitivity and drugs such as NSAIDs, antibiotics, and diuretics, among others, Dr. DeLeo said.

Another common reaction can occur with exposure to photosensitizing plant materials, resulting in blisters combined with altered pigmentation. Most frequently, these reactions are caused by exposure to limes, which contain psoralens that absorb light and produce the reaction. “That is a clinical diagnosis and we can recognize that because, like poison ivy, it is usually a streaky kind of reaction in a distinct pattern. You don’t need [additional] tests for that,” he said. This can occur, for example, after making cocktails, he said, describing an example of parents who had been mixing drinks and then picked up their child. Later, they brought the child to the ED with a hand-shaped rash, and treating physicians contacted social services out of fears of child abuse.

In some cases, patients who present with no rash can elicit the problem. Solar urticaria can produce hives on demand – ask a patient to go out in the sun and return after a few minutes, and a rash will generally appear, Dr. DeLeo advised.

Patients might want to take steps to avoid such problems and there are several options available to do so, Dr. DeLeo noted. There is some evidence of efficacy for photoprotection for an extract from a fern plant found in Central and South America, a product called Heliocare, in a study sponsored by the manufacturer, Ferndale Healthcare (J Clin Aesthet Dermatol. 2015 Feb;8[2]:19-23). Patients can also undergo two or three treatments of phototherapy for 3-4 weeks in advance of a trip in order to “harden” the skin and reduce the chances of an overreaction.

Dr. DeLeo presented a simplified guide to use when considering differential diagnoses in patients with photodermatoses.

• Solar urticaria occurs quickly upon exposure and is short lived.
• Polymorphous light eruption usually occurs during a vacation and does not affect the face.
• A sun-related eczematous rash affecting the face, which recurs, is typically photoallergy to sunscreen.
• A chronic, severe dermatitis seen in a photodistribution pattern could be chronic actinic dermatitis. The patient should undergo phototesting. A biopsy of a severe case may resemble lymphoma.
• In photosensitive individuals with an uncertain diagnosis, serology testing for connective tissue disease should be performed to rule out lupus or dermatomyositis.
• When the patient has a rash in only sun-exposed areas, as well as a history of exposure to photosensitizing drugs, the drug should be discontinued to see if the rash disappears.
• Porphyria cutanea tarda is diagnosed with a 24-hour urine test that reveals at least five times normal uroporphyrin levels, along with hemochromatosis polymorphisms. Levels of uroporphyrin that are elevated but not five times normal are suggestive of pseudoporphyria.
• Phototoxic contact dermatitis caused by plants often results in unusual distributions.
• Hispanic individuals with a photodistributed rash, especially in the presence of cheilitis, may have actinic prurigo.

Dr. DeLeo is a consultant for Estee Lauder. The annual Coastal Dermatology Symposium is jointly presented by the University of Louisville and Global Academy for Medical Education. This publication and Global Academy for Medical Education are owned by the same parent company.

SEATTLE – Photodermatoses are comparatively rare, and dermatologists may sometimes be reluctant to tackle them, according to Vincent DeLeo, MD, of the department of dermatology at the University of Southern California, Los Angeles, who discussed common diagnoses at the annual Coastal Dermatology Symposium.

“They’re not common bread-and-butter dermatitis, like acne rosacea. Many people feel uncomfortable trying to work out the differential diagnosis when they see someone who comes in with what either the patient or the physician thinks is a reaction to the sun,” Dr. DeLeo said in an interview at the meeting.

“Usually, the best clue is the distribution of the rash or lesion,” which often are on the backs of the hands or on the arms from the sleeves down, he added. “When you see that, you should think of a photosensitive eruption,” and consider a differential diagnosis, using “certain tests, asking questions, and looking at the morphology and distribution of the reaction.”

The most common of the photodermatoses is polymorphous light eruption, which typically occurs in people on vacation, often among those who live in temperate climates and react violently to sun overexposure. “You usually have to rule out things like connective tissue disease by getting serology,” Dr. DeLeo noted in the interview.

In general, these patients either present with a reaction or describe a rash that has since cleared up. When a patient is describing a problem that has disappeared, he or she may have a photo of the reaction on their phone, which can be helpful, he said at the meeting jointly presented by the University of Louisville and Global Academy for Medical Education.

Some photodermatoses are characterized by tell-tale rashes indicative of a connective tissue disease like lupus or dermatomyositis, which can be followed up with biopsy and serology to confirm a diagnosis, said Dr. DeLeo, who is also professor emeritus of dermatology at the Icahn School of Medicine at Mount Sinai, New York. Other patterns, such as blisters on the hands, should prompt tests for porphyria cutanea tarda, which requires a 24-hour urine test to confirm.

But reactions in sun-exposed areas can also be caused by drug-induced photosensitivity and drugs such as NSAIDs, antibiotics, and diuretics, among others, Dr. DeLeo said.

Another common reaction can occur with exposure to photosensitizing plant materials, resulting in blisters combined with altered pigmentation. Most frequently, these reactions are caused by exposure to limes, which contain psoralens that absorb light and produce the reaction. “That is a clinical diagnosis and we can recognize that because, like poison ivy, it is usually a streaky kind of reaction in a distinct pattern. You don’t need [additional] tests for that,” he said. This can occur, for example, after making cocktails, he said, describing an example of parents who had been mixing drinks and then picked up their child. Later, they brought the child to the ED with a hand-shaped rash, and treating physicians contacted social services out of fears of child abuse.

In some cases, patients who present with no rash can elicit the problem. Solar urticaria can produce hives on demand – ask a patient to go out in the sun and return after a few minutes, and a rash will generally appear, Dr. DeLeo advised.

Patients might want to take steps to avoid such problems and there are several options available to do so, Dr. DeLeo noted. There is some evidence of efficacy for photoprotection for an extract from a fern plant found in Central and South America, a product called Heliocare, in a study sponsored by the manufacturer, Ferndale Healthcare (J Clin Aesthet Dermatol. 2015 Feb;8[2]:19-23). Patients can also undergo two or three treatments of phototherapy for 3-4 weeks in advance of a trip in order to “harden” the skin and reduce the chances of an overreaction.

Dr. DeLeo presented a simplified guide to use when considering differential diagnoses in patients with photodermatoses.

• Solar urticaria occurs quickly upon exposure and is short lived.
• Polymorphous light eruption usually occurs during a vacation and does not affect the face.
• A sun-related eczematous rash affecting the face, which recurs, is typically photoallergy to sunscreen.
• A chronic, severe dermatitis seen in a photodistribution pattern could be chronic actinic dermatitis. The patient should undergo phototesting. A biopsy of a severe case may resemble lymphoma.
• In photosensitive individuals with an uncertain diagnosis, serology testing for connective tissue disease should be performed to rule out lupus or dermatomyositis.
• When the patient has a rash in only sun-exposed areas, as well as a history of exposure to photosensitizing drugs, the drug should be discontinued to see if the rash disappears.
• Porphyria cutanea tarda is diagnosed with a 24-hour urine test that reveals at least five times normal uroporphyrin levels, along with hemochromatosis polymorphisms. Levels of uroporphyrin that are elevated but not five times normal are suggestive of pseudoporphyria.
• Phototoxic contact dermatitis caused by plants often results in unusual distributions.
• Hispanic individuals with a photodistributed rash, especially in the presence of cheilitis, may have actinic prurigo.

Dr. DeLeo is a consultant for Estee Lauder. The annual Coastal Dermatology Symposium is jointly presented by the University of Louisville and Global Academy for Medical Education. This publication and Global Academy for Medical Education are owned by the same parent company.

A new study found no association between sleep position during pregnancy and risk of adverse pregnancy outcomes such as stillbirth, small-for-gestational-age (SGA) newborns, and gestational hypertensive disorders. The finding, published in the October issue of Obstetrics & Gynecology, conflicts with previous retrospective case-control studies that suggested left-side sleeping may lead to reduced risk. The disagreement may be due to the prospective nature of the new study, which followed 8,706 women over 4 years.

©Brand X Pictures/thinkstockphotos.com

Right-side or back sleeping had attracted suspicion because of its potential to compress uterine blood vessels and decrease uterine blood flow, and various public health campaigns urge pregnant women to sleep on their left side. Although case-control studies backed up those worries, those retrospective approaches can suffer from limitations including recall bias, in which grieving mothers overreport suspect sleeping behaviors, perhaps in search of an explanation for their loss.

Prospective analyses can counter some of those limitations. The researchers, led by Robert Silver, MD, of the University of Utah, Salt Lake City, conducted a secondary analysis of the nuMoM2b study, examining adverse pregnancy outcomes and risk factors. It was a multicenter observational cohort study of 8,706 nulliparous women with singleton gestations who completed two sleep questionnaires: one between 6 and 13 weeks of gestation, and one between 22 and 29 weeks.

