Key clinical point: Gleason scores within grade group 4 prostate cancer were associated with biochemical recurrence, but not cancer-specific mortality or all-cause mortality.

Major finding: Gleason score (GS) 5 + 3 was associated with significantly higher rates of GS upgrading in radical prostatectomy (RP) specimens than either GS 3 + 5 or GS 4 + 4.

Study details: The data come from a retrospective review of 1,791 adults with grade 4 prostate cancer, including 190 with Gleason score (GS) 3 + 5; 1,557 with GS 4 + 4; and 44 with GS 5 + 3).

Disclosures: The study was funded in part by the Medical University of Vienna. The researchers had no financial conflicts to disclose.

Source: Mori K et al. Ann Surg Oncol. 2021 Jun 11. doi: 10.1245/s10434-021-10257-x.

Key clinical point: Gleason scores within grade group 4 prostate cancer were associated with biochemical recurrence, but not cancer-specific mortality or all-cause mortality.

Major finding: Gleason score (GS) 5 + 3 was associated with significantly higher rates of GS upgrading in radical prostatectomy (RP) specimens than either GS 3 + 5 or GS 4 + 4.

Study details: The data come from a retrospective review of 1,791 adults with grade 4 prostate cancer, including 190 with Gleason score (GS) 3 + 5; 1,557 with GS 4 + 4; and 44 with GS 5 + 3).

Disclosures: The study was funded in part by the Medical University of Vienna. The researchers had no financial conflicts to disclose.

Source: Mori K et al. Ann Surg Oncol. 2021 Jun 11. doi: 10.1245/s10434-021-10257-x.

Key clinical point: Gleason scores within grade group 4 prostate cancer were associated with biochemical recurrence, but not cancer-specific mortality or all-cause mortality.

Major finding: Gleason score (GS) 5 + 3 was associated with significantly higher rates of GS upgrading in radical prostatectomy (RP) specimens than either GS 3 + 5 or GS 4 + 4.

Study details: The data come from a retrospective review of 1,791 adults with grade 4 prostate cancer, including 190 with Gleason score (GS) 3 + 5; 1,557 with GS 4 + 4; and 44 with GS 5 + 3).

Disclosures: The study was funded in part by the Medical University of Vienna. The researchers had no financial conflicts to disclose.

Source: Mori K et al. Ann Surg Oncol. 2021 Jun 11. doi: 10.1245/s10434-021-10257-x.

Key clinical point: The Briganti 2019 nomogram accurately predicted lymph node invasion in adults with high-risk, clinically localized prostate cancer.

Major finding: The area under the curve for the Briganti 2019 was 0.71. At a cutoff of 7%, sensitivity, specificity, and negative predictive values were 94.7%, 32.0%a, and 98.8%, respectively.

Study details: The data come from a review of 278 adults with prostate cancer who underwent radical prostatectomy and extended pelvic lymph node dissection. Patients were rated using the Briganti 2019 nomogram; researchers used the area under the curve of the receiver operating characteristic analysis to quantify accuracy.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Fukagawa E et al. Int J Clin Oncol. 2021 Jun 12. doi: 10.1007/s10147-021-01954-4. 

Key clinical point: The Briganti 2019 nomogram accurately predicted lymph node invasion in adults with high-risk, clinically localized prostate cancer.

Major finding: The area under the curve for the Briganti 2019 was 0.71. At a cutoff of 7%, sensitivity, specificity, and negative predictive values were 94.7%, 32.0%a, and 98.8%, respectively.

Study details: The data come from a review of 278 adults with prostate cancer who underwent radical prostatectomy and extended pelvic lymph node dissection. Patients were rated using the Briganti 2019 nomogram; researchers used the area under the curve of the receiver operating characteristic analysis to quantify accuracy.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Fukagawa E et al. Int J Clin Oncol. 2021 Jun 12. doi: 10.1007/s10147-021-01954-4. 

Key clinical point: The Briganti 2019 nomogram accurately predicted lymph node invasion in adults with high-risk, clinically localized prostate cancer.

Major finding: The area under the curve for the Briganti 2019 was 0.71. At a cutoff of 7%, sensitivity, specificity, and negative predictive values were 94.7%, 32.0%a, and 98.8%, respectively.

Study details: The data come from a review of 278 adults with prostate cancer who underwent radical prostatectomy and extended pelvic lymph node dissection. Patients were rated using the Briganti 2019 nomogram; researchers used the area under the curve of the receiver operating characteristic analysis to quantify accuracy.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Fukagawa E et al. Int J Clin Oncol. 2021 Jun 12. doi: 10.1007/s10147-021-01954-4. 

Newly updated COVID-19 vaccination guidance from the American College of Rheumatology offers detailed insight into how clinicians should proceed with use, timing, and prioritization of COVID-19 vaccines in patients with rheumatic and musculoskeletal diseases (RMDs).

“The task force advised health care providers to avoid being overly dogmatic in following these recommendations,” Jeffrey R. Curtis, MD, of the University of Alabama at Birmingham, and colleagues wrote. “The attempt to optimize vaccine response in relation to the use and timing of immunosuppressive medications should not compromise a willing patient’s ability to undergo vaccination in a timely manner and risk a missed vaccination opportunity.” The guidelines were published in Arthritis & Rheumatology.

To review the published literature and determine the safety and efficacy of the available COVID-19 vaccines for patients with RMDs, a task force made up of nine rheumatologists/immunologists, two infectious disease specialists, and two public health physicians was formed. The ACR COVID-19 Vaccine Guidance Task Force considered vaccine clinical trial data and overall COVID-19 risk and outcomes among RMD patients, along with the immunogenicity of other vaccines in patients on immunomodulatory therapies and the safety profile of non-COVID vaccines in RMD patients.

Using a 9-point numeric scoring system, the task force developed 74 draft guidance statements that were rated with a median score of 7, 8, or 9. Consensus was deemed strong for 16 of the statements and moderate for the remaining 58.

Of the general considerations related to COVID-19 vaccination, the only statement to achieve strong consensus called for the rheumatology health care provider to take responsibility for assessing their patients’ COVID-19 vaccination status. Other notable statements asserted that patients with autoimmune inflammatory rheumatic diseases (AIIRDs) are at higher risk for hospitalized COVID-19, compared with the general population, and should be prioritized for vaccination accordingly, even though a risk for disease flare or worsening exists and the expected vaccine response for patients on systemic immunomodulatory therapies is “likely to be blunted in its magnitude and duration.”
 

Takeaway advice

When asked about a top-line takeaway for rheumatologists, Dr. Curtis replied: “Make sure that your patients are getting vaccinated. Even though the vaccine in patients with compromised immune systems might not work quite as well and might not last quite as long, they still should get vaccinated. And vaccine hesitancy is a real thing.”

Citing unpublished survey data, he estimated that roughly 25% of people with rheumatic conditions remain unvaccinated, and more than half of them said they had no vaccination plans. “That’s a pretty important message when up to a quarter of your higher-risk people take a pass,” he said. “You’d expect it to be better in people at risk who are on steroids or immune medications. That’s something rheumatologists can help with the most.”

Regarding vaccine use, the task force strongly recommended that RMD patients be offered COVID-19 vaccinations consistent with the emergency use authorization’s current age restrictions and/or Food and Drug Administration approval. They also strongly recommended patients with AIIRDs receive the second dose of a multidose vaccine, even if the first dose led to nonserious adverse events, and that health care providers avoid ordering lab testing to assess COVID-19 immunity in vaccinated and unvaccinated patients.

The issues around testing for immunity are ample, Dr. Curtis said. For starters, “there are different antibodies, and one of them wouldn’t be expected to go up after vaccination.” And even if you are testing for the correct antibodies, “now I get a number. Is my number high enough that says that I’m protected? That’s what clinicians want, that’s what patients want. Unfortunately, we don’t have that test. There’s an antibody test; you can test against the spike protein and get a number, but whether that number has clinical relevance that says you’re protected, and how much, and for how long, we definitely don’t have that information. You could be falsely reassured or falsely alarmed by the results.”

This statement, he added, has been particularly divisive. “A bunch of rheumatologists have said to me: ‘Look, we’re doing this routinely for our patients.’ My rejoinder was: ‘That’s great to know; what’s the evidence base for what you’re doing there? Because I haven’t read that paper.’ I fully acknowledge that, in groups of patients on certain therapies, the antibody response seems somewhat lower. But doctors don’t treat groups of patients; we treat patients one at a time. And I want to know how to help the patient in front of me, and I want to know what to tell him or her if I get the results of an antibody test.”

Finally, the task force emphasized that all AIIRD patients should receive the COVID-19 vaccinations, exempting only those with life-threatening disease, and they stated no preference for one COVID-19 vaccine over the other.
 

Vaccine choice

“Should you prefer one vaccine or vaccine platform to another? That’s been incredibly controversial,” Dr. Curtis said. Though the efficacy of the mRNA vaccines is often cited at 90%, compared with the roughly 60%-70% efficacy of the Johnson and & Johnson single-dose vaccine, “they’re not head-to-head studies. They weren’t done in the same countries; they weren’t done with the same viral variants. They’re not being evaluated under similar conditions; it’s not fair to hold them up and say: ‘Apples to apples, this one is better than that one.’ ”

“On the other hand,” he added, “if you were choosing, which would you want? If you are given a choice, you’re probably going to have a preference. The downside for a public health group – this group, which is trying to help rheumatologists and their patients make prudent decisions in light of very imperfect and evolving evidence – is that most people don’t have a choice. So if you send the message that one vaccine might be better than another, if that makes people wait for the one that supposedly might be better, you’ve probably done something bad. They’re delaying for what may be a marginal reason, and some vaccine protection is better than no vaccine protection.”

Regarding vaccination timing in patients who are on immunomodulatory therapies, the task force strongly recommended not delaying or adjusting the timing for anyone on hydroxychloroquine, sulfasalazine, leflunomide, apremilast, or intravenous immunoglobulin. They moderately recommended the same for patients on numerous drugs, including methotrexate, tumor necrosis factor inhibitors, Janus kinase inhibitors, abatacept, and glucocorticoids. Patients on rituximab with a low COVID-19 risk were recommended to schedule their vaccination so that the vaccine series is initiated roughly 4 weeks before their next scheduled rituximab cycle.

Regarding the use and timing of immunomodulatory therapies in relation to vaccination, they strongly recommended no modifications for patients on hydroxychloroquine, apremilast, intravenous immunoglobulin, or glucocorticoids. They also moderately recommended no modifications for patients on numerous drugs, including sulfasalazine, leflunomide, azathioprine, oral cyclophosphamide, and TNF inhibitors.

Regarding limitations, the researchers noted that there is no direct evidence about COVID-19 vaccine safety and efficacy yet in this subset of patients. They also acknowledged that they did not follow the rigorous methodology typically used by the ACR in developing formal clinical practice guidelines, calling it an “expected limitation” given the need to issue timely and potentially lifesaving guidance for the rheumatology community.

The authors acknowledged several potential conflicts of interest, including receiving consulting fees, speaking fees, and research grants from various pharmaceutical companies.

Newly updated COVID-19 vaccination guidance from the American College of Rheumatology offers detailed insight into how clinicians should proceed with use, timing, and prioritization of COVID-19 vaccines in patients with rheumatic and musculoskeletal diseases (RMDs).

“The task force advised health care providers to avoid being overly dogmatic in following these recommendations,” Jeffrey R. Curtis, MD, of the University of Alabama at Birmingham, and colleagues wrote. “The attempt to optimize vaccine response in relation to the use and timing of immunosuppressive medications should not compromise a willing patient’s ability to undergo vaccination in a timely manner and risk a missed vaccination opportunity.” The guidelines were published in Arthritis & Rheumatology.

To review the published literature and determine the safety and efficacy of the available COVID-19 vaccines for patients with RMDs, a task force made up of nine rheumatologists/immunologists, two infectious disease specialists, and two public health physicians was formed. The ACR COVID-19 Vaccine Guidance Task Force considered vaccine clinical trial data and overall COVID-19 risk and outcomes among RMD patients, along with the immunogenicity of other vaccines in patients on immunomodulatory therapies and the safety profile of non-COVID vaccines in RMD patients.

Using a 9-point numeric scoring system, the task force developed 74 draft guidance statements that were rated with a median score of 7, 8, or 9. Consensus was deemed strong for 16 of the statements and moderate for the remaining 58.

Of the general considerations related to COVID-19 vaccination, the only statement to achieve strong consensus called for the rheumatology health care provider to take responsibility for assessing their patients’ COVID-19 vaccination status. Other notable statements asserted that patients with autoimmune inflammatory rheumatic diseases (AIIRDs) are at higher risk for hospitalized COVID-19, compared with the general population, and should be prioritized for vaccination accordingly, even though a risk for disease flare or worsening exists and the expected vaccine response for patients on systemic immunomodulatory therapies is “likely to be blunted in its magnitude and duration.”
 

Takeaway advice

When asked about a top-line takeaway for rheumatologists, Dr. Curtis replied: “Make sure that your patients are getting vaccinated. Even though the vaccine in patients with compromised immune systems might not work quite as well and might not last quite as long, they still should get vaccinated. And vaccine hesitancy is a real thing.”

Citing unpublished survey data, he estimated that roughly 25% of people with rheumatic conditions remain unvaccinated, and more than half of them said they had no vaccination plans. “That’s a pretty important message when up to a quarter of your higher-risk people take a pass,” he said. “You’d expect it to be better in people at risk who are on steroids or immune medications. That’s something rheumatologists can help with the most.”

Regarding vaccine use, the task force strongly recommended that RMD patients be offered COVID-19 vaccinations consistent with the emergency use authorization’s current age restrictions and/or Food and Drug Administration approval. They also strongly recommended patients with AIIRDs receive the second dose of a multidose vaccine, even if the first dose led to nonserious adverse events, and that health care providers avoid ordering lab testing to assess COVID-19 immunity in vaccinated and unvaccinated patients.

The issues around testing for immunity are ample, Dr. Curtis said. For starters, “there are different antibodies, and one of them wouldn’t be expected to go up after vaccination.” And even if you are testing for the correct antibodies, “now I get a number. Is my number high enough that says that I’m protected? That’s what clinicians want, that’s what patients want. Unfortunately, we don’t have that test. There’s an antibody test; you can test against the spike protein and get a number, but whether that number has clinical relevance that says you’re protected, and how much, and for how long, we definitely don’t have that information. You could be falsely reassured or falsely alarmed by the results.”

This statement, he added, has been particularly divisive. “A bunch of rheumatologists have said to me: ‘Look, we’re doing this routinely for our patients.’ My rejoinder was: ‘That’s great to know; what’s the evidence base for what you’re doing there? Because I haven’t read that paper.’ I fully acknowledge that, in groups of patients on certain therapies, the antibody response seems somewhat lower. But doctors don’t treat groups of patients; we treat patients one at a time. And I want to know how to help the patient in front of me, and I want to know what to tell him or her if I get the results of an antibody test.”

Finally, the task force emphasized that all AIIRD patients should receive the COVID-19 vaccinations, exempting only those with life-threatening disease, and they stated no preference for one COVID-19 vaccine over the other.
 

