A small, open-label, randomized trial of patients with chronic pain from hip and knee osteoarthritis in the Netherlands shows that adding duloxetine to usual care doesn’t significantly improve clinical outcomes.

The results, published on Jan. 6 in Arthritis & Rheumatology, also showed duloxetine did not affect outcomes for a subgroup of patients who had symptoms of centrally sensitized pain, according to Jacoline J. van den Driest, MD, of the department of general practice at Erasmus University Medical Center, Rotterdam, the Netherlands, and colleagues.

The researchers acknowledged their findings contrast with other studies that showed a “small to moderate effect of duloxetine” for patients with chronic pain from hip and knee OA. There was also a higher rate of discontinuation of duloxetine around 3 months in the current trial, compared with previous studies, the authors said, which they attributed to the fact that clinicians were asked to discontinue treatment at 3 months if patients saw no effect or increased side effects.

“This difference in outcome can be due to the fact that we studied the effectiveness of duloxetine in primary care, while the other studies examined the efficacy in placebo-controlled trials in secondary care,” the researchers wrote. Patients in the current trial were also older, had more comorbidities, and had been living with OA symptoms “for a longer time” than patients in other trials, they explained.

“It is known that, in these more ‘real-life’ primary care populations and in effectiveness studies, smaller effects are found than in highly controlled efficacy trials,” they noted.

Dr. van den Driest and colleagues evaluated 132 patients with hip or knee OA between January 2016 and February 2019 who were cluster randomized at 66 general practitioner practice sites to receive duloxetine (30 mg/day in the first week, 60 mg/day in the second week and beyond) in addition to usual care that consisted of analgesics, physiotherapy, patient education, diet, and lifestyle advice. Patients were included in the study if they were at least 18 years old, met the American College of Rheumatology criteria for hip or knee OA, and experienced chronic pain for “most days” over 3 months that was not improved through use of NSAIDs or acetaminophen or were unable to use NSAIDs because of contraindications or adverse effects. They were excluded if taking duloxetine was contraindicated for them, if they were taking an antidepressant or neuropathic pain medication, and if they had rheumatoid arthritis or were scheduled for total hip or total knee replacement.

The researchers assessed patients’ Western Ontario McMaster Universities (WOMAC) Osteoarthritis Index pain scores at 3 months, compared with baseline, as a primary outcome, with secondary outcomes of WOMAC pain and function at 1 year, and cost-effectiveness as measured by the EQ-5D-5L. A modified painDETECT questionnaire was also used at baseline to identify a subset of patients with presence of centralized pain, which was defined as a score >12.

At 12 months, 80.3% of patients in both groups completed follow-up. Patient characteristics differed in duloxetine and usual-care groups, with the duloxetine group being younger (63.2 years vs. 65.4 years) and having fewer women (59.1% vs. 75.8%). The duloxetine group also had a lower percentage of patients with knee OA (77.3% vs. 86.4%) and a lower percentage of patients with two or more comorbidities (15.2% vs. 33.2%).

Duloxetine led to a nonsignificant improvement in WOMAC-measured pain at 3 months, compared with usual care (adjusted difference, –0.58; 95% confidence interval, –1.80 to 0.63), and at 12 months (adjusted difference, –0.26; 95% CI, –1.86 to 1.34). Among a subgroup of patients with central sensitization symptoms, there was a nonsignificant improvement in WOMAC-measured pain at 3 months (adjusted difference, –0.32; 95% CI, –2.32 to 1.67) and 12 months (adjusted difference, 1.02; 95% CI, –1.22 to 3.27).

Duloxetine also did not significantly improve WOMAC-measured function at 3 months (adjusted difference, –2.10; 95% CI, –6.39 to 2.20) or 12 months (adjusted difference, –1.79; 95% CI, –7.22 to 3.64).

For other secondary outcomes of quality of life, patient satisfaction, and Outcome Measures in Rheumatology (OMERACT)-Osteoarthritis Research Society International (OARSI) responder criteria, Dr. van den Driest and colleagues noted that “none of the differences between the two groups were clinically relevant or statistically significant.”

Some patients may likely still benefit from duloxetine
Commenting on the results, Joshua F. Baker, MD, MSCE, associate professor of rheumatology and epidemiology at the University of Pennsylvania and Philadelphia VA Medical Center, said the study by van den Driest and colleagues is pragmatic and demonstrates the “ ‘real-world’ benefits of trying duloxetine” – one of the study’s strengths.

“As we would probably expect, the benefits are small, and somewhat smaller in this setting than what was observed in more standard clinical trials evaluating this question,” he said, noting that the study is limited by a small sample size and loss to follow-up, as well as its open-label design and the fact that most patients stopped treatment during follow-up.

Dr. Baker also explained that while patients on average did not have a meaningful effect after taking duloxetine, “that doesn’t mean that the therapy didn’t have a meaningful effect for some people.” 

“In fact, though most people didn’t receive a meaningful benefit in this study, some did,” he said. “[A]ccording to these data, treating 8 people would be expected to result in 1 person achieving an [OMERACT-OARSI] response. That’s pretty good for a disease with few things that work.”

Future study of duloxetine should focus on who is most likely to benefit from treatment “since while most probably don’t benefit a lot, some probably do,” he said.

Dr. Baker also called attention to the questions surrounding use of antidepressants. “Use of antidepressants has been questioned by some, since the average clinical benefit is low, even for conditions like depression,” he explained. “However, some would argue that even small benefits may be important since there are few things that do work very well, and because a multimodal approach that provides multiple small benefits to patients can add up to a meaningful benefit.”

This study was funded by The Netherlands Organization for Health Research and Development. One author reported receiving grants from The Netherlands Organization for Health Research and Development, the European Union, FOREUM, and the Dutch Arthritis Association, as well as personal fees from OARSI and Pfizer. The other authors reported no relevant financial disclosures.

* This story was updated 1/6/22.

A small, open-label, randomized trial of patients with chronic pain from hip and knee osteoarthritis in the Netherlands shows that adding duloxetine to usual care doesn’t significantly improve clinical outcomes.

The results, published on Jan. 6 in Arthritis & Rheumatology, also showed duloxetine did not affect outcomes for a subgroup of patients who had symptoms of centrally sensitized pain, according to Jacoline J. van den Driest, MD, of the department of general practice at Erasmus University Medical Center, Rotterdam, the Netherlands, and colleagues.

The researchers acknowledged their findings contrast with other studies that showed a “small to moderate effect of duloxetine” for patients with chronic pain from hip and knee OA. There was also a higher rate of discontinuation of duloxetine around 3 months in the current trial, compared with previous studies, the authors said, which they attributed to the fact that clinicians were asked to discontinue treatment at 3 months if patients saw no effect or increased side effects.

“This difference in outcome can be due to the fact that we studied the effectiveness of duloxetine in primary care, while the other studies examined the efficacy in placebo-controlled trials in secondary care,” the researchers wrote. Patients in the current trial were also older, had more comorbidities, and had been living with OA symptoms “for a longer time” than patients in other trials, they explained.

“It is known that, in these more ‘real-life’ primary care populations and in effectiveness studies, smaller effects are found than in highly controlled efficacy trials,” they noted.

Dr. van den Driest and colleagues evaluated 132 patients with hip or knee OA between January 2016 and February 2019 who were cluster randomized at 66 general practitioner practice sites to receive duloxetine (30 mg/day in the first week, 60 mg/day in the second week and beyond) in addition to usual care that consisted of analgesics, physiotherapy, patient education, diet, and lifestyle advice. Patients were included in the study if they were at least 18 years old, met the American College of Rheumatology criteria for hip or knee OA, and experienced chronic pain for “most days” over 3 months that was not improved through use of NSAIDs or acetaminophen or were unable to use NSAIDs because of contraindications or adverse effects. They were excluded if taking duloxetine was contraindicated for them, if they were taking an antidepressant or neuropathic pain medication, and if they had rheumatoid arthritis or were scheduled for total hip or total knee replacement.

The researchers assessed patients’ Western Ontario McMaster Universities (WOMAC) Osteoarthritis Index pain scores at 3 months, compared with baseline, as a primary outcome, with secondary outcomes of WOMAC pain and function at 1 year, and cost-effectiveness as measured by the EQ-5D-5L. A modified painDETECT questionnaire was also used at baseline to identify a subset of patients with presence of centralized pain, which was defined as a score >12.

At 12 months, 80.3% of patients in both groups completed follow-up. Patient characteristics differed in duloxetine and usual-care groups, with the duloxetine group being younger (63.2 years vs. 65.4 years) and having fewer women (59.1% vs. 75.8%). The duloxetine group also had a lower percentage of patients with knee OA (77.3% vs. 86.4%) and a lower percentage of patients with two or more comorbidities (15.2% vs. 33.2%).

Duloxetine led to a nonsignificant improvement in WOMAC-measured pain at 3 months, compared with usual care (adjusted difference, –0.58; 95% confidence interval, –1.80 to 0.63), and at 12 months (adjusted difference, –0.26; 95% CI, –1.86 to 1.34). Among a subgroup of patients with central sensitization symptoms, there was a nonsignificant improvement in WOMAC-measured pain at 3 months (adjusted difference, –0.32; 95% CI, –2.32 to 1.67) and 12 months (adjusted difference, 1.02; 95% CI, –1.22 to 3.27).

Duloxetine also did not significantly improve WOMAC-measured function at 3 months (adjusted difference, –2.10; 95% CI, –6.39 to 2.20) or 12 months (adjusted difference, –1.79; 95% CI, –7.22 to 3.64).

For other secondary outcomes of quality of life, patient satisfaction, and Outcome Measures in Rheumatology (OMERACT)-Osteoarthritis Research Society International (OARSI) responder criteria, Dr. van den Driest and colleagues noted that “none of the differences between the two groups were clinically relevant or statistically significant.”

Some patients may likely still benefit from duloxetine
Commenting on the results, Joshua F. Baker, MD, MSCE, associate professor of rheumatology and epidemiology at the University of Pennsylvania and Philadelphia VA Medical Center, said the study by van den Driest and colleagues is pragmatic and demonstrates the “ ‘real-world’ benefits of trying duloxetine” – one of the study’s strengths.

“As we would probably expect, the benefits are small, and somewhat smaller in this setting than what was observed in more standard clinical trials evaluating this question,” he said, noting that the study is limited by a small sample size and loss to follow-up, as well as its open-label design and the fact that most patients stopped treatment during follow-up.

Dr. Baker also explained that while patients on average did not have a meaningful effect after taking duloxetine, “that doesn’t mean that the therapy didn’t have a meaningful effect for some people.” 

“In fact, though most people didn’t receive a meaningful benefit in this study, some did,” he said. “[A]ccording to these data, treating 8 people would be expected to result in 1 person achieving an [OMERACT-OARSI] response. That’s pretty good for a disease with few things that work.”

Future study of duloxetine should focus on who is most likely to benefit from treatment “since while most probably don’t benefit a lot, some probably do,” he said.

Dr. Baker also called attention to the questions surrounding use of antidepressants. “Use of antidepressants has been questioned by some, since the average clinical benefit is low, even for conditions like depression,” he explained. “However, some would argue that even small benefits may be important since there are few things that do work very well, and because a multimodal approach that provides multiple small benefits to patients can add up to a meaningful benefit.”

This study was funded by The Netherlands Organization for Health Research and Development. One author reported receiving grants from The Netherlands Organization for Health Research and Development, the European Union, FOREUM, and the Dutch Arthritis Association, as well as personal fees from OARSI and Pfizer. The other authors reported no relevant financial disclosures.

* This story was updated 1/6/22.

A small, open-label, randomized trial of patients with chronic pain from hip and knee osteoarthritis in the Netherlands shows that adding duloxetine to usual care doesn’t significantly improve clinical outcomes.

The results, published on Jan. 6 in Arthritis & Rheumatology, also showed duloxetine did not affect outcomes for a subgroup of patients who had symptoms of centrally sensitized pain, according to Jacoline J. van den Driest, MD, of the department of general practice at Erasmus University Medical Center, Rotterdam, the Netherlands, and colleagues.

The researchers acknowledged their findings contrast with other studies that showed a “small to moderate effect of duloxetine” for patients with chronic pain from hip and knee OA. There was also a higher rate of discontinuation of duloxetine around 3 months in the current trial, compared with previous studies, the authors said, which they attributed to the fact that clinicians were asked to discontinue treatment at 3 months if patients saw no effect or increased side effects.

“This difference in outcome can be due to the fact that we studied the effectiveness of duloxetine in primary care, while the other studies examined the efficacy in placebo-controlled trials in secondary care,” the researchers wrote. Patients in the current trial were also older, had more comorbidities, and had been living with OA symptoms “for a longer time” than patients in other trials, they explained.

“It is known that, in these more ‘real-life’ primary care populations and in effectiveness studies, smaller effects are found than in highly controlled efficacy trials,” they noted.

Dr. van den Driest and colleagues evaluated 132 patients with hip or knee OA between January 2016 and February 2019 who were cluster randomized at 66 general practitioner practice sites to receive duloxetine (30 mg/day in the first week, 60 mg/day in the second week and beyond) in addition to usual care that consisted of analgesics, physiotherapy, patient education, diet, and lifestyle advice. Patients were included in the study if they were at least 18 years old, met the American College of Rheumatology criteria for hip or knee OA, and experienced chronic pain for “most days” over 3 months that was not improved through use of NSAIDs or acetaminophen or were unable to use NSAIDs because of contraindications or adverse effects. They were excluded if taking duloxetine was contraindicated for them, if they were taking an antidepressant or neuropathic pain medication, and if they had rheumatoid arthritis or were scheduled for total hip or total knee replacement.