Adverse outcomes occurred in 1,903 women, including 178 cases of both SGA and hypertensive disorders, 8 with SGA plus stillbirth, 3 with hypertensive disorders plus stillbirth, and 2 cases with all three complications.

The researchers found no association between any adverse outcomes and sleep position either at the first visit in early pregnancy (adjusted odds ratio, 1.00; 95% confidence interval, 0.89-1.14) or the third visit in midpregnancy (aOR, 0.99; 95% CI, 0.89-1.11). Propensity score matching to adjust non-left lateral positioning to the composite outcome also showed no association.

In midpregnancy, there was an association between non-left lateral sleeping and reduced risk of stillbirth (aOR, 0.27; 95% CI, 0.09-0.75). “This observation is likely spurious owing to small numbers of stillbirths, Dr. Silver and associates said.

A post hoc analysis indicated that the study was sufficiently powered to detect clinically meaningful risks; ORs of 1.2 for hypertensive disorders, 1.23 for SGA, 2.4 for stillbirth, and 1.2 for the composite outcome.
 

Let sleeping mothers lie

Pregnant women have enough on their minds. They shouldn’t have to worry about sleep position as well, according to Nathan Fox, MD, professor of obstetrics, gynecology, and reproductive science at Icahn School of Medicine at Mount Sinai, New York, and Emily Oster, PhD, economist at Brown University, Providence, R.I., who wrote an accompanying editorial.

It may seem harmless to direct women to sleep on their left side even if it has no benefit, but restricting a woman’s sleep options may leave her less well rested at a time when she is about to enter a period of sleep deprivation, as well as contribute to general discomfort, in their opinion.

Also, in the rare cases of a bad outcome, advice based on limited or poor quality evidence contributes to “devastating and unwarranted feelings of responsibility and guilt, and this harm to women already suffering from sadness and despair must not be minimized,” they said.

The study received funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and grants from multiple universities. One author received research funding from Kyndermed through her institution. Another receives royalties from UpToDate.com. Dr. Fox and Dr. Oster have no relevant financial disclosures.

SOURCES: Silver RM et al. Obstet Gynecol. 2019. doi: 10.1097/AOG.0000000000003458; Fox N and Oster E. Obstet. Gynecol. 2019 Oct. doi: 10.1097/AOG.0000000000003466

A new study found no association between sleep position during pregnancy and risk of adverse pregnancy outcomes such as stillbirth, small-for-gestational-age (SGA) newborns, and gestational hypertensive disorders. The finding, published in the October issue of Obstetrics & Gynecology, conflicts with previous retrospective case-control studies that suggested left-side sleeping may lead to reduced risk. The disagreement may be due to the prospective nature of the new study, which followed 8,706 women over 4 years.

©Brand X Pictures/thinkstockphotos.com

Right-side or back sleeping had attracted suspicion because of its potential to compress uterine blood vessels and decrease uterine blood flow, and various public health campaigns urge pregnant women to sleep on their left side. Although case-control studies backed up those worries, those retrospective approaches can suffer from limitations including recall bias, in which grieving mothers overreport suspect sleeping behaviors, perhaps in search of an explanation for their loss.

Prospective analyses can counter some of those limitations. The researchers, led by Robert Silver, MD, of the University of Utah, Salt Lake City, conducted a secondary analysis of the nuMoM2b study, examining adverse pregnancy outcomes and risk factors. It was a multicenter observational cohort study of 8,706 nulliparous women with singleton gestations who completed two sleep questionnaires: one between 6 and 13 weeks of gestation, and one between 22 and 29 weeks.

Adverse outcomes occurred in 1,903 women, including 178 cases of both SGA and hypertensive disorders, 8 with SGA plus stillbirth, 3 with hypertensive disorders plus stillbirth, and 2 cases with all three complications.

The researchers found no association between any adverse outcomes and sleep position either at the first visit in early pregnancy (adjusted odds ratio, 1.00; 95% confidence interval, 0.89-1.14) or the third visit in midpregnancy (aOR, 0.99; 95% CI, 0.89-1.11). Propensity score matching to adjust non-left lateral positioning to the composite outcome also showed no association.

In midpregnancy, there was an association between non-left lateral sleeping and reduced risk of stillbirth (aOR, 0.27; 95% CI, 0.09-0.75). “This observation is likely spurious owing to small numbers of stillbirths, Dr. Silver and associates said.

A post hoc analysis indicated that the study was sufficiently powered to detect clinically meaningful risks; ORs of 1.2 for hypertensive disorders, 1.23 for SGA, 2.4 for stillbirth, and 1.2 for the composite outcome.
 

Let sleeping mothers lie

Pregnant women have enough on their minds. They shouldn’t have to worry about sleep position as well, according to Nathan Fox, MD, professor of obstetrics, gynecology, and reproductive science at Icahn School of Medicine at Mount Sinai, New York, and Emily Oster, PhD, economist at Brown University, Providence, R.I., who wrote an accompanying editorial.

It may seem harmless to direct women to sleep on their left side even if it has no benefit, but restricting a woman’s sleep options may leave her less well rested at a time when she is about to enter a period of sleep deprivation, as well as contribute to general discomfort, in their opinion.

Also, in the rare cases of a bad outcome, advice based on limited or poor quality evidence contributes to “devastating and unwarranted feelings of responsibility and guilt, and this harm to women already suffering from sadness and despair must not be minimized,” they said.

The study received funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and grants from multiple universities. One author received research funding from Kyndermed through her institution. Another receives royalties from UpToDate.com. Dr. Fox and Dr. Oster have no relevant financial disclosures.

SOURCES: Silver RM et al. Obstet Gynecol. 2019. doi: 10.1097/AOG.0000000000003458; Fox N and Oster E. Obstet. Gynecol. 2019 Oct. doi: 10.1097/AOG.0000000000003466

A new study found no association between sleep position during pregnancy and risk of adverse pregnancy outcomes such as stillbirth, small-for-gestational-age (SGA) newborns, and gestational hypertensive disorders. The finding, published in the October issue of Obstetrics & Gynecology, conflicts with previous retrospective case-control studies that suggested left-side sleeping may lead to reduced risk. The disagreement may be due to the prospective nature of the new study, which followed 8,706 women over 4 years.

©Brand X Pictures/thinkstockphotos.com

Right-side or back sleeping had attracted suspicion because of its potential to compress uterine blood vessels and decrease uterine blood flow, and various public health campaigns urge pregnant women to sleep on their left side. Although case-control studies backed up those worries, those retrospective approaches can suffer from limitations including recall bias, in which grieving mothers overreport suspect sleeping behaviors, perhaps in search of an explanation for their loss.

Prospective analyses can counter some of those limitations. The researchers, led by Robert Silver, MD, of the University of Utah, Salt Lake City, conducted a secondary analysis of the nuMoM2b study, examining adverse pregnancy outcomes and risk factors. It was a multicenter observational cohort study of 8,706 nulliparous women with singleton gestations who completed two sleep questionnaires: one between 6 and 13 weeks of gestation, and one between 22 and 29 weeks.

Adverse outcomes occurred in 1,903 women, including 178 cases of both SGA and hypertensive disorders, 8 with SGA plus stillbirth, 3 with hypertensive disorders plus stillbirth, and 2 cases with all three complications.

The researchers found no association between any adverse outcomes and sleep position either at the first visit in early pregnancy (adjusted odds ratio, 1.00; 95% confidence interval, 0.89-1.14) or the third visit in midpregnancy (aOR, 0.99; 95% CI, 0.89-1.11). Propensity score matching to adjust non-left lateral positioning to the composite outcome also showed no association.

In midpregnancy, there was an association between non-left lateral sleeping and reduced risk of stillbirth (aOR, 0.27; 95% CI, 0.09-0.75). “This observation is likely spurious owing to small numbers of stillbirths, Dr. Silver and associates said.

A post hoc analysis indicated that the study was sufficiently powered to detect clinically meaningful risks; ORs of 1.2 for hypertensive disorders, 1.23 for SGA, 2.4 for stillbirth, and 1.2 for the composite outcome.
 

Let sleeping mothers lie

Pregnant women have enough on their minds. They shouldn’t have to worry about sleep position as well, according to Nathan Fox, MD, professor of obstetrics, gynecology, and reproductive science at Icahn School of Medicine at Mount Sinai, New York, and Emily Oster, PhD, economist at Brown University, Providence, R.I., who wrote an accompanying editorial.

It may seem harmless to direct women to sleep on their left side even if it has no benefit, but restricting a woman’s sleep options may leave her less well rested at a time when she is about to enter a period of sleep deprivation, as well as contribute to general discomfort, in their opinion.