Vaccine choice

“Should you prefer one vaccine or vaccine platform to another? That’s been incredibly controversial,” Dr. Curtis said. Though the efficacy of the mRNA vaccines is often cited at 90%, compared with the roughly 60%-70% efficacy of the Johnson and & Johnson single-dose vaccine, “they’re not head-to-head studies. They weren’t done in the same countries; they weren’t done with the same viral variants. They’re not being evaluated under similar conditions; it’s not fair to hold them up and say: ‘Apples to apples, this one is better than that one.’ ”

“On the other hand,” he added, “if you were choosing, which would you want? If you are given a choice, you’re probably going to have a preference. The downside for a public health group – this group, which is trying to help rheumatologists and their patients make prudent decisions in light of very imperfect and evolving evidence – is that most people don’t have a choice. So if you send the message that one vaccine might be better than another, if that makes people wait for the one that supposedly might be better, you’ve probably done something bad. They’re delaying for what may be a marginal reason, and some vaccine protection is better than no vaccine protection.”

Regarding vaccination timing in patients who are on immunomodulatory therapies, the task force strongly recommended not delaying or adjusting the timing for anyone on hydroxychloroquine, sulfasalazine, leflunomide, apremilast, or intravenous immunoglobulin. They moderately recommended the same for patients on numerous drugs, including methotrexate, tumor necrosis factor inhibitors, Janus kinase inhibitors, abatacept, and glucocorticoids. Patients on rituximab with a low COVID-19 risk were recommended to schedule their vaccination so that the vaccine series is initiated roughly 4 weeks before their next scheduled rituximab cycle.

Regarding the use and timing of immunomodulatory therapies in relation to vaccination, they strongly recommended no modifications for patients on hydroxychloroquine, apremilast, intravenous immunoglobulin, or glucocorticoids. They also moderately recommended no modifications for patients on numerous drugs, including sulfasalazine, leflunomide, azathioprine, oral cyclophosphamide, and TNF inhibitors.

Regarding limitations, the researchers noted that there is no direct evidence about COVID-19 vaccine safety and efficacy yet in this subset of patients. They also acknowledged that they did not follow the rigorous methodology typically used by the ACR in developing formal clinical practice guidelines, calling it an “expected limitation” given the need to issue timely and potentially lifesaving guidance for the rheumatology community.

The authors acknowledged several potential conflicts of interest, including receiving consulting fees, speaking fees, and research grants from various pharmaceutical companies.

Newly updated COVID-19 vaccination guidance from the American College of Rheumatology offers detailed insight into how clinicians should proceed with use, timing, and prioritization of COVID-19 vaccines in patients with rheumatic and musculoskeletal diseases (RMDs).

“The task force advised health care providers to avoid being overly dogmatic in following these recommendations,” Jeffrey R. Curtis, MD, of the University of Alabama at Birmingham, and colleagues wrote. “The attempt to optimize vaccine response in relation to the use and timing of immunosuppressive medications should not compromise a willing patient’s ability to undergo vaccination in a timely manner and risk a missed vaccination opportunity.” The guidelines were published in Arthritis & Rheumatology.

To review the published literature and determine the safety and efficacy of the available COVID-19 vaccines for patients with RMDs, a task force made up of nine rheumatologists/immunologists, two infectious disease specialists, and two public health physicians was formed. The ACR COVID-19 Vaccine Guidance Task Force considered vaccine clinical trial data and overall COVID-19 risk and outcomes among RMD patients, along with the immunogenicity of other vaccines in patients on immunomodulatory therapies and the safety profile of non-COVID vaccines in RMD patients.

Using a 9-point numeric scoring system, the task force developed 74 draft guidance statements that were rated with a median score of 7, 8, or 9. Consensus was deemed strong for 16 of the statements and moderate for the remaining 58.

Of the general considerations related to COVID-19 vaccination, the only statement to achieve strong consensus called for the rheumatology health care provider to take responsibility for assessing their patients’ COVID-19 vaccination status. Other notable statements asserted that patients with autoimmune inflammatory rheumatic diseases (AIIRDs) are at higher risk for hospitalized COVID-19, compared with the general population, and should be prioritized for vaccination accordingly, even though a risk for disease flare or worsening exists and the expected vaccine response for patients on systemic immunomodulatory therapies is “likely to be blunted in its magnitude and duration.”
 

Takeaway advice

When asked about a top-line takeaway for rheumatologists, Dr. Curtis replied: “Make sure that your patients are getting vaccinated. Even though the vaccine in patients with compromised immune systems might not work quite as well and might not last quite as long, they still should get vaccinated. And vaccine hesitancy is a real thing.”

Citing unpublished survey data, he estimated that roughly 25% of people with rheumatic conditions remain unvaccinated, and more than half of them said they had no vaccination plans. “That’s a pretty important message when up to a quarter of your higher-risk people take a pass,” he said. “You’d expect it to be better in people at risk who are on steroids or immune medications. That’s something rheumatologists can help with the most.”

Regarding vaccine use, the task force strongly recommended that RMD patients be offered COVID-19 vaccinations consistent with the emergency use authorization’s current age restrictions and/or Food and Drug Administration approval. They also strongly recommended patients with AIIRDs receive the second dose of a multidose vaccine, even if the first dose led to nonserious adverse events, and that health care providers avoid ordering lab testing to assess COVID-19 immunity in vaccinated and unvaccinated patients.

The issues around testing for immunity are ample, Dr. Curtis said. For starters, “there are different antibodies, and one of them wouldn’t be expected to go up after vaccination.” And even if you are testing for the correct antibodies, “now I get a number. Is my number high enough that says that I’m protected? That’s what clinicians want, that’s what patients want. Unfortunately, we don’t have that test. There’s an antibody test; you can test against the spike protein and get a number, but whether that number has clinical relevance that says you’re protected, and how much, and for how long, we definitely don’t have that information. You could be falsely reassured or falsely alarmed by the results.”

This statement, he added, has been particularly divisive. “A bunch of rheumatologists have said to me: ‘Look, we’re doing this routinely for our patients.’ My rejoinder was: ‘That’s great to know; what’s the evidence base for what you’re doing there? Because I haven’t read that paper.’ I fully acknowledge that, in groups of patients on certain therapies, the antibody response seems somewhat lower. But doctors don’t treat groups of patients; we treat patients one at a time. And I want to know how to help the patient in front of me, and I want to know what to tell him or her if I get the results of an antibody test.”

Finally, the task force emphasized that all AIIRD patients should receive the COVID-19 vaccinations, exempting only those with life-threatening disease, and they stated no preference for one COVID-19 vaccine over the other.
 

Vaccine choice

“Should you prefer one vaccine or vaccine platform to another? That’s been incredibly controversial,” Dr. Curtis said. Though the efficacy of the mRNA vaccines is often cited at 90%, compared with the roughly 60%-70% efficacy of the Johnson and & Johnson single-dose vaccine, “they’re not head-to-head studies. They weren’t done in the same countries; they weren’t done with the same viral variants. They’re not being evaluated under similar conditions; it’s not fair to hold them up and say: ‘Apples to apples, this one is better than that one.’ ”

“On the other hand,” he added, “if you were choosing, which would you want? If you are given a choice, you’re probably going to have a preference. The downside for a public health group – this group, which is trying to help rheumatologists and their patients make prudent decisions in light of very imperfect and evolving evidence – is that most people don’t have a choice. So if you send the message that one vaccine might be better than another, if that makes people wait for the one that supposedly might be better, you’ve probably done something bad. They’re delaying for what may be a marginal reason, and some vaccine protection is better than no vaccine protection.”

Regarding vaccination timing in patients who are on immunomodulatory therapies, the task force strongly recommended not delaying or adjusting the timing for anyone on hydroxychloroquine, sulfasalazine, leflunomide, apremilast, or intravenous immunoglobulin. They moderately recommended the same for patients on numerous drugs, including methotrexate, tumor necrosis factor inhibitors, Janus kinase inhibitors, abatacept, and glucocorticoids. Patients on rituximab with a low COVID-19 risk were recommended to schedule their vaccination so that the vaccine series is initiated roughly 4 weeks before their next scheduled rituximab cycle.

Regarding the use and timing of immunomodulatory therapies in relation to vaccination, they strongly recommended no modifications for patients on hydroxychloroquine, apremilast, intravenous immunoglobulin, or glucocorticoids. They also moderately recommended no modifications for patients on numerous drugs, including sulfasalazine, leflunomide, azathioprine, oral cyclophosphamide, and TNF inhibitors.

Regarding limitations, the researchers noted that there is no direct evidence about COVID-19 vaccine safety and efficacy yet in this subset of patients. They also acknowledged that they did not follow the rigorous methodology typically used by the ACR in developing formal clinical practice guidelines, calling it an “expected limitation” given the need to issue timely and potentially lifesaving guidance for the rheumatology community.

The authors acknowledged several potential conflicts of interest, including receiving consulting fees, speaking fees, and research grants from various pharmaceutical companies.

Treatment of prostate cancer presents significant challenges with respect to balancing efficacy and side effects of treatments. Thus, quality of life endpoints are included in studies of patients with prostate cancer to better understand and counsel patients with this heterogenous disease. In the 3 studies discussed here, functional or quality of life outcomes were included in the analyses.

            In the first study, Hagens et al evaluated the effects of postoperative complications of robot-assisted radical prostatectomy on the health-related quality of life (HRQoL) as measured via surveys and assessment of functional outcomes. While no significant association between HRQoL at 6 months and complications postoperatively were identified, there was an association between functional outcomes and HRQoL at 6 months identified. Thus, future studies designed to identify more optimal patient selection or improved surgical techniques may benefit patients.

            Studies have suggested that androgen deprivation therapy (ADT) may be associated with decreased cognitive function. However, other studies suggested that ADT via luteinizing hormone releasing hormone (LHRH) agonists or antagonists may actually have a protective effect against decreased cognitive function due to low gonadotropin exposure. Andela et al conducted a systematic review based on this hypothesis. Of the 31 studies included in the review, 16 demonstrated that ADT was not associated with decreased cognitive function, while 11 studies did support this association and 4 studies were inconclusive. Therefore, no definitive conclusions can be made based on this review, and further randomized studies are needed.

            Radiation to the prostate may affect the rectum with sometimes significant effects. Hydrogel spacers injected between the prostate and rectum have been evaluated in patients with conventional radiation previously with evidence of benefit, but the benefits for patients undergoing stereotactic body radiotherapy (SBRT) are unknown. Ogita et al conducted a phase II single-arm study designed to evaluate the effects of a hydrogel spacer on gastrointestinal toxicity within 3 months of SBRT. Physician-assessed toxicity was not reduced, but patient reported toxicity was improved compared with historical controls. While this study does not support routine use in the setting of prostate SBRT, it does suggest that future larger randomized studies are worth consideration.

Treatment of prostate cancer presents significant challenges with respect to balancing efficacy and side effects of treatments. Thus, quality of life endpoints are included in studies of patients with prostate cancer to better understand and counsel patients with this heterogenous disease. In the 3 studies discussed here, functional or quality of life outcomes were included in the analyses.

            In the first study, Hagens et al evaluated the effects of postoperative complications of robot-assisted radical prostatectomy on the health-related quality of life (HRQoL) as measured via surveys and assessment of functional outcomes. While no significant association between HRQoL at 6 months and complications postoperatively were identified, there was an association between functional outcomes and HRQoL at 6 months identified. Thus, future studies designed to identify more optimal patient selection or improved surgical techniques may benefit patients.

            Studies have suggested that androgen deprivation therapy (ADT) may be associated with decreased cognitive function. However, other studies suggested that ADT via luteinizing hormone releasing hormone (LHRH) agonists or antagonists may actually have a protective effect against decreased cognitive function due to low gonadotropin exposure. Andela et al conducted a systematic review based on this hypothesis. Of the 31 studies included in the review, 16 demonstrated that ADT was not associated with decreased cognitive function, while 11 studies did support this association and 4 studies were inconclusive. Therefore, no definitive conclusions can be made based on this review, and further randomized studies are needed.

            Radiation to the prostate may affect the rectum with sometimes significant effects. Hydrogel spacers injected between the prostate and rectum have been evaluated in patients with conventional radiation previously with evidence of benefit, but the benefits for patients undergoing stereotactic body radiotherapy (SBRT) are unknown. Ogita et al conducted a phase II single-arm study designed to evaluate the effects of a hydrogel spacer on gastrointestinal toxicity within 3 months of SBRT. Physician-assessed toxicity was not reduced, but patient reported toxicity was improved compared with historical controls. While this study does not support routine use in the setting of prostate SBRT, it does suggest that future larger randomized studies are worth consideration.

Treatment of prostate cancer presents significant challenges with respect to balancing efficacy and side effects of treatments. Thus, quality of life endpoints are included in studies of patients with prostate cancer to better understand and counsel patients with this heterogenous disease. In the 3 studies discussed here, functional or quality of life outcomes were included in the analyses.

            In the first study, Hagens et al evaluated the effects of postoperative complications of robot-assisted radical prostatectomy on the health-related quality of life (HRQoL) as measured via surveys and assessment of functional outcomes. While no significant association between HRQoL at 6 months and complications postoperatively were identified, there was an association between functional outcomes and HRQoL at 6 months identified. Thus, future studies designed to identify more optimal patient selection or improved surgical techniques may benefit patients.

            Studies have suggested that androgen deprivation therapy (ADT) may be associated with decreased cognitive function. However, other studies suggested that ADT via luteinizing hormone releasing hormone (LHRH) agonists or antagonists may actually have a protective effect against decreased cognitive function due to low gonadotropin exposure. Andela et al conducted a systematic review based on this hypothesis. Of the 31 studies included in the review, 16 demonstrated that ADT was not associated with decreased cognitive function, while 11 studies did support this association and 4 studies were inconclusive. Therefore, no definitive conclusions can be made based on this review, and further randomized studies are needed.

            Radiation to the prostate may affect the rectum with sometimes significant effects. Hydrogel spacers injected between the prostate and rectum have been evaluated in patients with conventional radiation previously with evidence of benefit, but the benefits for patients undergoing stereotactic body radiotherapy (SBRT) are unknown. Ogita et al conducted a phase II single-arm study designed to evaluate the effects of a hydrogel spacer on gastrointestinal toxicity within 3 months of SBRT. Physician-assessed toxicity was not reduced, but patient reported toxicity was improved compared with historical controls. While this study does not support routine use in the setting of prostate SBRT, it does suggest that future larger randomized studies are worth consideration.

Vitamin D deficiency amplifies the craving for, and the effects of, opioids, potentially raising the risk for opioid dependence and addiction, new research suggests. However, some experts are urging caution in interpreting the findings.

The study, which also linked vitamin D deficiency to sun-seeking behavior, points to the potential of vitamin D supplementation to help address the opioid epidemic, the investigators note.

“Even modest rescue of vitamin D deficiency could be beneficial in the prevention and treatment of opioid addiction, especially considering that vitamin D is generally inexpensive, accessible, and safe,” they write.

The study was published online June 11 in Science Advances.
 

Endorphin rush

In earlier work, researchers led by David Fisher, MD, PhD, with the Massachusetts General Hospital (MGH) and Harvard Medical School, Boston, found that exposure to ultraviolet rays causes the skin to produce the hormone endorphin, which is chemically related to morphine, heroin, and other opioids.

They also observed that UV exposure raises endorphin levels in mice, which leads the animals to display behavior consistent with opioid addiction.

In their latest research, they conducted a series of animal and human studies designed to better understand the relationship between vitamin D and UV-seeking and opioid-seeking behavior.