The researchers assessed patients’ Western Ontario McMaster Universities (WOMAC) Osteoarthritis Index pain scores at 3 months, compared with baseline, as a primary outcome, with secondary outcomes of WOMAC pain and function at 1 year, and cost-effectiveness as measured by the EQ-5D-5L. A modified painDETECT questionnaire was also used at baseline to identify a subset of patients with presence of centralized pain, which was defined as a score >12.

At 12 months, 80.3% of patients in both groups completed follow-up. Patient characteristics differed in duloxetine and usual-care groups, with the duloxetine group being younger (63.2 years vs. 65.4 years) and having fewer women (59.1% vs. 75.8%). The duloxetine group also had a lower percentage of patients with knee OA (77.3% vs. 86.4%) and a lower percentage of patients with two or more comorbidities (15.2% vs. 33.2%).

Duloxetine led to a nonsignificant improvement in WOMAC-measured pain at 3 months, compared with usual care (adjusted difference, –0.58; 95% confidence interval, –1.80 to 0.63), and at 12 months (adjusted difference, –0.26; 95% CI, –1.86 to 1.34). Among a subgroup of patients with central sensitization symptoms, there was a nonsignificant improvement in WOMAC-measured pain at 3 months (adjusted difference, –0.32; 95% CI, –2.32 to 1.67) and 12 months (adjusted difference, 1.02; 95% CI, –1.22 to 3.27).

Duloxetine also did not significantly improve WOMAC-measured function at 3 months (adjusted difference, –2.10; 95% CI, –6.39 to 2.20) or 12 months (adjusted difference, –1.79; 95% CI, –7.22 to 3.64).

For other secondary outcomes of quality of life, patient satisfaction, and Outcome Measures in Rheumatology (OMERACT)-Osteoarthritis Research Society International (OARSI) responder criteria, Dr. van den Driest and colleagues noted that “none of the differences between the two groups were clinically relevant or statistically significant.”

Some patients may likely still benefit from duloxetine
Commenting on the results, Joshua F. Baker, MD, MSCE, associate professor of rheumatology and epidemiology at the University of Pennsylvania and Philadelphia VA Medical Center, said the study by van den Driest and colleagues is pragmatic and demonstrates the “ ‘real-world’ benefits of trying duloxetine” – one of the study’s strengths.

“As we would probably expect, the benefits are small, and somewhat smaller in this setting than what was observed in more standard clinical trials evaluating this question,” he said, noting that the study is limited by a small sample size and loss to follow-up, as well as its open-label design and the fact that most patients stopped treatment during follow-up.

Dr. Baker also explained that while patients on average did not have a meaningful effect after taking duloxetine, “that doesn’t mean that the therapy didn’t have a meaningful effect for some people.” 

“In fact, though most people didn’t receive a meaningful benefit in this study, some did,” he said. “[A]ccording to these data, treating 8 people would be expected to result in 1 person achieving an [OMERACT-OARSI] response. That’s pretty good for a disease with few things that work.”

Future study of duloxetine should focus on who is most likely to benefit from treatment “since while most probably don’t benefit a lot, some probably do,” he said.

Dr. Baker also called attention to the questions surrounding use of antidepressants. “Use of antidepressants has been questioned by some, since the average clinical benefit is low, even for conditions like depression,” he explained. “However, some would argue that even small benefits may be important since there are few things that do work very well, and because a multimodal approach that provides multiple small benefits to patients can add up to a meaningful benefit.”

This study was funded by The Netherlands Organization for Health Research and Development. One author reported receiving grants from The Netherlands Organization for Health Research and Development, the European Union, FOREUM, and the Dutch Arthritis Association, as well as personal fees from OARSI and Pfizer. The other authors reported no relevant financial disclosures.

* This story was updated 1/6/22.

Jennifer Brown, MD, PhD, from the Dana-Farber Cancer Institute, highlights findings from chronic lymphocytic leukemia (CLL) studies presented at the 2021 American Society of Hematology (ASH) Annual Meeting.  

Dr Brown begins with several studies in the front-line setting. The CLL13 trial compared three venetoclax CD20 antibody regimens in young, fit patients. Most notably, obinutuzumab plus venetoclax demonstrated superiority over chemoimmunotherapy. 

Next, Dr Brown shares results from the FLAIR trial, in which oral ibrutinib plus intravenous rituximab showed superior progression-free survival over oral fludarabine, oral cyclophosphamide, and intravenous rituximab (FCR). 

She also discusses long-term results from a study of ibrutinib plus FCR in younger patients. The rate of undetectable minimal residual disease was sustained and the rate of complete remission increased compared with the initial analysis. 

Dr Brown also reports that in the SEQUOIA trial, zanubrutinib demonstrated superiority in progression-free survival, even in high-risk subgroups. 

In the relapsed/refractory setting, Dr Brown looks at the BRUIN study, in which pirtobrutinib demonstrated promising efficacy in patients who were previously treated with Bruton tyrosine kinase (BTK) inhibitors, as well as promising early data on the novel covalent inhibitor MK-1026.  

Dr Brown concludes with a review of two studies of humoral and T-cell responses to COVID-19 vaccines in patients with CLL, which both underscored the importance of vaccinations, boosters, and follow-up doses in this group. 

--

Jennifer Brown, MD, PhD, Worthington and Margaret Collette Professor of Medicine, Harvard Medical School; Institute Physician, Department of Medical Oncology, Dana-Farber Cancer Institute, Brigham & Women's Hospital, Boston, Massachusetts  

Jennifer Brown, MD, PhD, has disclosed the following relevant financial relationships:  

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AbbVie; Acerta/AstraZeneca; BeiGene; Catapult; Genentech/Roche; Hutchmed; Janssen; MEI Pharma 

Received research grant from: Gilead; Loxo/Lilly; TG Therapeutics; Verastem/SecuraBio 

Jennifer Brown, MD, PhD, from the Dana-Farber Cancer Institute, highlights findings from chronic lymphocytic leukemia (CLL) studies presented at the 2021 American Society of Hematology (ASH) Annual Meeting.  

Dr Brown begins with several studies in the front-line setting. The CLL13 trial compared three venetoclax CD20 antibody regimens in young, fit patients. Most notably, obinutuzumab plus venetoclax demonstrated superiority over chemoimmunotherapy. 

Next, Dr Brown shares results from the FLAIR trial, in which oral ibrutinib plus intravenous rituximab showed superior progression-free survival over oral fludarabine, oral cyclophosphamide, and intravenous rituximab (FCR). 

She also discusses long-term results from a study of ibrutinib plus FCR in younger patients. The rate of undetectable minimal residual disease was sustained and the rate of complete remission increased compared with the initial analysis. 

Dr Brown also reports that in the SEQUOIA trial, zanubrutinib demonstrated superiority in progression-free survival, even in high-risk subgroups. 

In the relapsed/refractory setting, Dr Brown looks at the BRUIN study, in which pirtobrutinib demonstrated promising efficacy in patients who were previously treated with Bruton tyrosine kinase (BTK) inhibitors, as well as promising early data on the novel covalent inhibitor MK-1026.  

Dr Brown concludes with a review of two studies of humoral and T-cell responses to COVID-19 vaccines in patients with CLL, which both underscored the importance of vaccinations, boosters, and follow-up doses in this group. 

--

Jennifer Brown, MD, PhD, Worthington and Margaret Collette Professor of Medicine, Harvard Medical School; Institute Physician, Department of Medical Oncology, Dana-Farber Cancer Institute, Brigham & Women's Hospital, Boston, Massachusetts  

Jennifer Brown, MD, PhD, has disclosed the following relevant financial relationships:  

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AbbVie; Acerta/AstraZeneca; BeiGene; Catapult; Genentech/Roche; Hutchmed; Janssen; MEI Pharma 

Received research grant from: Gilead; Loxo/Lilly; TG Therapeutics; Verastem/SecuraBio 

Jennifer Brown, MD, PhD, from the Dana-Farber Cancer Institute, highlights findings from chronic lymphocytic leukemia (CLL) studies presented at the 2021 American Society of Hematology (ASH) Annual Meeting.  

Dr Brown begins with several studies in the front-line setting. The CLL13 trial compared three venetoclax CD20 antibody regimens in young, fit patients. Most notably, obinutuzumab plus venetoclax demonstrated superiority over chemoimmunotherapy. 

Next, Dr Brown shares results from the FLAIR trial, in which oral ibrutinib plus intravenous rituximab showed superior progression-free survival over oral fludarabine, oral cyclophosphamide, and intravenous rituximab (FCR). 

She also discusses long-term results from a study of ibrutinib plus FCR in younger patients. The rate of undetectable minimal residual disease was sustained and the rate of complete remission increased compared with the initial analysis. 

Dr Brown also reports that in the SEQUOIA trial, zanubrutinib demonstrated superiority in progression-free survival, even in high-risk subgroups. 

In the relapsed/refractory setting, Dr Brown looks at the BRUIN study, in which pirtobrutinib demonstrated promising efficacy in patients who were previously treated with Bruton tyrosine kinase (BTK) inhibitors, as well as promising early data on the novel covalent inhibitor MK-1026.  

Dr Brown concludes with a review of two studies of humoral and T-cell responses to COVID-19 vaccines in patients with CLL, which both underscored the importance of vaccinations, boosters, and follow-up doses in this group. 

--

Jennifer Brown, MD, PhD, Worthington and Margaret Collette Professor of Medicine, Harvard Medical School; Institute Physician, Department of Medical Oncology, Dana-Farber Cancer Institute, Brigham & Women's Hospital, Boston, Massachusetts  

Jennifer Brown, MD, PhD, has disclosed the following relevant financial relationships:  

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AbbVie; Acerta/AstraZeneca; BeiGene; Catapult; Genentech/Roche; Hutchmed; Janssen; MEI Pharma 

Received research grant from: Gilead; Loxo/Lilly; TG Therapeutics; Verastem/SecuraBio 

Brad Kahl, MD, shares results from non-Hodgkin lymphoma clinical trials that were presented at the 2021 American Society of Hematology (ASH) Annual Meeting. 

Dr Kahl looks first at a frontline study examining a new combination therapy. The POLARIX study compared polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) with standard of care in patients with untreated diffuse large B-cell lymphoma (DLBCL). Pola-R-CHP demonstrated significant improvement in progression-free survival. 

In relapsed/refractory non-Hodgkin lymphoma, Dr Kahl highlights several studies in chimeric antigen receptor (CAR) T-cell therapy. He starts with a primary analysis of the ZUMA-7 trial, in which axicabtagene ciloleucel (axi-cel) demonstrated improved survival compared with standard of care in patients with relapsed/refractory DLBCL. 

Next, he reports on the TRANSFORM study, which compared lisocabtagene maraleucel (liso-cel) with standard of care in the second-line setting for patients with high-risk relapsed/refractory DLBCL. Liso-cel demonstrated favorable outcomes, with improved event-free survival and no new safety concerns. 

The third CAR T-cell study he discusses is an updated analysis from ZUMA-5 that shows longer-term data for axi-cel in patients with relapsed/refractory follicular lymphoma or marginal zone lymphoma. Consistent with the primary analysis, this study demonstrated positive survival and safety outcomes in both groups. 

Finally, Dr Kahl examines a phase 1/2 study of mosunetuzumab monotherapy for patients with relapsed/refractory follicular lymphoma who have received at least two lines of therapy. The study demonstrated improved response rates and favorable safety results.

--

Brad Kahl, MD, Professor of Medicine, Department of Medical Oncology; Director, Lymphoma Program, Washington University School of Medicine, St. Louis, Missouri 
 

Brad Kahl, MD, has disclosed the following relevant financial relationships:  

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AbbVie; ADC Therapeutics; AstraZeneca; BeiGene; Celgene: Epizyme; Genentech; Pharmacyclics; Roche; TG Therapeutics 

Received income in an amount equal to or greater than $250 from: Genentech; AbbVie; Janssen 

Brad Kahl, MD, shares results from non-Hodgkin lymphoma clinical trials that were presented at the 2021 American Society of Hematology (ASH) Annual Meeting. 

Dr Kahl looks first at a frontline study examining a new combination therapy. The POLARIX study compared polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) with standard of care in patients with untreated diffuse large B-cell lymphoma (DLBCL). Pola-R-CHP demonstrated significant improvement in progression-free survival. 

In relapsed/refractory non-Hodgkin lymphoma, Dr Kahl highlights several studies in chimeric antigen receptor (CAR) T-cell therapy. He starts with a primary analysis of the ZUMA-7 trial, in which axicabtagene ciloleucel (axi-cel) demonstrated improved survival compared with standard of care in patients with relapsed/refractory DLBCL. 

Next, he reports on the TRANSFORM study, which compared lisocabtagene maraleucel (liso-cel) with standard of care in the second-line setting for patients with high-risk relapsed/refractory DLBCL. Liso-cel demonstrated favorable outcomes, with improved event-free survival and no new safety concerns. 