Also, in the rare cases of a bad outcome, advice based on limited or poor quality evidence contributes to “devastating and unwarranted feelings of responsibility and guilt, and this harm to women already suffering from sadness and despair must not be minimized,” they said.

The study received funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and grants from multiple universities. One author received research funding from Kyndermed through her institution. Another receives royalties from UpToDate.com. Dr. Fox and Dr. Oster have no relevant financial disclosures.

SOURCES: Silver RM et al. Obstet Gynecol. 2019. doi: 10.1097/AOG.0000000000003458; Fox N and Oster E. Obstet. Gynecol. 2019 Oct. doi: 10.1097/AOG.0000000000003466

Antimalarial retinal complications occurred in about 5% of patients with systemic lupus erythematosus (SLE) exposed to hydroxychloroquine or chloroquine during an average of nearly 13 years of follow-up, without any cases of retinal toxicity occurring within the first 5 years of use, according to findings from a case-control study.

The rate of retinal complications observed in the study is slightly lower or within the range reported in other studies of antimalarial use by patients with SLE, first author Elvis-Raymond Mukwikwi of the University of Montreal and coauthors from McGill University, Montreal, reported in the Journal of Rheumatology.

Hydroxychloroquine (HCQ) and chloroquine (CQ) are commonly used to treat SLE and rheumatoid arthritis, and they are being investigated for use in diabetes, cancer, and cardiovascular disease. However, in rare cases, the drugs can lead to irreversible retinopathy.

To better understand the factors associated with retinopathy, the researchers analyzed data from 326 records obtained from the McGill University Health Center Lupus Clinic Registry. A total of 18 patients (5.5%) had confirmed retinal toxicity, and the investigators matched each of these patients to 3 control patients with SLE and exposure to HCQ/CQ who did not develop retinopathy and had the same duration of SLE and age at SLE diagnosis.

The minimum number of years of HCQ/CQ exposure before retinopathy developed was 8 years, and the maximum number was 33 years. Overall, 17 retinopathy cases had exposure to HCQ, and 12 of those cases (71%) received average doses higher than current recommendations. Eight patients were exposed to average daily doses of HCQ higher than 5 mg/kg and four to average daily doses of CQ above 2.3 mg/kg. Exposure to an average dose higher than currently recommended occurred in 49% of controls. The exposure to doses higher than current recommendations was “not surprising given that these were issued in 2016 and most of our patients had been taking HCQ for longer than this,” the authors wrote.

High-dose exposure was common, with 83% of controls and all retinopathy cases having been exposed to HCQ/CQ doses above recommendations, as determined during at least one annual assessment.

Among patients with retinopathy, exposure to CQ was three times more frequent than it was for those without the condition (39% vs. 13%; 95% confidence interval, 1.8%-52%), although all of the patients exposed to CQ also were exposed to long periods of HCQ, making it impossible to determine retinopathy risk to CQ exposure alone.

The researchers also found gaps in monitoring. In the 5 years before discontinuation of medication, 53% of cases had missed one or more annual ophthalmologic assessments to screen for retinal damage, compared with 75% of controls.

Concomitant renal damage, believed to be a risk factor for retinal toxicity, occurred more often in the retinopathy group, though the difference failed to meet statistical significance (23% versus 15%). Patients with retinopathy were less likely to be Caucasian (61% versus 74%), but this also did not reach statistical significance.

The authors did not disclose information on funding or conflicts of interest.

SOURCE: Mukwikwi ER et al. J Rheumatol. 2019 Sep 1. doi: 10.3899/jrheum.181102

Antimalarial retinal complications occurred in about 5% of patients with systemic lupus erythematosus (SLE) exposed to hydroxychloroquine or chloroquine during an average of nearly 13 years of follow-up, without any cases of retinal toxicity occurring within the first 5 years of use, according to findings from a case-control study.

The rate of retinal complications observed in the study is slightly lower or within the range reported in other studies of antimalarial use by patients with SLE, first author Elvis-Raymond Mukwikwi of the University of Montreal and coauthors from McGill University, Montreal, reported in the Journal of Rheumatology.

Hydroxychloroquine (HCQ) and chloroquine (CQ) are commonly used to treat SLE and rheumatoid arthritis, and they are being investigated for use in diabetes, cancer, and cardiovascular disease. However, in rare cases, the drugs can lead to irreversible retinopathy.

To better understand the factors associated with retinopathy, the researchers analyzed data from 326 records obtained from the McGill University Health Center Lupus Clinic Registry. A total of 18 patients (5.5%) had confirmed retinal toxicity, and the investigators matched each of these patients to 3 control patients with SLE and exposure to HCQ/CQ who did not develop retinopathy and had the same duration of SLE and age at SLE diagnosis.

The minimum number of years of HCQ/CQ exposure before retinopathy developed was 8 years, and the maximum number was 33 years. Overall, 17 retinopathy cases had exposure to HCQ, and 12 of those cases (71%) received average doses higher than current recommendations. Eight patients were exposed to average daily doses of HCQ higher than 5 mg/kg and four to average daily doses of CQ above 2.3 mg/kg. Exposure to an average dose higher than currently recommended occurred in 49% of controls. The exposure to doses higher than current recommendations was “not surprising given that these were issued in 2016 and most of our patients had been taking HCQ for longer than this,” the authors wrote.

High-dose exposure was common, with 83% of controls and all retinopathy cases having been exposed to HCQ/CQ doses above recommendations, as determined during at least one annual assessment.

Among patients with retinopathy, exposure to CQ was three times more frequent than it was for those without the condition (39% vs. 13%; 95% confidence interval, 1.8%-52%), although all of the patients exposed to CQ also were exposed to long periods of HCQ, making it impossible to determine retinopathy risk to CQ exposure alone.

The researchers also found gaps in monitoring. In the 5 years before discontinuation of medication, 53% of cases had missed one or more annual ophthalmologic assessments to screen for retinal damage, compared with 75% of controls.

Concomitant renal damage, believed to be a risk factor for retinal toxicity, occurred more often in the retinopathy group, though the difference failed to meet statistical significance (23% versus 15%). Patients with retinopathy were less likely to be Caucasian (61% versus 74%), but this also did not reach statistical significance.

The authors did not disclose information on funding or conflicts of interest.

SOURCE: Mukwikwi ER et al. J Rheumatol. 2019 Sep 1. doi: 10.3899/jrheum.181102

Antimalarial retinal complications occurred in about 5% of patients with systemic lupus erythematosus (SLE) exposed to hydroxychloroquine or chloroquine during an average of nearly 13 years of follow-up, without any cases of retinal toxicity occurring within the first 5 years of use, according to findings from a case-control study.

The rate of retinal complications observed in the study is slightly lower or within the range reported in other studies of antimalarial use by patients with SLE, first author Elvis-Raymond Mukwikwi of the University of Montreal and coauthors from McGill University, Montreal, reported in the Journal of Rheumatology.

Hydroxychloroquine (HCQ) and chloroquine (CQ) are commonly used to treat SLE and rheumatoid arthritis, and they are being investigated for use in diabetes, cancer, and cardiovascular disease. However, in rare cases, the drugs can lead to irreversible retinopathy.

To better understand the factors associated with retinopathy, the researchers analyzed data from 326 records obtained from the McGill University Health Center Lupus Clinic Registry. A total of 18 patients (5.5%) had confirmed retinal toxicity, and the investigators matched each of these patients to 3 control patients with SLE and exposure to HCQ/CQ who did not develop retinopathy and had the same duration of SLE and age at SLE diagnosis.

The minimum number of years of HCQ/CQ exposure before retinopathy developed was 8 years, and the maximum number was 33 years. Overall, 17 retinopathy cases had exposure to HCQ, and 12 of those cases (71%) received average doses higher than current recommendations. Eight patients were exposed to average daily doses of HCQ higher than 5 mg/kg and four to average daily doses of CQ above 2.3 mg/kg. Exposure to an average dose higher than currently recommended occurred in 49% of controls. The exposure to doses higher than current recommendations was “not surprising given that these were issued in 2016 and most of our patients had been taking HCQ for longer than this,” the authors wrote.

High-dose exposure was common, with 83% of controls and all retinopathy cases having been exposed to HCQ/CQ doses above recommendations, as determined during at least one annual assessment.

Among patients with retinopathy, exposure to CQ was three times more frequent than it was for those without the condition (39% vs. 13%; 95% confidence interval, 1.8%-52%), although all of the patients exposed to CQ also were exposed to long periods of HCQ, making it impossible to determine retinopathy risk to CQ exposure alone.

The researchers also found gaps in monitoring. In the 5 years before discontinuation of medication, 53% of cases had missed one or more annual ophthalmologic assessments to screen for retinal damage, compared with 75% of controls.

Concomitant renal damage, believed to be a risk factor for retinal toxicity, occurred more often in the retinopathy group, though the difference failed to meet statistical significance (23% versus 15%). Patients with retinopathy were less likely to be Caucasian (61% versus 74%), but this also did not reach statistical significance.