They first compared normal laboratory mice with vitamin D–deficient mice.

“We found that modulating vitamin D levels changes multiple addictive behaviors to both UV and opioids,” lead author Lajos Kemény, MD, PhD, a postdoctoral research fellow in dermatology at MGH, said in a statement.

When the mice were conditioned with modest doses of morphine, those deficient in vitamin D continued seeking out the drug. This behavior was less common in the normal mice. When morphine was withdrawn, the vitamin D–deficient mice were far more likely to show withdrawal symptoms.

Morphine also appeared to work more effectively as a pain reliever in the vitamin D–deficient mice, suggesting that response to the opioid was exaggerated in the setting of low vitamin D.

“When we corrected vitamin D levels in the deficient mice, their opioid responses reversed and returned to normal,” Dr. Fisher said in the statement.

The animal data that suggest vitamin D deficiency increases addictive behavior was supported by several analyses using National Health and Nutrition Examination Survey data and MGH patient health records.

The results show an increase in the prevalence of vitamin D deficiency among patients diagnosed with opioid use disorder (OUD) and an inverse and dose-dependent association of vitamin D levels with self-reported opioid use.

Patients with modestly low vitamin D levels were 50% more likely than peers with normal vitamin D levels to use opioids, whereas patients who were severely vitamin D deficient were 90% more likely to use opioids, the researchers report.

“Our results imply that vitamin D–deficient individuals may be at risk for developing tolerance and physiologic opioid dependence more rapidly, experiencing more significant withdrawal and experiencing greater reward from opioid exposure,” they note.

“Vitamin D supplementation might have a preventative benefit by decreasing opioid reward and possibly diminishing the risk of OUD. Vitamin D supplementation may also improve the beneficial effects of medications for OUD,” they add.
 

Interpret with caution

Weighing in on this research for this news organization, Richard Saitz, MD, MPH, professor, Boston University Schools of Medicine and Public Health, urged caution in interpreting the results.

“The human studies are cross-sectional and subject to many biases and may show that opioid use and disorder are associated with vitamin D deficiency (which is not news) and does not at all show deficiency causes disorder or use,” said Dr. Saitz.

“All in all, the studies are interesting and could generate hypotheses to be tested in well-designed prospective studies of vitamin D deficiency as a risk factor and vitamin D as a treatment,” he added.

However, he cautioned that it’s “going way beyond the data” to conclude that vitamin D causes or exacerbates opioid addiction in people, “but suggesting clinical studies be done is certainly reasonable.”

Also weighing in on this research, Kenneth Stoller, MD, director of the Johns Hopkins Broadway Center for Addiction and associate professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, noted that “95% of patients with co-occurring disorders coming to the inpatient unit are vitamin D deficient, so it’s very common in the population.

“It’s hard to know, but I really think that it’s unlikely that vitamin D deficiency is a common pathway for development of addiction – that is, that they developed an addiction specifically because of the vitamin D deficiency,” Dr. Stoller said.

“However, it does make me think that for my patients who are experiencing maybe a partial but not a full response to medications for opioid use disorder, maybe I’ll be more likely to check the vitamin D level, and if it’s really off, try them on some supplementation,” said Dr. Stoller.

He pointed to a recent study that showed some benefit of vitamin D supplementation on cognitive function and some mental health parameters for people on methadone, “but I don’t think this is necessarily a silver bullet.”

The work was supported by a grant from the National Institutes of Health and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation. Dr. Fisher, Dr. Saitz, and Dr. Stoller have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Vitamin D deficiency amplifies the craving for, and the effects of, opioids, potentially raising the risk for opioid dependence and addiction, new research suggests. However, some experts are urging caution in interpreting the findings.

The study, which also linked vitamin D deficiency to sun-seeking behavior, points to the potential of vitamin D supplementation to help address the opioid epidemic, the investigators note.

“Even modest rescue of vitamin D deficiency could be beneficial in the prevention and treatment of opioid addiction, especially considering that vitamin D is generally inexpensive, accessible, and safe,” they write.

The study was published online June 11 in Science Advances.
 

Endorphin rush

In earlier work, researchers led by David Fisher, MD, PhD, with the Massachusetts General Hospital (MGH) and Harvard Medical School, Boston, found that exposure to ultraviolet rays causes the skin to produce the hormone endorphin, which is chemically related to morphine, heroin, and other opioids.

They also observed that UV exposure raises endorphin levels in mice, which leads the animals to display behavior consistent with opioid addiction.

In their latest research, they conducted a series of animal and human studies designed to better understand the relationship between vitamin D and UV-seeking and opioid-seeking behavior.

They first compared normal laboratory mice with vitamin D–deficient mice.

“We found that modulating vitamin D levels changes multiple addictive behaviors to both UV and opioids,” lead author Lajos Kemény, MD, PhD, a postdoctoral research fellow in dermatology at MGH, said in a statement.

When the mice were conditioned with modest doses of morphine, those deficient in vitamin D continued seeking out the drug. This behavior was less common in the normal mice. When morphine was withdrawn, the vitamin D–deficient mice were far more likely to show withdrawal symptoms.

Morphine also appeared to work more effectively as a pain reliever in the vitamin D–deficient mice, suggesting that response to the opioid was exaggerated in the setting of low vitamin D.

“When we corrected vitamin D levels in the deficient mice, their opioid responses reversed and returned to normal,” Dr. Fisher said in the statement.

The animal data that suggest vitamin D deficiency increases addictive behavior was supported by several analyses using National Health and Nutrition Examination Survey data and MGH patient health records.

The results show an increase in the prevalence of vitamin D deficiency among patients diagnosed with opioid use disorder (OUD) and an inverse and dose-dependent association of vitamin D levels with self-reported opioid use.

Patients with modestly low vitamin D levels were 50% more likely than peers with normal vitamin D levels to use opioids, whereas patients who were severely vitamin D deficient were 90% more likely to use opioids, the researchers report.

“Our results imply that vitamin D–deficient individuals may be at risk for developing tolerance and physiologic opioid dependence more rapidly, experiencing more significant withdrawal and experiencing greater reward from opioid exposure,” they note.

“Vitamin D supplementation might have a preventative benefit by decreasing opioid reward and possibly diminishing the risk of OUD. Vitamin D supplementation may also improve the beneficial effects of medications for OUD,” they add.
 

Interpret with caution

Weighing in on this research for this news organization, Richard Saitz, MD, MPH, professor, Boston University Schools of Medicine and Public Health, urged caution in interpreting the results.

“The human studies are cross-sectional and subject to many biases and may show that opioid use and disorder are associated with vitamin D deficiency (which is not news) and does not at all show deficiency causes disorder or use,” said Dr. Saitz.

“All in all, the studies are interesting and could generate hypotheses to be tested in well-designed prospective studies of vitamin D deficiency as a risk factor and vitamin D as a treatment,” he added.

However, he cautioned that it’s “going way beyond the data” to conclude that vitamin D causes or exacerbates opioid addiction in people, “but suggesting clinical studies be done is certainly reasonable.”

Also weighing in on this research, Kenneth Stoller, MD, director of the Johns Hopkins Broadway Center for Addiction and associate professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, noted that “95% of patients with co-occurring disorders coming to the inpatient unit are vitamin D deficient, so it’s very common in the population.

“It’s hard to know, but I really think that it’s unlikely that vitamin D deficiency is a common pathway for development of addiction – that is, that they developed an addiction specifically because of the vitamin D deficiency,” Dr. Stoller said.

“However, it does make me think that for my patients who are experiencing maybe a partial but not a full response to medications for opioid use disorder, maybe I’ll be more likely to check the vitamin D level, and if it’s really off, try them on some supplementation,” said Dr. Stoller.

He pointed to a recent study that showed some benefit of vitamin D supplementation on cognitive function and some mental health parameters for people on methadone, “but I don’t think this is necessarily a silver bullet.”

The work was supported by a grant from the National Institutes of Health and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation. Dr. Fisher, Dr. Saitz, and Dr. Stoller have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Vitamin D deficiency amplifies the craving for, and the effects of, opioids, potentially raising the risk for opioid dependence and addiction, new research suggests. However, some experts are urging caution in interpreting the findings.

The study, which also linked vitamin D deficiency to sun-seeking behavior, points to the potential of vitamin D supplementation to help address the opioid epidemic, the investigators note.

“Even modest rescue of vitamin D deficiency could be beneficial in the prevention and treatment of opioid addiction, especially considering that vitamin D is generally inexpensive, accessible, and safe,” they write.

The study was published online June 11 in Science Advances.
 

Endorphin rush

In earlier work, researchers led by David Fisher, MD, PhD, with the Massachusetts General Hospital (MGH) and Harvard Medical School, Boston, found that exposure to ultraviolet rays causes the skin to produce the hormone endorphin, which is chemically related to morphine, heroin, and other opioids.

They also observed that UV exposure raises endorphin levels in mice, which leads the animals to display behavior consistent with opioid addiction.

In their latest research, they conducted a series of animal and human studies designed to better understand the relationship between vitamin D and UV-seeking and opioid-seeking behavior.

They first compared normal laboratory mice with vitamin D–deficient mice.

“We found that modulating vitamin D levels changes multiple addictive behaviors to both UV and opioids,” lead author Lajos Kemény, MD, PhD, a postdoctoral research fellow in dermatology at MGH, said in a statement.

When the mice were conditioned with modest doses of morphine, those deficient in vitamin D continued seeking out the drug. This behavior was less common in the normal mice. When morphine was withdrawn, the vitamin D–deficient mice were far more likely to show withdrawal symptoms.

Morphine also appeared to work more effectively as a pain reliever in the vitamin D–deficient mice, suggesting that response to the opioid was exaggerated in the setting of low vitamin D.

“When we corrected vitamin D levels in the deficient mice, their opioid responses reversed and returned to normal,” Dr. Fisher said in the statement.

The animal data that suggest vitamin D deficiency increases addictive behavior was supported by several analyses using National Health and Nutrition Examination Survey data and MGH patient health records.

The results show an increase in the prevalence of vitamin D deficiency among patients diagnosed with opioid use disorder (OUD) and an inverse and dose-dependent association of vitamin D levels with self-reported opioid use.

Patients with modestly low vitamin D levels were 50% more likely than peers with normal vitamin D levels to use opioids, whereas patients who were severely vitamin D deficient were 90% more likely to use opioids, the researchers report.

“Our results imply that vitamin D–deficient individuals may be at risk for developing tolerance and physiologic opioid dependence more rapidly, experiencing more significant withdrawal and experiencing greater reward from opioid exposure,” they note.

“Vitamin D supplementation might have a preventative benefit by decreasing opioid reward and possibly diminishing the risk of OUD. Vitamin D supplementation may also improve the beneficial effects of medications for OUD,” they add.
 

Interpret with caution

Weighing in on this research for this news organization, Richard Saitz, MD, MPH, professor, Boston University Schools of Medicine and Public Health, urged caution in interpreting the results.

“The human studies are cross-sectional and subject to many biases and may show that opioid use and disorder are associated with vitamin D deficiency (which is not news) and does not at all show deficiency causes disorder or use,” said Dr. Saitz.

“All in all, the studies are interesting and could generate hypotheses to be tested in well-designed prospective studies of vitamin D deficiency as a risk factor and vitamin D as a treatment,” he added.

However, he cautioned that it’s “going way beyond the data” to conclude that vitamin D causes or exacerbates opioid addiction in people, “but suggesting clinical studies be done is certainly reasonable.”

Also weighing in on this research, Kenneth Stoller, MD, director of the Johns Hopkins Broadway Center for Addiction and associate professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, noted that “95% of patients with co-occurring disorders coming to the inpatient unit are vitamin D deficient, so it’s very common in the population.

“It’s hard to know, but I really think that it’s unlikely that vitamin D deficiency is a common pathway for development of addiction – that is, that they developed an addiction specifically because of the vitamin D deficiency,” Dr. Stoller said.

“However, it does make me think that for my patients who are experiencing maybe a partial but not a full response to medications for opioid use disorder, maybe I’ll be more likely to check the vitamin D level, and if it’s really off, try them on some supplementation,” said Dr. Stoller.

He pointed to a recent study that showed some benefit of vitamin D supplementation on cognitive function and some mental health parameters for people on methadone, “but I don’t think this is necessarily a silver bullet.”

The work was supported by a grant from the National Institutes of Health and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation. Dr. Fisher, Dr. Saitz, and Dr. Stoller have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Congratulations! You’re about to start your first year as a hospitalist, and in many cases your first real job. Hospital medicine is an incredibly rewarding subspecialty, but the progression from resident to attending physician can be daunting. To facilitate this transition, we present FIND (Familiarity, Identity, Network, and Direction) – a novel, sequential framework for success as a first-year hospitalist. For each component, we provide a narrative overview and a summary bullet point for quick reference.

Familiarity

• Lay the foundation: Learn the ins and outs of your job, EMR, and team.

Familiarize yourself with your surroundings. Know where your patients are located, where you can document, where to find equipment for procedures, and how to reach information technology. Proactively set up the electronic medical record on your home computer and phone. Make sure to review your responsibilities, including your call schedule, your shifts, your assigned patient panel, when you can leave campus, and how people should contact you. Also, others should know your expectations of them, especially if you are working with trainees.

Maintain a file with all of your orientation materials, including phone numbers and emails of key personnel. Know who your people are – who can access your calendar, who you can call with a clinical question or to escalate care, who can assist you with billing, and who helps with the throughput of your patients in the hospital. Take time to review your benefits, including parental leave, insurance coverage, retirement planning, vacation time, and ancillary services like laundry for your white coat. Familiarizing yourself with these basics will provide comfort and lay the foundation for your first year.
 

Identity

• Perform self-reflection: Overcome imposter syndrome and invest in hobbies.

One of the fundamental realizations that will occur with your first hospitalist job is that you are the attending. You walk in with a vision of your first job; be prepared to be surprised. You have earned the privilege of deciding on patient plans, and you are no longer obligated to staff with a senior physician. This is both empowering and terrifying. In a way, it may oddly remind you of intern year. A new hospital, new EMR, new colleagues, and imposter syndrome will trick you into doubting your decisions.

How to battle it? Positive thinking. You do know the basics of inpatient medicine and you do have a support system to cheer you on. As part of imposter syndrome, you may feel pressured to focus solely on work. Yet, your first job as a hospitalist is finally an amazing opportunity to focus on you. What hobbies have you been neglecting: cooking, photography, reading, more time with family, a new pet? You have the power to schedule your off-weeks. Are you interested in academics? Reserve a portion of your time off to explore scholarship opportunities at your institution. Your first job as a hospitalist is a chance to develop your identity, both as a physician and as an individual.
 

Network

• Engage your support system: Communicate with nursing, administration, colleagues.

Networking, or building a web of mutually beneficial professional relationships, is imperative for long-term career success. Hospitalists should focus on developing their network across multiple departments, such as nursing, subspecialties, medical education, and hospital administration. Curating a broad network will increase your visibility within your organization, showcase your unique services, and demonstrate your value.

To make networking encounters impactful, express interest, actively listen, ask relevant questions, and seek areas of mutual benefit. It’s equally important to cultivate these new relationships after the initial encounter and to demonstrate how your skill set will aid colleagues in achieving their professional goals. Over time, as you establish your niche, deliberate networking with those who share similar interests can lead to a wealth of new experiences and opportunities. Intentionally mastering networking early in your career provides insight into different aspects of the hospital system, new perspectives on ideas, and access to valuable guidance from other professionals. Engaging in networking to establish your support system is an essential step towards success as a first-year hospitalist.
 

