PORTLAND—A lot of health care providers involved in the care of patients with HIV/AIDS think physical therapists (PTs) have a very narrow role to play in chronic pain when in actuality, "we have a very big footprint," says Michael DeArman, DPT, Fellow of the American Association of Orthopedic Manual Therapists.

In his session, "Physical therapy alternatives for people living with HIV and persistent pain," he reviewed how his role in the care of patients with HIV has evolved over the years. He explained that the emphasis in physical therapy used to be on exercises that would help to maintain lean body mass, because it was a predictor of survivability and helped patients avoid opportunistic infections.

After that, the role of the PT focused largely on helping patients deal with the adverse effects of medications. DeArman explained that back in the days of azathioprine (AZT), for example, many patients developed peripheral neuropathy, lipodystrophy, and low cervical fat deposition leading to neck pain. PTs also helped patients deal with the complications of surviving with HIV, including the effects of meningitis and stroke. "But we don't see much of that anymore because the medications are so much better,” DeArman said. “That's not the profile for HIV anymore."

But now patients are dealing with chronic pain

DeArman reported that 80% to 90% of people with HIV/AIDS have chronic pain for at least 2 months, if not much longer. He said, "PT can be an alternative to opioids," and explained that his efforts are twofold. "Graded activity to slowly build peoples' ability to do aerobic exercise is a really good way to manage pain,” he said, “but the other half of it is a lot of counseling and education, talking about how pain works and doesn't work, and how what you're told and what you believe and experience and your expectations can affect the experience of pain and the level of pain at any given moment."

He remarked that now about 60% of this professional time is devoted to the counseling and educational aspects of pain and 40% to movement and exercise: "It's not really the kind of therapist I trained to be, and it's not what most people think of as physical therapy work, but it's falling in our lap."

He said that as a society, we rely heavily on more formal counseling by psychotherapists and counselors, for example, to manage depression and anxiety, but that few others in the medical realm are picking up the slack when it comes to pain education for patients with HIV.

Tools for talking

DeArman discussed some of the tools and techniques he uses when talking to patients about their pain, such as motivational interviewing and assessing readiness for change. He uses the Fear-Avoidance Beliefs Questionnaire (FABQ) to uncover how a patient's fear-avoidance beliefs about physical activity may be affecting their pain. He also assesses levels of catastrophization, or how seriously a patient interprets a physical symptom; a high level correlates with greater pain states. Similarly, those with low self-efficacy—feelings about how well you can control your destiny and situations—are more likely to experience chronic pain states than those with high self-efficacy.

Continue to: He said that using...

He said that using these tools has made a huge difference in the way he and others in his field approach pain and its outcomes. He says that not only are they helping people get better, but "we are giving patients a way to manage their pain before they go down the road of pharmacologic solutions."

DeArman said his main message is "to think about physical therapy for your patients with chronic pain." He pointed out that there's a new generation of PTs coming out of school that have a much better understanding of how to manage chronic pain, so "expect [this type of treatment] to be available from those PTs to whom you refer patients. Just realize it may still take a little looking to find it."

PORTLAND—A lot of health care providers involved in the care of patients with HIV/AIDS think physical therapists (PTs) have a very narrow role to play in chronic pain when in actuality, "we have a very big footprint," says Michael DeArman, DPT, Fellow of the American Association of Orthopedic Manual Therapists.

In his session, "Physical therapy alternatives for people living with HIV and persistent pain," he reviewed how his role in the care of patients with HIV has evolved over the years. He explained that the emphasis in physical therapy used to be on exercises that would help to maintain lean body mass, because it was a predictor of survivability and helped patients avoid opportunistic infections.

After that, the role of the PT focused largely on helping patients deal with the adverse effects of medications. DeArman explained that back in the days of azathioprine (AZT), for example, many patients developed peripheral neuropathy, lipodystrophy, and low cervical fat deposition leading to neck pain. PTs also helped patients deal with the complications of surviving with HIV, including the effects of meningitis and stroke. "But we don't see much of that anymore because the medications are so much better,” DeArman said. “That's not the profile for HIV anymore."

But now patients are dealing with chronic pain

DeArman reported that 80% to 90% of people with HIV/AIDS have chronic pain for at least 2 months, if not much longer. He said, "PT can be an alternative to opioids," and explained that his efforts are twofold. "Graded activity to slowly build peoples' ability to do aerobic exercise is a really good way to manage pain,” he said, “but the other half of it is a lot of counseling and education, talking about how pain works and doesn't work, and how what you're told and what you believe and experience and your expectations can affect the experience of pain and the level of pain at any given moment."

He remarked that now about 60% of this professional time is devoted to the counseling and educational aspects of pain and 40% to movement and exercise: "It's not really the kind of therapist I trained to be, and it's not what most people think of as physical therapy work, but it's falling in our lap."

He said that as a society, we rely heavily on more formal counseling by psychotherapists and counselors, for example, to manage depression and anxiety, but that few others in the medical realm are picking up the slack when it comes to pain education for patients with HIV.

Tools for talking

DeArman discussed some of the tools and techniques he uses when talking to patients about their pain, such as motivational interviewing and assessing readiness for change. He uses the Fear-Avoidance Beliefs Questionnaire (FABQ) to uncover how a patient's fear-avoidance beliefs about physical activity may be affecting their pain. He also assesses levels of catastrophization, or how seriously a patient interprets a physical symptom; a high level correlates with greater pain states. Similarly, those with low self-efficacy—feelings about how well you can control your destiny and situations—are more likely to experience chronic pain states than those with high self-efficacy.

Continue to: He said that using...

He said that using these tools has made a huge difference in the way he and others in his field approach pain and its outcomes. He says that not only are they helping people get better, but "we are giving patients a way to manage their pain before they go down the road of pharmacologic solutions."

DeArman said his main message is "to think about physical therapy for your patients with chronic pain." He pointed out that there's a new generation of PTs coming out of school that have a much better understanding of how to manage chronic pain, so "expect [this type of treatment] to be available from those PTs to whom you refer patients. Just realize it may still take a little looking to find it."

PORTLAND—A lot of health care providers involved in the care of patients with HIV/AIDS think physical therapists (PTs) have a very narrow role to play in chronic pain when in actuality, "we have a very big footprint," says Michael DeArman, DPT, Fellow of the American Association of Orthopedic Manual Therapists.

In his session, "Physical therapy alternatives for people living with HIV and persistent pain," he reviewed how his role in the care of patients with HIV has evolved over the years. He explained that the emphasis in physical therapy used to be on exercises that would help to maintain lean body mass, because it was a predictor of survivability and helped patients avoid opportunistic infections.

After that, the role of the PT focused largely on helping patients deal with the adverse effects of medications. DeArman explained that back in the days of azathioprine (AZT), for example, many patients developed peripheral neuropathy, lipodystrophy, and low cervical fat deposition leading to neck pain. PTs also helped patients deal with the complications of surviving with HIV, including the effects of meningitis and stroke. "But we don't see much of that anymore because the medications are so much better,” DeArman said. “That's not the profile for HIV anymore."

But now patients are dealing with chronic pain

DeArman reported that 80% to 90% of people with HIV/AIDS have chronic pain for at least 2 months, if not much longer. He said, "PT can be an alternative to opioids," and explained that his efforts are twofold. "Graded activity to slowly build peoples' ability to do aerobic exercise is a really good way to manage pain,” he said, “but the other half of it is a lot of counseling and education, talking about how pain works and doesn't work, and how what you're told and what you believe and experience and your expectations can affect the experience of pain and the level of pain at any given moment."

He remarked that now about 60% of this professional time is devoted to the counseling and educational aspects of pain and 40% to movement and exercise: "It's not really the kind of therapist I trained to be, and it's not what most people think of as physical therapy work, but it's falling in our lap."

He said that as a society, we rely heavily on more formal counseling by psychotherapists and counselors, for example, to manage depression and anxiety, but that few others in the medical realm are picking up the slack when it comes to pain education for patients with HIV.

Tools for talking

DeArman discussed some of the tools and techniques he uses when talking to patients about their pain, such as motivational interviewing and assessing readiness for change. He uses the Fear-Avoidance Beliefs Questionnaire (FABQ) to uncover how a patient's fear-avoidance beliefs about physical activity may be affecting their pain. He also assesses levels of catastrophization, or how seriously a patient interprets a physical symptom; a high level correlates with greater pain states. Similarly, those with low self-efficacy—feelings about how well you can control your destiny and situations—are more likely to experience chronic pain states than those with high self-efficacy.

Continue to: He said that using...

He said that using these tools has made a huge difference in the way he and others in his field approach pain and its outcomes. He says that not only are they helping people get better, but "we are giving patients a way to manage their pain before they go down the road of pharmacologic solutions."

DeArman said his main message is "to think about physical therapy for your patients with chronic pain." He pointed out that there's a new generation of PTs coming out of school that have a much better understanding of how to manage chronic pain, so "expect [this type of treatment] to be available from those PTs to whom you refer patients. Just realize it may still take a little looking to find it."

PORTLAND—The investigational drug islatravir “could be a game changer in the field of HIV," said David H. Spach, MD, Professor of Medicine, Division of Infectious Diseases, University of Washington, Seattle, in a session called, "Antiretroviral therapy 2019 update: Mechanism of action, new medications, current guidelines, and controversies."

Dr. Spach reported that islatravir, a nucleoside reverse transcriptase translocation inhibitor (NRTTI), is highly potent, is well tolerated, has a high genetic barrier to resistance, and has an extremely long half-life, according to the findings of preliminary studies. Its long half-life enables subdermal implantation and maintenance of therapeutic levels even after a year in place. Researchers are studying the compound in combination with other agents for treatment and independently for preexposure prophylaxis.

Another noteworthy investigational agent, according to Dr. Spach, is cabotegravir, an integrase strand transfer inhibitor (INSTI) with the potential for intramuscular administration every 4 to 8 weeks. Dr. Spach explained that researchers are studying the agent in 3 different clinical situations: oral cabotegravir in combination with rilpivirine for lead-in therapy; an extended-release injectable of cabotegravir and rilpivirine for maintenance antiretroviral (ARV) treatment every 4 weeks; and an extended-release cabotegravir injectable for preexposure prophylaxis every 8 weeks. The agent is highly potent, with a high genetic barrier to resistance.

ARV: The current state of affairs

"We are in an era now where everyone who is living with HIV ideally should be receiving fully suppressive antiretroviral therapy," remarked Dr. Spach. He explained that not only does this benefit the person living with HIV by reducing the onset and progression of chronic inflammatory disease states that occur along with HIV, such as cardiovascular disease, stroke, and cancer, but also "fully suppressive ARV therapy virtually eliminates sexual transmission of HIV to another person."

Spach explained that the most recent (2018) Health and Human Services ARV therapy guidelines have greatly simplified the choices for ARV therapy. The current recommendations for initial ARV therapy for most people are to use a 2-drug backbone regimen, consisting of 2 nucleoside reverse transcriptase inhibitors (NRTIs), combined with a single anchor drug, which should be an INSTI. The INSTI should have the highest potency and highest genetic barrier to resistance available, which effectively means using a regimen that contains either dolutegravir or bictegravir. The latter is available only in combination with emtricitabine and tenofovir alafenamide as a single-tablet regimen.

Spach also explained that "the guidelines have moved away from using boosted regimens for initial therapy, so elvitegravir boosted with cobicistat and protease inhibitors (PIs) boosted with ritonavir or cobicistat are no longer recommended as preferred initial therapy, although boosted PIs are still very useful as second- or third-line therapies."

Newer medications

Doravirine, a nonnucleoside reverse transcriptase inhibitor (NNRTI), was approved by the FDA in 2018. "It probably won't have a big impact on initial therapy, but it is likely to have a significant effect on second- and third-line therapy," Dr. Spach said. "Because of its high potency and high genetic barrier to resistance, those taking etravirine twice a day, for example, may be able to simplify to once-a-day doravirine." In addition, "Doravirine may have advantages over rilpivirine in that it has no restrictions when used with acid-suppressing agents such as H2 blockers or proton pump inhibitors."