The authors did not disclose information on funding or conflicts of interest.

SOURCE: Mukwikwi ER et al. J Rheumatol. 2019 Sep 1. doi: 10.3899/jrheum.181102

A new guideline from the American Gastroenterological Association (AGA) aims to help physicians diagnose the cause of chronic watery diarrhea, particularly to exclude diagnoses other than functional diarrhea or diarrhea-predominant irritable bowel syndrome (IBS). The guideline, published in Gastroenterology, does not apply to patients with concerning presentations like weight loss/anemia, diarrhea with signs of fat malabsorption, bloody diarrhea, cases with a family history of inflammatory bowel disease (IBD), colon cancer, or celiac disease or to those who have traveled to diarrheal disease–related regions.

To rule out IBD, physicians can use either fecal calprotectin (threshold value of 50 microg/g, sensitivity, 0.81; specificity, 0.87) or fecal lactoferrin (threshold, 4.0-7.25 mcg/g; pooled sensitivity for IBD, 0.79; specificity, 0.93). Neither erythrocyte sedimentation rate (ESR) nor C-reactive protein (CRP) should be used to diagnose IBD because tests have shown low pooled sensitivity and specificity. CRP might be useful in settings in which fecal lactoferrin or calprotectin tests are not available or covered by insurance.

Patients should be tested for giardia infection, using the antigen test or PCR, because this pathogen is common in the United States and easily treated.

Patients who have not recently traveled to or from high-risk areas should not be tested for ova and parasites because this is unlikely to identify a culprit. There are other guidelines for treating patients who have traveled to high-risk countries.

Celiac disease should be tested for using immunoglobulin-A tissue transglutaminase (IgA tTG) and a second test (IgG tTG and IgG or IgA deamidated gliadin peptide, or DGP) in case the patient has IgA deficiency that could lead to a false negative on the primary test. Thresholds of 7-15 AU/mL in IgA tTG typically provide sensitivity and specificity greater than 90%. A quantitative IgA level found to be normal confirms the IgA tTG test. In abnormal findings, either IgG tTG or a test for IgG DGP can be used. If no information on IgA levels is available, IgG tTG or IgG DGP can be combined with IgA tTG. Positive celiac disease tests should be confirmed by duodenal biopsy.

Bile acid diarrhea should be tested for in the United States by measuring total bile acids in a 48-hour stool collection to document increased fecal bile acids, or serum fibroblast growth factor 19, to identify defective feedback of bile acid synthesis. The Selenium HomotauroCholic Acid Test (SeHCAT) has moderate diagnostic efficiency, but it is not available in North America. A measurement of serum levels of 7alpha-hydroxy-4-cholesten-3-one (C4), which measures bile acid synthesis, is not yet available.

No recommendation was made for using available serologic tests for the diagnosis of IBS because existing evidence suggests they lack the diagnostic accuracy needed for routine use.

The guideline development was funded by AGA and had no outside funding.

SOURCE: Smalley W et al. Gastroenterology. 2019 Jul 11. doi: 10.1053/j.gastro.2019.07.004.

A new guideline from the American Gastroenterological Association (AGA) aims to help physicians diagnose the cause of chronic watery diarrhea, particularly to exclude diagnoses other than functional diarrhea or diarrhea-predominant irritable bowel syndrome (IBS). The guideline, published in Gastroenterology, does not apply to patients with concerning presentations like weight loss/anemia, diarrhea with signs of fat malabsorption, bloody diarrhea, cases with a family history of inflammatory bowel disease (IBD), colon cancer, or celiac disease or to those who have traveled to diarrheal disease–related regions.

To rule out IBD, physicians can use either fecal calprotectin (threshold value of 50 microg/g, sensitivity, 0.81; specificity, 0.87) or fecal lactoferrin (threshold, 4.0-7.25 mcg/g; pooled sensitivity for IBD, 0.79; specificity, 0.93). Neither erythrocyte sedimentation rate (ESR) nor C-reactive protein (CRP) should be used to diagnose IBD because tests have shown low pooled sensitivity and specificity. CRP might be useful in settings in which fecal lactoferrin or calprotectin tests are not available or covered by insurance.

Patients should be tested for giardia infection, using the antigen test or PCR, because this pathogen is common in the United States and easily treated.

Patients who have not recently traveled to or from high-risk areas should not be tested for ova and parasites because this is unlikely to identify a culprit. There are other guidelines for treating patients who have traveled to high-risk countries.

Celiac disease should be tested for using immunoglobulin-A tissue transglutaminase (IgA tTG) and a second test (IgG tTG and IgG or IgA deamidated gliadin peptide, or DGP) in case the patient has IgA deficiency that could lead to a false negative on the primary test. Thresholds of 7-15 AU/mL in IgA tTG typically provide sensitivity and specificity greater than 90%. A quantitative IgA level found to be normal confirms the IgA tTG test. In abnormal findings, either IgG tTG or a test for IgG DGP can be used. If no information on IgA levels is available, IgG tTG or IgG DGP can be combined with IgA tTG. Positive celiac disease tests should be confirmed by duodenal biopsy.

Bile acid diarrhea should be tested for in the United States by measuring total bile acids in a 48-hour stool collection to document increased fecal bile acids, or serum fibroblast growth factor 19, to identify defective feedback of bile acid synthesis. The Selenium HomotauroCholic Acid Test (SeHCAT) has moderate diagnostic efficiency, but it is not available in North America. A measurement of serum levels of 7alpha-hydroxy-4-cholesten-3-one (C4), which measures bile acid synthesis, is not yet available.

No recommendation was made for using available serologic tests for the diagnosis of IBS because existing evidence suggests they lack the diagnostic accuracy needed for routine use.

The guideline development was funded by AGA and had no outside funding.

SOURCE: Smalley W et al. Gastroenterology. 2019 Jul 11. doi: 10.1053/j.gastro.2019.07.004.

A new guideline from the American Gastroenterological Association (AGA) aims to help physicians diagnose the cause of chronic watery diarrhea, particularly to exclude diagnoses other than functional diarrhea or diarrhea-predominant irritable bowel syndrome (IBS). The guideline, published in Gastroenterology, does not apply to patients with concerning presentations like weight loss/anemia, diarrhea with signs of fat malabsorption, bloody diarrhea, cases with a family history of inflammatory bowel disease (IBD), colon cancer, or celiac disease or to those who have traveled to diarrheal disease–related regions.

To rule out IBD, physicians can use either fecal calprotectin (threshold value of 50 microg/g, sensitivity, 0.81; specificity, 0.87) or fecal lactoferrin (threshold, 4.0-7.25 mcg/g; pooled sensitivity for IBD, 0.79; specificity, 0.93). Neither erythrocyte sedimentation rate (ESR) nor C-reactive protein (CRP) should be used to diagnose IBD because tests have shown low pooled sensitivity and specificity. CRP might be useful in settings in which fecal lactoferrin or calprotectin tests are not available or covered by insurance.

Patients should be tested for giardia infection, using the antigen test or PCR, because this pathogen is common in the United States and easily treated.

Patients who have not recently traveled to or from high-risk areas should not be tested for ova and parasites because this is unlikely to identify a culprit. There are other guidelines for treating patients who have traveled to high-risk countries.

Celiac disease should be tested for using immunoglobulin-A tissue transglutaminase (IgA tTG) and a second test (IgG tTG and IgG or IgA deamidated gliadin peptide, or DGP) in case the patient has IgA deficiency that could lead to a false negative on the primary test. Thresholds of 7-15 AU/mL in IgA tTG typically provide sensitivity and specificity greater than 90%. A quantitative IgA level found to be normal confirms the IgA tTG test. In abnormal findings, either IgG tTG or a test for IgG DGP can be used. If no information on IgA levels is available, IgG tTG or IgG DGP can be combined with IgA tTG. Positive celiac disease tests should be confirmed by duodenal biopsy.

Bile acid diarrhea should be tested for in the United States by measuring total bile acids in a 48-hour stool collection to document increased fecal bile acids, or serum fibroblast growth factor 19, to identify defective feedback of bile acid synthesis. The Selenium HomotauroCholic Acid Test (SeHCAT) has moderate diagnostic efficiency, but it is not available in North America. A measurement of serum levels of 7alpha-hydroxy-4-cholesten-3-one (C4), which measures bile acid synthesis, is not yet available.

No recommendation was made for using available serologic tests for the diagnosis of IBS because existing evidence suggests they lack the diagnostic accuracy needed for routine use.

The guideline development was funded by AGA and had no outside funding.

SOURCE: Smalley W et al. Gastroenterology. 2019 Jul 11. doi: 10.1053/j.gastro.2019.07.004.