Direction

• Visualize your path: Find a mentor and develop a mission statement and career plan.

Once you’re familiar with your work environment, confident in your identity, and acquainted with your support network, you’re ready for the final step – direction. Hospital medicine offers many professional avenues and clarifying your career path is challenging when attempted alone. A mentor is the necessary catalyst to find direction and purpose.

Selecting and engaging with a mentor will bolster your professional advancement, academic productivity, and most importantly, career satisfaction.¹ At its best, mentorship is a symbiotic relationship. Your mentor should inspire you, challenge you, and support your growth and emotional well-being. In turn, as the mentee, you should be proactive, establish expectations, and take responsibility for maintaining communication to ensure a successful relationship. As your career takes shape over time, you may require a mentorship team to fulfill your unique needs.

When you’ve established a relationship with your mentor, take time to develop 1-year and 5-year plans. Your 1-year plan should focus on a few “quick wins,” often projects or opportunities at your home institution. Small victories in your first year will boost your confidence, motivation, and sense of control. Your 5-year plan should delineate the steps necessary to make your first major career transition, such as from instructor to assistant professor. Working with your mentor to draft a career mission statement is a useful first step in this process. Beginning with the end in mind, will help you visualize your direction.²

We hope that the FIND framework will help you find your path to success as a first-year hospitalist.

Dr. Nelson is a hospitalist and instructor of medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, both in Boston. Dr. Ashford is assistant professor and program director, department of internal medicine/pediatrics, at the University of Nebraska Medical Center, Omaha. Dr. Rawal is clinical assistant professor of medicine at the University of Pittsburgh Medical Center. Dr. Crecelius is assistant professor of clinical medicine at Indiana University, Indianapolis. This article is sponsored by the SHM Physicians in Training committee, which submits quarterly content to the Hospitalist on topics relevant to trainees and early -career hospitalists.

References

1. Zerzan JT et al. Making the most of mentors: a guide for mentees. Acad Med. 2009;84:140-4. doi: 10.1097/ACM.0b013e3181906e8f.

2. Covey F. The seven habits of highly effective people. 25th anniversary edition. New York: Simon and Schuster, 2013.




 

Congratulations! You’re about to start your first year as a hospitalist, and in many cases your first real job. Hospital medicine is an incredibly rewarding subspecialty, but the progression from resident to attending physician can be daunting. To facilitate this transition, we present FIND (Familiarity, Identity, Network, and Direction) – a novel, sequential framework for success as a first-year hospitalist. For each component, we provide a narrative overview and a summary bullet point for quick reference.

Familiarity

• Lay the foundation: Learn the ins and outs of your job, EMR, and team.

Familiarize yourself with your surroundings. Know where your patients are located, where you can document, where to find equipment for procedures, and how to reach information technology. Proactively set up the electronic medical record on your home computer and phone. Make sure to review your responsibilities, including your call schedule, your shifts, your assigned patient panel, when you can leave campus, and how people should contact you. Also, others should know your expectations of them, especially if you are working with trainees.

Maintain a file with all of your orientation materials, including phone numbers and emails of key personnel. Know who your people are – who can access your calendar, who you can call with a clinical question or to escalate care, who can assist you with billing, and who helps with the throughput of your patients in the hospital. Take time to review your benefits, including parental leave, insurance coverage, retirement planning, vacation time, and ancillary services like laundry for your white coat. Familiarizing yourself with these basics will provide comfort and lay the foundation for your first year.
 

Identity

• Perform self-reflection: Overcome imposter syndrome and invest in hobbies.

One of the fundamental realizations that will occur with your first hospitalist job is that you are the attending. You walk in with a vision of your first job; be prepared to be surprised. You have earned the privilege of deciding on patient plans, and you are no longer obligated to staff with a senior physician. This is both empowering and terrifying. In a way, it may oddly remind you of intern year. A new hospital, new EMR, new colleagues, and imposter syndrome will trick you into doubting your decisions.

How to battle it? Positive thinking. You do know the basics of inpatient medicine and you do have a support system to cheer you on. As part of imposter syndrome, you may feel pressured to focus solely on work. Yet, your first job as a hospitalist is finally an amazing opportunity to focus on you. What hobbies have you been neglecting: cooking, photography, reading, more time with family, a new pet? You have the power to schedule your off-weeks. Are you interested in academics? Reserve a portion of your time off to explore scholarship opportunities at your institution. Your first job as a hospitalist is a chance to develop your identity, both as a physician and as an individual.
 

Network

• Engage your support system: Communicate with nursing, administration, colleagues.

Networking, or building a web of mutually beneficial professional relationships, is imperative for long-term career success. Hospitalists should focus on developing their network across multiple departments, such as nursing, subspecialties, medical education, and hospital administration. Curating a broad network will increase your visibility within your organization, showcase your unique services, and demonstrate your value.

To make networking encounters impactful, express interest, actively listen, ask relevant questions, and seek areas of mutual benefit. It’s equally important to cultivate these new relationships after the initial encounter and to demonstrate how your skill set will aid colleagues in achieving their professional goals. Over time, as you establish your niche, deliberate networking with those who share similar interests can lead to a wealth of new experiences and opportunities. Intentionally mastering networking early in your career provides insight into different aspects of the hospital system, new perspectives on ideas, and access to valuable guidance from other professionals. Engaging in networking to establish your support system is an essential step towards success as a first-year hospitalist.
 

Direction

• Visualize your path: Find a mentor and develop a mission statement and career plan.

Once you’re familiar with your work environment, confident in your identity, and acquainted with your support network, you’re ready for the final step – direction. Hospital medicine offers many professional avenues and clarifying your career path is challenging when attempted alone. A mentor is the necessary catalyst to find direction and purpose.

Selecting and engaging with a mentor will bolster your professional advancement, academic productivity, and most importantly, career satisfaction.¹ At its best, mentorship is a symbiotic relationship. Your mentor should inspire you, challenge you, and support your growth and emotional well-being. In turn, as the mentee, you should be proactive, establish expectations, and take responsibility for maintaining communication to ensure a successful relationship. As your career takes shape over time, you may require a mentorship team to fulfill your unique needs.

When you’ve established a relationship with your mentor, take time to develop 1-year and 5-year plans. Your 1-year plan should focus on a few “quick wins,” often projects or opportunities at your home institution. Small victories in your first year will boost your confidence, motivation, and sense of control. Your 5-year plan should delineate the steps necessary to make your first major career transition, such as from instructor to assistant professor. Working with your mentor to draft a career mission statement is a useful first step in this process. Beginning with the end in mind, will help you visualize your direction.²

We hope that the FIND framework will help you find your path to success as a first-year hospitalist.

Dr. Nelson is a hospitalist and instructor of medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, both in Boston. Dr. Ashford is assistant professor and program director, department of internal medicine/pediatrics, at the University of Nebraska Medical Center, Omaha. Dr. Rawal is clinical assistant professor of medicine at the University of Pittsburgh Medical Center. Dr. Crecelius is assistant professor of clinical medicine at Indiana University, Indianapolis. This article is sponsored by the SHM Physicians in Training committee, which submits quarterly content to the Hospitalist on topics relevant to trainees and early -career hospitalists.

References

1. Zerzan JT et al. Making the most of mentors: a guide for mentees. Acad Med. 2009;84:140-4. doi: 10.1097/ACM.0b013e3181906e8f.

2. Covey F. The seven habits of highly effective people. 25th anniversary edition. New York: Simon and Schuster, 2013.




 

Congratulations! You’re about to start your first year as a hospitalist, and in many cases your first real job. Hospital medicine is an incredibly rewarding subspecialty, but the progression from resident to attending physician can be daunting. To facilitate this transition, we present FIND (Familiarity, Identity, Network, and Direction) – a novel, sequential framework for success as a first-year hospitalist. For each component, we provide a narrative overview and a summary bullet point for quick reference.

Familiarity

• Lay the foundation: Learn the ins and outs of your job, EMR, and team.

Familiarize yourself with your surroundings. Know where your patients are located, where you can document, where to find equipment for procedures, and how to reach information technology. Proactively set up the electronic medical record on your home computer and phone. Make sure to review your responsibilities, including your call schedule, your shifts, your assigned patient panel, when you can leave campus, and how people should contact you. Also, others should know your expectations of them, especially if you are working with trainees.

Maintain a file with all of your orientation materials, including phone numbers and emails of key personnel. Know who your people are – who can access your calendar, who you can call with a clinical question or to escalate care, who can assist you with billing, and who helps with the throughput of your patients in the hospital. Take time to review your benefits, including parental leave, insurance coverage, retirement planning, vacation time, and ancillary services like laundry for your white coat. Familiarizing yourself with these basics will provide comfort and lay the foundation for your first year.
 

Identity

• Perform self-reflection: Overcome imposter syndrome and invest in hobbies.

One of the fundamental realizations that will occur with your first hospitalist job is that you are the attending. You walk in with a vision of your first job; be prepared to be surprised. You have earned the privilege of deciding on patient plans, and you are no longer obligated to staff with a senior physician. This is both empowering and terrifying. In a way, it may oddly remind you of intern year. A new hospital, new EMR, new colleagues, and imposter syndrome will trick you into doubting your decisions.

How to battle it? Positive thinking. You do know the basics of inpatient medicine and you do have a support system to cheer you on. As part of imposter syndrome, you may feel pressured to focus solely on work. Yet, your first job as a hospitalist is finally an amazing opportunity to focus on you. What hobbies have you been neglecting: cooking, photography, reading, more time with family, a new pet? You have the power to schedule your off-weeks. Are you interested in academics? Reserve a portion of your time off to explore scholarship opportunities at your institution. Your first job as a hospitalist is a chance to develop your identity, both as a physician and as an individual.
 

Network

• Engage your support system: Communicate with nursing, administration, colleagues.

Networking, or building a web of mutually beneficial professional relationships, is imperative for long-term career success. Hospitalists should focus on developing their network across multiple departments, such as nursing, subspecialties, medical education, and hospital administration. Curating a broad network will increase your visibility within your organization, showcase your unique services, and demonstrate your value.

To make networking encounters impactful, express interest, actively listen, ask relevant questions, and seek areas of mutual benefit. It’s equally important to cultivate these new relationships after the initial encounter and to demonstrate how your skill set will aid colleagues in achieving their professional goals. Over time, as you establish your niche, deliberate networking with those who share similar interests can lead to a wealth of new experiences and opportunities. Intentionally mastering networking early in your career provides insight into different aspects of the hospital system, new perspectives on ideas, and access to valuable guidance from other professionals. Engaging in networking to establish your support system is an essential step towards success as a first-year hospitalist.
 

Direction

• Visualize your path: Find a mentor and develop a mission statement and career plan.

Once you’re familiar with your work environment, confident in your identity, and acquainted with your support network, you’re ready for the final step – direction. Hospital medicine offers many professional avenues and clarifying your career path is challenging when attempted alone. A mentor is the necessary catalyst to find direction and purpose.

Selecting and engaging with a mentor will bolster your professional advancement, academic productivity, and most importantly, career satisfaction.¹ At its best, mentorship is a symbiotic relationship. Your mentor should inspire you, challenge you, and support your growth and emotional well-being. In turn, as the mentee, you should be proactive, establish expectations, and take responsibility for maintaining communication to ensure a successful relationship. As your career takes shape over time, you may require a mentorship team to fulfill your unique needs.

When you’ve established a relationship with your mentor, take time to develop 1-year and 5-year plans. Your 1-year plan should focus on a few “quick wins,” often projects or opportunities at your home institution. Small victories in your first year will boost your confidence, motivation, and sense of control. Your 5-year plan should delineate the steps necessary to make your first major career transition, such as from instructor to assistant professor. Working with your mentor to draft a career mission statement is a useful first step in this process. Beginning with the end in mind, will help you visualize your direction.²

We hope that the FIND framework will help you find your path to success as a first-year hospitalist.

Dr. Nelson is a hospitalist and instructor of medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, both in Boston. Dr. Ashford is assistant professor and program director, department of internal medicine/pediatrics, at the University of Nebraska Medical Center, Omaha. Dr. Rawal is clinical assistant professor of medicine at the University of Pittsburgh Medical Center. Dr. Crecelius is assistant professor of clinical medicine at Indiana University, Indianapolis. This article is sponsored by the SHM Physicians in Training committee, which submits quarterly content to the Hospitalist on topics relevant to trainees and early -career hospitalists.

References

1. Zerzan JT et al. Making the most of mentors: a guide for mentees. Acad Med. 2009;84:140-4. doi: 10.1097/ACM.0b013e3181906e8f.

2. Covey F. The seven habits of highly effective people. 25th anniversary edition. New York: Simon and Schuster, 2013.




 

If moderate to severe postpartum depression poses a risk to child development, that argues in favor of pharmacologic therapy, according to a detailed risk-benefit assessment presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

monkeybusinessimages/Thinkstock

“It is important to consider that there are potential risks of antidepressant drugs, but there are also potential risks from not providing effective treatment,” reported Neha Hudepohl, MD, at the virtual meeting, presented by MedscapeLive.

On a website maintained by the Centers for Disease Control and Prevention, the question of whether antidepressants pose a risk to breast-feeding children is answered with a “maybe.” Although many of these drugs can be detected in breast milk, according to the CDC, “most have little or no effect on milk supply or on infant well-being.”

This is enough uncertainty that antidepressants are not first-line intervention when postpartum depression is mild, said Dr. Hudepohl, director of women’s mental health at Prisma Health Upstate, Greenville, S.C. However, she noted that the American College of Obstetricians and Gynecologists is among the organizations that recommend drug treatment if symptoms are moderate to severe.

“Depression in the mother affects interactions in feeding practices, sleep routines and patterns, and safety practices,” said Dr. Hudepohl, citing published studies supporting each of these consequences.

For the child, there is some degree of uncertainty about risk from untreated maternal depression as well as from breast mild exposure to antidepressants. Conclusive statements are not offered by ACOG and others.

“Some but not all studies have shown an impact of either antenatal or postnatal depression on speech recognition in infancy of native versus nonnative languages, IQ, and cognitive development, and reduction in left frontal brain electrical activity associated with impaired positive emotions,” Dr. Hudepohl reported.

Sifting through published data, Dr. Hudepohl cited studies associating persistent postpartum depression with a more than fourfold risk of behavioral problems at the age of 3.5 years, lower grades in mathematics at age 16, and a higher prevalence of depression at age 18. Among children who had depressed mothers in infancy, there have also been studies showing a higher reactivity to stressors and higher baseline cortisol levels.

“The good news is that these effects in children appear to be largely reversible with maternal treatment,” Dr. Hudepohl said. In fact, she cited evidence of a correlation between improvement in maternal symptoms and a reduction in the complications in children, such as behavioral problems.

Postpartum depression, which can develop anytime in the first 12 months after childbirth, is not uncommon, occurring in approximately 15% of women, according to Dr. Hudepohl. Risk factors include personal or family history of depression, anxiety or depression during pregnancy, and a prior history of postpartum depression.

Postpartum depression increases the risk of maternal suicide by about 70-fold, Dr. Hudepohl reported. She noted that the peaks in suicide attempts in the 1st and 12th month after delivery. Adverse infant outcomes are not a predictor of increase risk of attempts, but fetal or infant death are.