The third CAR T-cell study he discusses is an updated analysis from ZUMA-5 that shows longer-term data for axi-cel in patients with relapsed/refractory follicular lymphoma or marginal zone lymphoma. Consistent with the primary analysis, this study demonstrated positive survival and safety outcomes in both groups. 

Finally, Dr Kahl examines a phase 1/2 study of mosunetuzumab monotherapy for patients with relapsed/refractory follicular lymphoma who have received at least two lines of therapy. The study demonstrated improved response rates and favorable safety results.

--

Brad Kahl, MD, Professor of Medicine, Department of Medical Oncology; Director, Lymphoma Program, Washington University School of Medicine, St. Louis, Missouri 
 

Brad Kahl, MD, has disclosed the following relevant financial relationships:  

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AbbVie; ADC Therapeutics; AstraZeneca; BeiGene; Celgene: Epizyme; Genentech; Pharmacyclics; Roche; TG Therapeutics 

Received income in an amount equal to or greater than $250 from: Genentech; AbbVie; Janssen 

Brad Kahl, MD, shares results from non-Hodgkin lymphoma clinical trials that were presented at the 2021 American Society of Hematology (ASH) Annual Meeting. 

Dr Kahl looks first at a frontline study examining a new combination therapy. The POLARIX study compared polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) with standard of care in patients with untreated diffuse large B-cell lymphoma (DLBCL). Pola-R-CHP demonstrated significant improvement in progression-free survival. 

In relapsed/refractory non-Hodgkin lymphoma, Dr Kahl highlights several studies in chimeric antigen receptor (CAR) T-cell therapy. He starts with a primary analysis of the ZUMA-7 trial, in which axicabtagene ciloleucel (axi-cel) demonstrated improved survival compared with standard of care in patients with relapsed/refractory DLBCL. 

Next, he reports on the TRANSFORM study, which compared lisocabtagene maraleucel (liso-cel) with standard of care in the second-line setting for patients with high-risk relapsed/refractory DLBCL. Liso-cel demonstrated favorable outcomes, with improved event-free survival and no new safety concerns. 

The third CAR T-cell study he discusses is an updated analysis from ZUMA-5 that shows longer-term data for axi-cel in patients with relapsed/refractory follicular lymphoma or marginal zone lymphoma. Consistent with the primary analysis, this study demonstrated positive survival and safety outcomes in both groups. 

Finally, Dr Kahl examines a phase 1/2 study of mosunetuzumab monotherapy for patients with relapsed/refractory follicular lymphoma who have received at least two lines of therapy. The study demonstrated improved response rates and favorable safety results.

--

Brad Kahl, MD, Professor of Medicine, Department of Medical Oncology; Director, Lymphoma Program, Washington University School of Medicine, St. Louis, Missouri 
 

Brad Kahl, MD, has disclosed the following relevant financial relationships:  

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AbbVie; ADC Therapeutics; AstraZeneca; BeiGene; Celgene: Epizyme; Genentech; Pharmacyclics; Roche; TG Therapeutics 

Received income in an amount equal to or greater than $250 from: Genentech; AbbVie; Janssen 

Ian Flinn, MD, PhD, director of lymphoma research at the Sarah Cannon Cancer Institute, highlights findings in Hodgkin lymphoma presented at the 2021 meeting of the American Society of Hematology. 

The first study that Dr Flinn discusses combined pembrolizumab with AVD in patients with untreated Hodgkin lymphoma. This regimen was found to be both safe and effective, with high overall response, progression-free survival, and overall survival rates. 

Another study he examines combined pembrolizumab with ICE chemotherapy prior to autologous hematologic stem cell transplant. The primary endpoint of complete metabolic response was met and the regimen demonstrated a tolerable safety profile. 

Next, Dr Flinn looks at a study comparing seven novel and conventional salvage therapies. Most notably, brentuximab vedotin plus nivolumab demonstrated a higher complete remission rate and better post-autologous stem cell transplant progression-free survival compared with chemotherapy. 

Dr Flinn concludes with a phase 2 study that evaluated first-line nivolumab in older frail patients. The primary objective of complete metabolic response rate was not reached, with safety findings comparable to those of published data in this population. 

--

Ian W. Flinn, MD, PhD, Director, Lymphoma Research; Principal Investigator, Sarah Cannon Cancer Institute, Nashville, Tennessee 

Ian W. Flinn, MD, PhD, has disclosed the following relevant financial relationships: 

Serve(d) as a consultant: AbbVie; AstraZeneca; BeiGene; Century Therapeutics; Genentech; Gilead Sciences; Great Point Partners; Hutchison MediPharma; Iksuda Therapeutics; Janssen; Juno Therapeutics; Kite Pharma; MorphoSys; Novartis; Nurix Therapeutics; Pharmacyclics; Roche; Seattle Genetics; Takeda; TG Therapeutics; Unum Therapeutics; Verastem; Vincerx Pharma; Yingli Pharmaceuticals 

Institute received research grant from: AbbVie; Acerta Pharma; Agios; ArQule; AstraZeneca; BeiGene; Calithera Biosciences; Celgene; Constellation Pharmaceuticals; Curis; Forma Therapeutics; Forty Seven; Genentech; Gilead Sciences; IGM Biosciences; Incyte; Infinity Pharmaceuticals; Janssen; Juno Therapeutics; Karyopharm Therapeutics; Kite Pharma; Loxo; Merck; MorphoSys; Novartis; Pfizer; Pharmacyclics; Portola Pharmaceuticals; Rhizen Pharmaceuticals; Roche; Seattle Genetics; Takeda; Teva Pharmaceuticals; TG Therapeutics; Trillium Therapeutics; Triphase Research & Development; Unum Therapeutics; Verastem 

Ian Flinn, MD, PhD, director of lymphoma research at the Sarah Cannon Cancer Institute, highlights findings in Hodgkin lymphoma presented at the 2021 meeting of the American Society of Hematology. 

The first study that Dr Flinn discusses combined pembrolizumab with AVD in patients with untreated Hodgkin lymphoma. This regimen was found to be both safe and effective, with high overall response, progression-free survival, and overall survival rates. 

Another study he examines combined pembrolizumab with ICE chemotherapy prior to autologous hematologic stem cell transplant. The primary endpoint of complete metabolic response was met and the regimen demonstrated a tolerable safety profile. 

Next, Dr Flinn looks at a study comparing seven novel and conventional salvage therapies. Most notably, brentuximab vedotin plus nivolumab demonstrated a higher complete remission rate and better post-autologous stem cell transplant progression-free survival compared with chemotherapy. 

Dr Flinn concludes with a phase 2 study that evaluated first-line nivolumab in older frail patients. The primary objective of complete metabolic response rate was not reached, with safety findings comparable to those of published data in this population. 

--

Ian W. Flinn, MD, PhD, Director, Lymphoma Research; Principal Investigator, Sarah Cannon Cancer Institute, Nashville, Tennessee 

Ian W. Flinn, MD, PhD, has disclosed the following relevant financial relationships: 

Serve(d) as a consultant: AbbVie; AstraZeneca; BeiGene; Century Therapeutics; Genentech; Gilead Sciences; Great Point Partners; Hutchison MediPharma; Iksuda Therapeutics; Janssen; Juno Therapeutics; Kite Pharma; MorphoSys; Novartis; Nurix Therapeutics; Pharmacyclics; Roche; Seattle Genetics; Takeda; TG Therapeutics; Unum Therapeutics; Verastem; Vincerx Pharma; Yingli Pharmaceuticals 

Institute received research grant from: AbbVie; Acerta Pharma; Agios; ArQule; AstraZeneca; BeiGene; Calithera Biosciences; Celgene; Constellation Pharmaceuticals; Curis; Forma Therapeutics; Forty Seven; Genentech; Gilead Sciences; IGM Biosciences; Incyte; Infinity Pharmaceuticals; Janssen; Juno Therapeutics; Karyopharm Therapeutics; Kite Pharma; Loxo; Merck; MorphoSys; Novartis; Pfizer; Pharmacyclics; Portola Pharmaceuticals; Rhizen Pharmaceuticals; Roche; Seattle Genetics; Takeda; Teva Pharmaceuticals; TG Therapeutics; Trillium Therapeutics; Triphase Research & Development; Unum Therapeutics; Verastem 

Ian Flinn, MD, PhD, director of lymphoma research at the Sarah Cannon Cancer Institute, highlights findings in Hodgkin lymphoma presented at the 2021 meeting of the American Society of Hematology. 

The first study that Dr Flinn discusses combined pembrolizumab with AVD in patients with untreated Hodgkin lymphoma. This regimen was found to be both safe and effective, with high overall response, progression-free survival, and overall survival rates. 

Another study he examines combined pembrolizumab with ICE chemotherapy prior to autologous hematologic stem cell transplant. The primary endpoint of complete metabolic response was met and the regimen demonstrated a tolerable safety profile. 

Next, Dr Flinn looks at a study comparing seven novel and conventional salvage therapies. Most notably, brentuximab vedotin plus nivolumab demonstrated a higher complete remission rate and better post-autologous stem cell transplant progression-free survival compared with chemotherapy. 

Dr Flinn concludes with a phase 2 study that evaluated first-line nivolumab in older frail patients. The primary objective of complete metabolic response rate was not reached, with safety findings comparable to those of published data in this population. 

--

Ian W. Flinn, MD, PhD, Director, Lymphoma Research; Principal Investigator, Sarah Cannon Cancer Institute, Nashville, Tennessee 

Ian W. Flinn, MD, PhD, has disclosed the following relevant financial relationships: 

Serve(d) as a consultant: AbbVie; AstraZeneca; BeiGene; Century Therapeutics; Genentech; Gilead Sciences; Great Point Partners; Hutchison MediPharma; Iksuda Therapeutics; Janssen; Juno Therapeutics; Kite Pharma; MorphoSys; Novartis; Nurix Therapeutics; Pharmacyclics; Roche; Seattle Genetics; Takeda; TG Therapeutics; Unum Therapeutics; Verastem; Vincerx Pharma; Yingli Pharmaceuticals 

Institute received research grant from: AbbVie; Acerta Pharma; Agios; ArQule; AstraZeneca; BeiGene; Calithera Biosciences; Celgene; Constellation Pharmaceuticals; Curis; Forma Therapeutics; Forty Seven; Genentech; Gilead Sciences; IGM Biosciences; Incyte; Infinity Pharmaceuticals; Janssen; Juno Therapeutics; Karyopharm Therapeutics; Kite Pharma; Loxo; Merck; MorphoSys; Novartis; Pfizer; Pharmacyclics; Portola Pharmaceuticals; Rhizen Pharmaceuticals; Roche; Seattle Genetics; Takeda; Teva Pharmaceuticals; TG Therapeutics; Trillium Therapeutics; Triphase Research & Development; Unum Therapeutics; Verastem 

The recently developed ACE index – which incorporates three variables at hospital admission (C-reactive protein [CRP], albumin, and endoscopic severity) – accurately predicts steroid response at hospital admission in patients with acute severe ulcerative colitis (ASUC). This is according to study findings presented at the annual Advances in Inflammatory Bowel Diseases conference by Marta Freitas, MD, of the Senhora da Oliveira Hospital in Guimarães, Portugal.*

Although intravenous steroids represent the first-line medical therapy for patients admitted to the hospital with acute UC, one study found that approximately 30% of patients with ASUC do not respond to this treatment approach and therefore require more advanced management options.

In patients with ASUC, delays in initiating therapy may be associated with an increased risk of mortality, explained Dr. Freitas and colleagues. Given this risk, there is a need for sensitive and accurate tools that can identify patients at admission who are at high risk of steroid nonresponse and who may likewise receive benefit from surgical intervention or earlier second-line therapy.

Early prediction of response to steroids in patients with ASUC at time of admission could also be helpful for prioritizing further assessment and counseling. The ACE index was recently developed to identify these patients to help improve risk stratification and facilitate earlier treatment delivery. A combination of three parameters is found within the ACE index: albumin ≤30 g/L; CRP ≥50 mg/L; and increased endoscopic severity as defined by a Mayo endoscopic score of 3.

Dr. Freitas and researchers retrospectively evaluated the performance of the ACE index in predicting steroid response in 65 patients with ASUC (mean age, 34 years). The study included a review of admissions for the disease between 2005 and 2020. The accuracy of the ACE index score was evaluated through the area under the curve.

Approximately 78.5% of patients in the retrospective cohort study had responded to steroids. Compared with nonresponders, responders had significantly different mean CRP (108.0 ± 60.0 vs. 66.0 ± 53.2 mg/dL, respectively; P = .01), mean albumin (2.9 ± 0.66 vs. 3.4 ± 0.71 g/L; P = .02), and median endoscopic severity score (3 vs. 3; interquartile range, 1 vs. 0; P = .005) at admission. In contrast, no statistically significant difference was found between responders versus nonresponders in regard to the median UC Endoscopic Index of Severity (UCEIS) score (8 vs. 7; P = .28).

Overall, the median ACE index score was 2. Steroid nonresponders had a significantly higher ACE index score (2.5 vs. 1; P = .001). The researchers noted that the ACE index score was a significant predictor of steroid response (AUC, 0.789; P = .001). Half (50.0%) of patients with an ACE index score of 3 had no response to steroids, while 86.3% of patients who had an ACE index score lower than 3 experienced a steroid response.