Continue to: Ibalizumab

Ibalizumab. Another newer agent “worth mentioning,” according to Dr. Spach, is ibalizumab. This monoclonal antibody has a unique mechanism of action. It is 1 of only 2 drugs used for HIV treatment that targets human receptors (all of the others work by inhibiting either an HIV enzyme or binding to the HIV virus itself). Ibalizumab targets the D2 region of the CD4 receptor. It is an injectable (intravenous) compound administered with an initial loading dose and then every 2 weeks thereafter. Dr. Spach reported that the data surrounding ibalizumab show that it is effective as an add-on medication in more advanced resistant settings. Also, it provides an option for people who can't take oral drugs, such as those who have had major surgery or trauma.

Remaining questions

Dr. Spach explained that 1 of the questions that remains is whether to prescribe ARV therapy for patients who are viremic controllers (those who inherently control HIV through their own immunologic response to a level < 200 copies) or elite controllers (those whose own immunologic response controls the virus to a level < 50 copies, which is in the undetectable range). Both of these groups still have a higher risk for hospitalization and for HIV-related inflammatory conditions such as heart disease, according to Dr. Spach. Current thinking among most experts is to initiate and maintain therapy as long as it is tolerated well.

3 drugs to 2? Another question that remains is whether to switch patients who are doing well on 3-drug maintenance therapy to 2-drug maintenance therapy. According to Dr Spach, studies involving the combination dolutegravir/rilpivirine indicate that patients who have suppressed HIV RNA levels for at least 6 months on a 3-drug maintenance regimen do well after switching to the 2-drug combination dolutegravir/rilpivirine, as long as they do not have baseline resistance to either dolutegravir or rilpivirine. But he questioned the need for the change if the individual is tolerating a 3-drug regimen well, saying that given the safety of current regimens, the only broader motivating force may be cost savings. For now, he said, if patients are without complaints or tolerability issues on 3 drugs, leave them alone.

INSTIs and weight gain. The last issue is weight gain with the use of INSTIs. Preliminary data suggest disproportionate weight gain with these drugs (on the order of about 6 kg over a year and half, which may be 2-3 kg greater than that which occurs with PI-based and NNRTI-based regimens). At this point, experts do not recommend avoiding these agents, mainly because of the tremendous benefits that have been observed with INSTIs. Dr. Spach concluded, "Although we will continue to use INSTIs widely in clinical practice, there may be a subset of individuals taking an INSTI who have pronounced weight gain and may need to switch to another regimen that does not contain an INSTI.”

PORTLAND—The investigational drug islatravir “could be a game changer in the field of HIV," said David H. Spach, MD, Professor of Medicine, Division of Infectious Diseases, University of Washington, Seattle, in a session called, "Antiretroviral therapy 2019 update: Mechanism of action, new medications, current guidelines, and controversies."

Dr. Spach reported that islatravir, a nucleoside reverse transcriptase translocation inhibitor (NRTTI), is highly potent, is well tolerated, has a high genetic barrier to resistance, and has an extremely long half-life, according to the findings of preliminary studies. Its long half-life enables subdermal implantation and maintenance of therapeutic levels even after a year in place. Researchers are studying the compound in combination with other agents for treatment and independently for preexposure prophylaxis.

Another noteworthy investigational agent, according to Dr. Spach, is cabotegravir, an integrase strand transfer inhibitor (INSTI) with the potential for intramuscular administration every 4 to 8 weeks. Dr. Spach explained that researchers are studying the agent in 3 different clinical situations: oral cabotegravir in combination with rilpivirine for lead-in therapy; an extended-release injectable of cabotegravir and rilpivirine for maintenance antiretroviral (ARV) treatment every 4 weeks; and an extended-release cabotegravir injectable for preexposure prophylaxis every 8 weeks. The agent is highly potent, with a high genetic barrier to resistance.

ARV: The current state of affairs

"We are in an era now where everyone who is living with HIV ideally should be receiving fully suppressive antiretroviral therapy," remarked Dr. Spach. He explained that not only does this benefit the person living with HIV by reducing the onset and progression of chronic inflammatory disease states that occur along with HIV, such as cardiovascular disease, stroke, and cancer, but also "fully suppressive ARV therapy virtually eliminates sexual transmission of HIV to another person."

Spach explained that the most recent (2018) Health and Human Services ARV therapy guidelines have greatly simplified the choices for ARV therapy. The current recommendations for initial ARV therapy for most people are to use a 2-drug backbone regimen, consisting of 2 nucleoside reverse transcriptase inhibitors (NRTIs), combined with a single anchor drug, which should be an INSTI. The INSTI should have the highest potency and highest genetic barrier to resistance available, which effectively means using a regimen that contains either dolutegravir or bictegravir. The latter is available only in combination with emtricitabine and tenofovir alafenamide as a single-tablet regimen.

Spach also explained that "the guidelines have moved away from using boosted regimens for initial therapy, so elvitegravir boosted with cobicistat and protease inhibitors (PIs) boosted with ritonavir or cobicistat are no longer recommended as preferred initial therapy, although boosted PIs are still very useful as second- or third-line therapies."

Newer medications

Doravirine, a nonnucleoside reverse transcriptase inhibitor (NNRTI), was approved by the FDA in 2018. "It probably won't have a big impact on initial therapy, but it is likely to have a significant effect on second- and third-line therapy," Dr. Spach said. "Because of its high potency and high genetic barrier to resistance, those taking etravirine twice a day, for example, may be able to simplify to once-a-day doravirine." In addition, "Doravirine may have advantages over rilpivirine in that it has no restrictions when used with acid-suppressing agents such as H2 blockers or proton pump inhibitors."

Continue to: Ibalizumab

Ibalizumab. Another newer agent “worth mentioning,” according to Dr. Spach, is ibalizumab. This monoclonal antibody has a unique mechanism of action. It is 1 of only 2 drugs used for HIV treatment that targets human receptors (all of the others work by inhibiting either an HIV enzyme or binding to the HIV virus itself). Ibalizumab targets the D2 region of the CD4 receptor. It is an injectable (intravenous) compound administered with an initial loading dose and then every 2 weeks thereafter. Dr. Spach reported that the data surrounding ibalizumab show that it is effective as an add-on medication in more advanced resistant settings. Also, it provides an option for people who can't take oral drugs, such as those who have had major surgery or trauma.

Remaining questions

Dr. Spach explained that 1 of the questions that remains is whether to prescribe ARV therapy for patients who are viremic controllers (those who inherently control HIV through their own immunologic response to a level < 200 copies) or elite controllers (those whose own immunologic response controls the virus to a level < 50 copies, which is in the undetectable range). Both of these groups still have a higher risk for hospitalization and for HIV-related inflammatory conditions such as heart disease, according to Dr. Spach. Current thinking among most experts is to initiate and maintain therapy as long as it is tolerated well.

3 drugs to 2? Another question that remains is whether to switch patients who are doing well on 3-drug maintenance therapy to 2-drug maintenance therapy. According to Dr Spach, studies involving the combination dolutegravir/rilpivirine indicate that patients who have suppressed HIV RNA levels for at least 6 months on a 3-drug maintenance regimen do well after switching to the 2-drug combination dolutegravir/rilpivirine, as long as they do not have baseline resistance to either dolutegravir or rilpivirine. But he questioned the need for the change if the individual is tolerating a 3-drug regimen well, saying that given the safety of current regimens, the only broader motivating force may be cost savings. For now, he said, if patients are without complaints or tolerability issues on 3 drugs, leave them alone.

INSTIs and weight gain. The last issue is weight gain with the use of INSTIs. Preliminary data suggest disproportionate weight gain with these drugs (on the order of about 6 kg over a year and half, which may be 2-3 kg greater than that which occurs with PI-based and NNRTI-based regimens). At this point, experts do not recommend avoiding these agents, mainly because of the tremendous benefits that have been observed with INSTIs. Dr. Spach concluded, "Although we will continue to use INSTIs widely in clinical practice, there may be a subset of individuals taking an INSTI who have pronounced weight gain and may need to switch to another regimen that does not contain an INSTI.”

PORTLAND—The investigational drug islatravir “could be a game changer in the field of HIV," said David H. Spach, MD, Professor of Medicine, Division of Infectious Diseases, University of Washington, Seattle, in a session called, "Antiretroviral therapy 2019 update: Mechanism of action, new medications, current guidelines, and controversies."

Dr. Spach reported that islatravir, a nucleoside reverse transcriptase translocation inhibitor (NRTTI), is highly potent, is well tolerated, has a high genetic barrier to resistance, and has an extremely long half-life, according to the findings of preliminary studies. Its long half-life enables subdermal implantation and maintenance of therapeutic levels even after a year in place. Researchers are studying the compound in combination with other agents for treatment and independently for preexposure prophylaxis.

Another noteworthy investigational agent, according to Dr. Spach, is cabotegravir, an integrase strand transfer inhibitor (INSTI) with the potential for intramuscular administration every 4 to 8 weeks. Dr. Spach explained that researchers are studying the agent in 3 different clinical situations: oral cabotegravir in combination with rilpivirine for lead-in therapy; an extended-release injectable of cabotegravir and rilpivirine for maintenance antiretroviral (ARV) treatment every 4 weeks; and an extended-release cabotegravir injectable for preexposure prophylaxis every 8 weeks. The agent is highly potent, with a high genetic barrier to resistance.

ARV: The current state of affairs

"We are in an era now where everyone who is living with HIV ideally should be receiving fully suppressive antiretroviral therapy," remarked Dr. Spach. He explained that not only does this benefit the person living with HIV by reducing the onset and progression of chronic inflammatory disease states that occur along with HIV, such as cardiovascular disease, stroke, and cancer, but also "fully suppressive ARV therapy virtually eliminates sexual transmission of HIV to another person."

Spach explained that the most recent (2018) Health and Human Services ARV therapy guidelines have greatly simplified the choices for ARV therapy. The current recommendations for initial ARV therapy for most people are to use a 2-drug backbone regimen, consisting of 2 nucleoside reverse transcriptase inhibitors (NRTIs), combined with a single anchor drug, which should be an INSTI. The INSTI should have the highest potency and highest genetic barrier to resistance available, which effectively means using a regimen that contains either dolutegravir or bictegravir. The latter is available only in combination with emtricitabine and tenofovir alafenamide as a single-tablet regimen.

Spach also explained that "the guidelines have moved away from using boosted regimens for initial therapy, so elvitegravir boosted with cobicistat and protease inhibitors (PIs) boosted with ritonavir or cobicistat are no longer recommended as preferred initial therapy, although boosted PIs are still very useful as second- or third-line therapies."

Newer medications

Doravirine, a nonnucleoside reverse transcriptase inhibitor (NNRTI), was approved by the FDA in 2018. "It probably won't have a big impact on initial therapy, but it is likely to have a significant effect on second- and third-line therapy," Dr. Spach said. "Because of its high potency and high genetic barrier to resistance, those taking etravirine twice a day, for example, may be able to simplify to once-a-day doravirine." In addition, "Doravirine may have advantages over rilpivirine in that it has no restrictions when used with acid-suppressing agents such as H2 blockers or proton pump inhibitors."

Continue to: Ibalizumab

Ibalizumab. Another newer agent “worth mentioning,” according to Dr. Spach, is ibalizumab. This monoclonal antibody has a unique mechanism of action. It is 1 of only 2 drugs used for HIV treatment that targets human receptors (all of the others work by inhibiting either an HIV enzyme or binding to the HIV virus itself). Ibalizumab targets the D2 region of the CD4 receptor. It is an injectable (intravenous) compound administered with an initial loading dose and then every 2 weeks thereafter. Dr. Spach reported that the data surrounding ibalizumab show that it is effective as an add-on medication in more advanced resistant settings. Also, it provides an option for people who can't take oral drugs, such as those who have had major surgery or trauma.

Remaining questions

Dr. Spach explained that 1 of the questions that remains is whether to prescribe ARV therapy for patients who are viremic controllers (those who inherently control HIV through their own immunologic response to a level < 200 copies) or elite controllers (those whose own immunologic response controls the virus to a level < 50 copies, which is in the undetectable range). Both of these groups still have a higher risk for hospitalization and for HIV-related inflammatory conditions such as heart disease, according to Dr. Spach. Current thinking among most experts is to initiate and maintain therapy as long as it is tolerated well.