According to one study, about 40% of mothers with postpartum depression have intrusive thoughts that involve harming their child. About 15% fear being alone with their infant. Behaviors such as decreased playfulness, less talking, or other interactions with the child, and inconsistent response to the child are all likely to contribute to impaired maternal-child bonding, Dr. Hudepohl reported.

For women who discontinued antidepressants for pregnancy but have now developed significant postpartum depression, Dr. Hudepohl recommended using “what has worked in the past.” She considered monotherapy preferable if possible, but severe symptoms warrant more aggressive intervention. Dr. Hudepohl pointed out that the risks of antidepressants taken by the breast-feeding mother to the infant remain unclear despite multiple studies attempting to establish and quantify risk.

“Antidepressants are the most researched medication in pregnancy,” she said.

Conversely, the risks of untreated symptoms to the mother are significant, and the potential risks to the infant and family – if variable – are not insignificant.

Overall, “nonpharmacologic treatment is preferred first line for mild symptoms,” Dr. Hudepohl, but she and others consider a risk-benefit ratio growing increasingly in favor of drug therapy when this approach is the best option for bringing moderate to severe symptoms under control.

Whether depression arises during pregnancy or in the postpartum period, “psychotherapy is generally considered first-line treatment,” agreed Nancy Byatt, DO, MS, MBA, professor of psychiatry and of obstetrics and gynecology at the University of Massachusetts, Worcester.

Dr. Byatt, who has published frequently on this topic, further agreed that risks to the mother and the child increase with uncontrolled depression in the postpartum period. With symptoms of greater intensity, the uncertain risks of medication are outweighed by substantial potential benefits.

“When a pregnant or postpartum individual has moderate to severe illness, treatment with medication is typically recommended, because the benefits are thought to outweigh the risks,” she said, echoing a consensus opinion among experts and organized medicine.

MedscapeLive and this news organization are owned by the same parent company. Dr. Hudepohl and Dr. Byatt reported no potential financial conflicts of interest.
 

If moderate to severe postpartum depression poses a risk to child development, that argues in favor of pharmacologic therapy, according to a detailed risk-benefit assessment presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

monkeybusinessimages/Thinkstock

“It is important to consider that there are potential risks of antidepressant drugs, but there are also potential risks from not providing effective treatment,” reported Neha Hudepohl, MD, at the virtual meeting, presented by MedscapeLive.

On a website maintained by the Centers for Disease Control and Prevention, the question of whether antidepressants pose a risk to breast-feeding children is answered with a “maybe.” Although many of these drugs can be detected in breast milk, according to the CDC, “most have little or no effect on milk supply or on infant well-being.”

This is enough uncertainty that antidepressants are not first-line intervention when postpartum depression is mild, said Dr. Hudepohl, director of women’s mental health at Prisma Health Upstate, Greenville, S.C. However, she noted that the American College of Obstetricians and Gynecologists is among the organizations that recommend drug treatment if symptoms are moderate to severe.

“Depression in the mother affects interactions in feeding practices, sleep routines and patterns, and safety practices,” said Dr. Hudepohl, citing published studies supporting each of these consequences.

For the child, there is some degree of uncertainty about risk from untreated maternal depression as well as from breast mild exposure to antidepressants. Conclusive statements are not offered by ACOG and others.

“Some but not all studies have shown an impact of either antenatal or postnatal depression on speech recognition in infancy of native versus nonnative languages, IQ, and cognitive development, and reduction in left frontal brain electrical activity associated with impaired positive emotions,” Dr. Hudepohl reported.

Sifting through published data, Dr. Hudepohl cited studies associating persistent postpartum depression with a more than fourfold risk of behavioral problems at the age of 3.5 years, lower grades in mathematics at age 16, and a higher prevalence of depression at age 18. Among children who had depressed mothers in infancy, there have also been studies showing a higher reactivity to stressors and higher baseline cortisol levels.

“The good news is that these effects in children appear to be largely reversible with maternal treatment,” Dr. Hudepohl said. In fact, she cited evidence of a correlation between improvement in maternal symptoms and a reduction in the complications in children, such as behavioral problems.

Postpartum depression, which can develop anytime in the first 12 months after childbirth, is not uncommon, occurring in approximately 15% of women, according to Dr. Hudepohl. Risk factors include personal or family history of depression, anxiety or depression during pregnancy, and a prior history of postpartum depression.

Postpartum depression increases the risk of maternal suicide by about 70-fold, Dr. Hudepohl reported. She noted that the peaks in suicide attempts in the 1st and 12th month after delivery. Adverse infant outcomes are not a predictor of increase risk of attempts, but fetal or infant death are.

According to one study, about 40% of mothers with postpartum depression have intrusive thoughts that involve harming their child. About 15% fear being alone with their infant. Behaviors such as decreased playfulness, less talking, or other interactions with the child, and inconsistent response to the child are all likely to contribute to impaired maternal-child bonding, Dr. Hudepohl reported.

For women who discontinued antidepressants for pregnancy but have now developed significant postpartum depression, Dr. Hudepohl recommended using “what has worked in the past.” She considered monotherapy preferable if possible, but severe symptoms warrant more aggressive intervention. Dr. Hudepohl pointed out that the risks of antidepressants taken by the breast-feeding mother to the infant remain unclear despite multiple studies attempting to establish and quantify risk.

“Antidepressants are the most researched medication in pregnancy,” she said.

Conversely, the risks of untreated symptoms to the mother are significant, and the potential risks to the infant and family – if variable – are not insignificant.

Overall, “nonpharmacologic treatment is preferred first line for mild symptoms,” Dr. Hudepohl, but she and others consider a risk-benefit ratio growing increasingly in favor of drug therapy when this approach is the best option for bringing moderate to severe symptoms under control.

Whether depression arises during pregnancy or in the postpartum period, “psychotherapy is generally considered first-line treatment,” agreed Nancy Byatt, DO, MS, MBA, professor of psychiatry and of obstetrics and gynecology at the University of Massachusetts, Worcester.

Dr. Byatt, who has published frequently on this topic, further agreed that risks to the mother and the child increase with uncontrolled depression in the postpartum period. With symptoms of greater intensity, the uncertain risks of medication are outweighed by substantial potential benefits.

“When a pregnant or postpartum individual has moderate to severe illness, treatment with medication is typically recommended, because the benefits are thought to outweigh the risks,” she said, echoing a consensus opinion among experts and organized medicine.

MedscapeLive and this news organization are owned by the same parent company. Dr. Hudepohl and Dr. Byatt reported no potential financial conflicts of interest.
 

If moderate to severe postpartum depression poses a risk to child development, that argues in favor of pharmacologic therapy, according to a detailed risk-benefit assessment presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

monkeybusinessimages/Thinkstock

“It is important to consider that there are potential risks of antidepressant drugs, but there are also potential risks from not providing effective treatment,” reported Neha Hudepohl, MD, at the virtual meeting, presented by MedscapeLive.

On a website maintained by the Centers for Disease Control and Prevention, the question of whether antidepressants pose a risk to breast-feeding children is answered with a “maybe.” Although many of these drugs can be detected in breast milk, according to the CDC, “most have little or no effect on milk supply or on infant well-being.”

This is enough uncertainty that antidepressants are not first-line intervention when postpartum depression is mild, said Dr. Hudepohl, director of women’s mental health at Prisma Health Upstate, Greenville, S.C. However, she noted that the American College of Obstetricians and Gynecologists is among the organizations that recommend drug treatment if symptoms are moderate to severe.

“Depression in the mother affects interactions in feeding practices, sleep routines and patterns, and safety practices,” said Dr. Hudepohl, citing published studies supporting each of these consequences.

For the child, there is some degree of uncertainty about risk from untreated maternal depression as well as from breast mild exposure to antidepressants. Conclusive statements are not offered by ACOG and others.

“Some but not all studies have shown an impact of either antenatal or postnatal depression on speech recognition in infancy of native versus nonnative languages, IQ, and cognitive development, and reduction in left frontal brain electrical activity associated with impaired positive emotions,” Dr. Hudepohl reported.

Sifting through published data, Dr. Hudepohl cited studies associating persistent postpartum depression with a more than fourfold risk of behavioral problems at the age of 3.5 years, lower grades in mathematics at age 16, and a higher prevalence of depression at age 18. Among children who had depressed mothers in infancy, there have also been studies showing a higher reactivity to stressors and higher baseline cortisol levels.

“The good news is that these effects in children appear to be largely reversible with maternal treatment,” Dr. Hudepohl said. In fact, she cited evidence of a correlation between improvement in maternal symptoms and a reduction in the complications in children, such as behavioral problems.

Postpartum depression, which can develop anytime in the first 12 months after childbirth, is not uncommon, occurring in approximately 15% of women, according to Dr. Hudepohl. Risk factors include personal or family history of depression, anxiety or depression during pregnancy, and a prior history of postpartum depression.

Postpartum depression increases the risk of maternal suicide by about 70-fold, Dr. Hudepohl reported. She noted that the peaks in suicide attempts in the 1st and 12th month after delivery. Adverse infant outcomes are not a predictor of increase risk of attempts, but fetal or infant death are.

According to one study, about 40% of mothers with postpartum depression have intrusive thoughts that involve harming their child. About 15% fear being alone with their infant. Behaviors such as decreased playfulness, less talking, or other interactions with the child, and inconsistent response to the child are all likely to contribute to impaired maternal-child bonding, Dr. Hudepohl reported.

For women who discontinued antidepressants for pregnancy but have now developed significant postpartum depression, Dr. Hudepohl recommended using “what has worked in the past.” She considered monotherapy preferable if possible, but severe symptoms warrant more aggressive intervention. Dr. Hudepohl pointed out that the risks of antidepressants taken by the breast-feeding mother to the infant remain unclear despite multiple studies attempting to establish and quantify risk.

“Antidepressants are the most researched medication in pregnancy,” she said.

Conversely, the risks of untreated symptoms to the mother are significant, and the potential risks to the infant and family – if variable – are not insignificant.

Overall, “nonpharmacologic treatment is preferred first line for mild symptoms,” Dr. Hudepohl, but she and others consider a risk-benefit ratio growing increasingly in favor of drug therapy when this approach is the best option for bringing moderate to severe symptoms under control.

Whether depression arises during pregnancy or in the postpartum period, “psychotherapy is generally considered first-line treatment,” agreed Nancy Byatt, DO, MS, MBA, professor of psychiatry and of obstetrics and gynecology at the University of Massachusetts, Worcester.

Dr. Byatt, who has published frequently on this topic, further agreed that risks to the mother and the child increase with uncontrolled depression in the postpartum period. With symptoms of greater intensity, the uncertain risks of medication are outweighed by substantial potential benefits.

“When a pregnant or postpartum individual has moderate to severe illness, treatment with medication is typically recommended, because the benefits are thought to outweigh the risks,” she said, echoing a consensus opinion among experts and organized medicine.

MedscapeLive and this news organization are owned by the same parent company. Dr. Hudepohl and Dr. Byatt reported no potential financial conflicts of interest.
 

A novel formulation containing meloxicam and rizatriptan provides effective pain relief for patients with migraine, new research suggests. Results from the phase 3 INTERCEPT trial show that the treatment, known as AXS-07 (Axsome Therapeutics), also provided greater relief from the patients’ most bothersome symptom (MBS) compared with placebo.

In addition, about 74% of patients who received AXS-07 experienced no progression of pain from 2 to 24 hours after dosing and were less than half as likely to use rescue medication through 24 hours than those who received placebo.

Similar to a previous formulation combining naproxen sodium and sumatriptan, AXS-07 combines a nonsteroidal anti-inflammatory drug with a triptan. The combination is synergistic, investigators note, because one drug addresses pain mechanisms that the other does not.

“Rizatriptan’s primary mechanism is peripheral, and NSAIDs have both peripheral and central benefit,” said study investigator Stewart J. Tepper, MD, professor of neurology, Geisel School of Medicine at Dartmouth, Hanover, N.H. “That is why the whole is greater than the sum of the parts,” Dr. Tepper added.

The findings were presented at the American Headache Society’s 2021 annual meeting.
 

Acute treatments needed

For many patients, current migraine treatments are inadequate. In addition, suboptimal acute treatment can increase risk for progression from episodic migraine to chronic migraine. It also increases the risk for medication-overuse headache.

The search for optimal acute treatments is therefore “really important for patients,” Dr. Tepper noted.

Because it contains rizatriptan, AXS-07 is believed to inhibit the release of calcitonin gene-related peptide, reverse the vasodilation that it causes, and decrease the transmission of pain signals. Meloxicam, on the other hand, is thought to reduce neuroinflammation and reverse central sensitization, which maintains chronic pain.

In the phase 3, double-blind INTERCEPT trial, the investigators examined AXS-07 for early treatment of migraine. Eligible patients were aged 18 to 65 years, had been diagnosed with migraine in accordance with ICHD-3 criteria, and averaged two to eight migraines per month.

The researchers randomly assigned a single dose of AXS-07 (n = 152) or placebo (n = 150). Participants were asked to administer treatment to themselves at the earliest sign of migraine pain.

The trial’s two primary endpoints were pain freedom and freedom from the MBS 2 hours after dosing. Secondary endpoints included sustained pain freedom and freedom from pain progression, functional disability, and use of rescue medication.

Demographic characteristics of the study population reflected those of the general population of people with migraine, according to the researchers. More than 85% of participants were women, and the study group’s mean age was 41 years. There were no demographic differences between the two treatment groups.
 

Reduced pain progression

Results showed that 2 hours after treatment, rate of pain freedom was 32.6% in the AXS-07 group and 16.3% in the placebo group (P = .002). At the same time point, rate of freedom from MBS was 43.9% and 26.7%, respectively (P = .003).

Approximately 64% of patients who received AXS-07 were pain free at 12 hours, and 69% were pain free at 24 hours. In contrast, 42% of the placebo group were pain free at 12 hours, and 47% were pain free at 24 hours (P < .001 for both comparisons).

The benefits AXS-07 provided were sustained; 22.7% of the active-treatment group achieved sustained pain freedom from 2 to 24 hours after treatment, compared with 12.6% of the placebo group (P = .03). Results were similar for sustained pain freedom from 2 to 48 hours after treatment (20.5% vs. 9.6%; P = .013).

In addition, 73.5% of patients who received AXS-07 had freedom from pain progression from 2 to 24 hours after treatment, versus 47.4% of those who received placebo (P < .001). The rate of rescue medication use through 24 hours was 15.3% and 42.2%, respectively (P < .001).

AXS-07 was also linked to significant reductions in functional disability. About 74% of patients who received it reported no disability at 24 hours, compared with 47% of patients who received placebo (P < .001). Scores on the Patient Global Impression of Change scale were very much improved or much improved 2 hours after dosing for 52.4% of the AXS-07 group, versus 27.7% of the placebo group (P < .001).

The overall rate of treatment-emergent adverse events (AEs) was 17.9% in the active group and 7.7% among the control group. The rate of somnolence was 4.3%, versus 2.1%; the rate of dizziness was 2.9%, versus 1.4%; and the rate of paresthesia was 2.1%, versus 0%. There were no serious AEs.

“Unexpectedly, and it’s hard to interpret this, but the nausea associated with the use of AXS-07 is less than with either of the active components or the placebo,” said Dr. Tepper. “It’s not dramatically different for dizziness.”
 