In a poster presentation by Hartman Brunt, MD, of the Louisiana State University Health Sciences Center in Baton Rouge, real-world data suggest there exists several inconsistencies in the use of UC-monitoring strategies recommended by clinical practice guidelines. According to a single-center retrospective chart review of adult patients with moderate to severe UC, Dr. Brunt and colleagues found that measurement of CRP decreased over time as did measurement of fecal calprotectin.

Given the lack of standardization for IBD monitoring, Dr. Hartman and colleagues noted “there is inevitably increased variability in provider care.” Consequently, this variability and lack of guideline adherence may lead to heterogeneous effects among the IBD patient population, including those that may drive suboptimal long-term outcomes.

In addition to disease monitoring, assessment of treatment response remains highly valuable, yet no clinical guidance currently exists on the use of the ACE index score in ASUC. Further research is needed to determine the validity of the ACE Index in a larger patient population to inform future clinical practice guidelines and expert consensus statements.

Ashwin Ananthakrishnan, MBBS, a gastroenterologist from Massachusetts General Hospital in Boston, said in an email to this news organization that there is an urgent need for tools that “accurately predict treatment response in severe UC because of the higher morbidity and rate of surgery in this population.” Dr. Ananthakrishnan is a co–primary investigator of the MASCC (Multi-center Acute Severe UC Cohort Study), sponsored by Johns Hopkins University, which is investigating the ACE index and other predictors of outcomes in severe UC.

“In addition, treatment decisions need to be made fairly quickly as clinical condition may change day to day,” further emphasizing the need for these predictors, added Dr. Ananthakrishnan. “At this point, the ACE index and other prediction scores have been described from observational studies, but the key is to prospectively incorporate this into a treatment algorithm.”

Dr. Ananthakrishnan explained that patients with a high ACE index, or those with UC who satisfy the high-risk criteria of other prediction models, may benefit from early or even upfront rescue therapy rather than trying steroids for 3-5 days first. He added that “the field is not quite there, and we need more study of this” approach.

Dr. Freitas, Dr. Brunt, and Dr. Ananthakrishnan declared no relevant conflicts of interest.

This article was updated 1/11/22. 

*Correction, 1/11/22: An earlier version of this article misstated Dr. Martha Freitas' name.

The recently developed ACE index – which incorporates three variables at hospital admission (C-reactive protein [CRP], albumin, and endoscopic severity) – accurately predicts steroid response at hospital admission in patients with acute severe ulcerative colitis (ASUC). This is according to study findings presented at the annual Advances in Inflammatory Bowel Diseases conference by Marta Freitas, MD, of the Senhora da Oliveira Hospital in Guimarães, Portugal.*

Although intravenous steroids represent the first-line medical therapy for patients admitted to the hospital with acute UC, one study found that approximately 30% of patients with ASUC do not respond to this treatment approach and therefore require more advanced management options.

In patients with ASUC, delays in initiating therapy may be associated with an increased risk of mortality, explained Dr. Freitas and colleagues. Given this risk, there is a need for sensitive and accurate tools that can identify patients at admission who are at high risk of steroid nonresponse and who may likewise receive benefit from surgical intervention or earlier second-line therapy.

Early prediction of response to steroids in patients with ASUC at time of admission could also be helpful for prioritizing further assessment and counseling. The ACE index was recently developed to identify these patients to help improve risk stratification and facilitate earlier treatment delivery. A combination of three parameters is found within the ACE index: albumin ≤30 g/L; CRP ≥50 mg/L; and increased endoscopic severity as defined by a Mayo endoscopic score of 3.

Dr. Freitas and researchers retrospectively evaluated the performance of the ACE index in predicting steroid response in 65 patients with ASUC (mean age, 34 years). The study included a review of admissions for the disease between 2005 and 2020. The accuracy of the ACE index score was evaluated through the area under the curve.

Approximately 78.5% of patients in the retrospective cohort study had responded to steroids. Compared with nonresponders, responders had significantly different mean CRP (108.0 ± 60.0 vs. 66.0 ± 53.2 mg/dL, respectively; P = .01), mean albumin (2.9 ± 0.66 vs. 3.4 ± 0.71 g/L; P = .02), and median endoscopic severity score (3 vs. 3; interquartile range, 1 vs. 0; P = .005) at admission. In contrast, no statistically significant difference was found between responders versus nonresponders in regard to the median UC Endoscopic Index of Severity (UCEIS) score (8 vs. 7; P = .28).

Overall, the median ACE index score was 2. Steroid nonresponders had a significantly higher ACE index score (2.5 vs. 1; P = .001). The researchers noted that the ACE index score was a significant predictor of steroid response (AUC, 0.789; P = .001). Half (50.0%) of patients with an ACE index score of 3 had no response to steroids, while 86.3% of patients who had an ACE index score lower than 3 experienced a steroid response.

In a poster presentation by Hartman Brunt, MD, of the Louisiana State University Health Sciences Center in Baton Rouge, real-world data suggest there exists several inconsistencies in the use of UC-monitoring strategies recommended by clinical practice guidelines. According to a single-center retrospective chart review of adult patients with moderate to severe UC, Dr. Brunt and colleagues found that measurement of CRP decreased over time as did measurement of fecal calprotectin.

Given the lack of standardization for IBD monitoring, Dr. Hartman and colleagues noted “there is inevitably increased variability in provider care.” Consequently, this variability and lack of guideline adherence may lead to heterogeneous effects among the IBD patient population, including those that may drive suboptimal long-term outcomes.

In addition to disease monitoring, assessment of treatment response remains highly valuable, yet no clinical guidance currently exists on the use of the ACE index score in ASUC. Further research is needed to determine the validity of the ACE Index in a larger patient population to inform future clinical practice guidelines and expert consensus statements.

Ashwin Ananthakrishnan, MBBS, a gastroenterologist from Massachusetts General Hospital in Boston, said in an email to this news organization that there is an urgent need for tools that “accurately predict treatment response in severe UC because of the higher morbidity and rate of surgery in this population.” Dr. Ananthakrishnan is a co–primary investigator of the MASCC (Multi-center Acute Severe UC Cohort Study), sponsored by Johns Hopkins University, which is investigating the ACE index and other predictors of outcomes in severe UC.

“In addition, treatment decisions need to be made fairly quickly as clinical condition may change day to day,” further emphasizing the need for these predictors, added Dr. Ananthakrishnan. “At this point, the ACE index and other prediction scores have been described from observational studies, but the key is to prospectively incorporate this into a treatment algorithm.”

Dr. Ananthakrishnan explained that patients with a high ACE index, or those with UC who satisfy the high-risk criteria of other prediction models, may benefit from early or even upfront rescue therapy rather than trying steroids for 3-5 days first. He added that “the field is not quite there, and we need more study of this” approach.

Dr. Freitas, Dr. Brunt, and Dr. Ananthakrishnan declared no relevant conflicts of interest.

This article was updated 1/11/22. 

*Correction, 1/11/22: An earlier version of this article misstated Dr. Martha Freitas' name.

The recently developed ACE index – which incorporates three variables at hospital admission (C-reactive protein [CRP], albumin, and endoscopic severity) – accurately predicts steroid response at hospital admission in patients with acute severe ulcerative colitis (ASUC). This is according to study findings presented at the annual Advances in Inflammatory Bowel Diseases conference by Marta Freitas, MD, of the Senhora da Oliveira Hospital in Guimarães, Portugal.*

Although intravenous steroids represent the first-line medical therapy for patients admitted to the hospital with acute UC, one study found that approximately 30% of patients with ASUC do not respond to this treatment approach and therefore require more advanced management options.

In patients with ASUC, delays in initiating therapy may be associated with an increased risk of mortality, explained Dr. Freitas and colleagues. Given this risk, there is a need for sensitive and accurate tools that can identify patients at admission who are at high risk of steroid nonresponse and who may likewise receive benefit from surgical intervention or earlier second-line therapy.

Early prediction of response to steroids in patients with ASUC at time of admission could also be helpful for prioritizing further assessment and counseling. The ACE index was recently developed to identify these patients to help improve risk stratification and facilitate earlier treatment delivery. A combination of three parameters is found within the ACE index: albumin ≤30 g/L; CRP ≥50 mg/L; and increased endoscopic severity as defined by a Mayo endoscopic score of 3.

Dr. Freitas and researchers retrospectively evaluated the performance of the ACE index in predicting steroid response in 65 patients with ASUC (mean age, 34 years). The study included a review of admissions for the disease between 2005 and 2020. The accuracy of the ACE index score was evaluated through the area under the curve.

Approximately 78.5% of patients in the retrospective cohort study had responded to steroids. Compared with nonresponders, responders had significantly different mean CRP (108.0 ± 60.0 vs. 66.0 ± 53.2 mg/dL, respectively; P = .01), mean albumin (2.9 ± 0.66 vs. 3.4 ± 0.71 g/L; P = .02), and median endoscopic severity score (3 vs. 3; interquartile range, 1 vs. 0; P = .005) at admission. In contrast, no statistically significant difference was found between responders versus nonresponders in regard to the median UC Endoscopic Index of Severity (UCEIS) score (8 vs. 7; P = .28).

Overall, the median ACE index score was 2. Steroid nonresponders had a significantly higher ACE index score (2.5 vs. 1; P = .001). The researchers noted that the ACE index score was a significant predictor of steroid response (AUC, 0.789; P = .001). Half (50.0%) of patients with an ACE index score of 3 had no response to steroids, while 86.3% of patients who had an ACE index score lower than 3 experienced a steroid response.

In a poster presentation by Hartman Brunt, MD, of the Louisiana State University Health Sciences Center in Baton Rouge, real-world data suggest there exists several inconsistencies in the use of UC-monitoring strategies recommended by clinical practice guidelines. According to a single-center retrospective chart review of adult patients with moderate to severe UC, Dr. Brunt and colleagues found that measurement of CRP decreased over time as did measurement of fecal calprotectin.

Given the lack of standardization for IBD monitoring, Dr. Hartman and colleagues noted “there is inevitably increased variability in provider care.” Consequently, this variability and lack of guideline adherence may lead to heterogeneous effects among the IBD patient population, including those that may drive suboptimal long-term outcomes.

In addition to disease monitoring, assessment of treatment response remains highly valuable, yet no clinical guidance currently exists on the use of the ACE index score in ASUC. Further research is needed to determine the validity of the ACE Index in a larger patient population to inform future clinical practice guidelines and expert consensus statements.

Ashwin Ananthakrishnan, MBBS, a gastroenterologist from Massachusetts General Hospital in Boston, said in an email to this news organization that there is an urgent need for tools that “accurately predict treatment response in severe UC because of the higher morbidity and rate of surgery in this population.” Dr. Ananthakrishnan is a co–primary investigator of the MASCC (Multi-center Acute Severe UC Cohort Study), sponsored by Johns Hopkins University, which is investigating the ACE index and other predictors of outcomes in severe UC.

“In addition, treatment decisions need to be made fairly quickly as clinical condition may change day to day,” further emphasizing the need for these predictors, added Dr. Ananthakrishnan. “At this point, the ACE index and other prediction scores have been described from observational studies, but the key is to prospectively incorporate this into a treatment algorithm.”

Dr. Ananthakrishnan explained that patients with a high ACE index, or those with UC who satisfy the high-risk criteria of other prediction models, may benefit from early or even upfront rescue therapy rather than trying steroids for 3-5 days first. He added that “the field is not quite there, and we need more study of this” approach.

Dr. Freitas, Dr. Brunt, and Dr. Ananthakrishnan declared no relevant conflicts of interest.

This article was updated 1/11/22. 

*Correction, 1/11/22: An earlier version of this article misstated Dr. Martha Freitas' name.

Mutations in genes associated with cardiac and seizure disorders appear to be linked to sudden unexplained deaths in young children and may explain nearly 9% of such cases, researchers have found.

Previous studies have found de novo genetic variants – those not found in either parent but which occur for the first time in their offspring – that increase the risk of cardiac and seizure disorders, but research on sudden unexplained deaths in children (SUDC) is limited, according to Matthew Halvorsen, PhD, of the University of North Carolina at Chapel Hill, and colleagues. Most cases of SUDC occur in children aged 1-4 years, and a lack of standardized investigation systems likely leads to misclassification of these deaths, they said.

Compared with sudden infant death syndrome (SIDS), which occurs in approximately 1,400 children in the United States each year, approximately 400 children aged 1 year and older die from SUDC annually. A major obstacle to studying these cases is that so-called molecular autopsies – which incorporate genetic analysis into the postmortem examination – typically do not assess the parents’ genetic information and thus limit the ability to identify de novo mutations, they added.

In a study published in the Proceedings of the National Academy of Sciences, Dr. Halvorsen’s group obtained whole exome sequence data from 124 “trios,” meaning a dead child and two living parents. They tested for excessive de novo mutations for different genes involved in conditions that included cardiac arrhythmias and epilepsy. The average age at the time of death for the children was 34.2 months; 54% were male, and 82% were White.

Children who died of SUDC were nearly 10 times as likely to have de novo mutations in genes associated with cardiac and seizure disorders as were unrelated healthy controls (odds ratio, 9.76). Most pathogenic variants were de novo, which highlights the importance of trio studies, the researchers noted.