Months of spaceflight can leave astronauts feeling dizzy when they get back to terra firma. A new study published online in Circulation shows that up to 2 hours of daily resistance and endurance training during the mission, combined with IV fluid replacement upon return to Earth, completely eliminated dizziness and fainting during normal activity. The exercise regimen counters cardiovascular, bone, and muscular deconditioning.

The dizziness is related to low blood pressure after standing up from a sitting or lying down position. It results when blood rushes to the feet and away from the brain because of the movement. The phenomenon, known as orthostatic hypotension, has plagued the space program even before the Apollo 11 mission, which celebrates its 50th anniversary this week.

The finding is good news for astronauts, but the findings extend to full-time Earthlings as well. The same fitness program is helping patients with postural orthostatic tachycardia syndrome (POTS), which most often affects women aged 13-50 years, said senior author Benjamin Levine, MD. About 450,000 people suffer from the condition in the United States.

The program held up well against a difficult challenge. “What surprised me the most was how well the astronauts did after spending 6 months in space. I thought there would be frequent episodes of fainting when they returned to Earth, but they didn’t have any. It’s compelling evidence of the effectiveness of the countermeasures – the exercise regimen and fluid replenishment,” said Dr. Levine, who is professor of Exercise Sciences at UT Southwestern Medical Center, said in a press release.

The researchers studied 12 astronauts (8 men, 4 women) who were aboard the International Space Station for roughly 6 months. To monitor for orthostatic hypotension, the researchers used ambulatory beat-to-beat blood pressure monitoring during activities of daily living. The device was used for 24 hour periods before, during (day 15, 30, and 75, as well as 15 days before return to Earth), and immediately following space flight.

The research showed that 24-hour systolic blood pressure decreased, compared with preflight levels, during flight time (106 vs 120 mm Hg; P less than .01), but the values returned to normal after return to Earth (122 mm Hg). There was no change in diastolic BP during or after flight. Systolic and diastolic BP variability did not change before, during, and after flight.

The study was funded by NASA. Dr. Levine has no disclosures.

SOURCE: Qi Fu et al. Circulation. 2019 July 19. doi: 10.1161/CIRCULATIONAHA.119.041050.

Months of spaceflight can leave astronauts feeling dizzy when they get back to terra firma. A new study published online in Circulation shows that up to 2 hours of daily resistance and endurance training during the mission, combined with IV fluid replacement upon return to Earth, completely eliminated dizziness and fainting during normal activity. The exercise regimen counters cardiovascular, bone, and muscular deconditioning.

The dizziness is related to low blood pressure after standing up from a sitting or lying down position. It results when blood rushes to the feet and away from the brain because of the movement. The phenomenon, known as orthostatic hypotension, has plagued the space program even before the Apollo 11 mission, which celebrates its 50th anniversary this week.

The finding is good news for astronauts, but the findings extend to full-time Earthlings as well. The same fitness program is helping patients with postural orthostatic tachycardia syndrome (POTS), which most often affects women aged 13-50 years, said senior author Benjamin Levine, MD. About 450,000 people suffer from the condition in the United States.

The program held up well against a difficult challenge. “What surprised me the most was how well the astronauts did after spending 6 months in space. I thought there would be frequent episodes of fainting when they returned to Earth, but they didn’t have any. It’s compelling evidence of the effectiveness of the countermeasures – the exercise regimen and fluid replenishment,” said Dr. Levine, who is professor of Exercise Sciences at UT Southwestern Medical Center, said in a press release.

The researchers studied 12 astronauts (8 men, 4 women) who were aboard the International Space Station for roughly 6 months. To monitor for orthostatic hypotension, the researchers used ambulatory beat-to-beat blood pressure monitoring during activities of daily living. The device was used for 24 hour periods before, during (day 15, 30, and 75, as well as 15 days before return to Earth), and immediately following space flight.

The research showed that 24-hour systolic blood pressure decreased, compared with preflight levels, during flight time (106 vs 120 mm Hg; P less than .01), but the values returned to normal after return to Earth (122 mm Hg). There was no change in diastolic BP during or after flight. Systolic and diastolic BP variability did not change before, during, and after flight.

The study was funded by NASA. Dr. Levine has no disclosures.

SOURCE: Qi Fu et al. Circulation. 2019 July 19. doi: 10.1161/CIRCULATIONAHA.119.041050.

Months of spaceflight can leave astronauts feeling dizzy when they get back to terra firma. A new study published online in Circulation shows that up to 2 hours of daily resistance and endurance training during the mission, combined with IV fluid replacement upon return to Earth, completely eliminated dizziness and fainting during normal activity. The exercise regimen counters cardiovascular, bone, and muscular deconditioning.

The dizziness is related to low blood pressure after standing up from a sitting or lying down position. It results when blood rushes to the feet and away from the brain because of the movement. The phenomenon, known as orthostatic hypotension, has plagued the space program even before the Apollo 11 mission, which celebrates its 50th anniversary this week.

The finding is good news for astronauts, but the findings extend to full-time Earthlings as well. The same fitness program is helping patients with postural orthostatic tachycardia syndrome (POTS), which most often affects women aged 13-50 years, said senior author Benjamin Levine, MD. About 450,000 people suffer from the condition in the United States.

The program held up well against a difficult challenge. “What surprised me the most was how well the astronauts did after spending 6 months in space. I thought there would be frequent episodes of fainting when they returned to Earth, but they didn’t have any. It’s compelling evidence of the effectiveness of the countermeasures – the exercise regimen and fluid replenishment,” said Dr. Levine, who is professor of Exercise Sciences at UT Southwestern Medical Center, said in a press release.

The researchers studied 12 astronauts (8 men, 4 women) who were aboard the International Space Station for roughly 6 months. To monitor for orthostatic hypotension, the researchers used ambulatory beat-to-beat blood pressure monitoring during activities of daily living. The device was used for 24 hour periods before, during (day 15, 30, and 75, as well as 15 days before return to Earth), and immediately following space flight.

The research showed that 24-hour systolic blood pressure decreased, compared with preflight levels, during flight time (106 vs 120 mm Hg; P less than .01), but the values returned to normal after return to Earth (122 mm Hg). There was no change in diastolic BP during or after flight. Systolic and diastolic BP variability did not change before, during, and after flight.

The study was funded by NASA. Dr. Levine has no disclosures.

SOURCE: Qi Fu et al. Circulation. 2019 July 19. doi: 10.1161/CIRCULATIONAHA.119.041050.

In a phase 3, active comparator controlled trial, treatment with risankizumab led to better skin clearance than treatment with adalimumab in patients with moderate-to-severe plaque psoriasis. Results of the IMMvent trial were published online ahead of print July 4 in the Lancet.

Risankizumab targets the p19 subunit of the cytokine IL-23. Selectivity for p19 has the potential to be safer than some other approaches that target the p40 subunit, because p19 is specific to IL-23, and many immune defense processes can function without IL-23. The p40 subunit is shared with IL-12, and blocking it can therefore lead to off-target effects.

Risankizumab was previously shown to have superior safety and efficacy over ustekinumab, which inhibits a subunit shared by IL-23 and IL-12 (Gordon KB et al. Lancet. 2018;392[10148]:650-61). Adalimumab is a TNF-alpha inhibitor that is frequently used to treat psoriasis, and which became available in biosimilar form in Europe in 2018.

The researchers randomized 605 adult patients from 66 sites in 11 countries to receive either risankizumab or adalimumab. The first phase (Part A) of the trial lasted up to 16 weeks, and tested the general superiority of risankizumab over adalimumab. The second phase (Part B), from week 16 to 44, evaluated the efficacy of risankizumab in participants who experienced an intermediate response, defined as Psoriasis Area and Severity Index (PASI) score of 50-90.

At the start of Part B, subjects initially receiving adalimumab who had at least a 90% improvement in PASI stayed on adalimumab (PASI 90), while those who had less than 50% improvement in PASI were switched to risankizumab. The remaining intermediate responders (PASI 50-90) were re-randomized to continue adalimumab or switch to risankizumab. All subjects initially randomized to risankizumab continued risankizumab during part B.

At the end of Part A, 72% of the risankizumab group achieved PASI 90, compared with 47% in the adalimumab group (p < 0.0001). A total of 84% in the risankizumab group had a static Physician’s Global Assessment (sPGA) score of 0 or 1 at the end of Part A, compared with 60% in the adalimumab group (p < 0.0001).

During Part B, among intermediate adalimumab responders, 66% of those switched to risankizumab achieved PASI 90, compared with 21% of continued on adalimumab (p < 0.0001).

In Part A, 56% of patients taking risankizumab experienced an adverse event, as did 57% of those taking adalimumab. Among adalimumab intermediate responders, 75% of those who switched to risankizumab during Part B had an adverse event, compared with 66% of those who continued adalimumab.