3 drugs to 2? Another question that remains is whether to switch patients who are doing well on 3-drug maintenance therapy to 2-drug maintenance therapy. According to Dr Spach, studies involving the combination dolutegravir/rilpivirine indicate that patients who have suppressed HIV RNA levels for at least 6 months on a 3-drug maintenance regimen do well after switching to the 2-drug combination dolutegravir/rilpivirine, as long as they do not have baseline resistance to either dolutegravir or rilpivirine. But he questioned the need for the change if the individual is tolerating a 3-drug regimen well, saying that given the safety of current regimens, the only broader motivating force may be cost savings. For now, he said, if patients are without complaints or tolerability issues on 3 drugs, leave them alone.

INSTIs and weight gain. The last issue is weight gain with the use of INSTIs. Preliminary data suggest disproportionate weight gain with these drugs (on the order of about 6 kg over a year and half, which may be 2-3 kg greater than that which occurs with PI-based and NNRTI-based regimens). At this point, experts do not recommend avoiding these agents, mainly because of the tremendous benefits that have been observed with INSTIs. Dr. Spach concluded, "Although we will continue to use INSTIs widely in clinical practice, there may be a subset of individuals taking an INSTI who have pronounced weight gain and may need to switch to another regimen that does not contain an INSTI.”

COPENHAGEN – The traditional treatment paradigm for patients with comorbid depression and insomnia has been to focus on the depression in expectation that the sleep problems will fade away with the depressive symptoms.

Big mistake, Kerstin Blom, PhD, said during the annual congress of the European College of Neuropsychopharmacology.

That treatment strategy is insufficient, because untreated insomnia seldom improves. It hinders recovery from depression, increases the risk of new depressive episodes, and causes continued suffering because of poor sleep, asserted Dr. Blom, a clinical psychologist and researcher at the Internet Psychiatry Clinic at the Karolinska Institute in Stockholm.

She presented highlights of a series of three randomized, controlled trials for which she was first author. The take-home message: Insomnia with comorbid depression is not merely a symptom of depression; it requires specific treatment.

“Insomnia needs to be treated according to guidelines – that is, with cognitive-behavioral therapy – when it’s comorbid with depression,” she declared. “Insomnia therapy also treats comorbid depression, but it’s not so much the other way around. There are some effects on insomnia when you treat depression, but they’re not very large.”

The first study in her series included 43 adults with psychiatrist-diagnosed comorbid insomnia and major depression who were randomized to an 8-week course of psychologist-guided, Internet-delivered cognitive-behavioral therapy (ICBT) for one disorder or the other. At 6- and 12-month follow-up, patients who received ICBT for insomnia had significantly greater improvement in their insomnia as measured by the self-rated Insomnia Severity Index than did those who got ICBT for depression, while both forms of treatment were similarly effective in reducing depression severity as reflected in Montgomery-Åsberg Depression Rating Scale (MADRS) scores (Sleep. 2015 Feb 1;38[2]:267-77).

At 3-year follow-up, the beneficial impact of ICBT for insomnia remained strong, with recipients reporting less need for additional sleep treatment and less use of sleep medication than did the patients who got ICBT for depression. Both groups were left with mild depression, pointing to the need to develop a combined form of CBT that would simultaneously address both disorders in patients with comorbid depression and insomnia (Sleep. 2017 Aug 1;40[8]. doi. 10.1093/sleep/zsx108).

The Swedish investigators went on to create a 9-week course of psychologist-guided combination ICBT for both insomnia and depression. Then they randomized 126 dual-diagnosis patients to that treatment program or to therapist-guided ICBT for depression plus a placebo sleep intervention, which included education about sleep hygiene, stress management, and use of a sleep diary. At 6 months of follow-up, the dual-target ICBT group had a significantly greater reduction in Insomnia Severity Index scores than those who got ICBT for depression plus placebo. No between-group difference were found in the reduction in MADRS scores.

“This means treating patients with insomnia therapy was as effective for the treatment of depression as was depression therapy,” Dr. Blom observed. Follow-up out to 36 months is ongoing.

The third study included 148 nondepressed adults with insomnia who were randomized to the 8-week ICBT insomnia intervention or an active control treatment, which again included patient education, stress management, and a sleep diary. At 6 months, the active CBT-insomnia group had significantly lower Insomnia Severity Index scores than controls. However, at 12 and 36 months, the control group caught up, and there was no longer a between-group difference, with 74% of participants no longer meeting diagnostic criteria for insomnia at 36 months. The explanation for the catch-up? The control group used significantly more hypnotic sleep medications and more frequently sought additional insomnia treatments, including yoga and mindfulness, outside of the study setting during follow-up (Sleep. 2016 Jun 1;39[6]:1267-74).

It was Dr. Blom’s intent to also use this randomized, controlled trials to test the hypothesis that improving insomnia in nondepressed patients prevents future episodes of depression. She was thwarted in this attempt.

“After they got our low-intensity control version of a sleep intervention, they went out and got more treatment and that seems to have helped them, which is great,” Dr. Blom said. “But it sort of ruined our prediction study.”

However, in a post hoc analysis, study participants who were poor sleepers at 12 months had significantly more depressive symptoms at 36 months than did those with improved sleep at 12 months. The effect size was quite large, with a between-group 5.5-point difference in MADRS scores at 36 months in a study population that was nondepressed at baseline.

“So improved sleep may prevent depression long term,” Dr. Blom said. “The jury is still out on that one.”

She reported having no financial conflicts regarding her studies, which were supported by government research funding.

[email protected]

COPENHAGEN – The traditional treatment paradigm for patients with comorbid depression and insomnia has been to focus on the depression in expectation that the sleep problems will fade away with the depressive symptoms.

Big mistake, Kerstin Blom, PhD, said during the annual congress of the European College of Neuropsychopharmacology.

That treatment strategy is insufficient, because untreated insomnia seldom improves. It hinders recovery from depression, increases the risk of new depressive episodes, and causes continued suffering because of poor sleep, asserted Dr. Blom, a clinical psychologist and researcher at the Internet Psychiatry Clinic at the Karolinska Institute in Stockholm.

She presented highlights of a series of three randomized, controlled trials for which she was first author. The take-home message: Insomnia with comorbid depression is not merely a symptom of depression; it requires specific treatment.

“Insomnia needs to be treated according to guidelines – that is, with cognitive-behavioral therapy – when it’s comorbid with depression,” she declared. “Insomnia therapy also treats comorbid depression, but it’s not so much the other way around. There are some effects on insomnia when you treat depression, but they’re not very large.”

The first study in her series included 43 adults with psychiatrist-diagnosed comorbid insomnia and major depression who were randomized to an 8-week course of psychologist-guided, Internet-delivered cognitive-behavioral therapy (ICBT) for one disorder or the other. At 6- and 12-month follow-up, patients who received ICBT for insomnia had significantly greater improvement in their insomnia as measured by the self-rated Insomnia Severity Index than did those who got ICBT for depression, while both forms of treatment were similarly effective in reducing depression severity as reflected in Montgomery-Åsberg Depression Rating Scale (MADRS) scores (Sleep. 2015 Feb 1;38[2]:267-77).

At 3-year follow-up, the beneficial impact of ICBT for insomnia remained strong, with recipients reporting less need for additional sleep treatment and less use of sleep medication than did the patients who got ICBT for depression. Both groups were left with mild depression, pointing to the need to develop a combined form of CBT that would simultaneously address both disorders in patients with comorbid depression and insomnia (Sleep. 2017 Aug 1;40[8]. doi. 10.1093/sleep/zsx108).

The Swedish investigators went on to create a 9-week course of psychologist-guided combination ICBT for both insomnia and depression. Then they randomized 126 dual-diagnosis patients to that treatment program or to therapist-guided ICBT for depression plus a placebo sleep intervention, which included education about sleep hygiene, stress management, and use of a sleep diary. At 6 months of follow-up, the dual-target ICBT group had a significantly greater reduction in Insomnia Severity Index scores than those who got ICBT for depression plus placebo. No between-group difference were found in the reduction in MADRS scores.

“This means treating patients with insomnia therapy was as effective for the treatment of depression as was depression therapy,” Dr. Blom observed. Follow-up out to 36 months is ongoing.

The third study included 148 nondepressed adults with insomnia who were randomized to the 8-week ICBT insomnia intervention or an active control treatment, which again included patient education, stress management, and a sleep diary. At 6 months, the active CBT-insomnia group had significantly lower Insomnia Severity Index scores than controls. However, at 12 and 36 months, the control group caught up, and there was no longer a between-group difference, with 74% of participants no longer meeting diagnostic criteria for insomnia at 36 months. The explanation for the catch-up? The control group used significantly more hypnotic sleep medications and more frequently sought additional insomnia treatments, including yoga and mindfulness, outside of the study setting during follow-up (Sleep. 2016 Jun 1;39[6]:1267-74).

It was Dr. Blom’s intent to also use this randomized, controlled trials to test the hypothesis that improving insomnia in nondepressed patients prevents future episodes of depression. She was thwarted in this attempt.

“After they got our low-intensity control version of a sleep intervention, they went out and got more treatment and that seems to have helped them, which is great,” Dr. Blom said. “But it sort of ruined our prediction study.”

However, in a post hoc analysis, study participants who were poor sleepers at 12 months had significantly more depressive symptoms at 36 months than did those with improved sleep at 12 months. The effect size was quite large, with a between-group 5.5-point difference in MADRS scores at 36 months in a study population that was nondepressed at baseline.

“So improved sleep may prevent depression long term,” Dr. Blom said. “The jury is still out on that one.”

She reported having no financial conflicts regarding her studies, which were supported by government research funding.

[email protected]

COPENHAGEN – The traditional treatment paradigm for patients with comorbid depression and insomnia has been to focus on the depression in expectation that the sleep problems will fade away with the depressive symptoms.

Big mistake, Kerstin Blom, PhD, said during the annual congress of the European College of Neuropsychopharmacology.

That treatment strategy is insufficient, because untreated insomnia seldom improves. It hinders recovery from depression, increases the risk of new depressive episodes, and causes continued suffering because of poor sleep, asserted Dr. Blom, a clinical psychologist and researcher at the Internet Psychiatry Clinic at the Karolinska Institute in Stockholm.

She presented highlights of a series of three randomized, controlled trials for which she was first author. The take-home message: Insomnia with comorbid depression is not merely a symptom of depression; it requires specific treatment.

“Insomnia needs to be treated according to guidelines – that is, with cognitive-behavioral therapy – when it’s comorbid with depression,” she declared. “Insomnia therapy also treats comorbid depression, but it’s not so much the other way around. There are some effects on insomnia when you treat depression, but they’re not very large.”

The first study in her series included 43 adults with psychiatrist-diagnosed comorbid insomnia and major depression who were randomized to an 8-week course of psychologist-guided, Internet-delivered cognitive-behavioral therapy (ICBT) for one disorder or the other. At 6- and 12-month follow-up, patients who received ICBT for insomnia had significantly greater improvement in their insomnia as measured by the self-rated Insomnia Severity Index than did those who got ICBT for depression, while both forms of treatment were similarly effective in reducing depression severity as reflected in Montgomery-Åsberg Depression Rating Scale (MADRS) scores (Sleep. 2015 Feb 1;38[2]:267-77).

At 3-year follow-up, the beneficial impact of ICBT for insomnia remained strong, with recipients reporting less need for additional sleep treatment and less use of sleep medication than did the patients who got ICBT for depression. Both groups were left with mild depression, pointing to the need to develop a combined form of CBT that would simultaneously address both disorders in patients with comorbid depression and insomnia (Sleep. 2017 Aug 1;40[8]. doi. 10.1093/sleep/zsx108).

The Swedish investigators went on to create a 9-week course of psychologist-guided combination ICBT for both insomnia and depression. Then they randomized 126 dual-diagnosis patients to that treatment program or to therapist-guided ICBT for depression plus a placebo sleep intervention, which included education about sleep hygiene, stress management, and use of a sleep diary. At 6 months of follow-up, the dual-target ICBT group had a significantly greater reduction in Insomnia Severity Index scores than those who got ICBT for depression plus placebo. No between-group difference were found in the reduction in MADRS scores.

“This means treating patients with insomnia therapy was as effective for the treatment of depression as was depression therapy,” Dr. Blom observed. Follow-up out to 36 months is ongoing.