The researchers identified 11 variants associated with increased risk of SUDC, 7 of which were de novo. Three of the 124 cases carried mutations (two for RYR2 and 1 for TNNI3) affecting genes in the CardiacEpilepsy dataset proposed by the American College of Medical Genetics and Genomics, strengthening the connection to seizure disorders.

Another notable finding was the identification of six de novo mutations involved in altering calcium-related regulation, which suggests a cardiac susceptibility to sudden death.

The data support “novel genetic causes of pediatric sudden deaths that could be discovered with larger cohorts,” the researchers noted. Taken together, they say, the gene mutations could play a role in approximately 9% of SUDC cases.

The study findings were limited by several factors, including lack of population-based case ascertainment, exclusive focus on unexplained deaths, potentially missed mutations, and use of DNA from blood as opposed to organs, the researchers noted.

However, they concluded, “the data indicate that deleterious de novo mutations are significant genetic risk factors for childhood sudden unexplained death, and that their identification may lead to medical intervention that ultimately saves lives.”

Findings highlight impact of SUDC

“This study is important because SUDC is a much more pressing medical need than most people realize,” said Richard Tsien, PhD, of New York University Langone Medical Center, and the corresponding author of the study.

Although SUDC is less common than SIDS, SUDC has essentially no targeted research funding, Dr. Tsien said. Study coauthor Laura Gould, MA, a researcher and mother who lost a young child to SUDC, worked with Orrin Devinsky, MD, to create a registry for families with cases of SUDC. This registry was instrumental in allowing the researchers to “do the molecular detective work we need to do” to see whether a genetic basis exists for SUDC, Dr. Tsien said.

“The detective work comes up with a consistent story,” he said. “More than half of the genes that we found are involved in the normal function of the heart and brain,” performing such functions as delivering calcium ions to the inside of the heart cells and nerve cells.

The study “is the first of its kind,” given the difficulty of acquiring DNA from the child and two parents in SUDC cases, Dr. Tsien said.

Overall, approximately 10% of the cases have a compelling explanation based on the coding of DNA, Dr. Tsien said. From a clinical standpoint, that information might affect what a clinician says to a parent.

A key takeaway is that most of the genetic mutations are spontaneous and are not inherited from the parents, Dr. Tsien said. The study findings indicate that parents who suffer an SUDC loss need not be discouraged from having children, he added.

For the long term, “the more we understand about these disorders, the more information we can offer to families,” he said. Eventually, clinicians might be able to use genetics to identify signs of when SUDC might be more likely. “For example, if a child shows a very mild seizure, this would alert them that there might be potential for a more drastic outcome.”

Meanwhile, families with SUDC cases may find support and benefit in signing up for the registry and knowing that other families have been through a similar experience, Dr. Tsien said.

Genetic studies create opportunities

A significant portion of pediatric mortality remains unexplained, according to Richard D. Goldstein, MD, of Boston Children’s Hospital. One reason is the lack of a formal diagnostic code to identify these deaths.

Research to date has suggested links between SUDC and a family history of febrile seizures, as well as differences in brain structure associated with epilepsy, Dr. Goldstein said.

“An important hypothesis is that these deaths are part of a continuum that also includes stillbirths, SIDS, and sudden unexpected death in epilepsy [SUDEP],” Dr. Goldstein said. “By mandate, investigations of these deaths occur under the jurisdiction of medical examiners and coroners and have, for the most part, been insulated from developments in modern medicine like genomics and proteomics, elements of what are referred to as the molecular autopsy, and studies such as the current study bring attention to what is being missed.”

Dr. Goldstein said the new study buttresses the “conventional clinical suspicion” about the likely causes of SUDC, “but also strengthens the association between sudden unexpected death in pediatrics (SUDP) and SUDEP that we and others have been positing. I think the researchers very nicely make the point that epilepsy and cardiac arrhythmia genes are not as separated in their effects as many would believe.”

As for the clinical applicability of the findings, Dr. Goldstein said medicine needs to offer parents more: “Pediatric deaths without explanation deserve more than a forensic investigation that concerns itself mostly with whether there has been foul play,” he said. “We need to figure out how to engage families, at an incredibly vulnerable time, in helping find the cause of the child’s death and also contributing to needed research. Most of the reported variants were de novo, which means that parent participation is needed to figure out these genetic factors but also that we can offer reassurance to families that other children are not at risk.”

The study was supported by the SUDC Foundation and Finding a Cure for Epilepsy and Seizures (New York University). Dr. Tsien disclosed support from the National Institutes of Health and a grant from FACES. Dr. Goldstein reported no relevant financial relationships.

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

Mutations in genes associated with cardiac and seizure disorders appear to be linked to sudden unexplained deaths in young children and may explain nearly 9% of such cases, researchers have found.

Previous studies have found de novo genetic variants – those not found in either parent but which occur for the first time in their offspring – that increase the risk of cardiac and seizure disorders, but research on sudden unexplained deaths in children (SUDC) is limited, according to Matthew Halvorsen, PhD, of the University of North Carolina at Chapel Hill, and colleagues. Most cases of SUDC occur in children aged 1-4 years, and a lack of standardized investigation systems likely leads to misclassification of these deaths, they said.

Compared with sudden infant death syndrome (SIDS), which occurs in approximately 1,400 children in the United States each year, approximately 400 children aged 1 year and older die from SUDC annually. A major obstacle to studying these cases is that so-called molecular autopsies – which incorporate genetic analysis into the postmortem examination – typically do not assess the parents’ genetic information and thus limit the ability to identify de novo mutations, they added.

In a study published in the Proceedings of the National Academy of Sciences, Dr. Halvorsen’s group obtained whole exome sequence data from 124 “trios,” meaning a dead child and two living parents. They tested for excessive de novo mutations for different genes involved in conditions that included cardiac arrhythmias and epilepsy. The average age at the time of death for the children was 34.2 months; 54% were male, and 82% were White.

Children who died of SUDC were nearly 10 times as likely to have de novo mutations in genes associated with cardiac and seizure disorders as were unrelated healthy controls (odds ratio, 9.76). Most pathogenic variants were de novo, which highlights the importance of trio studies, the researchers noted.

The researchers identified 11 variants associated with increased risk of SUDC, 7 of which were de novo. Three of the 124 cases carried mutations (two for RYR2 and 1 for TNNI3) affecting genes in the CardiacEpilepsy dataset proposed by the American College of Medical Genetics and Genomics, strengthening the connection to seizure disorders.

Another notable finding was the identification of six de novo mutations involved in altering calcium-related regulation, which suggests a cardiac susceptibility to sudden death.

The data support “novel genetic causes of pediatric sudden deaths that could be discovered with larger cohorts,” the researchers noted. Taken together, they say, the gene mutations could play a role in approximately 9% of SUDC cases.

The study findings were limited by several factors, including lack of population-based case ascertainment, exclusive focus on unexplained deaths, potentially missed mutations, and use of DNA from blood as opposed to organs, the researchers noted.

However, they concluded, “the data indicate that deleterious de novo mutations are significant genetic risk factors for childhood sudden unexplained death, and that their identification may lead to medical intervention that ultimately saves lives.”

Findings highlight impact of SUDC

“This study is important because SUDC is a much more pressing medical need than most people realize,” said Richard Tsien, PhD, of New York University Langone Medical Center, and the corresponding author of the study.

Although SUDC is less common than SIDS, SUDC has essentially no targeted research funding, Dr. Tsien said. Study coauthor Laura Gould, MA, a researcher and mother who lost a young child to SUDC, worked with Orrin Devinsky, MD, to create a registry for families with cases of SUDC. This registry was instrumental in allowing the researchers to “do the molecular detective work we need to do” to see whether a genetic basis exists for SUDC, Dr. Tsien said.

“The detective work comes up with a consistent story,” he said. “More than half of the genes that we found are involved in the normal function of the heart and brain,” performing such functions as delivering calcium ions to the inside of the heart cells and nerve cells.

The study “is the first of its kind,” given the difficulty of acquiring DNA from the child and two parents in SUDC cases, Dr. Tsien said.

Overall, approximately 10% of the cases have a compelling explanation based on the coding of DNA, Dr. Tsien said. From a clinical standpoint, that information might affect what a clinician says to a parent.

A key takeaway is that most of the genetic mutations are spontaneous and are not inherited from the parents, Dr. Tsien said. The study findings indicate that parents who suffer an SUDC loss need not be discouraged from having children, he added.

For the long term, “the more we understand about these disorders, the more information we can offer to families,” he said. Eventually, clinicians might be able to use genetics to identify signs of when SUDC might be more likely. “For example, if a child shows a very mild seizure, this would alert them that there might be potential for a more drastic outcome.”

Meanwhile, families with SUDC cases may find support and benefit in signing up for the registry and knowing that other families have been through a similar experience, Dr. Tsien said.

Genetic studies create opportunities

A significant portion of pediatric mortality remains unexplained, according to Richard D. Goldstein, MD, of Boston Children’s Hospital. One reason is the lack of a formal diagnostic code to identify these deaths.

Research to date has suggested links between SUDC and a family history of febrile seizures, as well as differences in brain structure associated with epilepsy, Dr. Goldstein said.

“An important hypothesis is that these deaths are part of a continuum that also includes stillbirths, SIDS, and sudden unexpected death in epilepsy [SUDEP],” Dr. Goldstein said. “By mandate, investigations of these deaths occur under the jurisdiction of medical examiners and coroners and have, for the most part, been insulated from developments in modern medicine like genomics and proteomics, elements of what are referred to as the molecular autopsy, and studies such as the current study bring attention to what is being missed.”

Dr. Goldstein said the new study buttresses the “conventional clinical suspicion” about the likely causes of SUDC, “but also strengthens the association between sudden unexpected death in pediatrics (SUDP) and SUDEP that we and others have been positing. I think the researchers very nicely make the point that epilepsy and cardiac arrhythmia genes are not as separated in their effects as many would believe.”

As for the clinical applicability of the findings, Dr. Goldstein said medicine needs to offer parents more: “Pediatric deaths without explanation deserve more than a forensic investigation that concerns itself mostly with whether there has been foul play,” he said. “We need to figure out how to engage families, at an incredibly vulnerable time, in helping find the cause of the child’s death and also contributing to needed research. Most of the reported variants were de novo, which means that parent participation is needed to figure out these genetic factors but also that we can offer reassurance to families that other children are not at risk.”

The study was supported by the SUDC Foundation and Finding a Cure for Epilepsy and Seizures (New York University). Dr. Tsien disclosed support from the National Institutes of Health and a grant from FACES. Dr. Goldstein reported no relevant financial relationships.

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

Mutations in genes associated with cardiac and seizure disorders appear to be linked to sudden unexplained deaths in young children and may explain nearly 9% of such cases, researchers have found.

Previous studies have found de novo genetic variants – those not found in either parent but which occur for the first time in their offspring – that increase the risk of cardiac and seizure disorders, but research on sudden unexplained deaths in children (SUDC) is limited, according to Matthew Halvorsen, PhD, of the University of North Carolina at Chapel Hill, and colleagues. Most cases of SUDC occur in children aged 1-4 years, and a lack of standardized investigation systems likely leads to misclassification of these deaths, they said.

Compared with sudden infant death syndrome (SIDS), which occurs in approximately 1,400 children in the United States each year, approximately 400 children aged 1 year and older die from SUDC annually. A major obstacle to studying these cases is that so-called molecular autopsies – which incorporate genetic analysis into the postmortem examination – typically do not assess the parents’ genetic information and thus limit the ability to identify de novo mutations, they added.

In a study published in the Proceedings of the National Academy of Sciences, Dr. Halvorsen’s group obtained whole exome sequence data from 124 “trios,” meaning a dead child and two living parents. They tested for excessive de novo mutations for different genes involved in conditions that included cardiac arrhythmias and epilepsy. The average age at the time of death for the children was 34.2 months; 54% were male, and 82% were White.

Children who died of SUDC were nearly 10 times as likely to have de novo mutations in genes associated with cardiac and seizure disorders as were unrelated healthy controls (odds ratio, 9.76). Most pathogenic variants were de novo, which highlights the importance of trio studies, the researchers noted.

The researchers identified 11 variants associated with increased risk of SUDC, 7 of which were de novo. Three of the 124 cases carried mutations (two for RYR2 and 1 for TNNI3) affecting genes in the CardiacEpilepsy dataset proposed by the American College of Medical Genetics and Genomics, strengthening the connection to seizure disorders.

Another notable finding was the identification of six de novo mutations involved in altering calcium-related regulation, which suggests a cardiac susceptibility to sudden death.

The data support “novel genetic causes of pediatric sudden deaths that could be discovered with larger cohorts,” the researchers noted. Taken together, they say, the gene mutations could play a role in approximately 9% of SUDC cases.

The study findings were limited by several factors, including lack of population-based case ascertainment, exclusive focus on unexplained deaths, potentially missed mutations, and use of DNA from blood as opposed to organs, the researchers noted.

However, they concluded, “the data indicate that deleterious de novo mutations are significant genetic risk factors for childhood sudden unexplained death, and that their identification may lead to medical intervention that ultimately saves lives.”

Findings highlight impact of SUDC

“This study is important because SUDC is a much more pressing medical need than most people realize,” said Richard Tsien, PhD, of New York University Langone Medical Center, and the corresponding author of the study.