Improved adherence?

Meloxicam is generally used not as an acute medication but for prevention, Dr. Tepper noted. The drug is often administered to reduce inflammation in conditions such as chronic arthritis.

AXS-07 incorporates an altered pharmacokinetic delivery system to provide a quicker onset of effect for meloxicam.

“Most headache specialists would say that of all the oral triptans, rizatriptan is the fastest,” said Dr. Tepper.

The idea for the new agent was to hasten the onset of meloxicam’s effect so that both active components would work rapidly. “We know that there is a synergy between NSAIDs and triptans, in terms of complete headache response,” Dr. Tepper said.

Data indicate that when neurologists recommend that patients take an NSAID and triptan together at the beginning of an attack, patients rarely comply. “It’s a big adherence issue,” said Dr. Tepper. “They’re more likely to get a complete response if they take them together, especially if the tablet is designed to deliver the two products together in an optimal way.”
 

Uncertain therapeutic advantage

Commenting on the findings, Robert Shapiro, MD, PhD, professor of neurologic science at the University of Vermont, Burlington, noted that because of favorable data from past studies for the combination of 85 mg of sumatriptan with 500 mg of naproxen sodium, the coadministration of a triptan with an NSAID has been a standard of care for the past decade.

“It’s therefore unsurprising that a combination of rizatriptan 10 mg plus meloxicam 20 mg in a proprietary MoSEIC formulation might also prove to be more effective than either individual medication taken alone for acute migraine attacks,” said Dr. Shapiro, who was not involved with the research.

It is not possible to compare the efficacy and tolerability of AXS-07 with those of sumatriptan–naproxen sodium without head-to-head trials. However, the available data suggest that the latter formulation is superior, he added.

In 2008, researchers conducted two parallel-group, placebo-controlled trials of sumatriptan–naproxen sodium taken early in a migraine attack. These trials had protocols comparable to that of the current INTERCEPT trial for AXS-07, said Dr. Shapiro.

For the key primary endpoint of 2-hour pain freedom, the two sumatriptan–naproxen sodium trials found therapeutic gains of 35% and 36%, respectively, versus 16.3% for the AXS-07 trial. The placebo response rates (17% and 15% for sumatriptan–naproxen sodium, vs. 16.3% for the AXS-07 trial) were comparable.

Similarly, for the endpoint of 2- to 24-hour pain freedom, the sumatriptan–naproxen sodium trials found therapeutic gains of 33% and 26%, respectively, versus 15.1% for the AXS-07 trial. Again, response rates for placebo were comparable (12% and 14% for sumatriptan–naproxen sodium, vs. 12.6% for AXS-07).
The placebo-adjusted differences for reporting any treatment-emergent AE, otherwise known as “therapeutic penalty,” was 10.2% for AXS-07 in the INTERCEPT trial, versus 7% and 5%, respectively for participants in the two sumatriptan–naproxen sodium trials.

“In light of these data, it’s not immediately apparent what advantage AXS-07 might offer over sumatriptan–naproxen sodium,” said Dr. Shapiro.

“Furthermore, sumatriptan–naproxen sodium is currently available in generic form,” he added.

The study was funded by Axsome Therapeutics. Dr. Tepper is a consultant to Axsome Therapeutics. Dr. Shapiro has previously performed research consulting for Lilly and Lundbeck.

A version of this article first appeared on Medscape.com.

A novel formulation containing meloxicam and rizatriptan provides effective pain relief for patients with migraine, new research suggests. Results from the phase 3 INTERCEPT trial show that the treatment, known as AXS-07 (Axsome Therapeutics), also provided greater relief from the patients’ most bothersome symptom (MBS) compared with placebo.

In addition, about 74% of patients who received AXS-07 experienced no progression of pain from 2 to 24 hours after dosing and were less than half as likely to use rescue medication through 24 hours than those who received placebo.

Similar to a previous formulation combining naproxen sodium and sumatriptan, AXS-07 combines a nonsteroidal anti-inflammatory drug with a triptan. The combination is synergistic, investigators note, because one drug addresses pain mechanisms that the other does not.

“Rizatriptan’s primary mechanism is peripheral, and NSAIDs have both peripheral and central benefit,” said study investigator Stewart J. Tepper, MD, professor of neurology, Geisel School of Medicine at Dartmouth, Hanover, N.H. “That is why the whole is greater than the sum of the parts,” Dr. Tepper added.

The findings were presented at the American Headache Society’s 2021 annual meeting.
 

Acute treatments needed

For many patients, current migraine treatments are inadequate. In addition, suboptimal acute treatment can increase risk for progression from episodic migraine to chronic migraine. It also increases the risk for medication-overuse headache.

The search for optimal acute treatments is therefore “really important for patients,” Dr. Tepper noted.

Because it contains rizatriptan, AXS-07 is believed to inhibit the release of calcitonin gene-related peptide, reverse the vasodilation that it causes, and decrease the transmission of pain signals. Meloxicam, on the other hand, is thought to reduce neuroinflammation and reverse central sensitization, which maintains chronic pain.

In the phase 3, double-blind INTERCEPT trial, the investigators examined AXS-07 for early treatment of migraine. Eligible patients were aged 18 to 65 years, had been diagnosed with migraine in accordance with ICHD-3 criteria, and averaged two to eight migraines per month.

The researchers randomly assigned a single dose of AXS-07 (n = 152) or placebo (n = 150). Participants were asked to administer treatment to themselves at the earliest sign of migraine pain.

The trial’s two primary endpoints were pain freedom and freedom from the MBS 2 hours after dosing. Secondary endpoints included sustained pain freedom and freedom from pain progression, functional disability, and use of rescue medication.

Demographic characteristics of the study population reflected those of the general population of people with migraine, according to the researchers. More than 85% of participants were women, and the study group’s mean age was 41 years. There were no demographic differences between the two treatment groups.
 

Reduced pain progression

Results showed that 2 hours after treatment, rate of pain freedom was 32.6% in the AXS-07 group and 16.3% in the placebo group (P = .002). At the same time point, rate of freedom from MBS was 43.9% and 26.7%, respectively (P = .003).

Approximately 64% of patients who received AXS-07 were pain free at 12 hours, and 69% were pain free at 24 hours. In contrast, 42% of the placebo group were pain free at 12 hours, and 47% were pain free at 24 hours (P < .001 for both comparisons).

The benefits AXS-07 provided were sustained; 22.7% of the active-treatment group achieved sustained pain freedom from 2 to 24 hours after treatment, compared with 12.6% of the placebo group (P = .03). Results were similar for sustained pain freedom from 2 to 48 hours after treatment (20.5% vs. 9.6%; P = .013).

In addition, 73.5% of patients who received AXS-07 had freedom from pain progression from 2 to 24 hours after treatment, versus 47.4% of those who received placebo (P < .001). The rate of rescue medication use through 24 hours was 15.3% and 42.2%, respectively (P < .001).

AXS-07 was also linked to significant reductions in functional disability. About 74% of patients who received it reported no disability at 24 hours, compared with 47% of patients who received placebo (P < .001). Scores on the Patient Global Impression of Change scale were very much improved or much improved 2 hours after dosing for 52.4% of the AXS-07 group, versus 27.7% of the placebo group (P < .001).

The overall rate of treatment-emergent adverse events (AEs) was 17.9% in the active group and 7.7% among the control group. The rate of somnolence was 4.3%, versus 2.1%; the rate of dizziness was 2.9%, versus 1.4%; and the rate of paresthesia was 2.1%, versus 0%. There were no serious AEs.

“Unexpectedly, and it’s hard to interpret this, but the nausea associated with the use of AXS-07 is less than with either of the active components or the placebo,” said Dr. Tepper. “It’s not dramatically different for dizziness.”
 

Improved adherence?

Meloxicam is generally used not as an acute medication but for prevention, Dr. Tepper noted. The drug is often administered to reduce inflammation in conditions such as chronic arthritis.

AXS-07 incorporates an altered pharmacokinetic delivery system to provide a quicker onset of effect for meloxicam.

“Most headache specialists would say that of all the oral triptans, rizatriptan is the fastest,” said Dr. Tepper.

The idea for the new agent was to hasten the onset of meloxicam’s effect so that both active components would work rapidly. “We know that there is a synergy between NSAIDs and triptans, in terms of complete headache response,” Dr. Tepper said.

Data indicate that when neurologists recommend that patients take an NSAID and triptan together at the beginning of an attack, patients rarely comply. “It’s a big adherence issue,” said Dr. Tepper. “They’re more likely to get a complete response if they take them together, especially if the tablet is designed to deliver the two products together in an optimal way.”
 

Uncertain therapeutic advantage

Commenting on the findings, Robert Shapiro, MD, PhD, professor of neurologic science at the University of Vermont, Burlington, noted that because of favorable data from past studies for the combination of 85 mg of sumatriptan with 500 mg of naproxen sodium, the coadministration of a triptan with an NSAID has been a standard of care for the past decade.

“It’s therefore unsurprising that a combination of rizatriptan 10 mg plus meloxicam 20 mg in a proprietary MoSEIC formulation might also prove to be more effective than either individual medication taken alone for acute migraine attacks,” said Dr. Shapiro, who was not involved with the research.

It is not possible to compare the efficacy and tolerability of AXS-07 with those of sumatriptan–naproxen sodium without head-to-head trials. However, the available data suggest that the latter formulation is superior, he added.

In 2008, researchers conducted two parallel-group, placebo-controlled trials of sumatriptan–naproxen sodium taken early in a migraine attack. These trials had protocols comparable to that of the current INTERCEPT trial for AXS-07, said Dr. Shapiro.

For the key primary endpoint of 2-hour pain freedom, the two sumatriptan–naproxen sodium trials found therapeutic gains of 35% and 36%, respectively, versus 16.3% for the AXS-07 trial. The placebo response rates (17% and 15% for sumatriptan–naproxen sodium, vs. 16.3% for the AXS-07 trial) were comparable.

Similarly, for the endpoint of 2- to 24-hour pain freedom, the sumatriptan–naproxen sodium trials found therapeutic gains of 33% and 26%, respectively, versus 15.1% for the AXS-07 trial. Again, response rates for placebo were comparable (12% and 14% for sumatriptan–naproxen sodium, vs. 12.6% for AXS-07).
The placebo-adjusted differences for reporting any treatment-emergent AE, otherwise known as “therapeutic penalty,” was 10.2% for AXS-07 in the INTERCEPT trial, versus 7% and 5%, respectively for participants in the two sumatriptan–naproxen sodium trials.

“In light of these data, it’s not immediately apparent what advantage AXS-07 might offer over sumatriptan–naproxen sodium,” said Dr. Shapiro.

“Furthermore, sumatriptan–naproxen sodium is currently available in generic form,” he added.

The study was funded by Axsome Therapeutics. Dr. Tepper is a consultant to Axsome Therapeutics. Dr. Shapiro has previously performed research consulting for Lilly and Lundbeck.

A version of this article first appeared on Medscape.com.

A novel formulation containing meloxicam and rizatriptan provides effective pain relief for patients with migraine, new research suggests. Results from the phase 3 INTERCEPT trial show that the treatment, known as AXS-07 (Axsome Therapeutics), also provided greater relief from the patients’ most bothersome symptom (MBS) compared with placebo.

In addition, about 74% of patients who received AXS-07 experienced no progression of pain from 2 to 24 hours after dosing and were less than half as likely to use rescue medication through 24 hours than those who received placebo.

Similar to a previous formulation combining naproxen sodium and sumatriptan, AXS-07 combines a nonsteroidal anti-inflammatory drug with a triptan. The combination is synergistic, investigators note, because one drug addresses pain mechanisms that the other does not.

“Rizatriptan’s primary mechanism is peripheral, and NSAIDs have both peripheral and central benefit,” said study investigator Stewart J. Tepper, MD, professor of neurology, Geisel School of Medicine at Dartmouth, Hanover, N.H. “That is why the whole is greater than the sum of the parts,” Dr. Tepper added.

The findings were presented at the American Headache Society’s 2021 annual meeting.
 

Acute treatments needed

For many patients, current migraine treatments are inadequate. In addition, suboptimal acute treatment can increase risk for progression from episodic migraine to chronic migraine. It also increases the risk for medication-overuse headache.

The search for optimal acute treatments is therefore “really important for patients,” Dr. Tepper noted.

Because it contains rizatriptan, AXS-07 is believed to inhibit the release of calcitonin gene-related peptide, reverse the vasodilation that it causes, and decrease the transmission of pain signals. Meloxicam, on the other hand, is thought to reduce neuroinflammation and reverse central sensitization, which maintains chronic pain.

In the phase 3, double-blind INTERCEPT trial, the investigators examined AXS-07 for early treatment of migraine. Eligible patients were aged 18 to 65 years, had been diagnosed with migraine in accordance with ICHD-3 criteria, and averaged two to eight migraines per month.

The researchers randomly assigned a single dose of AXS-07 (n = 152) or placebo (n = 150). Participants were asked to administer treatment to themselves at the earliest sign of migraine pain.

The trial’s two primary endpoints were pain freedom and freedom from the MBS 2 hours after dosing. Secondary endpoints included sustained pain freedom and freedom from pain progression, functional disability, and use of rescue medication.

Demographic characteristics of the study population reflected those of the general population of people with migraine, according to the researchers. More than 85% of participants were women, and the study group’s mean age was 41 years. There were no demographic differences between the two treatment groups.
 

Reduced pain progression

Results showed that 2 hours after treatment, rate of pain freedom was 32.6% in the AXS-07 group and 16.3% in the placebo group (P = .002). At the same time point, rate of freedom from MBS was 43.9% and 26.7%, respectively (P = .003).

Approximately 64% of patients who received AXS-07 were pain free at 12 hours, and 69% were pain free at 24 hours. In contrast, 42% of the placebo group were pain free at 12 hours, and 47% were pain free at 24 hours (P < .001 for both comparisons).

The benefits AXS-07 provided were sustained; 22.7% of the active-treatment group achieved sustained pain freedom from 2 to 24 hours after treatment, compared with 12.6% of the placebo group (P = .03). Results were similar for sustained pain freedom from 2 to 48 hours after treatment (20.5% vs. 9.6%; P = .013).

In addition, 73.5% of patients who received AXS-07 had freedom from pain progression from 2 to 24 hours after treatment, versus 47.4% of those who received placebo (P < .001). The rate of rescue medication use through 24 hours was 15.3% and 42.2%, respectively (P < .001).

AXS-07 was also linked to significant reductions in functional disability. About 74% of patients who received it reported no disability at 24 hours, compared with 47% of patients who received placebo (P < .001). Scores on the Patient Global Impression of Change scale were very much improved or much improved 2 hours after dosing for 52.4% of the AXS-07 group, versus 27.7% of the placebo group (P < .001).

The overall rate of treatment-emergent adverse events (AEs) was 17.9% in the active group and 7.7% among the control group. The rate of somnolence was 4.3%, versus 2.1%; the rate of dizziness was 2.9%, versus 1.4%; and the rate of paresthesia was 2.1%, versus 0%. There were no serious AEs.

“Unexpectedly, and it’s hard to interpret this, but the nausea associated with the use of AXS-07 is less than with either of the active components or the placebo,” said Dr. Tepper. “It’s not dramatically different for dizziness.”
 