The third study included 148 nondepressed adults with insomnia who were randomized to the 8-week ICBT insomnia intervention or an active control treatment, which again included patient education, stress management, and a sleep diary. At 6 months, the active CBT-insomnia group had significantly lower Insomnia Severity Index scores than controls. However, at 12 and 36 months, the control group caught up, and there was no longer a between-group difference, with 74% of participants no longer meeting diagnostic criteria for insomnia at 36 months. The explanation for the catch-up? The control group used significantly more hypnotic sleep medications and more frequently sought additional insomnia treatments, including yoga and mindfulness, outside of the study setting during follow-up (Sleep. 2016 Jun 1;39[6]:1267-74).

It was Dr. Blom’s intent to also use this randomized, controlled trials to test the hypothesis that improving insomnia in nondepressed patients prevents future episodes of depression. She was thwarted in this attempt.

“After they got our low-intensity control version of a sleep intervention, they went out and got more treatment and that seems to have helped them, which is great,” Dr. Blom said. “But it sort of ruined our prediction study.”

However, in a post hoc analysis, study participants who were poor sleepers at 12 months had significantly more depressive symptoms at 36 months than did those with improved sleep at 12 months. The effect size was quite large, with a between-group 5.5-point difference in MADRS scores at 36 months in a study population that was nondepressed at baseline.

“So improved sleep may prevent depression long term,” Dr. Blom said. “The jury is still out on that one.”

She reported having no financial conflicts regarding her studies, which were supported by government research funding.

[email protected]

Tumor necrosis factor–alpha (TNF-alpha) inhibitors are therapeutic agents used to treat a variety of inflammatory conditions such as rheumatoid arthritis and inflammatory bowel disease, as well as psoriasis of the skin (PSO) and psoriatic arthritis. Paradoxically, some individuals report new onset of psoriasiform lesions with treatment with TNF-alpha inhibitors for other conditions. In a 2017 systematic review, there were 216 reported cases of new-onset TNF-alpha inhibitor–induced psoriasis, with an estimated rate of 1 per 1,000. The cases thus far have had a wide range of presentations, the most common being plaque psoriasis, scalp psoriasis, as well as palmoplantar pustular psoriasis.¹

Courtesy Dr. Lawrence F. Eichenfield

A retrospective chart review study at Mayo clinic published in 2017 evaluated children younger than 19 years seen in 2003-2015 who developed new-onset or recurrent PSO with a history of inflammatory bowel disease being treated with anti-TNF-alpha therapy. The review showed variable latency in the development of PSO in these patients, although it typically occurred during inflammatory bowel disease remission.² It is unclear whether there is an association between a personal or family history of psoriasis and development of these lesions.

TNF-alpha, interleukin (IL)–17) and interferon-alpha (IFN-alpha) are main cytokines that contribute to the development of psoriasis. The mechanism of action for paradoxical PSO/psoriasis in patients treated with anti-TNF is not clearly understood; however, many hypotheses are based on an imbalance between TNF-alpha and interferon-alpha – more specifically, an increased production of interferon-alpha. TNF-alpha inhibits the activity of plasmacytoid dendritic cells which are key producers of IFN-alpha. Because of this blockade, there is unopposed IFN-alpha production. Interferon-alpha allows for the expression of chemokines such as CXCR3, which favor T cells homing to the skin. IFN-alpha also stimulates and activates T cells to produce TNF-alpha and IL-17, which in turn sustains inflammatory mechanisms and allows for the development of psoriatic lesions.3

Courtesy Dr. Lawrence F. Eichenfield

There are no universal management guidelines. Most of these patients’ treatment plans mirror standard psoriasis therapies while the main question remains the decision to continue the same anti-TNF therapy, change anti-TNF agents, or entirely switch classes of biologic or other systemic therapy. This decision in management requires several considerations: treatability of TNF-alpha inhibitor-induced psoriasis, the severity of background disease (i.e., rheumatoid arthritis, inflammatory bowel disease, other systemic condition), and whether the underlying disease is well controlled on current therapy, as well as the consideration of possible loss in efficacy if a drug is discontinued and then restarted at a later date.⁴

A reasonable initial approach in patients with well-controlled underlying disease and mild skin eruption is to continue anti-TNF therapy and manage skin topically with topical corticosteroids and/or phototherapy. In patients that either do not have well-controlled underlying disease or moderate skin involvement, changing to an alternative anti-TNF or other agent may be reasonable, and requires coordinated care with involved specialists. In the 2017 pediatric review mentioned previously, nearly half of the patients required a change in their initial anti-TNF-alpha agent despite conventional skin-directed therapies, and one-third of patients discontinued all anti-TNF-alpha therapy because of PSO.²

The psoriasiform papulosquamous features of this case along with the history suggests the diagnosis. Pityriasis rosea would be highly atypical on the feet and with the duration of findings. Lichen planus and atopic dermatitis morphology are inconsistent with this eruption, and coxsackie viral infection would have a shorter course.

Dr. Tracy is a research fellow in pediatric dermatology at Rady Children’s Hospital–San Diego and the University of California, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. Email them at [email protected].

References

1. J Am Acad Dermatol. 2017 Feb;76(2):334-41.

2. Pediatr Dermatol. 2017 May;34(3):253-60.

3. RMD Open. 2016 Jul 15;2(2):e000239.

4. J Psoriasis Psoriatic Arthritis. 2019 Apr;4(2):70-80.

Tumor necrosis factor–alpha (TNF-alpha) inhibitors are therapeutic agents used to treat a variety of inflammatory conditions such as rheumatoid arthritis and inflammatory bowel disease, as well as psoriasis of the skin (PSO) and psoriatic arthritis. Paradoxically, some individuals report new onset of psoriasiform lesions with treatment with TNF-alpha inhibitors for other conditions. In a 2017 systematic review, there were 216 reported cases of new-onset TNF-alpha inhibitor–induced psoriasis, with an estimated rate of 1 per 1,000. The cases thus far have had a wide range of presentations, the most common being plaque psoriasis, scalp psoriasis, as well as palmoplantar pustular psoriasis.¹

Courtesy Dr. Lawrence F. Eichenfield

A retrospective chart review study at Mayo clinic published in 2017 evaluated children younger than 19 years seen in 2003-2015 who developed new-onset or recurrent PSO with a history of inflammatory bowel disease being treated with anti-TNF-alpha therapy. The review showed variable latency in the development of PSO in these patients, although it typically occurred during inflammatory bowel disease remission.² It is unclear whether there is an association between a personal or family history of psoriasis and development of these lesions.

TNF-alpha, interleukin (IL)–17) and interferon-alpha (IFN-alpha) are main cytokines that contribute to the development of psoriasis. The mechanism of action for paradoxical PSO/psoriasis in patients treated with anti-TNF is not clearly understood; however, many hypotheses are based on an imbalance between TNF-alpha and interferon-alpha – more specifically, an increased production of interferon-alpha. TNF-alpha inhibits the activity of plasmacytoid dendritic cells which are key producers of IFN-alpha. Because of this blockade, there is unopposed IFN-alpha production. Interferon-alpha allows for the expression of chemokines such as CXCR3, which favor T cells homing to the skin. IFN-alpha also stimulates and activates T cells to produce TNF-alpha and IL-17, which in turn sustains inflammatory mechanisms and allows for the development of psoriatic lesions.3

Courtesy Dr. Lawrence F. Eichenfield

There are no universal management guidelines. Most of these patients’ treatment plans mirror standard psoriasis therapies while the main question remains the decision to continue the same anti-TNF therapy, change anti-TNF agents, or entirely switch classes of biologic or other systemic therapy. This decision in management requires several considerations: treatability of TNF-alpha inhibitor-induced psoriasis, the severity of background disease (i.e., rheumatoid arthritis, inflammatory bowel disease, other systemic condition), and whether the underlying disease is well controlled on current therapy, as well as the consideration of possible loss in efficacy if a drug is discontinued and then restarted at a later date.⁴

A reasonable initial approach in patients with well-controlled underlying disease and mild skin eruption is to continue anti-TNF therapy and manage skin topically with topical corticosteroids and/or phototherapy. In patients that either do not have well-controlled underlying disease or moderate skin involvement, changing to an alternative anti-TNF or other agent may be reasonable, and requires coordinated care with involved specialists. In the 2017 pediatric review mentioned previously, nearly half of the patients required a change in their initial anti-TNF-alpha agent despite conventional skin-directed therapies, and one-third of patients discontinued all anti-TNF-alpha therapy because of PSO.²

The psoriasiform papulosquamous features of this case along with the history suggests the diagnosis. Pityriasis rosea would be highly atypical on the feet and with the duration of findings. Lichen planus and atopic dermatitis morphology are inconsistent with this eruption, and coxsackie viral infection would have a shorter course.

Dr. Tracy is a research fellow in pediatric dermatology at Rady Children’s Hospital–San Diego and the University of California, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. Email them at [email protected].

References

1. J Am Acad Dermatol. 2017 Feb;76(2):334-41.

2. Pediatr Dermatol. 2017 May;34(3):253-60.

3. RMD Open. 2016 Jul 15;2(2):e000239.

4. J Psoriasis Psoriatic Arthritis. 2019 Apr;4(2):70-80.

Tumor necrosis factor–alpha (TNF-alpha) inhibitors are therapeutic agents used to treat a variety of inflammatory conditions such as rheumatoid arthritis and inflammatory bowel disease, as well as psoriasis of the skin (PSO) and psoriatic arthritis. Paradoxically, some individuals report new onset of psoriasiform lesions with treatment with TNF-alpha inhibitors for other conditions. In a 2017 systematic review, there were 216 reported cases of new-onset TNF-alpha inhibitor–induced psoriasis, with an estimated rate of 1 per 1,000. The cases thus far have had a wide range of presentations, the most common being plaque psoriasis, scalp psoriasis, as well as palmoplantar pustular psoriasis.¹

Courtesy Dr. Lawrence F. Eichenfield

A retrospective chart review study at Mayo clinic published in 2017 evaluated children younger than 19 years seen in 2003-2015 who developed new-onset or recurrent PSO with a history of inflammatory bowel disease being treated with anti-TNF-alpha therapy. The review showed variable latency in the development of PSO in these patients, although it typically occurred during inflammatory bowel disease remission.² It is unclear whether there is an association between a personal or family history of psoriasis and development of these lesions.

TNF-alpha, interleukin (IL)–17) and interferon-alpha (IFN-alpha) are main cytokines that contribute to the development of psoriasis. The mechanism of action for paradoxical PSO/psoriasis in patients treated with anti-TNF is not clearly understood; however, many hypotheses are based on an imbalance between TNF-alpha and interferon-alpha – more specifically, an increased production of interferon-alpha. TNF-alpha inhibits the activity of plasmacytoid dendritic cells which are key producers of IFN-alpha. Because of this blockade, there is unopposed IFN-alpha production. Interferon-alpha allows for the expression of chemokines such as CXCR3, which favor T cells homing to the skin. IFN-alpha also stimulates and activates T cells to produce TNF-alpha and IL-17, which in turn sustains inflammatory mechanisms and allows for the development of psoriatic lesions.3

Courtesy Dr. Lawrence F. Eichenfield

There are no universal management guidelines. Most of these patients’ treatment plans mirror standard psoriasis therapies while the main question remains the decision to continue the same anti-TNF therapy, change anti-TNF agents, or entirely switch classes of biologic or other systemic therapy. This decision in management requires several considerations: treatability of TNF-alpha inhibitor-induced psoriasis, the severity of background disease (i.e., rheumatoid arthritis, inflammatory bowel disease, other systemic condition), and whether the underlying disease is well controlled on current therapy, as well as the consideration of possible loss in efficacy if a drug is discontinued and then restarted at a later date.⁴

A reasonable initial approach in patients with well-controlled underlying disease and mild skin eruption is to continue anti-TNF therapy and manage skin topically with topical corticosteroids and/or phototherapy. In patients that either do not have well-controlled underlying disease or moderate skin involvement, changing to an alternative anti-TNF or other agent may be reasonable, and requires coordinated care with involved specialists. In the 2017 pediatric review mentioned previously, nearly half of the patients required a change in their initial anti-TNF-alpha agent despite conventional skin-directed therapies, and one-third of patients discontinued all anti-TNF-alpha therapy because of PSO.²

The psoriasiform papulosquamous features of this case along with the history suggests the diagnosis. Pityriasis rosea would be highly atypical on the feet and with the duration of findings. Lichen planus and atopic dermatitis morphology are inconsistent with this eruption, and coxsackie viral infection would have a shorter course.