Although SUDC is less common than SIDS, SUDC has essentially no targeted research funding, Dr. Tsien said. Study coauthor Laura Gould, MA, a researcher and mother who lost a young child to SUDC, worked with Orrin Devinsky, MD, to create a registry for families with cases of SUDC. This registry was instrumental in allowing the researchers to “do the molecular detective work we need to do” to see whether a genetic basis exists for SUDC, Dr. Tsien said.

“The detective work comes up with a consistent story,” he said. “More than half of the genes that we found are involved in the normal function of the heart and brain,” performing such functions as delivering calcium ions to the inside of the heart cells and nerve cells.

The study “is the first of its kind,” given the difficulty of acquiring DNA from the child and two parents in SUDC cases, Dr. Tsien said.

Overall, approximately 10% of the cases have a compelling explanation based on the coding of DNA, Dr. Tsien said. From a clinical standpoint, that information might affect what a clinician says to a parent.

A key takeaway is that most of the genetic mutations are spontaneous and are not inherited from the parents, Dr. Tsien said. The study findings indicate that parents who suffer an SUDC loss need not be discouraged from having children, he added.

For the long term, “the more we understand about these disorders, the more information we can offer to families,” he said. Eventually, clinicians might be able to use genetics to identify signs of when SUDC might be more likely. “For example, if a child shows a very mild seizure, this would alert them that there might be potential for a more drastic outcome.”

Meanwhile, families with SUDC cases may find support and benefit in signing up for the registry and knowing that other families have been through a similar experience, Dr. Tsien said.

Genetic studies create opportunities

A significant portion of pediatric mortality remains unexplained, according to Richard D. Goldstein, MD, of Boston Children’s Hospital. One reason is the lack of a formal diagnostic code to identify these deaths.

Research to date has suggested links between SUDC and a family history of febrile seizures, as well as differences in brain structure associated with epilepsy, Dr. Goldstein said.

“An important hypothesis is that these deaths are part of a continuum that also includes stillbirths, SIDS, and sudden unexpected death in epilepsy [SUDEP],” Dr. Goldstein said. “By mandate, investigations of these deaths occur under the jurisdiction of medical examiners and coroners and have, for the most part, been insulated from developments in modern medicine like genomics and proteomics, elements of what are referred to as the molecular autopsy, and studies such as the current study bring attention to what is being missed.”

Dr. Goldstein said the new study buttresses the “conventional clinical suspicion” about the likely causes of SUDC, “but also strengthens the association between sudden unexpected death in pediatrics (SUDP) and SUDEP that we and others have been positing. I think the researchers very nicely make the point that epilepsy and cardiac arrhythmia genes are not as separated in their effects as many would believe.”

As for the clinical applicability of the findings, Dr. Goldstein said medicine needs to offer parents more: “Pediatric deaths without explanation deserve more than a forensic investigation that concerns itself mostly with whether there has been foul play,” he said. “We need to figure out how to engage families, at an incredibly vulnerable time, in helping find the cause of the child’s death and also contributing to needed research. Most of the reported variants were de novo, which means that parent participation is needed to figure out these genetic factors but also that we can offer reassurance to families that other children are not at risk.”

The study was supported by the SUDC Foundation and Finding a Cure for Epilepsy and Seizures (New York University). Dr. Tsien disclosed support from the National Institutes of Health and a grant from FACES. Dr. Goldstein reported no relevant financial relationships.

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

In a large-scale study among Danish children, no statistically significant association was found between maternal hormonal contraception use and increased risk for central nervous system (CNS) tumors in their offspring.

The study was based on population-based registry data and included 1.1 million children age 19 or younger born in Denmark between 1996 and 2014.

The study, by Marie Hargreave, PhD, Danish Cancer Society Research Center, and colleagues, was published online Jan. 4 in the Journal of the American Medical Association.

Exposure to sex hormones in utero is a recognized cause of cancer in affected offspring, note the authors. Also, the incidence of CNS tumors, among the most common and lethal childhood cancer types, appears to be increasing. Hence, they sought to investigate if there may be a relationship between the two.

During a mean follow-up of 12.9 years, the team found that 725 children were diagnosed with a CNS tumor (47.2% female). Mean age at diagnosis was 7 years. The team noted that 11.5%, 65.7%, and 22.8% of diagnosed children were born to mothers with recent, previous, or no use of hormonal contraception, respectively.

The adjusted incidence rate of CNS tumors was 5.0 per 100,000 person-years for children born to mothers with recent hormonal contraception use (hazard ratio, 0.95), 4.5 per 100,000 person-years for children born to mothers with previous use (HR, 0.86), and 5.3 per 100,000 person-years for children born to mothers with no use.

While recent use of implants (HR, 0.9) and intrauterine devices (HR, 1.5) showed no statistically significant associations for the subgroups of nonoral progestin-only hormonal contraception assessed, the team found that progestin-only injections were significantly associated with an increased risk compared with no use (HR, 6.7). Also, in all post hoc sensitivity analyses, recent use of the main group of nonoral progestin-only products was significantly associated with CNS tumors.

The authors observe that an association between maternal use of injectable contraceptives and increased risk of chromosomal anomalies and major malformations in children has previously been reported. Those results for injections, however, were based on a small number of cases, the result of the likelihood test was null, and adjustments for multiple comparisons were not made. Even if the results for this subgroup are confirmed, the authors point out, because CNS tumors in children are uncommon, the high relative risk estimates would translate to low absolute risk increases.

Although the large number of person-years and cancers increases the statistical precision, and the population-based nationwide design increases the generalizability of the results, the authors caution that uncommonness of CNS tumors in children and the small number of cases in the studied cohort limit subgroup analyses and the statistical precision of certain estimates.

In an accompanying editorial, Logan G. Spector, PhD, and Christopher L. Moertel, MD, from the University of Minnesota Medical School, and H. Irene Su, MD, from the University of California, San Diego, echo the authors’ conclusions, and state: “Thus, women should be reassured about the use of hormonal contraception, including progestin-only injections, and the lack of any increased risk of CNS tumors in their offspring.”

The study was supported by the Danish Cancer Research Foundation, the Arvid Nilssons Foundation, the Gangsted Foundation, the Harboe Foundation, and the Johannes Clemmesens Foundation. Co-author Lina S. Mørch, PhD, reported receiving personal fees from Novo Nordisk as an employee from 2017 to 2019 and grants from Novo Nordisk for a collaborative research project outside the submitted work. Editorialist Christopher Moertel, MD, reported receiving personal fees from OX2 Therapeutics, a spin-off of the University of Minnesota that is involved in the development of brain tumor therapeutics.

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

In a large-scale study among Danish children, no statistically significant association was found between maternal hormonal contraception use and increased risk for central nervous system (CNS) tumors in their offspring.

The study was based on population-based registry data and included 1.1 million children age 19 or younger born in Denmark between 1996 and 2014.

The study, by Marie Hargreave, PhD, Danish Cancer Society Research Center, and colleagues, was published online Jan. 4 in the Journal of the American Medical Association.

Exposure to sex hormones in utero is a recognized cause of cancer in affected offspring, note the authors. Also, the incidence of CNS tumors, among the most common and lethal childhood cancer types, appears to be increasing. Hence, they sought to investigate if there may be a relationship between the two.

During a mean follow-up of 12.9 years, the team found that 725 children were diagnosed with a CNS tumor (47.2% female). Mean age at diagnosis was 7 years. The team noted that 11.5%, 65.7%, and 22.8% of diagnosed children were born to mothers with recent, previous, or no use of hormonal contraception, respectively.

The adjusted incidence rate of CNS tumors was 5.0 per 100,000 person-years for children born to mothers with recent hormonal contraception use (hazard ratio, 0.95), 4.5 per 100,000 person-years for children born to mothers with previous use (HR, 0.86), and 5.3 per 100,000 person-years for children born to mothers with no use.

While recent use of implants (HR, 0.9) and intrauterine devices (HR, 1.5) showed no statistically significant associations for the subgroups of nonoral progestin-only hormonal contraception assessed, the team found that progestin-only injections were significantly associated with an increased risk compared with no use (HR, 6.7). Also, in all post hoc sensitivity analyses, recent use of the main group of nonoral progestin-only products was significantly associated with CNS tumors.

The authors observe that an association between maternal use of injectable contraceptives and increased risk of chromosomal anomalies and major malformations in children has previously been reported. Those results for injections, however, were based on a small number of cases, the result of the likelihood test was null, and adjustments for multiple comparisons were not made. Even if the results for this subgroup are confirmed, the authors point out, because CNS tumors in children are uncommon, the high relative risk estimates would translate to low absolute risk increases.

Although the large number of person-years and cancers increases the statistical precision, and the population-based nationwide design increases the generalizability of the results, the authors caution that uncommonness of CNS tumors in children and the small number of cases in the studied cohort limit subgroup analyses and the statistical precision of certain estimates.

In an accompanying editorial, Logan G. Spector, PhD, and Christopher L. Moertel, MD, from the University of Minnesota Medical School, and H. Irene Su, MD, from the University of California, San Diego, echo the authors’ conclusions, and state: “Thus, women should be reassured about the use of hormonal contraception, including progestin-only injections, and the lack of any increased risk of CNS tumors in their offspring.”

The study was supported by the Danish Cancer Research Foundation, the Arvid Nilssons Foundation, the Gangsted Foundation, the Harboe Foundation, and the Johannes Clemmesens Foundation. Co-author Lina S. Mørch, PhD, reported receiving personal fees from Novo Nordisk as an employee from 2017 to 2019 and grants from Novo Nordisk for a collaborative research project outside the submitted work. Editorialist Christopher Moertel, MD, reported receiving personal fees from OX2 Therapeutics, a spin-off of the University of Minnesota that is involved in the development of brain tumor therapeutics.

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

In a large-scale study among Danish children, no statistically significant association was found between maternal hormonal contraception use and increased risk for central nervous system (CNS) tumors in their offspring.

The study was based on population-based registry data and included 1.1 million children age 19 or younger born in Denmark between 1996 and 2014.

The study, by Marie Hargreave, PhD, Danish Cancer Society Research Center, and colleagues, was published online Jan. 4 in the Journal of the American Medical Association.

Exposure to sex hormones in utero is a recognized cause of cancer in affected offspring, note the authors. Also, the incidence of CNS tumors, among the most common and lethal childhood cancer types, appears to be increasing. Hence, they sought to investigate if there may be a relationship between the two.

During a mean follow-up of 12.9 years, the team found that 725 children were diagnosed with a CNS tumor (47.2% female). Mean age at diagnosis was 7 years. The team noted that 11.5%, 65.7%, and 22.8% of diagnosed children were born to mothers with recent, previous, or no use of hormonal contraception, respectively.

The adjusted incidence rate of CNS tumors was 5.0 per 100,000 person-years for children born to mothers with recent hormonal contraception use (hazard ratio, 0.95), 4.5 per 100,000 person-years for children born to mothers with previous use (HR, 0.86), and 5.3 per 100,000 person-years for children born to mothers with no use.

While recent use of implants (HR, 0.9) and intrauterine devices (HR, 1.5) showed no statistically significant associations for the subgroups of nonoral progestin-only hormonal contraception assessed, the team found that progestin-only injections were significantly associated with an increased risk compared with no use (HR, 6.7). Also, in all post hoc sensitivity analyses, recent use of the main group of nonoral progestin-only products was significantly associated with CNS tumors.

The authors observe that an association between maternal use of injectable contraceptives and increased risk of chromosomal anomalies and major malformations in children has previously been reported. Those results for injections, however, were based on a small number of cases, the result of the likelihood test was null, and adjustments for multiple comparisons were not made. Even if the results for this subgroup are confirmed, the authors point out, because CNS tumors in children are uncommon, the high relative risk estimates would translate to low absolute risk increases.

Although the large number of person-years and cancers increases the statistical precision, and the population-based nationwide design increases the generalizability of the results, the authors caution that uncommonness of CNS tumors in children and the small number of cases in the studied cohort limit subgroup analyses and the statistical precision of certain estimates.

In an accompanying editorial, Logan G. Spector, PhD, and Christopher L. Moertel, MD, from the University of Minnesota Medical School, and H. Irene Su, MD, from the University of California, San Diego, echo the authors’ conclusions, and state: “Thus, women should be reassured about the use of hormonal contraception, including progestin-only injections, and the lack of any increased risk of CNS tumors in their offspring.”

The study was supported by the Danish Cancer Research Foundation, the Arvid Nilssons Foundation, the Gangsted Foundation, the Harboe Foundation, and the Johannes Clemmesens Foundation. Co-author Lina S. Mørch, PhD, reported receiving personal fees from Novo Nordisk as an employee from 2017 to 2019 and grants from Novo Nordisk for a collaborative research project outside the submitted work. Editorialist Christopher Moertel, MD, reported receiving personal fees from OX2 Therapeutics, a spin-off of the University of Minnesota that is involved in the development of brain tumor therapeutics.

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

Laura Dover, MD, had carefully timed her pregnancy around the four exams required to achieve board certification in radiation oncology. But when the pandemic hit in 2020, the final test, offered each May, was pushed to October – the week of her due date.

It would be impossible for her to fly the 2,500 miles from New York to the test site in Tucson, Ariz., when she could go into labor at any moment. She asked the American Board of Radiology – which oversees the process – if she could take the oral exam on Zoom or shift the timing a few weeks earlier or later.