SOURCE: Reich K, et al. Lancet 2019, July 4 .

In a phase 3, active comparator controlled trial, treatment with risankizumab led to better skin clearance than treatment with adalimumab in patients with moderate-to-severe plaque psoriasis. Results of the IMMvent trial were published online ahead of print July 4 in the Lancet.

Risankizumab targets the p19 subunit of the cytokine IL-23. Selectivity for p19 has the potential to be safer than some other approaches that target the p40 subunit, because p19 is specific to IL-23, and many immune defense processes can function without IL-23. The p40 subunit is shared with IL-12, and blocking it can therefore lead to off-target effects.

Risankizumab was previously shown to have superior safety and efficacy over ustekinumab, which inhibits a subunit shared by IL-23 and IL-12 (Gordon KB et al. Lancet. 2018;392[10148]:650-61). Adalimumab is a TNF-alpha inhibitor that is frequently used to treat psoriasis, and which became available in biosimilar form in Europe in 2018.

The researchers randomized 605 adult patients from 66 sites in 11 countries to receive either risankizumab or adalimumab. The first phase (Part A) of the trial lasted up to 16 weeks, and tested the general superiority of risankizumab over adalimumab. The second phase (Part B), from week 16 to 44, evaluated the efficacy of risankizumab in participants who experienced an intermediate response, defined as Psoriasis Area and Severity Index (PASI) score of 50-90.

At the start of Part B, subjects initially receiving adalimumab who had at least a 90% improvement in PASI stayed on adalimumab (PASI 90), while those who had less than 50% improvement in PASI were switched to risankizumab. The remaining intermediate responders (PASI 50-90) were re-randomized to continue adalimumab or switch to risankizumab. All subjects initially randomized to risankizumab continued risankizumab during part B.

At the end of Part A, 72% of the risankizumab group achieved PASI 90, compared with 47% in the adalimumab group (p < 0.0001). A total of 84% in the risankizumab group had a static Physician’s Global Assessment (sPGA) score of 0 or 1 at the end of Part A, compared with 60% in the adalimumab group (p < 0.0001).

During Part B, among intermediate adalimumab responders, 66% of those switched to risankizumab achieved PASI 90, compared with 21% of continued on adalimumab (p < 0.0001).

In Part A, 56% of patients taking risankizumab experienced an adverse event, as did 57% of those taking adalimumab. Among adalimumab intermediate responders, 75% of those who switched to risankizumab during Part B had an adverse event, compared with 66% of those who continued adalimumab.

SOURCE: Reich K, et al. Lancet 2019, July 4 .

In a phase 3, active comparator controlled trial, treatment with risankizumab led to better skin clearance than treatment with adalimumab in patients with moderate-to-severe plaque psoriasis. Results of the IMMvent trial were published online ahead of print July 4 in the Lancet.

Risankizumab targets the p19 subunit of the cytokine IL-23. Selectivity for p19 has the potential to be safer than some other approaches that target the p40 subunit, because p19 is specific to IL-23, and many immune defense processes can function without IL-23. The p40 subunit is shared with IL-12, and blocking it can therefore lead to off-target effects.

Risankizumab was previously shown to have superior safety and efficacy over ustekinumab, which inhibits a subunit shared by IL-23 and IL-12 (Gordon KB et al. Lancet. 2018;392[10148]:650-61). Adalimumab is a TNF-alpha inhibitor that is frequently used to treat psoriasis, and which became available in biosimilar form in Europe in 2018.

The researchers randomized 605 adult patients from 66 sites in 11 countries to receive either risankizumab or adalimumab. The first phase (Part A) of the trial lasted up to 16 weeks, and tested the general superiority of risankizumab over adalimumab. The second phase (Part B), from week 16 to 44, evaluated the efficacy of risankizumab in participants who experienced an intermediate response, defined as Psoriasis Area and Severity Index (PASI) score of 50-90.

At the start of Part B, subjects initially receiving adalimumab who had at least a 90% improvement in PASI stayed on adalimumab (PASI 90), while those who had less than 50% improvement in PASI were switched to risankizumab. The remaining intermediate responders (PASI 50-90) were re-randomized to continue adalimumab or switch to risankizumab. All subjects initially randomized to risankizumab continued risankizumab during part B.

At the end of Part A, 72% of the risankizumab group achieved PASI 90, compared with 47% in the adalimumab group (p < 0.0001). A total of 84% in the risankizumab group had a static Physician’s Global Assessment (sPGA) score of 0 or 1 at the end of Part A, compared with 60% in the adalimumab group (p < 0.0001).

During Part B, among intermediate adalimumab responders, 66% of those switched to risankizumab achieved PASI 90, compared with 21% of continued on adalimumab (p < 0.0001).

In Part A, 56% of patients taking risankizumab experienced an adverse event, as did 57% of those taking adalimumab. Among adalimumab intermediate responders, 75% of those who switched to risankizumab during Part B had an adverse event, compared with 66% of those who continued adalimumab.

SOURCE: Reich K, et al. Lancet 2019, July 4 .

Deep sedation during colonoscopies did not confer any improvement in the detection rate for adenomas or polyps among average-risk patients, based on results from a retrospective analysis at a single institution that switched from moderate to deep sedation.

There remains a question as to whether moderate sedation, such as benzodiazepine plus opioids, might affect adenoma detection rate (ADR). The issue is important in part because of the recent push to use propofol in outpatient colonoscopy clinics, according to Erica Turse, DO, MPH, of the University of Missouri–Columbia, and colleagues.

Previous studies looking at moderate versus deep sedation have yielded mixed results, possibly as a result of confounding variables arising from mixed patient populations and conditions.

The current study, published in Gastrointestinal Endoscopy, aimed to eliminate potential confounders by focusing only on average-risk index colonoscopies, with similar patient populations in both groups.

The researchers examined data from a tertiary care outpatient center at the University of Missouri, which switched from moderate to deep sedation in the spring of 2016. Moderate sedation was achieved using midazolam and fentanyl, and propofol was later used for deep sedation. The study included a total of 585 colonoscopies, with 338 patients in the moderate-sedation group and 247 in the deep-sedation group. The overall polyp detection rate (PDR) was 70.1%, and the ADR was 41.7%.

The two groups did not significantly differ in PDR (71.9% moderate vs. 67.6% deep, P = .27) or ADR (44.1% vs. 38.5%; P = .18). Among women, there was no difference in PDR (69.3% vs. 64.8%; P = .41) or ADR (42.2% vs. 32.4%; P = .09). Among men, the results were the same (PDR, 75.3% vs. 71.4%; P = .56; ADR, 46.6% vs. 46.7%; P = 1.0).

A strength of the study was that the populations in both the moderate- and deep-sedation groups were similar. A weakness is that the study was conducted at a single center. The authors called for a randomized, controlled trial to gain more insight into the benefits of moderate versus deep sedation.

The study had no external funding. The authors reported having no financial conflicts of interest.

SOURCE: Turse E et al. Gastrointest Endosc. 2019 May 15. doi: 10.1016/j.gie.2019.05.011.

Deep sedation during colonoscopies did not confer any improvement in the detection rate for adenomas or polyps among average-risk patients, based on results from a retrospective analysis at a single institution that switched from moderate to deep sedation.

There remains a question as to whether moderate sedation, such as benzodiazepine plus opioids, might affect adenoma detection rate (ADR). The issue is important in part because of the recent push to use propofol in outpatient colonoscopy clinics, according to Erica Turse, DO, MPH, of the University of Missouri–Columbia, and colleagues.

Previous studies looking at moderate versus deep sedation have yielded mixed results, possibly as a result of confounding variables arising from mixed patient populations and conditions.

The current study, published in Gastrointestinal Endoscopy, aimed to eliminate potential confounders by focusing only on average-risk index colonoscopies, with similar patient populations in both groups.

The researchers examined data from a tertiary care outpatient center at the University of Missouri, which switched from moderate to deep sedation in the spring of 2016. Moderate sedation was achieved using midazolam and fentanyl, and propofol was later used for deep sedation. The study included a total of 585 colonoscopies, with 338 patients in the moderate-sedation group and 247 in the deep-sedation group. The overall polyp detection rate (PDR) was 70.1%, and the ADR was 41.7%.

The two groups did not significantly differ in PDR (71.9% moderate vs. 67.6% deep, P = .27) or ADR (44.1% vs. 38.5%; P = .18). Among women, there was no difference in PDR (69.3% vs. 64.8%; P = .41) or ADR (42.2% vs. 32.4%; P = .09). Among men, the results were the same (PDR, 75.3% vs. 71.4%; P = .56; ADR, 46.6% vs. 46.7%; P = 1.0).

A strength of the study was that the populations in both the moderate- and deep-sedation groups were similar. A weakness is that the study was conducted at a single center. The authors called for a randomized, controlled trial to gain more insight into the benefits of moderate versus deep sedation.