Dr. Tracy is a research fellow in pediatric dermatology at Rady Children’s Hospital–San Diego and the University of California, San Diego. Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. Email them at [email protected].

References

1. J Am Acad Dermatol. 2017 Feb;76(2):334-41.

2. Pediatr Dermatol. 2017 May;34(3):253-60.

3. RMD Open. 2016 Jul 15;2(2):e000239.

4. J Psoriasis Psoriatic Arthritis. 2019 Apr;4(2):70-80.

The Food and Drug Administration has issued another safety communication warning that biotin can significantly interfere with laboratory tests for troponin.

However, not all troponin tests are affected, according to the update. “Since the FDA’s safety communication on this topic in 2017, some lab test developers have been successful at mitigating the biotin interference of their assays, but others have not yet addressed it,” according to the new communication, issued in early November.

Also known as vitamin B₇ and appearing in many dietary supplements, including prenatal multivitamins and supplements for hair, skin, and nail growth, biotin can lead to falsely low results on some troponin tests, especially at high levels. The worry is that biotin interference could therefore lead to missed diagnoses. The FDA has provided a list of those tests that have not taken biotin’s effects into account, titled “Biotin Interference with Troponin Lab Tests – Assays Subject to Biotin Interference.”

The daily recommended allowance for biotin, according to the communication, is about 0.3 mg, but it isn’t always clear how much is actually included in supplements – some can contain 20 mg or even as much as 100 mg per pill of biotin. The communication includes recommendations for patients, health care professionals, laboratory personnel, and lab test manufacturers and developers.

The full safety communication can be found on the FDA website, and problems with tests can be reported via the FDA’s MedWatch Voluntary Reporting Form.

[email protected]

The Food and Drug Administration has issued another safety communication warning that biotin can significantly interfere with laboratory tests for troponin.

However, not all troponin tests are affected, according to the update. “Since the FDA’s safety communication on this topic in 2017, some lab test developers have been successful at mitigating the biotin interference of their assays, but others have not yet addressed it,” according to the new communication, issued in early November.

Also known as vitamin B₇ and appearing in many dietary supplements, including prenatal multivitamins and supplements for hair, skin, and nail growth, biotin can lead to falsely low results on some troponin tests, especially at high levels. The worry is that biotin interference could therefore lead to missed diagnoses. The FDA has provided a list of those tests that have not taken biotin’s effects into account, titled “Biotin Interference with Troponin Lab Tests – Assays Subject to Biotin Interference.”

The daily recommended allowance for biotin, according to the communication, is about 0.3 mg, but it isn’t always clear how much is actually included in supplements – some can contain 20 mg or even as much as 100 mg per pill of biotin. The communication includes recommendations for patients, health care professionals, laboratory personnel, and lab test manufacturers and developers.

The full safety communication can be found on the FDA website, and problems with tests can be reported via the FDA’s MedWatch Voluntary Reporting Form.

[email protected]

The Food and Drug Administration has issued another safety communication warning that biotin can significantly interfere with laboratory tests for troponin.

However, not all troponin tests are affected, according to the update. “Since the FDA’s safety communication on this topic in 2017, some lab test developers have been successful at mitigating the biotin interference of their assays, but others have not yet addressed it,” according to the new communication, issued in early November.

Also known as vitamin B₇ and appearing in many dietary supplements, including prenatal multivitamins and supplements for hair, skin, and nail growth, biotin can lead to falsely low results on some troponin tests, especially at high levels. The worry is that biotin interference could therefore lead to missed diagnoses. The FDA has provided a list of those tests that have not taken biotin’s effects into account, titled “Biotin Interference with Troponin Lab Tests – Assays Subject to Biotin Interference.”

The daily recommended allowance for biotin, according to the communication, is about 0.3 mg, but it isn’t always clear how much is actually included in supplements – some can contain 20 mg or even as much as 100 mg per pill of biotin. The communication includes recommendations for patients, health care professionals, laboratory personnel, and lab test manufacturers and developers.

The full safety communication can be found on the FDA website, and problems with tests can be reported via the FDA’s MedWatch Voluntary Reporting Form.

[email protected]

ATLANTA – Opportunities to escalate or deescalate medications for patients with rheumatoid arthritis via an electronic health record at the point of care led rheumatologists at the Geisinger Medical Center in Danville, Pa., to increase the number of such decisions in their practice.

Jeff Craven/MDedge News

“Opportunities for escalation and de-escalation of therapy are common, even in a well-managed RA population,” Eric D. Newman, MD, director of the department of rheumatology at Geisinger, said in a presentation at the annual meeting of the American College of Rheumatology. “In our hands, over a third of the time, there was an opportunity to change therapy.”

Dr. Newman and colleagues developed a new treat-to-target tab for their (Patient Centric Electronic Redesign) PACER project, an EHR-adjacent system that captures patient and provider data and presents the information in different views, based on desired action items. The target in the study was low disease activity or remission, which was assessed using Clinical Disease Activity Index (CDAI) scores.

The treat-to-target tab offered three options to rheumatologists in real time when meeting with a patient: an escalation opportunity, which was defined as the patient’s two most recent CDAI scores showing moderate to high disease activity; and a deescalation opportunity, defined as a look-back up to 1 year during which at least two CDAI measures were within low to-moderate disease range. There was also a third “leave-alone” option to neither escalate nor deescalate therapy, but the rheumatologist was prompted to explain why if that option is selected, Dr. Newman noted.

In the first phase of releasing the treat-to-target tab, there was low adoption among the 17 rheumatologists at Geisinger: 82% of rheumatologists did not use the tab for escalation therapy, and 64% did not use the tab for deescalation therapy.

That prompted Dr. Newman and colleagues to develop a new version of the treat-to-target tab for phase 2 of the program. “Once they complete their CDAI, if there’s an opportunity, there would be a bright orange button that would glow right in front of them,” Dr. Newman said. “It was really hard to miss, and all they would have to do is click it and it would bring them right to the treat-to-target tab.”

To increase rheumatologists’ use of the new treat-to-target tab, the amount of time spent using the tab and making decisions is presented to them, he said. “It’s actually now part of our quality measure bundle, so every month, they get a leaderboard to see how they compare with their partners,” he noted. “It’s a great way to drive down variability and get everybody approaching the same sort of mean.”

Overall, between July 2018 and May 2019, there were 1,428 treat-to-target opportunities, consisting of 34.2% of RA office visits. Of these, 11.3% were escalation opportunities and 22.9% were deescalation opportunities, Dr. Newman said.

Between phase 1 and phase 2, the rheumatologists’ nonuse of the treat-to-target tab decreased from 82% to 36% for escalation opportunities, and decisions to escalate therapy increased from 10% to 46%. Similarly, nonuse of the treat-to-target tab for deescalation therapy decreased from 64% to 34%, and decisions to deescalate therapy increased from 5% to 17%.

In 49% of escalation opportunities and 80% of deescalation opportunities in phase 2 of the program, rheumatologists made the decision to leave the patient alone. The reasons for not escalating therapy for a patient included an inaccurate CDAI (34%), patient decision (15%), risks outweighing the benefits (15%), and other (37%). “This is interesting, because if you take 49% times 34%, that means that only 17% of the time they felt it didn’t represent what was going on in our department, which is not what we heard from them verbally before this project,” he said. For deescalation opportunities in which the rheumatologist left the patient alone, the most common reasons were hard-to-control disease (46%), patient preference (29%), and poor prognostic factors (25%).

“Keep in mind, some of these patients may have actually already been deescalated prior to this,” Dr. Newman noted. “We’ve actually done some previous work 3 years ago – we provided a visual signal to our physicians that there was a deescalation opportunity, so we may have already accounted for that portion of the population to some extent.”

Dr. Newman said a future goal of the treat-to-target system is to developed more specific treat-to-target strategies to improve the “signal-to-noise” ratio in the system. “Now [that] it’s fully embedded into our routine RA care delivery across our system, our next steps are going to be to use this tool to proactively drive value-concordant decision making and monitor the effect this has on both disease control as well as cost of care,” he said.

Dr. Newman reported no relevant financial disclosures.
 

SOURCE: Newman ED et al. Arthritis Rheumatol. 2019;71(suppl 10). Abstract 1862.

ATLANTA – Opportunities to escalate or deescalate medications for patients with rheumatoid arthritis via an electronic health record at the point of care led rheumatologists at the Geisinger Medical Center in Danville, Pa., to increase the number of such decisions in their practice.

Jeff Craven/MDedge News

“Opportunities for escalation and de-escalation of therapy are common, even in a well-managed RA population,” Eric D. Newman, MD, director of the department of rheumatology at Geisinger, said in a presentation at the annual meeting of the American College of Rheumatology. “In our hands, over a third of the time, there was an opportunity to change therapy.”

Dr. Newman and colleagues developed a new treat-to-target tab for their (Patient Centric Electronic Redesign) PACER project, an EHR-adjacent system that captures patient and provider data and presents the information in different views, based on desired action items. The target in the study was low disease activity or remission, which was assessed using Clinical Disease Activity Index (CDAI) scores.

The treat-to-target tab offered three options to rheumatologists in real time when meeting with a patient: an escalation opportunity, which was defined as the patient’s two most recent CDAI scores showing moderate to high disease activity; and a deescalation opportunity, defined as a look-back up to 1 year during which at least two CDAI measures were within low to-moderate disease range. There was also a third “leave-alone” option to neither escalate nor deescalate therapy, but the rheumatologist was prompted to explain why if that option is selected, Dr. Newman noted.

In the first phase of releasing the treat-to-target tab, there was low adoption among the 17 rheumatologists at Geisinger: 82% of rheumatologists did not use the tab for escalation therapy, and 64% did not use the tab for deescalation therapy.

That prompted Dr. Newman and colleagues to develop a new version of the treat-to-target tab for phase 2 of the program. “Once they complete their CDAI, if there’s an opportunity, there would be a bright orange button that would glow right in front of them,” Dr. Newman said. “It was really hard to miss, and all they would have to do is click it and it would bring them right to the treat-to-target tab.”

To increase rheumatologists’ use of the new treat-to-target tab, the amount of time spent using the tab and making decisions is presented to them, he said. “It’s actually now part of our quality measure bundle, so every month, they get a leaderboard to see how they compare with their partners,” he noted. “It’s a great way to drive down variability and get everybody approaching the same sort of mean.”

Overall, between July 2018 and May 2019, there were 1,428 treat-to-target opportunities, consisting of 34.2% of RA office visits. Of these, 11.3% were escalation opportunities and 22.9% were deescalation opportunities, Dr. Newman said.

Between phase 1 and phase 2, the rheumatologists’ nonuse of the treat-to-target tab decreased from 82% to 36% for escalation opportunities, and decisions to escalate therapy increased from 10% to 46%. Similarly, nonuse of the treat-to-target tab for deescalation therapy decreased from 64% to 34%, and decisions to deescalate therapy increased from 5% to 17%.

In 49% of escalation opportunities and 80% of deescalation opportunities in phase 2 of the program, rheumatologists made the decision to leave the patient alone. The reasons for not escalating therapy for a patient included an inaccurate CDAI (34%), patient decision (15%), risks outweighing the benefits (15%), and other (37%). “This is interesting, because if you take 49% times 34%, that means that only 17% of the time they felt it didn’t represent what was going on in our department, which is not what we heard from them verbally before this project,” he said. For deescalation opportunities in which the rheumatologist left the patient alone, the most common reasons were hard-to-control disease (46%), patient preference (29%), and poor prognostic factors (25%).

“Keep in mind, some of these patients may have actually already been deescalated prior to this,” Dr. Newman noted. “We’ve actually done some previous work 3 years ago – we provided a visual signal to our physicians that there was a deescalation opportunity, so we may have already accounted for that portion of the population to some extent.”