Improved adherence?

Meloxicam is generally used not as an acute medication but for prevention, Dr. Tepper noted. The drug is often administered to reduce inflammation in conditions such as chronic arthritis.

AXS-07 incorporates an altered pharmacokinetic delivery system to provide a quicker onset of effect for meloxicam.

“Most headache specialists would say that of all the oral triptans, rizatriptan is the fastest,” said Dr. Tepper.

The idea for the new agent was to hasten the onset of meloxicam’s effect so that both active components would work rapidly. “We know that there is a synergy between NSAIDs and triptans, in terms of complete headache response,” Dr. Tepper said.

Data indicate that when neurologists recommend that patients take an NSAID and triptan together at the beginning of an attack, patients rarely comply. “It’s a big adherence issue,” said Dr. Tepper. “They’re more likely to get a complete response if they take them together, especially if the tablet is designed to deliver the two products together in an optimal way.”
 

Uncertain therapeutic advantage

Commenting on the findings, Robert Shapiro, MD, PhD, professor of neurologic science at the University of Vermont, Burlington, noted that because of favorable data from past studies for the combination of 85 mg of sumatriptan with 500 mg of naproxen sodium, the coadministration of a triptan with an NSAID has been a standard of care for the past decade.

“It’s therefore unsurprising that a combination of rizatriptan 10 mg plus meloxicam 20 mg in a proprietary MoSEIC formulation might also prove to be more effective than either individual medication taken alone for acute migraine attacks,” said Dr. Shapiro, who was not involved with the research.

It is not possible to compare the efficacy and tolerability of AXS-07 with those of sumatriptan–naproxen sodium without head-to-head trials. However, the available data suggest that the latter formulation is superior, he added.

In 2008, researchers conducted two parallel-group, placebo-controlled trials of sumatriptan–naproxen sodium taken early in a migraine attack. These trials had protocols comparable to that of the current INTERCEPT trial for AXS-07, said Dr. Shapiro.

For the key primary endpoint of 2-hour pain freedom, the two sumatriptan–naproxen sodium trials found therapeutic gains of 35% and 36%, respectively, versus 16.3% for the AXS-07 trial. The placebo response rates (17% and 15% for sumatriptan–naproxen sodium, vs. 16.3% for the AXS-07 trial) were comparable.

Similarly, for the endpoint of 2- to 24-hour pain freedom, the sumatriptan–naproxen sodium trials found therapeutic gains of 33% and 26%, respectively, versus 15.1% for the AXS-07 trial. Again, response rates for placebo were comparable (12% and 14% for sumatriptan–naproxen sodium, vs. 12.6% for AXS-07).
The placebo-adjusted differences for reporting any treatment-emergent AE, otherwise known as “therapeutic penalty,” was 10.2% for AXS-07 in the INTERCEPT trial, versus 7% and 5%, respectively for participants in the two sumatriptan–naproxen sodium trials.

“In light of these data, it’s not immediately apparent what advantage AXS-07 might offer over sumatriptan–naproxen sodium,” said Dr. Shapiro.

“Furthermore, sumatriptan–naproxen sodium is currently available in generic form,” he added.

The study was funded by Axsome Therapeutics. Dr. Tepper is a consultant to Axsome Therapeutics. Dr. Shapiro has previously performed research consulting for Lilly and Lundbeck.

A version of this article first appeared on Medscape.com.

Approximately one-third of individuals with autism spectrum disorder (ASD) are prescribed multiple medications to manage comorbidities and symptoms, according to data from a retrospective cohort study of more than 26,000 patients.

“Clinicians caring for patients with ASD are tasked with the challenges of managing the primary disease, as well as co-occurring medical conditions, and coordinating with educational and social service professionals to provide holistic care,” wrote Aliya G. Feroe of Harvard Medical School, Boston, and colleagues.

The medication classes used to treat individuals with ASD include ADHD medications, antipsychotics, antidepressants, mood stabilizers, benzodiazepines, anxiolytics, and hypnotics, but the prescription rates of these medications in ASD patients have not been examined in large studies, the researchers said.

In a study published in JAMA Pediatrics, the researchers identified 26,722 individuals with ASD using a United States health care database from Jan. 1, 2014, to Dec. 31, 2019. Data included records of inpatient and outpatient claims, and records of prescriptions filled through commercial pharmacies. Individuals received at least 1 of 24 of the most common medication groups for ASD or comorbidities. The average age of the study participants was 14 years, and 78% were male. Diagnostic codes for ASD were based on the International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision.

Over the 6-year study period, approximately one-third of the participants were taking three or more medications at once, ranging from 28.6% to 31.5%. In any 1 year, approximately 41% of children were prescribed a single medication, 17% received two prescriptions, 7.9% received four, and 3.4% received five. Medication changes occurred more frequently within classes than between classes, and reasons for these changes may include patient preference, adverse effects, and cost, the researchers noted.

The overall number of children prescribed particular drugs remained consistent, the researchers noted. “For example, the total number of individuals prescribed methylphenidate shifted from 832 in 2014 to 850 in 2015, 899 in 2016, 863 in 2017, and 838 in 2018,” they wrote.

In 15 of the 24 medication groups included in the study, at least 15% of the individuals had unspecified anxiety disorder, anxiety neurosis, or major depressive disorder; in 11 of the medication groups, at least 15% had some form of ADHD. ADHD prevalence in patients taking stimulants varied based on ADHD type, the researchers said.

The most common comorbidities in patients taking antipsychotics were combined type ADHD (11.6%-17.8%) and anxiety disorder (13.1%-30.1%). The study findings suggest that many clinicians are incorporating medications into ASD management, the researchers said.

“Although there is no medical treatment for the core deficits of social communication and repetitive behavioral patterns in ASD, the American Academy of Pediatrics recommends that clinicians consider medications in the management of common comorbid conditions, including seizures, ADHD, anxiety disorders, mood disorders, and disruptive behavior disorders,” they said.

The findings were limited by several factors including the potential for inconsistent reporting of diagnoses and pharmacy claims, the researchers noted. Other limitations included a lack of direct clinical assessment to validate diagnoses and the absence of validated diagnostic instruments to screen for comorbidities, they added.

“Our findings suggest that clinicians may be increasingly using integrated approaches to treating patients with ASD and co-occurring conditions, and further work is necessary to determine the relative effects of pharmacotherapy vs. behavioral interventions on outcomes in patients with ASD,” the researchers concluded.
 

Many reasons for multiple medications

“The researchers put in a lot of effort to provide data on a large scale,” Herschel Lessin, MD, of Children’s Medical Group, Poughkeepsie, N.Y., said in an interview.

“The findings illustrate the reality that autistic children are prescribed a lot of medications for a lot of reasons, some of which are not entirely clear,” Dr. Lessin said. The study also reflects the chronic lack of behavioral health services for children, he noted. Many children with ASD are referred for services they are unable to access, he said. “As a result, they see doctors who can only prescribe medications to try to control behavior or symptoms for which the cause is unclear,” and which could be ASD or other comorbidities, he emphasized.

The large sample size strengthens the study findings, but some of the challenges include the use of claims data, which do not indicate how diagnoses were made, said Dr. Lessin. An additional limitation is the fact that many medications for children with autism are used off label, so the specific reason for their use may be unknown, he said.

The take-home message for clinicians is that children with ASD are getting a lot of medications, and pediatricians are not usually responsible for multiple medications,” Dr. Lessin said. Ultimately, the study is “a plea for more research,” to tease out details of what medications are indicated and helpful, he said.

The study received no outside funding. The researchers and Dr. Lessin had no financial conflicts to disclose. Dr. Lessin serves on the Pediatric News editorial advisory board.

Approximately one-third of individuals with autism spectrum disorder (ASD) are prescribed multiple medications to manage comorbidities and symptoms, according to data from a retrospective cohort study of more than 26,000 patients.

“Clinicians caring for patients with ASD are tasked with the challenges of managing the primary disease, as well as co-occurring medical conditions, and coordinating with educational and social service professionals to provide holistic care,” wrote Aliya G. Feroe of Harvard Medical School, Boston, and colleagues.

The medication classes used to treat individuals with ASD include ADHD medications, antipsychotics, antidepressants, mood stabilizers, benzodiazepines, anxiolytics, and hypnotics, but the prescription rates of these medications in ASD patients have not been examined in large studies, the researchers said.

In a study published in JAMA Pediatrics, the researchers identified 26,722 individuals with ASD using a United States health care database from Jan. 1, 2014, to Dec. 31, 2019. Data included records of inpatient and outpatient claims, and records of prescriptions filled through commercial pharmacies. Individuals received at least 1 of 24 of the most common medication groups for ASD or comorbidities. The average age of the study participants was 14 years, and 78% were male. Diagnostic codes for ASD were based on the International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision.

Over the 6-year study period, approximately one-third of the participants were taking three or more medications at once, ranging from 28.6% to 31.5%. In any 1 year, approximately 41% of children were prescribed a single medication, 17% received two prescriptions, 7.9% received four, and 3.4% received five. Medication changes occurred more frequently within classes than between classes, and reasons for these changes may include patient preference, adverse effects, and cost, the researchers noted.

The overall number of children prescribed particular drugs remained consistent, the researchers noted. “For example, the total number of individuals prescribed methylphenidate shifted from 832 in 2014 to 850 in 2015, 899 in 2016, 863 in 2017, and 838 in 2018,” they wrote.

In 15 of the 24 medication groups included in the study, at least 15% of the individuals had unspecified anxiety disorder, anxiety neurosis, or major depressive disorder; in 11 of the medication groups, at least 15% had some form of ADHD. ADHD prevalence in patients taking stimulants varied based on ADHD type, the researchers said.

The most common comorbidities in patients taking antipsychotics were combined type ADHD (11.6%-17.8%) and anxiety disorder (13.1%-30.1%). The study findings suggest that many clinicians are incorporating medications into ASD management, the researchers said.

“Although there is no medical treatment for the core deficits of social communication and repetitive behavioral patterns in ASD, the American Academy of Pediatrics recommends that clinicians consider medications in the management of common comorbid conditions, including seizures, ADHD, anxiety disorders, mood disorders, and disruptive behavior disorders,” they said.

The findings were limited by several factors including the potential for inconsistent reporting of diagnoses and pharmacy claims, the researchers noted. Other limitations included a lack of direct clinical assessment to validate diagnoses and the absence of validated diagnostic instruments to screen for comorbidities, they added.

“Our findings suggest that clinicians may be increasingly using integrated approaches to treating patients with ASD and co-occurring conditions, and further work is necessary to determine the relative effects of pharmacotherapy vs. behavioral interventions on outcomes in patients with ASD,” the researchers concluded.
 

Many reasons for multiple medications

“The researchers put in a lot of effort to provide data on a large scale,” Herschel Lessin, MD, of Children’s Medical Group, Poughkeepsie, N.Y., said in an interview.

“The findings illustrate the reality that autistic children are prescribed a lot of medications for a lot of reasons, some of which are not entirely clear,” Dr. Lessin said. The study also reflects the chronic lack of behavioral health services for children, he noted. Many children with ASD are referred for services they are unable to access, he said. “As a result, they see doctors who can only prescribe medications to try to control behavior or symptoms for which the cause is unclear,” and which could be ASD or other comorbidities, he emphasized.

The large sample size strengthens the study findings, but some of the challenges include the use of claims data, which do not indicate how diagnoses were made, said Dr. Lessin. An additional limitation is the fact that many medications for children with autism are used off label, so the specific reason for their use may be unknown, he said.

The take-home message for clinicians is that children with ASD are getting a lot of medications, and pediatricians are not usually responsible for multiple medications,” Dr. Lessin said. Ultimately, the study is “a plea for more research,” to tease out details of what medications are indicated and helpful, he said.

The study received no outside funding. The researchers and Dr. Lessin had no financial conflicts to disclose. Dr. Lessin serves on the Pediatric News editorial advisory board.

Approximately one-third of individuals with autism spectrum disorder (ASD) are prescribed multiple medications to manage comorbidities and symptoms, according to data from a retrospective cohort study of more than 26,000 patients.

“Clinicians caring for patients with ASD are tasked with the challenges of managing the primary disease, as well as co-occurring medical conditions, and coordinating with educational and social service professionals to provide holistic care,” wrote Aliya G. Feroe of Harvard Medical School, Boston, and colleagues.

The medication classes used to treat individuals with ASD include ADHD medications, antipsychotics, antidepressants, mood stabilizers, benzodiazepines, anxiolytics, and hypnotics, but the prescription rates of these medications in ASD patients have not been examined in large studies, the researchers said.

In a study published in JAMA Pediatrics, the researchers identified 26,722 individuals with ASD using a United States health care database from Jan. 1, 2014, to Dec. 31, 2019. Data included records of inpatient and outpatient claims, and records of prescriptions filled through commercial pharmacies. Individuals received at least 1 of 24 of the most common medication groups for ASD or comorbidities. The average age of the study participants was 14 years, and 78% were male. Diagnostic codes for ASD were based on the International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision.

Over the 6-year study period, approximately one-third of the participants were taking three or more medications at once, ranging from 28.6% to 31.5%. In any 1 year, approximately 41% of children were prescribed a single medication, 17% received two prescriptions, 7.9% received four, and 3.4% received five. Medication changes occurred more frequently within classes than between classes, and reasons for these changes may include patient preference, adverse effects, and cost, the researchers noted.

The overall number of children prescribed particular drugs remained consistent, the researchers noted. “For example, the total number of individuals prescribed methylphenidate shifted from 832 in 2014 to 850 in 2015, 899 in 2016, 863 in 2017, and 838 in 2018,” they wrote.

In 15 of the 24 medication groups included in the study, at least 15% of the individuals had unspecified anxiety disorder, anxiety neurosis, or major depressive disorder; in 11 of the medication groups, at least 15% had some form of ADHD. ADHD prevalence in patients taking stimulants varied based on ADHD type, the researchers said.

The most common comorbidities in patients taking antipsychotics were combined type ADHD (11.6%-17.8%) and anxiety disorder (13.1%-30.1%). The study findings suggest that many clinicians are incorporating medications into ASD management, the researchers said.

“Although there is no medical treatment for the core deficits of social communication and repetitive behavioral patterns in ASD, the American Academy of Pediatrics recommends that clinicians consider medications in the management of common comorbid conditions, including seizures, ADHD, anxiety disorders, mood disorders, and disruptive behavior disorders,” they said.

The findings were limited by several factors including the potential for inconsistent reporting of diagnoses and pharmacy claims, the researchers noted. Other limitations included a lack of direct clinical assessment to validate diagnoses and the absence of validated diagnostic instruments to screen for comorbidities, they added.

“Our findings suggest that clinicians may be increasingly using integrated approaches to treating patients with ASD and co-occurring conditions, and further work is necessary to determine the relative effects of pharmacotherapy vs. behavioral interventions on outcomes in patients with ASD,” the researchers concluded.
 

Many reasons for multiple medications

“The researchers put in a lot of effort to provide data on a large scale,” Herschel Lessin, MD, of Children’s Medical Group, Poughkeepsie, N.Y., said in an interview.

“The findings illustrate the reality that autistic children are prescribed a lot of medications for a lot of reasons, some of which are not entirely clear,” Dr. Lessin said. The study also reflects the chronic lack of behavioral health services for children, he noted. Many children with ASD are referred for services they are unable to access, he said. “As a result, they see doctors who can only prescribe medications to try to control behavior or symptoms for which the cause is unclear,” and which could be ASD or other comorbidities, he emphasized.