The study had no external funding. The authors reported having no financial conflicts of interest.

SOURCE: Turse E et al. Gastrointest Endosc. 2019 May 15. doi: 10.1016/j.gie.2019.05.011.

Deep sedation during colonoscopies did not confer any improvement in the detection rate for adenomas or polyps among average-risk patients, based on results from a retrospective analysis at a single institution that switched from moderate to deep sedation.

There remains a question as to whether moderate sedation, such as benzodiazepine plus opioids, might affect adenoma detection rate (ADR). The issue is important in part because of the recent push to use propofol in outpatient colonoscopy clinics, according to Erica Turse, DO, MPH, of the University of Missouri–Columbia, and colleagues.

Previous studies looking at moderate versus deep sedation have yielded mixed results, possibly as a result of confounding variables arising from mixed patient populations and conditions.

The current study, published in Gastrointestinal Endoscopy, aimed to eliminate potential confounders by focusing only on average-risk index colonoscopies, with similar patient populations in both groups.

The researchers examined data from a tertiary care outpatient center at the University of Missouri, which switched from moderate to deep sedation in the spring of 2016. Moderate sedation was achieved using midazolam and fentanyl, and propofol was later used for deep sedation. The study included a total of 585 colonoscopies, with 338 patients in the moderate-sedation group and 247 in the deep-sedation group. The overall polyp detection rate (PDR) was 70.1%, and the ADR was 41.7%.

The two groups did not significantly differ in PDR (71.9% moderate vs. 67.6% deep, P = .27) or ADR (44.1% vs. 38.5%; P = .18). Among women, there was no difference in PDR (69.3% vs. 64.8%; P = .41) or ADR (42.2% vs. 32.4%; P = .09). Among men, the results were the same (PDR, 75.3% vs. 71.4%; P = .56; ADR, 46.6% vs. 46.7%; P = 1.0).

A strength of the study was that the populations in both the moderate- and deep-sedation groups were similar. A weakness is that the study was conducted at a single center. The authors called for a randomized, controlled trial to gain more insight into the benefits of moderate versus deep sedation.

The study had no external funding. The authors reported having no financial conflicts of interest.

SOURCE: Turse E et al. Gastrointest Endosc. 2019 May 15. doi: 10.1016/j.gie.2019.05.011.

SAN FRANCISCO – Children with autism often struggle with repairing “messy” interactions with others, and this can impair their ability to communicate and develop properly. The interactive mismatch and repair technique, developed by Ed Tronick, PhD, when he was a researcher at Harvard Medical School and Children’s Hospital, Boston, may be able to guide communication development between an adult and a child with autism.

At the annual meeting of the American Psychiatric Association, Alexandra Harrison, MD, assistant professor of psychiatry at Harvard Medical School, described her experiences applying the technique to her work with autism patients, and showed a video of an awkward interaction she had with a 3-year-old boy with autism. By working to synchronize body movements with “Hal,” as well as inserting 1-second gaps between her statements, she helped him resolve an awkward moment, and Hal ultimately defused the tension by making a joke.

Hal managed to regulate his own uncertainty in the moment and navigate through tension. That small triumph has the potential to grow. “Once they’ve been able to secure some form of regulation with one or two or three individuals who are devoted to them, the hope is that this will spread and they will be able to regulate with individuals who are not as adjusted to them,” Gisele Apter, MD, PhD, a colleague of Dr. Harrison’s and professor of child psychiatry at Normandy Medical School, France, said in an interview. Dr. Apter moderated the session where the video was shown.

Dr. Tronick believes that the infant and caretaker grow together, making meanings together that are increasingly complex and coherent. That growth occurs in part through mismatch and repair interactions. Communication between infants and caregivers is nearly always a messy dance, with waxing and waning attention, changing intentions, and other dynamic factors leading to stops and starts, and awkward moments that the two must find a way to repair before carrying on.

These momentary mismatches, which happen all the time, are in fact a key element of childhood development, according to Dr. Apter. “There’s a lack of synchrony, and we want to get back on track because we push to communicate again. To do that, we have to repair the interaction, and one of the most beautiful things about development with this unbalanced couple is that the adult is generally there to support, to scaffold the child, but just one small step ahead of the infant so that it will enrich its development,” she said. 

But a caregiver with depression or another mental illness, or a child with impaired communication development because of autism, can impede that natural process.

Dr. Tronick’s method aims to provide some structure to the interaction by likening the nonverbal part of the interaction to music and dance. There are vocal rhythms, tone, and pitch, and then there are coordinated patterns of movement, gaze, and facial expressions such as smiles or frowns. The idea is that developmental growth occurs when the infant and the adult create meanings through their interactions.

Such growth can occur in microprocesses – extended moments in which child and caregiver iron out a mismatch in intent or action. Resolving these situations, and then moving forward with the rest of the interaction, helps the child grow in complexity and development by acquiring new meanings.

One-second beats after each statement or sentence lead to predictability. “He can develop an expectancy, and he can anticipate my vocal turns, and that is going to be reassuring to him,” Dr. Harrison said during the presentation. It also allows the caregiver to think through a messy moment, to try something different if one action seems not to be working. “It’s very hard to know how to repair the messiness, because it’s actually not messy enough. It’s too black and white. Something works or it doesn’t work, whereas with most kids you can be a little messy and you have time to get back on track with them.

“With these children [with autism], it requires a level of awareness which is higher. It is helpful for the adult to try to adjust and learn to interact in a different way that is more attuned to the child,” Dr. Apter said.

In the video shown by Dr. Harrison, she and Hal are in the therapy/play area, and Hal’s mother has just left before he could say goodbye. He was very upset by this, but then turned to work building a “map” out of construction toys called H-links that he had been playing with, along with his mother, before she left. Throughout the video, Dr. Harrison attempts to synchronize her body movements with Hal’s, shifting her position when he shifts his, and these get out of alignment and come back in alignment at different times. Several times, body motion synchrony is followed by a statement from Hal.

Dr. Harrison sits on the floor next to him, with Hal faced away from her. At a loss for what to do, she makes a small pile of H-links next to her. Hal notices this, and then moves some of the H-links back to their original position.

Hal says, “The H-links don’t go together that much.”

“They don’t go together that much?” repeats Dr. Harrison.

“Yeah.” He takes more H-block pieces from her pile.

“You wanted to take my ones, too?”

At this point, there is an obvious mismatch, with Hal claiming Dr. Harrison’s H-blocks.

Hal smiles as he takes a few more H-blocks and then says, “Only for boys.”

Then his smile widens and he gazes directly at Dr. Harrison, who meets his with an expression of mock surprise.

“What?”

“Only for boys,” Hal repeats.

Dr. Harrison then strings a long a series of phrases, each separated by 1-second beats. Hal orients himself away from her, smiling slightly: “You mean only boys can play with these? ... Uh oh ... Guess that means ... I’m not allowed! ... Is that right? ... Oh, my gosh ... How did they ever make up that rule, I wonder?”

At this, Hal orients himself toward Dr. Harrison again and smiles widely this time. “You’re tricking me,” says Dr. Harrison, and he gazes downward, though toward her. “But I think you’re trying to tell me that you don’t want me to hand them to you ... You want to get them yourself. ... That right?”

“Yeah. No more giving me pieces,” says Hal.

“Oh, I’m glad I understood. ... I will not give you any more pieces.”

SAN FRANCISCO – Children with autism often struggle with repairing “messy” interactions with others, and this can impair their ability to communicate and develop properly. The interactive mismatch and repair technique, developed by Ed Tronick, PhD, when he was a researcher at Harvard Medical School and Children’s Hospital, Boston, may be able to guide communication development between an adult and a child with autism.

At the annual meeting of the American Psychiatric Association, Alexandra Harrison, MD, assistant professor of psychiatry at Harvard Medical School, described her experiences applying the technique to her work with autism patients, and showed a video of an awkward interaction she had with a 3-year-old boy with autism. By working to synchronize body movements with “Hal,” as well as inserting 1-second gaps between her statements, she helped him resolve an awkward moment, and Hal ultimately defused the tension by making a joke.

Hal managed to regulate his own uncertainty in the moment and navigate through tension. That small triumph has the potential to grow. “Once they’ve been able to secure some form of regulation with one or two or three individuals who are devoted to them, the hope is that this will spread and they will be able to regulate with individuals who are not as adjusted to them,” Gisele Apter, MD, PhD, a colleague of Dr. Harrison’s and professor of child psychiatry at Normandy Medical School, France, said in an interview. Dr. Apter moderated the session where the video was shown.