Dr. Newman said a future goal of the treat-to-target system is to developed more specific treat-to-target strategies to improve the “signal-to-noise” ratio in the system. “Now [that] it’s fully embedded into our routine RA care delivery across our system, our next steps are going to be to use this tool to proactively drive value-concordant decision making and monitor the effect this has on both disease control as well as cost of care,” he said.

Dr. Newman reported no relevant financial disclosures.
 

SOURCE: Newman ED et al. Arthritis Rheumatol. 2019;71(suppl 10). Abstract 1862.

ATLANTA – Opportunities to escalate or deescalate medications for patients with rheumatoid arthritis via an electronic health record at the point of care led rheumatologists at the Geisinger Medical Center in Danville, Pa., to increase the number of such decisions in their practice.

Jeff Craven/MDedge News

“Opportunities for escalation and de-escalation of therapy are common, even in a well-managed RA population,” Eric D. Newman, MD, director of the department of rheumatology at Geisinger, said in a presentation at the annual meeting of the American College of Rheumatology. “In our hands, over a third of the time, there was an opportunity to change therapy.”

Dr. Newman and colleagues developed a new treat-to-target tab for their (Patient Centric Electronic Redesign) PACER project, an EHR-adjacent system that captures patient and provider data and presents the information in different views, based on desired action items. The target in the study was low disease activity or remission, which was assessed using Clinical Disease Activity Index (CDAI) scores.

The treat-to-target tab offered three options to rheumatologists in real time when meeting with a patient: an escalation opportunity, which was defined as the patient’s two most recent CDAI scores showing moderate to high disease activity; and a deescalation opportunity, defined as a look-back up to 1 year during which at least two CDAI measures were within low to-moderate disease range. There was also a third “leave-alone” option to neither escalate nor deescalate therapy, but the rheumatologist was prompted to explain why if that option is selected, Dr. Newman noted.

In the first phase of releasing the treat-to-target tab, there was low adoption among the 17 rheumatologists at Geisinger: 82% of rheumatologists did not use the tab for escalation therapy, and 64% did not use the tab for deescalation therapy.

That prompted Dr. Newman and colleagues to develop a new version of the treat-to-target tab for phase 2 of the program. “Once they complete their CDAI, if there’s an opportunity, there would be a bright orange button that would glow right in front of them,” Dr. Newman said. “It was really hard to miss, and all they would have to do is click it and it would bring them right to the treat-to-target tab.”

To increase rheumatologists’ use of the new treat-to-target tab, the amount of time spent using the tab and making decisions is presented to them, he said. “It’s actually now part of our quality measure bundle, so every month, they get a leaderboard to see how they compare with their partners,” he noted. “It’s a great way to drive down variability and get everybody approaching the same sort of mean.”

Overall, between July 2018 and May 2019, there were 1,428 treat-to-target opportunities, consisting of 34.2% of RA office visits. Of these, 11.3% were escalation opportunities and 22.9% were deescalation opportunities, Dr. Newman said.

Between phase 1 and phase 2, the rheumatologists’ nonuse of the treat-to-target tab decreased from 82% to 36% for escalation opportunities, and decisions to escalate therapy increased from 10% to 46%. Similarly, nonuse of the treat-to-target tab for deescalation therapy decreased from 64% to 34%, and decisions to deescalate therapy increased from 5% to 17%.

In 49% of escalation opportunities and 80% of deescalation opportunities in phase 2 of the program, rheumatologists made the decision to leave the patient alone. The reasons for not escalating therapy for a patient included an inaccurate CDAI (34%), patient decision (15%), risks outweighing the benefits (15%), and other (37%). “This is interesting, because if you take 49% times 34%, that means that only 17% of the time they felt it didn’t represent what was going on in our department, which is not what we heard from them verbally before this project,” he said. For deescalation opportunities in which the rheumatologist left the patient alone, the most common reasons were hard-to-control disease (46%), patient preference (29%), and poor prognostic factors (25%).

“Keep in mind, some of these patients may have actually already been deescalated prior to this,” Dr. Newman noted. “We’ve actually done some previous work 3 years ago – we provided a visual signal to our physicians that there was a deescalation opportunity, so we may have already accounted for that portion of the population to some extent.”

Dr. Newman said a future goal of the treat-to-target system is to developed more specific treat-to-target strategies to improve the “signal-to-noise” ratio in the system. “Now [that] it’s fully embedded into our routine RA care delivery across our system, our next steps are going to be to use this tool to proactively drive value-concordant decision making and monitor the effect this has on both disease control as well as cost of care,” he said.

Dr. Newman reported no relevant financial disclosures.
 

SOURCE: Newman ED et al. Arthritis Rheumatol. 2019;71(suppl 10). Abstract 1862.

BOSTON – Cilofexor, a nonsteroidal farnesoid X receptor (FXR) agonist, can improve disease biomarkers in patients with primary biliary cholangitis (PBC), based on results of a phase 2 trial.

Will Pass/MDedge News

Compared with placebo, patients treated with cilofexor had significant reductions in serum alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), C-reactive protein (CRP), and primary bile acids, reported lead author Kris V. Kowdley, MD, of Swedish Medical Center in Seattle, and colleagues.

Dr. Kowdley, who presented findings at the annual meeting of the American Association for the Study of Liver Diseases, began by offering some context for the trial.

“There’s a strong rationale for FXR agonist therapy in PBC,” he said. “FXR is the key regulator of bile acid homeostasis, and FXR agonists have shown favorable effects on fibrosis, inflammatory activity, bile acid export and synthesis, as well as possibly effects on the microbiome and downstream in the gut.” He went on to explain that cilofexor may benefit patients with PBC, primary sclerosing cholangitis, or nonalcoholic steatohepatitis (NASH), noting preclinical data that have demonstrated reductions in bile acids, inflammation, fibrosis, and portal pressure.

The present trial involved 71 patients with PBC who lacked cirrhosis and had a serum ALP level that was at least 1.67 times greater than the upper limit of normal, and an elevated serum total bilirubin that was less than 2 times the upper limit of normal. Patients were randomized to receive either cilofexor 30 mg, cilofexor 100 mg, or placebo, once daily for 12 weeks. Stratification was based on use of ursodeoxycholic acid, which was stable for at least the preceding year. Safety and efficacy were evaluated, with the latter based on liver biochemistry, serum C4, bile acids, and serum fibrosis markers.

Across the entire population, baseline median serum bilirubin was 0.6 mg/dL and median serum ALP was 286 U/L. After 12 weeks, compared with placebo, patients treated with cilofexor, particularly those who received the 100-mg dose, showed significant improvements across multiple measures of liver health. Specifically, patients in the 100-mg group achieved median reductions in ALP (–13.8%; P = .005), GGT (–47.7%; P less than .001), CRP (–33.6%; P = .03), and primary bile acids (–30.5%; P = .008). These patients also exhibited trends toward reduced aspartate aminotransferase and aminoterminal propeptide of type III procollagen; Dr. Kowdley attributed the lack of statistical significance to insufficient population size.

Highlighting magnitude of ALP improvement, Dr. Kowdley noted that reductions in ALP greater than 25% were observed in 17% and 18% of patients in the 100-mg and 30-mg cilofexor groups, respectively, versus 0% of patients in the placebo group.

Although the 100-mg dose of cilofexor appeared more effective, the higher dose did come with some trade-offs in tolerability; grade 2 or 3 pruritus was more common in patients treated with the higher dose than in those who received the 30-mg dose (39% vs. 10%). As such, 7% of patients in the 100-mg group discontinued therapy because of the pruritus, compared with no patients in the 30-mg or placebo group.

Responding to a question from a conference attendee, Dr. Kowdley said that ALP reductions to below the 1.67-fold threshold were achieved by 9% and 14% of patients who received the 30-mg dose and 100-mg dose of cilofexor, respectively.

“We believe these data support further evaluation of cilofexor for the treatment of cholestatic liver disorders,” Dr. Kowdley concluded.

The study was funded by Gilead. The investigators disclosed additional relationships with Allergan, Novartis, GlaxoSmithKline, and others.

SOURCE: Kowdley KV et al. The Liver Meeting 2019. Abstract 45.

BOSTON – Cilofexor, a nonsteroidal farnesoid X receptor (FXR) agonist, can improve disease biomarkers in patients with primary biliary cholangitis (PBC), based on results of a phase 2 trial.

Will Pass/MDedge News

Compared with placebo, patients treated with cilofexor had significant reductions in serum alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), C-reactive protein (CRP), and primary bile acids, reported lead author Kris V. Kowdley, MD, of Swedish Medical Center in Seattle, and colleagues.

Dr. Kowdley, who presented findings at the annual meeting of the American Association for the Study of Liver Diseases, began by offering some context for the trial.

“There’s a strong rationale for FXR agonist therapy in PBC,” he said. “FXR is the key regulator of bile acid homeostasis, and FXR agonists have shown favorable effects on fibrosis, inflammatory activity, bile acid export and synthesis, as well as possibly effects on the microbiome and downstream in the gut.” He went on to explain that cilofexor may benefit patients with PBC, primary sclerosing cholangitis, or nonalcoholic steatohepatitis (NASH), noting preclinical data that have demonstrated reductions in bile acids, inflammation, fibrosis, and portal pressure.

The present trial involved 71 patients with PBC who lacked cirrhosis and had a serum ALP level that was at least 1.67 times greater than the upper limit of normal, and an elevated serum total bilirubin that was less than 2 times the upper limit of normal. Patients were randomized to receive either cilofexor 30 mg, cilofexor 100 mg, or placebo, once daily for 12 weeks. Stratification was based on use of ursodeoxycholic acid, which was stable for at least the preceding year. Safety and efficacy were evaluated, with the latter based on liver biochemistry, serum C4, bile acids, and serum fibrosis markers.

Across the entire population, baseline median serum bilirubin was 0.6 mg/dL and median serum ALP was 286 U/L. After 12 weeks, compared with placebo, patients treated with cilofexor, particularly those who received the 100-mg dose, showed significant improvements across multiple measures of liver health. Specifically, patients in the 100-mg group achieved median reductions in ALP (–13.8%; P = .005), GGT (–47.7%; P less than .001), CRP (–33.6%; P = .03), and primary bile acids (–30.5%; P = .008). These patients also exhibited trends toward reduced aspartate aminotransferase and aminoterminal propeptide of type III procollagen; Dr. Kowdley attributed the lack of statistical significance to insufficient population size.

Highlighting magnitude of ALP improvement, Dr. Kowdley noted that reductions in ALP greater than 25% were observed in 17% and 18% of patients in the 100-mg and 30-mg cilofexor groups, respectively, versus 0% of patients in the placebo group.

Although the 100-mg dose of cilofexor appeared more effective, the higher dose did come with some trade-offs in tolerability; grade 2 or 3 pruritus was more common in patients treated with the higher dose than in those who received the 30-mg dose (39% vs. 10%). As such, 7% of patients in the 100-mg group discontinued therapy because of the pruritus, compared with no patients in the 30-mg or placebo group.

Responding to a question from a conference attendee, Dr. Kowdley said that ALP reductions to below the 1.67-fold threshold were achieved by 9% and 14% of patients who received the 30-mg dose and 100-mg dose of cilofexor, respectively.

“We believe these data support further evaluation of cilofexor for the treatment of cholestatic liver disorders,” Dr. Kowdley concluded.

The study was funded by Gilead. The investigators disclosed additional relationships with Allergan, Novartis, GlaxoSmithKline, and others.

SOURCE: Kowdley KV et al. The Liver Meeting 2019. Abstract 45.

BOSTON – Cilofexor, a nonsteroidal farnesoid X receptor (FXR) agonist, can improve disease biomarkers in patients with primary biliary cholangitis (PBC), based on results of a phase 2 trial.

Will Pass/MDedge News

Compared with placebo, patients treated with cilofexor had significant reductions in serum alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), C-reactive protein (CRP), and primary bile acids, reported lead author Kris V. Kowdley, MD, of Swedish Medical Center in Seattle, and colleagues.

Dr. Kowdley, who presented findings at the annual meeting of the American Association for the Study of Liver Diseases, began by offering some context for the trial.