The response: If she decided not to sit for the exam in person on the date specified, she would have to wait an entire year for the next test.

“I felt: Angry. Sad. Helpless. Inconsequential,” Dr. Dover tweeted. “But I will not be silent.”

The experience motivated Dr. Dover and six colleagues to conduct a study about how radiation oncology’s onerous four-exam board certification process has disproportionately burdened women.

The study, published online in Practical Radiation Oncology on Nov. 3, 2021, revealed that almost 60% of the early-career female radiation oncologists surveyed had delayed or were timing their pregnancies to accommodate their board exams. Women who chose to delay pregnancy were 2.5 times more likely to experience infertility.

“When we started doing the study, we didn’t realize just how common it was for people to wrap so much of their [family planning decisions] around taking these board exams,” said study coauthor Adrianna Henson Masters, MD, a radiation oncologist at Springfield (Ill.) Clinic. “How crazy is that? And no one’s talking about it.”

However, once the study appeared online, physicians took to Twitter to comment on the challenges of the board certification process, while others demanded change. One radiation oncologist even shared her decision not to have a child until she passed her board exams.

The study also got the attention of the American Board of Radiology, which governs certification for the specialty. In a response, leaders of the organization agreed that “the issues raised are significant and worthy of thoughtful consideration” and highlighted how, in light of the COVID-19 pandemic, the board has provided greater flexibility to the exam process – transitioning to remote testing and offering two dates for each exam in 2021.

But will the changes last? And will they help reduce the burden these exams place on families and family planning?
 

Inside board certification before the pandemic

While other specialties require one or two exams for board certification, radiation oncology is the only medical field that requires candidates pass four exams – three qualifying written tests, followed by a certifying oral exam. Since 2004, these exams, which cover physics, radiation biology, and clinical radiation oncology, have taken place over 3 years at specific locations across the country.

Radiation oncology residents have reported spending hundreds of hours preparing for each of these high-stakes evaluations. Fail or miss one and an already time-consuming process draws out, with major repercussions for career advancement and earnings.

“Passing and achieving board certification is the capstone of medical specialty training and, for many, is a prerequisite for attaining partnership or a promotion,” said study coauthor Chelain Goodman, MD, PhD, a radiation oncologist at the University of Texas MD Anderson Cancer Center, Houston.

To top it off, this process may be contributing to the gender disparity in radiation oncology, the study suggests. Only 25%-30% of practicing radiation oncologists are women, making it one of the lowest-ranking specialties when it comes to female representation.

“I think [this exam process] creates some disincentive when female medical students see that these are issues that early-career radiation oncologists are facing,” said Dr. Dover, who practices at Memorial Sloan Kettering Cancer Center, New York. “[Students may instead] choose a specialty that they believe will be more supportive of them and their family planning goals. That’s definitely a big concern for a field that wants to attract the top candidates.”

For those who do pick radiation oncology, the system of board exams often requires prospective parents to choose among three options: Try to time delivery before or between exams, put off pregnancy or adoption until exams are done, or delay board certification.
 

A balancing act: Board exams and family planning

Like Dr. Dover, Dr. Masters opted for door No. 1. She tried to time the birth of her daughter to fall several months before her first board exam.

She hoped her careful planning would reduce the stress of both major life events. But that was not the case. At 35 weeks, Dr. Masters found herself in the hospital with preeclampsia and symptomatic hypertension.

While receiving a magnesium sulfate drip to prevent a seizure, she frantically typed her patient list before her vision got too blurry to see the screen.

“That is ridiculous,” Dr. Masters said. “But so is a system that makes this the expectation [for pregnant physicians].”

During her hospital stay, Dr. Masters was induced. She suspects the stress of prepping for the board exam coupled with being pregnant and continuing to work long hours as a resident contributed to her pregnancy complications.

This juggling act can bleed into exam day as well. When interviewing women for their study, Dr. Masters and colleagues uncovered personal accounts of the challenges pregnant women and new mothers faced during their exams.

One woman described being granted lactation accommodation ahead of time, but when she arrived for her first two written exams, the testing center had no record of her request. She ended up breast-pumping in a coat closet next to the cleaning supplies while her male coresidents ate lunch and reviewed their notes.

“I started my physics exam in tears, completely anxious,” she reported. “I didn’t get to eat lunch. I was physically uncomfortable and emotionally wiped during both exams.”

Another woman had contractions during her written clinical boards, but “thankfully” passed her exam and gave birth 2 days later.

“It might sound crazy that we would put ourselves through things like that just to take an exam,” Dr. Dover said. “But because it does have the potential to sharply shape our early professional trajectory, we push through it. Otherwise, we’re going to be left behind by our male peers.”

This pressure to push through can be intense.

Still recovering from a difficult pregnancy, Dr. Masters returned to work when her daughter was just 5 weeks old. Although not ready to return to work, she felt too scared to ask for more time off after seeing other new mothers receive negative comments about not working hard enough.

Enter door No. 2: The pregnancy and postpregnancy experiences were so traumatizing that she decided to put off trying for a second child until after her exams.

Now board certified and 38 years old, Dr. Masters is worried she won’t be able to conceive as easily as before.

“So, we’re stuck in limbo, starting the process again and being nervous about it because what if it’s not so easy at this age?” she said. “And what if it could have been easy, in different circumstances, with a different specialty?”

Dr. Masters’ concerns are justified. Of the 126 women interviewed for the study, those who delayed pregnancy because of the board exams were significantly more likely to have fertility problems (46% vs. 18%), and 20% reported experiencing infertility.

This finding dovetails with previous research showing that almost 25% of female physicians who attempt to become pregnant are diagnosed with infertility – nearly twice the rate of the general population. This high rate of infertility has been attributed to professional pressures and stress, long hours on the job, and delaying pregnancy during medical training.

But choosing door No. 3 – focusing on family over exams – has downsides as well. Board certification is a prerequisite for almost every partnership position or promotion track within academic medicine and delaying certification can significantly hinder a physician’s career and finances.

Radiation oncologists who aren’t certified often remain in salaried positions until they can make partnership and earn a portion of the practice’s profits, “which could easily change your annual compensation by six digits,” Dr. Dover said.

According to the team’s study, annual compensation typically increases by $30,000-$50,000 after board certification, with some reporting an increase of over $100,000. That salary hike also impacts physicians’ ability to pay off medical school loans, make financial investments, and afford the cost of childcare.

In other words, when it comes to family planning, there’s often no good option.
 

Change on the horizon

When the pandemic struck, the American Board of Radiology quickly went into triage mode, postponing in-person board certification exams scheduled in 2020 and brainstorming solutions.

By June, the organization announced that the exams would switch to a virtual format in 2021. Each test would be offered twice – once early in the year for candidates like Dover whose postponed 2020 exams had ultimately been canceled, and then again for those already planning to take their tests in 2021.

The shift to remote testing was a boon. Taking the tests from home not only allowed candidates to forgo the cost, stress, and time of travel, it also mitigated the burden of juggling pregnancy and parenting needs.

For example, Courtney Hentz, MD, a pediatric radiation oncologist at Loyola University Chicago, Maywood, Ill., and a study coauthor, was given the choice to take a virtual exam in one day with two breastfeeding breaks or to spread the exam over 2 days with one breastfeeding break each day.

“Transitioning exams to a virtual format has been a really big achievement that the American Board of Radiology should be applauded for,” Dr. Dover said.

Not only that, offering the exams multiple times a year has “significantly increased flexibility for candidates as they juggle completing residency, starting at their first practice, and balancing time with their family,” Dr. Goodman added.

Brent Wagner, MD, MBA, executive director of the American Board of Radiology, Tucson, Ariz., said in an interviewthat remote exams are here to stay. “I don’t foresee us ever going back to in-person board exams,” said Dr. Wagner, a diagnostic radiologist. “Administering exams remotely last year worked better than I could have expected.”

Dr. Wagner said the American Board of Radiology also plans to keep two dates for the oral certifying exam for the foreseeable future, though will revert to one date for the written qualifying exams.

“In a perfect world, we’d offer an exam every quarter,” he said. However, providing multiple dates for the written exams “is not practical with a cohort of a few hundred people,” given the staff resources needed to create and score twice the number of items each year. The board did not rule out reassessing this decision in the future, “as examination development software improves and more resources become available.”

Another big change, proposed by Dr. Dover, Dr. Goodman, and others, would be to combine the four exams into fewer tests, such as consolidating the three written exams into one. Such a shift would allow physicians to launch their careers sooner and begin focusing on other career-advancing endeavors such as research and publishing. It would also significantly improve radiation oncologists’ quality of life.

“The amount of time that you spend studying for these very high-level, high-stakes exams really puts a toll on your mental health,” Dr. Dover said. “The longer it’s dragged out, the longer you’re dealing with that, and it contributes tremendously to poor job satisfaction and work-life balance.” 

The American Board of Radiology said it is discussing options for consolidating the exams, but the challenge with combining the three written exams into one comes down to scoring. “We need to get a statistically valid result in all three categories,” Dr. Wagner said.

Another recent change: The American Board of Radiology is now allowing residents flexibility on the sequence of the written exams.

“In the past, we said you had to pass the physics exam before moving on to clinical radiology, but now we’re letting residents decide the order for themselves,” Dr. Wagner said. “This change may introduce more flexibility for someone who missed their first opportunity to take the physics exam but is ready to take the clinical exam.”

Dr. Wagner added: “We’re learning as we go, and I tell our staff that there’s no reason we should think we’re done making improvements. It’s going to keep getting better.”

The recent changes have already made a difference to radiation oncologists. And many hope to build on this new foundation to move the specialty toward a more family-friendly, equitable culture.

“I think as people in a caregiver profession, it’s hard to prioritize doing things for yourself or your own family sometimes; it’s hard to speak up and say: ‘We need something different,’ ” Dr. Masters said. “I think we have [an opportunity] to capitalize on the momentum we have now.”

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

Laura Dover, MD, had carefully timed her pregnancy around the four exams required to achieve board certification in radiation oncology. But when the pandemic hit in 2020, the final test, offered each May, was pushed to October – the week of her due date.

It would be impossible for her to fly the 2,500 miles from New York to the test site in Tucson, Ariz., when she could go into labor at any moment. She asked the American Board of Radiology – which oversees the process – if she could take the oral exam on Zoom or shift the timing a few weeks earlier or later.

The response: If she decided not to sit for the exam in person on the date specified, she would have to wait an entire year for the next test.

“I felt: Angry. Sad. Helpless. Inconsequential,” Dr. Dover tweeted. “But I will not be silent.”

The experience motivated Dr. Dover and six colleagues to conduct a study about how radiation oncology’s onerous four-exam board certification process has disproportionately burdened women.

The study, published online in Practical Radiation Oncology on Nov. 3, 2021, revealed that almost 60% of the early-career female radiation oncologists surveyed had delayed or were timing their pregnancies to accommodate their board exams. Women who chose to delay pregnancy were 2.5 times more likely to experience infertility.

“When we started doing the study, we didn’t realize just how common it was for people to wrap so much of their [family planning decisions] around taking these board exams,” said study coauthor Adrianna Henson Masters, MD, a radiation oncologist at Springfield (Ill.) Clinic. “How crazy is that? And no one’s talking about it.”

However, once the study appeared online, physicians took to Twitter to comment on the challenges of the board certification process, while others demanded change. One radiation oncologist even shared her decision not to have a child until she passed her board exams.

The study also got the attention of the American Board of Radiology, which governs certification for the specialty. In a response, leaders of the organization agreed that “the issues raised are significant and worthy of thoughtful consideration” and highlighted how, in light of the COVID-19 pandemic, the board has provided greater flexibility to the exam process – transitioning to remote testing and offering two dates for each exam in 2021.

But will the changes last? And will they help reduce the burden these exams place on families and family planning?
 

Inside board certification before the pandemic

While other specialties require one or two exams for board certification, radiation oncology is the only medical field that requires candidates pass four exams – three qualifying written tests, followed by a certifying oral exam. Since 2004, these exams, which cover physics, radiation biology, and clinical radiation oncology, have taken place over 3 years at specific locations across the country.

Radiation oncology residents have reported spending hundreds of hours preparing for each of these high-stakes evaluations. Fail or miss one and an already time-consuming process draws out, with major repercussions for career advancement and earnings.

“Passing and achieving board certification is the capstone of medical specialty training and, for many, is a prerequisite for attaining partnership or a promotion,” said study coauthor Chelain Goodman, MD, PhD, a radiation oncologist at the University of Texas MD Anderson Cancer Center, Houston.

To top it off, this process may be contributing to the gender disparity in radiation oncology, the study suggests. Only 25%-30% of practicing radiation oncologists are women, making it one of the lowest-ranking specialties when it comes to female representation.

“I think [this exam process] creates some disincentive when female medical students see that these are issues that early-career radiation oncologists are facing,” said Dr. Dover, who practices at Memorial Sloan Kettering Cancer Center, New York. “[Students may instead] choose a specialty that they believe will be more supportive of them and their family planning goals. That’s definitely a big concern for a field that wants to attract the top candidates.”

For those who do pick radiation oncology, the system of board exams often requires prospective parents to choose among three options: Try to time delivery before or between exams, put off pregnancy or adoption until exams are done, or delay board certification.
 