Dr. Tronick believes that the infant and caretaker grow together, making meanings together that are increasingly complex and coherent. That growth occurs in part through mismatch and repair interactions. Communication between infants and caregivers is nearly always a messy dance, with waxing and waning attention, changing intentions, and other dynamic factors leading to stops and starts, and awkward moments that the two must find a way to repair before carrying on.

These momentary mismatches, which happen all the time, are in fact a key element of childhood development, according to Dr. Apter. “There’s a lack of synchrony, and we want to get back on track because we push to communicate again. To do that, we have to repair the interaction, and one of the most beautiful things about development with this unbalanced couple is that the adult is generally there to support, to scaffold the child, but just one small step ahead of the infant so that it will enrich its development,” she said. 

But a caregiver with depression or another mental illness, or a child with impaired communication development because of autism, can impede that natural process.

Dr. Tronick’s method aims to provide some structure to the interaction by likening the nonverbal part of the interaction to music and dance. There are vocal rhythms, tone, and pitch, and then there are coordinated patterns of movement, gaze, and facial expressions such as smiles or frowns. The idea is that developmental growth occurs when the infant and the adult create meanings through their interactions.

Such growth can occur in microprocesses – extended moments in which child and caregiver iron out a mismatch in intent or action. Resolving these situations, and then moving forward with the rest of the interaction, helps the child grow in complexity and development by acquiring new meanings.

One-second beats after each statement or sentence lead to predictability. “He can develop an expectancy, and he can anticipate my vocal turns, and that is going to be reassuring to him,” Dr. Harrison said during the presentation. It also allows the caregiver to think through a messy moment, to try something different if one action seems not to be working. “It’s very hard to know how to repair the messiness, because it’s actually not messy enough. It’s too black and white. Something works or it doesn’t work, whereas with most kids you can be a little messy and you have time to get back on track with them.

“With these children [with autism], it requires a level of awareness which is higher. It is helpful for the adult to try to adjust and learn to interact in a different way that is more attuned to the child,” Dr. Apter said.

In the video shown by Dr. Harrison, she and Hal are in the therapy/play area, and Hal’s mother has just left before he could say goodbye. He was very upset by this, but then turned to work building a “map” out of construction toys called H-links that he had been playing with, along with his mother, before she left. Throughout the video, Dr. Harrison attempts to synchronize her body movements with Hal’s, shifting her position when he shifts his, and these get out of alignment and come back in alignment at different times. Several times, body motion synchrony is followed by a statement from Hal.

Dr. Harrison sits on the floor next to him, with Hal faced away from her. At a loss for what to do, she makes a small pile of H-links next to her. Hal notices this, and then moves some of the H-links back to their original position.

Hal says, “The H-links don’t go together that much.”

“They don’t go together that much?” repeats Dr. Harrison.

“Yeah.” He takes more H-block pieces from her pile.

“You wanted to take my ones, too?”

At this point, there is an obvious mismatch, with Hal claiming Dr. Harrison’s H-blocks.

Hal smiles as he takes a few more H-blocks and then says, “Only for boys.”

Then his smile widens and he gazes directly at Dr. Harrison, who meets his with an expression of mock surprise.

“What?”

“Only for boys,” Hal repeats.

Dr. Harrison then strings a long a series of phrases, each separated by 1-second beats. Hal orients himself away from her, smiling slightly: “You mean only boys can play with these? ... Uh oh ... Guess that means ... I’m not allowed! ... Is that right? ... Oh, my gosh ... How did they ever make up that rule, I wonder?”

At this, Hal orients himself toward Dr. Harrison again and smiles widely this time. “You’re tricking me,” says Dr. Harrison, and he gazes downward, though toward her. “But I think you’re trying to tell me that you don’t want me to hand them to you ... You want to get them yourself. ... That right?”

“Yeah. No more giving me pieces,” says Hal.

“Oh, I’m glad I understood. ... I will not give you any more pieces.”

SAN FRANCISCO – Children with autism often struggle with repairing “messy” interactions with others, and this can impair their ability to communicate and develop properly. The interactive mismatch and repair technique, developed by Ed Tronick, PhD, when he was a researcher at Harvard Medical School and Children’s Hospital, Boston, may be able to guide communication development between an adult and a child with autism.

At the annual meeting of the American Psychiatric Association, Alexandra Harrison, MD, assistant professor of psychiatry at Harvard Medical School, described her experiences applying the technique to her work with autism patients, and showed a video of an awkward interaction she had with a 3-year-old boy with autism. By working to synchronize body movements with “Hal,” as well as inserting 1-second gaps between her statements, she helped him resolve an awkward moment, and Hal ultimately defused the tension by making a joke.

Hal managed to regulate his own uncertainty in the moment and navigate through tension. That small triumph has the potential to grow. “Once they’ve been able to secure some form of regulation with one or two or three individuals who are devoted to them, the hope is that this will spread and they will be able to regulate with individuals who are not as adjusted to them,” Gisele Apter, MD, PhD, a colleague of Dr. Harrison’s and professor of child psychiatry at Normandy Medical School, France, said in an interview. Dr. Apter moderated the session where the video was shown.

Dr. Tronick believes that the infant and caretaker grow together, making meanings together that are increasingly complex and coherent. That growth occurs in part through mismatch and repair interactions. Communication between infants and caregivers is nearly always a messy dance, with waxing and waning attention, changing intentions, and other dynamic factors leading to stops and starts, and awkward moments that the two must find a way to repair before carrying on.

These momentary mismatches, which happen all the time, are in fact a key element of childhood development, according to Dr. Apter. “There’s a lack of synchrony, and we want to get back on track because we push to communicate again. To do that, we have to repair the interaction, and one of the most beautiful things about development with this unbalanced couple is that the adult is generally there to support, to scaffold the child, but just one small step ahead of the infant so that it will enrich its development,” she said. 

But a caregiver with depression or another mental illness, or a child with impaired communication development because of autism, can impede that natural process.

Dr. Tronick’s method aims to provide some structure to the interaction by likening the nonverbal part of the interaction to music and dance. There are vocal rhythms, tone, and pitch, and then there are coordinated patterns of movement, gaze, and facial expressions such as smiles or frowns. The idea is that developmental growth occurs when the infant and the adult create meanings through their interactions.

Such growth can occur in microprocesses – extended moments in which child and caregiver iron out a mismatch in intent or action. Resolving these situations, and then moving forward with the rest of the interaction, helps the child grow in complexity and development by acquiring new meanings.

One-second beats after each statement or sentence lead to predictability. “He can develop an expectancy, and he can anticipate my vocal turns, and that is going to be reassuring to him,” Dr. Harrison said during the presentation. It also allows the caregiver to think through a messy moment, to try something different if one action seems not to be working. “It’s very hard to know how to repair the messiness, because it’s actually not messy enough. It’s too black and white. Something works or it doesn’t work, whereas with most kids you can be a little messy and you have time to get back on track with them.

“With these children [with autism], it requires a level of awareness which is higher. It is helpful for the adult to try to adjust and learn to interact in a different way that is more attuned to the child,” Dr. Apter said.

In the video shown by Dr. Harrison, she and Hal are in the therapy/play area, and Hal’s mother has just left before he could say goodbye. He was very upset by this, but then turned to work building a “map” out of construction toys called H-links that he had been playing with, along with his mother, before she left. Throughout the video, Dr. Harrison attempts to synchronize her body movements with Hal’s, shifting her position when he shifts his, and these get out of alignment and come back in alignment at different times. Several times, body motion synchrony is followed by a statement from Hal.

Dr. Harrison sits on the floor next to him, with Hal faced away from her. At a loss for what to do, she makes a small pile of H-links next to her. Hal notices this, and then moves some of the H-links back to their original position.

Hal says, “The H-links don’t go together that much.”

“They don’t go together that much?” repeats Dr. Harrison.

“Yeah.” He takes more H-block pieces from her pile.

“You wanted to take my ones, too?”

At this point, there is an obvious mismatch, with Hal claiming Dr. Harrison’s H-blocks.

Hal smiles as he takes a few more H-blocks and then says, “Only for boys.”

Then his smile widens and he gazes directly at Dr. Harrison, who meets his with an expression of mock surprise.

“What?”

“Only for boys,” Hal repeats.

Dr. Harrison then strings a long a series of phrases, each separated by 1-second beats. Hal orients himself away from her, smiling slightly: “You mean only boys can play with these? ... Uh oh ... Guess that means ... I’m not allowed! ... Is that right? ... Oh, my gosh ... How did they ever make up that rule, I wonder?”

At this, Hal orients himself toward Dr. Harrison again and smiles widely this time. “You’re tricking me,” says Dr. Harrison, and he gazes downward, though toward her. “But I think you’re trying to tell me that you don’t want me to hand them to you ... You want to get them yourself. ... That right?”

“Yeah. No more giving me pieces,” says Hal.

“Oh, I’m glad I understood. ... I will not give you any more pieces.”