“There’s a strong rationale for FXR agonist therapy in PBC,” he said. “FXR is the key regulator of bile acid homeostasis, and FXR agonists have shown favorable effects on fibrosis, inflammatory activity, bile acid export and synthesis, as well as possibly effects on the microbiome and downstream in the gut.” He went on to explain that cilofexor may benefit patients with PBC, primary sclerosing cholangitis, or nonalcoholic steatohepatitis (NASH), noting preclinical data that have demonstrated reductions in bile acids, inflammation, fibrosis, and portal pressure.

The present trial involved 71 patients with PBC who lacked cirrhosis and had a serum ALP level that was at least 1.67 times greater than the upper limit of normal, and an elevated serum total bilirubin that was less than 2 times the upper limit of normal. Patients were randomized to receive either cilofexor 30 mg, cilofexor 100 mg, or placebo, once daily for 12 weeks. Stratification was based on use of ursodeoxycholic acid, which was stable for at least the preceding year. Safety and efficacy were evaluated, with the latter based on liver biochemistry, serum C4, bile acids, and serum fibrosis markers.

Across the entire population, baseline median serum bilirubin was 0.6 mg/dL and median serum ALP was 286 U/L. After 12 weeks, compared with placebo, patients treated with cilofexor, particularly those who received the 100-mg dose, showed significant improvements across multiple measures of liver health. Specifically, patients in the 100-mg group achieved median reductions in ALP (–13.8%; P = .005), GGT (–47.7%; P less than .001), CRP (–33.6%; P = .03), and primary bile acids (–30.5%; P = .008). These patients also exhibited trends toward reduced aspartate aminotransferase and aminoterminal propeptide of type III procollagen; Dr. Kowdley attributed the lack of statistical significance to insufficient population size.

Highlighting magnitude of ALP improvement, Dr. Kowdley noted that reductions in ALP greater than 25% were observed in 17% and 18% of patients in the 100-mg and 30-mg cilofexor groups, respectively, versus 0% of patients in the placebo group.

Although the 100-mg dose of cilofexor appeared more effective, the higher dose did come with some trade-offs in tolerability; grade 2 or 3 pruritus was more common in patients treated with the higher dose than in those who received the 30-mg dose (39% vs. 10%). As such, 7% of patients in the 100-mg group discontinued therapy because of the pruritus, compared with no patients in the 30-mg or placebo group.

Responding to a question from a conference attendee, Dr. Kowdley said that ALP reductions to below the 1.67-fold threshold were achieved by 9% and 14% of patients who received the 30-mg dose and 100-mg dose of cilofexor, respectively.

“We believe these data support further evaluation of cilofexor for the treatment of cholestatic liver disorders,” Dr. Kowdley concluded.

The study was funded by Gilead. The investigators disclosed additional relationships with Allergan, Novartis, GlaxoSmithKline, and others.

SOURCE: Kowdley KV et al. The Liver Meeting 2019. Abstract 45.

BOSTON – A machine-learning model based on standard clinical and laboratory values is able to predict nonalcoholic steatohepatitis (NASH) with a sensitivity of 72%-81%, an investigator reported at the annual meeting of the American Association for the Study of Liver Diseases.

The tool, dubbed NASHmap, could serve as an initial screening tool to reveal more potential undiagnosed patients with NASH, according to Jörn M. Schattenberg, MD, with the metabolic liver research program in the department of medicine at University Medical Centre Mainz (Germany).

While not intended to replace current scoring systems, NASHmap potentially could be applied as a clinical decision support tool within electronic medical record systems, allowing greater numbers of patients with suspected NASH to be evaluated and referred to specialists for further testing, according to Dr. Schattenberg.

“To me, this is an at-risk population,” Dr. Schattenberg said in an interview. “There’s a lot of talk of increasing numbers of end-stage liver disease, and these are the cases that are waiting to happen. I think if we identify them, we can manage them better.”

“I’m not saying they should all get drugs – I’m saying they have to be informed about their condition because they may not have a clue they have liver disease,” he continued.

The machine-learning approach described here by Dr. Schattenberg included an exploratory analysis based on 704 patients with NASH or non-NASH nonalcoholic fatty liver disease (NAFLD) in the NAFLD Adult Database from the National Institute of Diabetes, Digestive, and Kidney Diseases.

The best-performing model they identified included 14 variables. Ranked by contribution to predictive power, those variables included hemoglobin A_1c, aspartate aminotransferase, alanine aminotransferase, total protein, AST/ALT ratio, body mass index, triglycerides, height, platelets, white blood cells, hematocrit, albumin, hypertension, and sex.

That 14-variable model had good performance when tested on the Optum Humedica electronic medical record database, according to Dr. Schattenberg and colleagues.

In the analysis for final evaluation, including 1,016 patients with histologically confirmed NASH, the area under the curve was 0.76, they reported.

A simplified, five-variable model including just hemoglobin A_1c, AST, ALT, total protein, and AST/ALT ratio also had good performance, with an area under the curve of 0.74, they said in their report.

Dr. Schattenberg provided disclosures related to AbbVie, Novartis, MSD, Pfizer, Boehringer Ingelheim, BMS, Intercept Pharmaceuticals, Genfit, Gilead, and Echosens. Several study coauthors reported employment with Novartis and stock ownership.

BOSTON – A machine-learning model based on standard clinical and laboratory values is able to predict nonalcoholic steatohepatitis (NASH) with a sensitivity of 72%-81%, an investigator reported at the annual meeting of the American Association for the Study of Liver Diseases.

The tool, dubbed NASHmap, could serve as an initial screening tool to reveal more potential undiagnosed patients with NASH, according to Jörn M. Schattenberg, MD, with the metabolic liver research program in the department of medicine at University Medical Centre Mainz (Germany).

While not intended to replace current scoring systems, NASHmap potentially could be applied as a clinical decision support tool within electronic medical record systems, allowing greater numbers of patients with suspected NASH to be evaluated and referred to specialists for further testing, according to Dr. Schattenberg.

“To me, this is an at-risk population,” Dr. Schattenberg said in an interview. “There’s a lot of talk of increasing numbers of end-stage liver disease, and these are the cases that are waiting to happen. I think if we identify them, we can manage them better.”

“I’m not saying they should all get drugs – I’m saying they have to be informed about their condition because they may not have a clue they have liver disease,” he continued.

The machine-learning approach described here by Dr. Schattenberg included an exploratory analysis based on 704 patients with NASH or non-NASH nonalcoholic fatty liver disease (NAFLD) in the NAFLD Adult Database from the National Institute of Diabetes, Digestive, and Kidney Diseases.

The best-performing model they identified included 14 variables. Ranked by contribution to predictive power, those variables included hemoglobin A_1c, aspartate aminotransferase, alanine aminotransferase, total protein, AST/ALT ratio, body mass index, triglycerides, height, platelets, white blood cells, hematocrit, albumin, hypertension, and sex.

That 14-variable model had good performance when tested on the Optum Humedica electronic medical record database, according to Dr. Schattenberg and colleagues.

In the analysis for final evaluation, including 1,016 patients with histologically confirmed NASH, the area under the curve was 0.76, they reported.

A simplified, five-variable model including just hemoglobin A_1c, AST, ALT, total protein, and AST/ALT ratio also had good performance, with an area under the curve of 0.74, they said in their report.

Dr. Schattenberg provided disclosures related to AbbVie, Novartis, MSD, Pfizer, Boehringer Ingelheim, BMS, Intercept Pharmaceuticals, Genfit, Gilead, and Echosens. Several study coauthors reported employment with Novartis and stock ownership.

BOSTON – A machine-learning model based on standard clinical and laboratory values is able to predict nonalcoholic steatohepatitis (NASH) with a sensitivity of 72%-81%, an investigator reported at the annual meeting of the American Association for the Study of Liver Diseases.

The tool, dubbed NASHmap, could serve as an initial screening tool to reveal more potential undiagnosed patients with NASH, according to Jörn M. Schattenberg, MD, with the metabolic liver research program in the department of medicine at University Medical Centre Mainz (Germany).

While not intended to replace current scoring systems, NASHmap potentially could be applied as a clinical decision support tool within electronic medical record systems, allowing greater numbers of patients with suspected NASH to be evaluated and referred to specialists for further testing, according to Dr. Schattenberg.

“To me, this is an at-risk population,” Dr. Schattenberg said in an interview. “There’s a lot of talk of increasing numbers of end-stage liver disease, and these are the cases that are waiting to happen. I think if we identify them, we can manage them better.”

“I’m not saying they should all get drugs – I’m saying they have to be informed about their condition because they may not have a clue they have liver disease,” he continued.

The machine-learning approach described here by Dr. Schattenberg included an exploratory analysis based on 704 patients with NASH or non-NASH nonalcoholic fatty liver disease (NAFLD) in the NAFLD Adult Database from the National Institute of Diabetes, Digestive, and Kidney Diseases.

The best-performing model they identified included 14 variables. Ranked by contribution to predictive power, those variables included hemoglobin A_1c, aspartate aminotransferase, alanine aminotransferase, total protein, AST/ALT ratio, body mass index, triglycerides, height, platelets, white blood cells, hematocrit, albumin, hypertension, and sex.

That 14-variable model had good performance when tested on the Optum Humedica electronic medical record database, according to Dr. Schattenberg and colleagues.

In the analysis for final evaluation, including 1,016 patients with histologically confirmed NASH, the area under the curve was 0.76, they reported.

A simplified, five-variable model including just hemoglobin A_1c, AST, ALT, total protein, and AST/ALT ratio also had good performance, with an area under the curve of 0.74, they said in their report.

Dr. Schattenberg provided disclosures related to AbbVie, Novartis, MSD, Pfizer, Boehringer Ingelheim, BMS, Intercept Pharmaceuticals, Genfit, Gilead, and Echosens. Several study coauthors reported employment with Novartis and stock ownership.

SAN FRANCISCO – A “Best Case/Worst Case” (BCWC) framework tool has been adapted for use with geriatric trauma patients in the ICU, where it can help track a patient’s progress and enable better communication with patients and loved ones. The tool relies on a combination of graphics and text that surgeons update daily during rounds, and creates a longitudinal view of a patient’s trajectory during their stay in the ICU.

Andrei Malov/Thinkstock

The aim is to have surgeons incorporate story telling into care, by updating the best-case scenario in light of new clinical developments – for example, after a complication has arisen.

“Each day during rounds, the ICU team records important events on the graphic aid that change the patient’s course. The team draws a star to represent the best case, and a line to represent prognostic uncertainty. The attending trauma surgeon then uses the geriatric trauma outcome score, their knowledge of the health state of the patient, and their own clinical experience to tell a story about treatments, recovery, and outcomes if everything goes as well as we might hope. This story is written down in the best-case scenario box,” Christopher Zimmerman, MD, a general surgery resident at the University of Wisconsin–Madison, said during a presentation about the BCWC tool at the annual clinical congress of the American College of Surgeons

“We often like to talk to patients and their families [about best- and worst-case scenarios] anyway, but [the research team] have tried to formalize it,” said Tam Pham, MD, professor of surgery at the University of Washington, in an interview. Dr. Pham comoderated the session where the research was presented.

“When we’re able to communicate where the uncertainty is and where the boundaries are around the course of care and possible outcomes, we can build an alliance with patients and families that will be helpful when there is a big decision to make, say about a laparotomy for a perforated viscus,” said Dr. Zimmerman.

Dr. Zimmerman gave an example of a patient who came into the ICU after suffering multiple fractures from falling down a set of stairs. The team created an initial BCWC with a hoped-for best-case scenario. Later, the patient developed hypoxemic respiratory failure and had to be intubated overnight. “This event is recorded on the graphic, and her star representing the best case has changed position, the line representing uncertainty has shortened, and the contents of her best-case scenario has changed. Each day in rounds, this process is repeated,” said Dr. Zimmerman.

Palliative care physicians, education experts, and surgeons at the University of Wisconsin–Madison developed the tool in an effort to reduce unwanted care at the end of life, in the context of high-risk surgeries. The researchers adapted the tool to the trauma setting by gathering six focus groups of trauma practitioners at the University of Wisconsin; University of Texas, Dallas; and Oregon Health & Science University, Portland. They modified the tool after incorporating comments, and then iteratively modified it through tasks carried out in the ICU as part of a qualitative improvement initiative at the University of Wisconsin–Madison. They generated a change to the tool, implemented it in the ICU during subsequent rounds, then collected observations and field notes, then revised and repeated the process, streamlining it to fit into the ICU environment, according to Dr. Zimmerman.