The large sample size strengthens the study findings, but some of the challenges include the use of claims data, which do not indicate how diagnoses were made, said Dr. Lessin. An additional limitation is the fact that many medications for children with autism are used off label, so the specific reason for their use may be unknown, he said.

The take-home message for clinicians is that children with ASD are getting a lot of medications, and pediatricians are not usually responsible for multiple medications,” Dr. Lessin said. Ultimately, the study is “a plea for more research,” to tease out details of what medications are indicated and helpful, he said.

The study received no outside funding. The researchers and Dr. Lessin had no financial conflicts to disclose. Dr. Lessin serves on the Pediatric News editorial advisory board.

The Food and Drug Administration is adding a warning to mRNA COVID-19 vaccines’ fact sheets as medical experts continue to investigate cases of heart inflammation, which are rare but are more likely to occur in young men and teen boys.

Doran Fink, MD, PhD, deputy director of the FDA’s division of vaccines and related products applications, told a Centers for Disease Control and Prevention expert panel on June 23 that the FDA is finalizing language on a warning statement for health care providers, vaccine recipients, and parents or caregivers of teens.

The incidents are more likely to follow the second dose of the Pfizer or Moderna vaccine, with chest pain and other symptoms occurring within several days to a week, the warning will note.

“Based on limited follow-up, most cases appear to have been associated with resolution of symptoms, but limited information is available about potential long-term sequelae,” Dr. Fink said, describing the statement to the Advisory Committee on Immunization Practices, independent experts who advise the CDC.

“Symptoms suggestive of myocarditis or pericarditis should result in vaccine recipients seeking medical attention,” he said.
 

Benefits outweigh risks

Although no formal vote occurred after the meeting, the ACIP members delivered a strong endorsement for continuing to vaccinate 12- to 29-year-olds with the Pfizer and Moderna vaccines despite the warning.

“To me it’s clear, based on current information, that the benefits of vaccine clearly outweigh the risks,” said ACIP member Veronica McNally, president and CEO of the Franny Strong Foundation in Bloomfield, Mich., a sentiment echoed by other members.

As ACIP was meeting, leaders of the nation’s major physician, nurse, and public health associations issued a statement supporting continued vaccination: “The facts are clear: this is an extremely rare side effect, and only an exceedingly small number of people will experience it after vaccination.

“Importantly, for the young people who do, most cases are mild, and individuals recover often on their own or with minimal treatment. In addition, we know that myocarditis and pericarditis are much more common if you get COVID-19, and the risks to the heart from COVID-19 infection can be more severe.”

ACIP heard the evidence behind that claim. According to the Vaccine Safety Datalink, which contains data from more than 12 million medical records, myocarditis or pericarditis occurs in 12- to 39-year-olds at a rate of 8 per 1 million after the second Pfizer dose and 19.8 per 1 million after the second Moderna dose.

The CDC continues to investigate the link between the mRNA vaccines and heart inflammation, including any differences between the vaccines.

Most of the symptoms resolved quickly, said Tom Shimabukuro, deputy director of CDC’s Immunization Safety Office. Of 323 cases analyzed by the CDC, 309 were hospitalized, 295 were discharged, and 218, or 79%, had recovered from symptoms.

“Most postvaccine myocarditis has been responding to minimal treatment,” pediatric cardiologist Matthew Oster, MD, MPH, from Children’s Healthcare of Atlanta, told the panel.
 

COVID ‘risks are higher’

Overall, the CDC has reported 2,767 COVID-19 deaths among people aged 12-29 years, and there have been 4,018 reported cases of the COVID-linked inflammatory disorder MIS-C since the beginning of the pandemic.

That amounts to 1 MIS-C case in every 3,200 COVID infections – 36% of them among teens aged 12-20 years and 62% among children who are Hispanic or Black and non-Hispanic, according to a CDC presentation.

The CDC estimated that every 1 million second-dose COVID vaccines administered to 12- to 17-year-old boys could prevent 5,700 cases of COVID-19, 215 hospitalizations, 71 ICU admissions, and 2 deaths. There could also be 56-69 myocarditis cases.

The emergence of new variants in the United States and the skewed pattern of vaccination around the country also may increase the risk to unvaccinated young people, noted Grace Lee, MD, MPH, chair of the ACIP’s COVID-19 Vaccine Safety Technical Subgroup and a pediatric infectious disease physician at Stanford (Calif.) Children’s Health.

“If you’re in an area with low vaccination, the risks are higher,” she said. “The benefits [of the vaccine] are going to be far, far greater than any risk.”

Individuals, parents, and their clinicians should consider the full scope of risk when making decisions about vaccination, she said.

As the pandemic evolves, medical experts have to balance the known risks and benefits while they gather more information, said William Schaffner, MD, an infectious disease physician at Vanderbilt University, Nashville, Tenn., and medical director of the National Foundation for Infectious Diseases.

“The story is not over,” Dr. Schaffner said in an interview. “Clearly, we are still working in the face of a pandemic, so there’s urgency to continue vaccinating. But they would like to know more about the long-term consequences of the myocarditis.”
 

Booster possibilities

Meanwhile, ACIP began conversations on the parameters for a possible vaccine booster. For now, there are simply questions: Would a third vaccine help the immunocompromised gain protection? Should people get a different type of vaccine – mRNA versus adenovirus vector – for their booster? Most important, how long do antibodies last?

“Prior to going around giving everyone boosters, we really need to improve the overall vaccination coverage,” said Helen Keipp Talbot, MD, associate professor of medicine at Vanderbilt University. “That will protect everyone.”

A version of this article first appeared on Medscape.com.

The Food and Drug Administration is adding a warning to mRNA COVID-19 vaccines’ fact sheets as medical experts continue to investigate cases of heart inflammation, which are rare but are more likely to occur in young men and teen boys.

Doran Fink, MD, PhD, deputy director of the FDA’s division of vaccines and related products applications, told a Centers for Disease Control and Prevention expert panel on June 23 that the FDA is finalizing language on a warning statement for health care providers, vaccine recipients, and parents or caregivers of teens.

The incidents are more likely to follow the second dose of the Pfizer or Moderna vaccine, with chest pain and other symptoms occurring within several days to a week, the warning will note.

“Based on limited follow-up, most cases appear to have been associated with resolution of symptoms, but limited information is available about potential long-term sequelae,” Dr. Fink said, describing the statement to the Advisory Committee on Immunization Practices, independent experts who advise the CDC.

“Symptoms suggestive of myocarditis or pericarditis should result in vaccine recipients seeking medical attention,” he said.
 

Benefits outweigh risks

Although no formal vote occurred after the meeting, the ACIP members delivered a strong endorsement for continuing to vaccinate 12- to 29-year-olds with the Pfizer and Moderna vaccines despite the warning.

“To me it’s clear, based on current information, that the benefits of vaccine clearly outweigh the risks,” said ACIP member Veronica McNally, president and CEO of the Franny Strong Foundation in Bloomfield, Mich., a sentiment echoed by other members.

As ACIP was meeting, leaders of the nation’s major physician, nurse, and public health associations issued a statement supporting continued vaccination: “The facts are clear: this is an extremely rare side effect, and only an exceedingly small number of people will experience it after vaccination.

“Importantly, for the young people who do, most cases are mild, and individuals recover often on their own or with minimal treatment. In addition, we know that myocarditis and pericarditis are much more common if you get COVID-19, and the risks to the heart from COVID-19 infection can be more severe.”

ACIP heard the evidence behind that claim. According to the Vaccine Safety Datalink, which contains data from more than 12 million medical records, myocarditis or pericarditis occurs in 12- to 39-year-olds at a rate of 8 per 1 million after the second Pfizer dose and 19.8 per 1 million after the second Moderna dose.

The CDC continues to investigate the link between the mRNA vaccines and heart inflammation, including any differences between the vaccines.

Most of the symptoms resolved quickly, said Tom Shimabukuro, deputy director of CDC’s Immunization Safety Office. Of 323 cases analyzed by the CDC, 309 were hospitalized, 295 were discharged, and 218, or 79%, had recovered from symptoms.

“Most postvaccine myocarditis has been responding to minimal treatment,” pediatric cardiologist Matthew Oster, MD, MPH, from Children’s Healthcare of Atlanta, told the panel.
 

COVID ‘risks are higher’

Overall, the CDC has reported 2,767 COVID-19 deaths among people aged 12-29 years, and there have been 4,018 reported cases of the COVID-linked inflammatory disorder MIS-C since the beginning of the pandemic.

That amounts to 1 MIS-C case in every 3,200 COVID infections – 36% of them among teens aged 12-20 years and 62% among children who are Hispanic or Black and non-Hispanic, according to a CDC presentation.

The CDC estimated that every 1 million second-dose COVID vaccines administered to 12- to 17-year-old boys could prevent 5,700 cases of COVID-19, 215 hospitalizations, 71 ICU admissions, and 2 deaths. There could also be 56-69 myocarditis cases.

The emergence of new variants in the United States and the skewed pattern of vaccination around the country also may increase the risk to unvaccinated young people, noted Grace Lee, MD, MPH, chair of the ACIP’s COVID-19 Vaccine Safety Technical Subgroup and a pediatric infectious disease physician at Stanford (Calif.) Children’s Health.

“If you’re in an area with low vaccination, the risks are higher,” she said. “The benefits [of the vaccine] are going to be far, far greater than any risk.”

Individuals, parents, and their clinicians should consider the full scope of risk when making decisions about vaccination, she said.

As the pandemic evolves, medical experts have to balance the known risks and benefits while they gather more information, said William Schaffner, MD, an infectious disease physician at Vanderbilt University, Nashville, Tenn., and medical director of the National Foundation for Infectious Diseases.

“The story is not over,” Dr. Schaffner said in an interview. “Clearly, we are still working in the face of a pandemic, so there’s urgency to continue vaccinating. But they would like to know more about the long-term consequences of the myocarditis.”
 

Booster possibilities

Meanwhile, ACIP began conversations on the parameters for a possible vaccine booster. For now, there are simply questions: Would a third vaccine help the immunocompromised gain protection? Should people get a different type of vaccine – mRNA versus adenovirus vector – for their booster? Most important, how long do antibodies last?

“Prior to going around giving everyone boosters, we really need to improve the overall vaccination coverage,” said Helen Keipp Talbot, MD, associate professor of medicine at Vanderbilt University. “That will protect everyone.”

A version of this article first appeared on Medscape.com.

The Food and Drug Administration is adding a warning to mRNA COVID-19 vaccines’ fact sheets as medical experts continue to investigate cases of heart inflammation, which are rare but are more likely to occur in young men and teen boys.

Doran Fink, MD, PhD, deputy director of the FDA’s division of vaccines and related products applications, told a Centers for Disease Control and Prevention expert panel on June 23 that the FDA is finalizing language on a warning statement for health care providers, vaccine recipients, and parents or caregivers of teens.

The incidents are more likely to follow the second dose of the Pfizer or Moderna vaccine, with chest pain and other symptoms occurring within several days to a week, the warning will note.

“Based on limited follow-up, most cases appear to have been associated with resolution of symptoms, but limited information is available about potential long-term sequelae,” Dr. Fink said, describing the statement to the Advisory Committee on Immunization Practices, independent experts who advise the CDC.

“Symptoms suggestive of myocarditis or pericarditis should result in vaccine recipients seeking medical attention,” he said.
 

Benefits outweigh risks

Although no formal vote occurred after the meeting, the ACIP members delivered a strong endorsement for continuing to vaccinate 12- to 29-year-olds with the Pfizer and Moderna vaccines despite the warning.

“To me it’s clear, based on current information, that the benefits of vaccine clearly outweigh the risks,” said ACIP member Veronica McNally, president and CEO of the Franny Strong Foundation in Bloomfield, Mich., a sentiment echoed by other members.

As ACIP was meeting, leaders of the nation’s major physician, nurse, and public health associations issued a statement supporting continued vaccination: “The facts are clear: this is an extremely rare side effect, and only an exceedingly small number of people will experience it after vaccination.

“Importantly, for the young people who do, most cases are mild, and individuals recover often on their own or with minimal treatment. In addition, we know that myocarditis and pericarditis are much more common if you get COVID-19, and the risks to the heart from COVID-19 infection can be more severe.”

ACIP heard the evidence behind that claim. According to the Vaccine Safety Datalink, which contains data from more than 12 million medical records, myocarditis or pericarditis occurs in 12- to 39-year-olds at a rate of 8 per 1 million after the second Pfizer dose and 19.8 per 1 million after the second Moderna dose.

The CDC continues to investigate the link between the mRNA vaccines and heart inflammation, including any differences between the vaccines.

Most of the symptoms resolved quickly, said Tom Shimabukuro, deputy director of CDC’s Immunization Safety Office. Of 323 cases analyzed by the CDC, 309 were hospitalized, 295 were discharged, and 218, or 79%, had recovered from symptoms.

“Most postvaccine myocarditis has been responding to minimal treatment,” pediatric cardiologist Matthew Oster, MD, MPH, from Children’s Healthcare of Atlanta, told the panel.
 

COVID ‘risks are higher’

Overall, the CDC has reported 2,767 COVID-19 deaths among people aged 12-29 years, and there have been 4,018 reported cases of the COVID-linked inflammatory disorder MIS-C since the beginning of the pandemic.

That amounts to 1 MIS-C case in every 3,200 COVID infections – 36% of them among teens aged 12-20 years and 62% among children who are Hispanic or Black and non-Hispanic, according to a CDC presentation.

The CDC estimated that every 1 million second-dose COVID vaccines administered to 12- to 17-year-old boys could prevent 5,700 cases of COVID-19, 215 hospitalizations, 71 ICU admissions, and 2 deaths. There could also be 56-69 myocarditis cases.

The emergence of new variants in the United States and the skewed pattern of vaccination around the country also may increase the risk to unvaccinated young people, noted Grace Lee, MD, MPH, chair of the ACIP’s COVID-19 Vaccine Safety Technical Subgroup and a pediatric infectious disease physician at Stanford (Calif.) Children’s Health.

“If you’re in an area with low vaccination, the risks are higher,” she said. “The benefits [of the vaccine] are going to be far, far greater than any risk.”

Individuals, parents, and their clinicians should consider the full scope of risk when making decisions about vaccination, she said.

As the pandemic evolves, medical experts have to balance the known risks and benefits while they gather more information, said William Schaffner, MD, an infectious disease physician at Vanderbilt University, Nashville, Tenn., and medical director of the National Foundation for Infectious Diseases.

“The story is not over,” Dr. Schaffner said in an interview. “Clearly, we are still working in the face of a pandemic, so there’s urgency to continue vaccinating. But they would like to know more about the long-term consequences of the myocarditis.”
 

Booster possibilities

Meanwhile, ACIP began conversations on the parameters for a possible vaccine booster. For now, there are simply questions: Would a third vaccine help the immunocompromised gain protection? Should people get a different type of vaccine – mRNA versus adenovirus vector – for their booster? Most important, how long do antibodies last?

“Prior to going around giving everyone boosters, we really need to improve the overall vaccination coverage,” said Helen Keipp Talbot, MD, associate professor of medicine at Vanderbilt University. “That will protect everyone.”

A version of this article first appeared on Medscape.com.