The back side of the tool is available for family members to write important details about their loved ones, leading insight into the patient’s personality and desires, such as favorite music or affection for a family pet.

The work was supported by the National Institutes of Health. Dr. Zimmerman and Dr. Pham have no relevant financial disclosures.

SOURCE: Zimmerman C et al. Clinical Congress 2019, Abstract.

SAN FRANCISCO – A “Best Case/Worst Case” (BCWC) framework tool has been adapted for use with geriatric trauma patients in the ICU, where it can help track a patient’s progress and enable better communication with patients and loved ones. The tool relies on a combination of graphics and text that surgeons update daily during rounds, and creates a longitudinal view of a patient’s trajectory during their stay in the ICU.

Andrei Malov/Thinkstock

The aim is to have surgeons incorporate story telling into care, by updating the best-case scenario in light of new clinical developments – for example, after a complication has arisen.

“Each day during rounds, the ICU team records important events on the graphic aid that change the patient’s course. The team draws a star to represent the best case, and a line to represent prognostic uncertainty. The attending trauma surgeon then uses the geriatric trauma outcome score, their knowledge of the health state of the patient, and their own clinical experience to tell a story about treatments, recovery, and outcomes if everything goes as well as we might hope. This story is written down in the best-case scenario box,” Christopher Zimmerman, MD, a general surgery resident at the University of Wisconsin–Madison, said during a presentation about the BCWC tool at the annual clinical congress of the American College of Surgeons

“We often like to talk to patients and their families [about best- and worst-case scenarios] anyway, but [the research team] have tried to formalize it,” said Tam Pham, MD, professor of surgery at the University of Washington, in an interview. Dr. Pham comoderated the session where the research was presented.

“When we’re able to communicate where the uncertainty is and where the boundaries are around the course of care and possible outcomes, we can build an alliance with patients and families that will be helpful when there is a big decision to make, say about a laparotomy for a perforated viscus,” said Dr. Zimmerman.

Dr. Zimmerman gave an example of a patient who came into the ICU after suffering multiple fractures from falling down a set of stairs. The team created an initial BCWC with a hoped-for best-case scenario. Later, the patient developed hypoxemic respiratory failure and had to be intubated overnight. “This event is recorded on the graphic, and her star representing the best case has changed position, the line representing uncertainty has shortened, and the contents of her best-case scenario has changed. Each day in rounds, this process is repeated,” said Dr. Zimmerman.

Palliative care physicians, education experts, and surgeons at the University of Wisconsin–Madison developed the tool in an effort to reduce unwanted care at the end of life, in the context of high-risk surgeries. The researchers adapted the tool to the trauma setting by gathering six focus groups of trauma practitioners at the University of Wisconsin; University of Texas, Dallas; and Oregon Health & Science University, Portland. They modified the tool after incorporating comments, and then iteratively modified it through tasks carried out in the ICU as part of a qualitative improvement initiative at the University of Wisconsin–Madison. They generated a change to the tool, implemented it in the ICU during subsequent rounds, then collected observations and field notes, then revised and repeated the process, streamlining it to fit into the ICU environment, according to Dr. Zimmerman.

The back side of the tool is available for family members to write important details about their loved ones, leading insight into the patient’s personality and desires, such as favorite music or affection for a family pet.

The work was supported by the National Institutes of Health. Dr. Zimmerman and Dr. Pham have no relevant financial disclosures.

SOURCE: Zimmerman C et al. Clinical Congress 2019, Abstract.

SAN FRANCISCO – A “Best Case/Worst Case” (BCWC) framework tool has been adapted for use with geriatric trauma patients in the ICU, where it can help track a patient’s progress and enable better communication with patients and loved ones. The tool relies on a combination of graphics and text that surgeons update daily during rounds, and creates a longitudinal view of a patient’s trajectory during their stay in the ICU.

Andrei Malov/Thinkstock

The aim is to have surgeons incorporate story telling into care, by updating the best-case scenario in light of new clinical developments – for example, after a complication has arisen.

“Each day during rounds, the ICU team records important events on the graphic aid that change the patient’s course. The team draws a star to represent the best case, and a line to represent prognostic uncertainty. The attending trauma surgeon then uses the geriatric trauma outcome score, their knowledge of the health state of the patient, and their own clinical experience to tell a story about treatments, recovery, and outcomes if everything goes as well as we might hope. This story is written down in the best-case scenario box,” Christopher Zimmerman, MD, a general surgery resident at the University of Wisconsin–Madison, said during a presentation about the BCWC tool at the annual clinical congress of the American College of Surgeons

“We often like to talk to patients and their families [about best- and worst-case scenarios] anyway, but [the research team] have tried to formalize it,” said Tam Pham, MD, professor of surgery at the University of Washington, in an interview. Dr. Pham comoderated the session where the research was presented.

“When we’re able to communicate where the uncertainty is and where the boundaries are around the course of care and possible outcomes, we can build an alliance with patients and families that will be helpful when there is a big decision to make, say about a laparotomy for a perforated viscus,” said Dr. Zimmerman.

Dr. Zimmerman gave an example of a patient who came into the ICU after suffering multiple fractures from falling down a set of stairs. The team created an initial BCWC with a hoped-for best-case scenario. Later, the patient developed hypoxemic respiratory failure and had to be intubated overnight. “This event is recorded on the graphic, and her star representing the best case has changed position, the line representing uncertainty has shortened, and the contents of her best-case scenario has changed. Each day in rounds, this process is repeated,” said Dr. Zimmerman.

Palliative care physicians, education experts, and surgeons at the University of Wisconsin–Madison developed the tool in an effort to reduce unwanted care at the end of life, in the context of high-risk surgeries. The researchers adapted the tool to the trauma setting by gathering six focus groups of trauma practitioners at the University of Wisconsin; University of Texas, Dallas; and Oregon Health & Science University, Portland. They modified the tool after incorporating comments, and then iteratively modified it through tasks carried out in the ICU as part of a qualitative improvement initiative at the University of Wisconsin–Madison. They generated a change to the tool, implemented it in the ICU during subsequent rounds, then collected observations and field notes, then revised and repeated the process, streamlining it to fit into the ICU environment, according to Dr. Zimmerman.

The back side of the tool is available for family members to write important details about their loved ones, leading insight into the patient’s personality and desires, such as favorite music or affection for a family pet.

The work was supported by the National Institutes of Health. Dr. Zimmerman and Dr. Pham have no relevant financial disclosures.

SOURCE: Zimmerman C et al. Clinical Congress 2019, Abstract.

Tinea versicolor (TV), or pityriasis versicolor, is a noninflammatory, superficial cutaneous fungal infection caused by Malassezia furfur, also known as Pityrosporum orbiculare or P. ovale. In its hyphal form, it produces skin lesions that appear as scaly, round or oval, hypopigmented, hyperpigmented, or pink macules or patches. Lesions are asymptomatic. The condition is more commonly seen in warm climates or during the summer months. Malassezia requires an oily environment for growth. Typically, TV appears in sebum-producing areas on the trunk. However, other sites may be affected such as the scalp, groin, and flexural areas. Infants may have facial lesions. Hypopigmentation may persist for months, even after lesions are treated, and takes time to resolve.

The differential diagnosis of hypopigmented lesions of tinea versicolor includes vitiligo, hypopigmented mycosis fungoides, progressive macular hypomelanosis (PMH), secondary syphilis, and pityriasis alba. Potassium hydroxide (KOH) preparations can be performed in the office for TV to reveal short, thick fungal hyphae with multiple spores, often referred to as “spaghetti and meatballs.” Use of a Wood’s light may aid in diagnosis. In TV, lesions may fluoresce yellow-green in adjacent follicles, unlike PMH, which characteristically show orange-red follicular fluorescence. A skin biopsy is necessary to rule out hypopgimented mycosis fungoides or syphilis. Histologically in TV, hyphae and spores will be present in the stratum corneum or in hair follicles. These are readily seen with PAS or GMS (Grocott methenamine silver) stains. There is usually no inflammation and skin appears “normal.” A biopsy was performed in this patient that revealed PAS positive hyphae.

Treatment for TV can be topical or systemic. Antifungal azole shampoo or creams, selenium sulfide shampoo, sulfur preparations, and allylamine creams have all been reported as useful treatments. Oral itraconazole or fluconazole are often given as systemic treatments. Monthly or weekly topical therapy may help prevent relapse.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

Tinea versicolor (TV), or pityriasis versicolor, is a noninflammatory, superficial cutaneous fungal infection caused by Malassezia furfur, also known as Pityrosporum orbiculare or P. ovale. In its hyphal form, it produces skin lesions that appear as scaly, round or oval, hypopigmented, hyperpigmented, or pink macules or patches. Lesions are asymptomatic. The condition is more commonly seen in warm climates or during the summer months. Malassezia requires an oily environment for growth. Typically, TV appears in sebum-producing areas on the trunk. However, other sites may be affected such as the scalp, groin, and flexural areas. Infants may have facial lesions. Hypopigmentation may persist for months, even after lesions are treated, and takes time to resolve.

The differential diagnosis of hypopigmented lesions of tinea versicolor includes vitiligo, hypopigmented mycosis fungoides, progressive macular hypomelanosis (PMH), secondary syphilis, and pityriasis alba. Potassium hydroxide (KOH) preparations can be performed in the office for TV to reveal short, thick fungal hyphae with multiple spores, often referred to as “spaghetti and meatballs.” Use of a Wood’s light may aid in diagnosis. In TV, lesions may fluoresce yellow-green in adjacent follicles, unlike PMH, which characteristically show orange-red follicular fluorescence. A skin biopsy is necessary to rule out hypopgimented mycosis fungoides or syphilis. Histologically in TV, hyphae and spores will be present in the stratum corneum or in hair follicles. These are readily seen with PAS or GMS (Grocott methenamine silver) stains. There is usually no inflammation and skin appears “normal.” A biopsy was performed in this patient that revealed PAS positive hyphae.

Treatment for TV can be topical or systemic. Antifungal azole shampoo or creams, selenium sulfide shampoo, sulfur preparations, and allylamine creams have all been reported as useful treatments. Oral itraconazole or fluconazole are often given as systemic treatments. Monthly or weekly topical therapy may help prevent relapse.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

Tinea versicolor (TV), or pityriasis versicolor, is a noninflammatory, superficial cutaneous fungal infection caused by Malassezia furfur, also known as Pityrosporum orbiculare or P. ovale. In its hyphal form, it produces skin lesions that appear as scaly, round or oval, hypopigmented, hyperpigmented, or pink macules or patches. Lesions are asymptomatic. The condition is more commonly seen in warm climates or during the summer months. Malassezia requires an oily environment for growth. Typically, TV appears in sebum-producing areas on the trunk. However, other sites may be affected such as the scalp, groin, and flexural areas. Infants may have facial lesions. Hypopigmentation may persist for months, even after lesions are treated, and takes time to resolve.

The differential diagnosis of hypopigmented lesions of tinea versicolor includes vitiligo, hypopigmented mycosis fungoides, progressive macular hypomelanosis (PMH), secondary syphilis, and pityriasis alba. Potassium hydroxide (KOH) preparations can be performed in the office for TV to reveal short, thick fungal hyphae with multiple spores, often referred to as “spaghetti and meatballs.” Use of a Wood’s light may aid in diagnosis. In TV, lesions may fluoresce yellow-green in adjacent follicles, unlike PMH, which characteristically show orange-red follicular fluorescence. A skin biopsy is necessary to rule out hypopgimented mycosis fungoides or syphilis. Histologically in TV, hyphae and spores will be present in the stratum corneum or in hair follicles. These are readily seen with PAS or GMS (Grocott methenamine silver) stains. There is usually no inflammation and skin appears “normal.” A biopsy was performed in this patient that revealed PAS positive hyphae.

Treatment for TV can be topical or systemic. Antifungal azole shampoo or creams, selenium sulfide shampoo, sulfur preparations, and allylamine creams have all been reported as useful treatments. Oral itraconazole or fluconazole are often given as systemic treatments. Monthly or weekly topical therapy may help prevent relapse.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].