A balancing act: Board exams and family planning

Like Dr. Dover, Dr. Masters opted for door No. 1. She tried to time the birth of her daughter to fall several months before her first board exam.

She hoped her careful planning would reduce the stress of both major life events. But that was not the case. At 35 weeks, Dr. Masters found herself in the hospital with preeclampsia and symptomatic hypertension.

While receiving a magnesium sulfate drip to prevent a seizure, she frantically typed her patient list before her vision got too blurry to see the screen.

“That is ridiculous,” Dr. Masters said. “But so is a system that makes this the expectation [for pregnant physicians].”

During her hospital stay, Dr. Masters was induced. She suspects the stress of prepping for the board exam coupled with being pregnant and continuing to work long hours as a resident contributed to her pregnancy complications.

This juggling act can bleed into exam day as well. When interviewing women for their study, Dr. Masters and colleagues uncovered personal accounts of the challenges pregnant women and new mothers faced during their exams.

One woman described being granted lactation accommodation ahead of time, but when she arrived for her first two written exams, the testing center had no record of her request. She ended up breast-pumping in a coat closet next to the cleaning supplies while her male coresidents ate lunch and reviewed their notes.

“I started my physics exam in tears, completely anxious,” she reported. “I didn’t get to eat lunch. I was physically uncomfortable and emotionally wiped during both exams.”

Another woman had contractions during her written clinical boards, but “thankfully” passed her exam and gave birth 2 days later.

“It might sound crazy that we would put ourselves through things like that just to take an exam,” Dr. Dover said. “But because it does have the potential to sharply shape our early professional trajectory, we push through it. Otherwise, we’re going to be left behind by our male peers.”

This pressure to push through can be intense.

Still recovering from a difficult pregnancy, Dr. Masters returned to work when her daughter was just 5 weeks old. Although not ready to return to work, she felt too scared to ask for more time off after seeing other new mothers receive negative comments about not working hard enough.

Enter door No. 2: The pregnancy and postpregnancy experiences were so traumatizing that she decided to put off trying for a second child until after her exams.

Now board certified and 38 years old, Dr. Masters is worried she won’t be able to conceive as easily as before.

“So, we’re stuck in limbo, starting the process again and being nervous about it because what if it’s not so easy at this age?” she said. “And what if it could have been easy, in different circumstances, with a different specialty?”

Dr. Masters’ concerns are justified. Of the 126 women interviewed for the study, those who delayed pregnancy because of the board exams were significantly more likely to have fertility problems (46% vs. 18%), and 20% reported experiencing infertility.

This finding dovetails with previous research showing that almost 25% of female physicians who attempt to become pregnant are diagnosed with infertility – nearly twice the rate of the general population. This high rate of infertility has been attributed to professional pressures and stress, long hours on the job, and delaying pregnancy during medical training.

But choosing door No. 3 – focusing on family over exams – has downsides as well. Board certification is a prerequisite for almost every partnership position or promotion track within academic medicine and delaying certification can significantly hinder a physician’s career and finances.

Radiation oncologists who aren’t certified often remain in salaried positions until they can make partnership and earn a portion of the practice’s profits, “which could easily change your annual compensation by six digits,” Dr. Dover said.

According to the team’s study, annual compensation typically increases by $30,000-$50,000 after board certification, with some reporting an increase of over $100,000. That salary hike also impacts physicians’ ability to pay off medical school loans, make financial investments, and afford the cost of childcare.

In other words, when it comes to family planning, there’s often no good option.
 

Change on the horizon

When the pandemic struck, the American Board of Radiology quickly went into triage mode, postponing in-person board certification exams scheduled in 2020 and brainstorming solutions.

By June, the organization announced that the exams would switch to a virtual format in 2021. Each test would be offered twice – once early in the year for candidates like Dover whose postponed 2020 exams had ultimately been canceled, and then again for those already planning to take their tests in 2021.

The shift to remote testing was a boon. Taking the tests from home not only allowed candidates to forgo the cost, stress, and time of travel, it also mitigated the burden of juggling pregnancy and parenting needs.

For example, Courtney Hentz, MD, a pediatric radiation oncologist at Loyola University Chicago, Maywood, Ill., and a study coauthor, was given the choice to take a virtual exam in one day with two breastfeeding breaks or to spread the exam over 2 days with one breastfeeding break each day.

“Transitioning exams to a virtual format has been a really big achievement that the American Board of Radiology should be applauded for,” Dr. Dover said.

Not only that, offering the exams multiple times a year has “significantly increased flexibility for candidates as they juggle completing residency, starting at their first practice, and balancing time with their family,” Dr. Goodman added.

Brent Wagner, MD, MBA, executive director of the American Board of Radiology, Tucson, Ariz., said in an interviewthat remote exams are here to stay. “I don’t foresee us ever going back to in-person board exams,” said Dr. Wagner, a diagnostic radiologist. “Administering exams remotely last year worked better than I could have expected.”

Dr. Wagner said the American Board of Radiology also plans to keep two dates for the oral certifying exam for the foreseeable future, though will revert to one date for the written qualifying exams.

“In a perfect world, we’d offer an exam every quarter,” he said. However, providing multiple dates for the written exams “is not practical with a cohort of a few hundred people,” given the staff resources needed to create and score twice the number of items each year. The board did not rule out reassessing this decision in the future, “as examination development software improves and more resources become available.”

Another big change, proposed by Dr. Dover, Dr. Goodman, and others, would be to combine the four exams into fewer tests, such as consolidating the three written exams into one. Such a shift would allow physicians to launch their careers sooner and begin focusing on other career-advancing endeavors such as research and publishing. It would also significantly improve radiation oncologists’ quality of life.

“The amount of time that you spend studying for these very high-level, high-stakes exams really puts a toll on your mental health,” Dr. Dover said. “The longer it’s dragged out, the longer you’re dealing with that, and it contributes tremendously to poor job satisfaction and work-life balance.” 

The American Board of Radiology said it is discussing options for consolidating the exams, but the challenge with combining the three written exams into one comes down to scoring. “We need to get a statistically valid result in all three categories,” Dr. Wagner said.

Another recent change: The American Board of Radiology is now allowing residents flexibility on the sequence of the written exams.

“In the past, we said you had to pass the physics exam before moving on to clinical radiology, but now we’re letting residents decide the order for themselves,” Dr. Wagner said. “This change may introduce more flexibility for someone who missed their first opportunity to take the physics exam but is ready to take the clinical exam.”

Dr. Wagner added: “We’re learning as we go, and I tell our staff that there’s no reason we should think we’re done making improvements. It’s going to keep getting better.”

The recent changes have already made a difference to radiation oncologists. And many hope to build on this new foundation to move the specialty toward a more family-friendly, equitable culture.

“I think as people in a caregiver profession, it’s hard to prioritize doing things for yourself or your own family sometimes; it’s hard to speak up and say: ‘We need something different,’ ” Dr. Masters said. “I think we have [an opportunity] to capitalize on the momentum we have now.”

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

Laura Dover, MD, had carefully timed her pregnancy around the four exams required to achieve board certification in radiation oncology. But when the pandemic hit in 2020, the final test, offered each May, was pushed to October – the week of her due date.

It would be impossible for her to fly the 2,500 miles from New York to the test site in Tucson, Ariz., when she could go into labor at any moment. She asked the American Board of Radiology – which oversees the process – if she could take the oral exam on Zoom or shift the timing a few weeks earlier or later.

The response: If she decided not to sit for the exam in person on the date specified, she would have to wait an entire year for the next test.

“I felt: Angry. Sad. Helpless. Inconsequential,” Dr. Dover tweeted. “But I will not be silent.”

The experience motivated Dr. Dover and six colleagues to conduct a study about how radiation oncology’s onerous four-exam board certification process has disproportionately burdened women.

The study, published online in Practical Radiation Oncology on Nov. 3, 2021, revealed that almost 60% of the early-career female radiation oncologists surveyed had delayed or were timing their pregnancies to accommodate their board exams. Women who chose to delay pregnancy were 2.5 times more likely to experience infertility.

“When we started doing the study, we didn’t realize just how common it was for people to wrap so much of their [family planning decisions] around taking these board exams,” said study coauthor Adrianna Henson Masters, MD, a radiation oncologist at Springfield (Ill.) Clinic. “How crazy is that? And no one’s talking about it.”

However, once the study appeared online, physicians took to Twitter to comment on the challenges of the board certification process, while others demanded change. One radiation oncologist even shared her decision not to have a child until she passed her board exams.

The study also got the attention of the American Board of Radiology, which governs certification for the specialty. In a response, leaders of the organization agreed that “the issues raised are significant and worthy of thoughtful consideration” and highlighted how, in light of the COVID-19 pandemic, the board has provided greater flexibility to the exam process – transitioning to remote testing and offering two dates for each exam in 2021.

But will the changes last? And will they help reduce the burden these exams place on families and family planning?
 

Inside board certification before the pandemic

While other specialties require one or two exams for board certification, radiation oncology is the only medical field that requires candidates pass four exams – three qualifying written tests, followed by a certifying oral exam. Since 2004, these exams, which cover physics, radiation biology, and clinical radiation oncology, have taken place over 3 years at specific locations across the country.

Radiation oncology residents have reported spending hundreds of hours preparing for each of these high-stakes evaluations. Fail or miss one and an already time-consuming process draws out, with major repercussions for career advancement and earnings.

“Passing and achieving board certification is the capstone of medical specialty training and, for many, is a prerequisite for attaining partnership or a promotion,” said study coauthor Chelain Goodman, MD, PhD, a radiation oncologist at the University of Texas MD Anderson Cancer Center, Houston.

To top it off, this process may be contributing to the gender disparity in radiation oncology, the study suggests. Only 25%-30% of practicing radiation oncologists are women, making it one of the lowest-ranking specialties when it comes to female representation.

“I think [this exam process] creates some disincentive when female medical students see that these are issues that early-career radiation oncologists are facing,” said Dr. Dover, who practices at Memorial Sloan Kettering Cancer Center, New York. “[Students may instead] choose a specialty that they believe will be more supportive of them and their family planning goals. That’s definitely a big concern for a field that wants to attract the top candidates.”

For those who do pick radiation oncology, the system of board exams often requires prospective parents to choose among three options: Try to time delivery before or between exams, put off pregnancy or adoption until exams are done, or delay board certification.
 

A balancing act: Board exams and family planning

Like Dr. Dover, Dr. Masters opted for door No. 1. She tried to time the birth of her daughter to fall several months before her first board exam.

She hoped her careful planning would reduce the stress of both major life events. But that was not the case. At 35 weeks, Dr. Masters found herself in the hospital with preeclampsia and symptomatic hypertension.

While receiving a magnesium sulfate drip to prevent a seizure, she frantically typed her patient list before her vision got too blurry to see the screen.

“That is ridiculous,” Dr. Masters said. “But so is a system that makes this the expectation [for pregnant physicians].”

During her hospital stay, Dr. Masters was induced. She suspects the stress of prepping for the board exam coupled with being pregnant and continuing to work long hours as a resident contributed to her pregnancy complications.

This juggling act can bleed into exam day as well. When interviewing women for their study, Dr. Masters and colleagues uncovered personal accounts of the challenges pregnant women and new mothers faced during their exams.

One woman described being granted lactation accommodation ahead of time, but when she arrived for her first two written exams, the testing center had no record of her request. She ended up breast-pumping in a coat closet next to the cleaning supplies while her male coresidents ate lunch and reviewed their notes.

“I started my physics exam in tears, completely anxious,” she reported. “I didn’t get to eat lunch. I was physically uncomfortable and emotionally wiped during both exams.”

Another woman had contractions during her written clinical boards, but “thankfully” passed her exam and gave birth 2 days later.

“It might sound crazy that we would put ourselves through things like that just to take an exam,” Dr. Dover said. “But because it does have the potential to sharply shape our early professional trajectory, we push through it. Otherwise, we’re going to be left behind by our male peers.”

This pressure to push through can be intense.

Still recovering from a difficult pregnancy, Dr. Masters returned to work when her daughter was just 5 weeks old. Although not ready to return to work, she felt too scared to ask for more time off after seeing other new mothers receive negative comments about not working hard enough.

Enter door No. 2: The pregnancy and postpregnancy experiences were so traumatizing that she decided to put off trying for a second child until after her exams.

Now board certified and 38 years old, Dr. Masters is worried she won’t be able to conceive as easily as before.

“So, we’re stuck in limbo, starting the process again and being nervous about it because what if it’s not so easy at this age?” she said. “And what if it could have been easy, in different circumstances, with a different specialty?”

Dr. Masters’ concerns are justified. Of the 126 women interviewed for the study, those who delayed pregnancy because of the board exams were significantly more likely to have fertility problems (46% vs. 18%), and 20% reported experiencing infertility.

This finding dovetails with previous research showing that almost 25% of female physicians who attempt to become pregnant are diagnosed with infertility – nearly twice the rate of the general population. This high rate of infertility has been attributed to professional pressures and stress, long hours on the job, and delaying pregnancy during medical training.

But choosing door No. 3 – focusing on family over exams – has downsides as well. Board certification is a prerequisite for almost every partnership position or promotion track within academic medicine and delaying certification can significantly hinder a physician’s career and finances.

Radiation oncologists who aren’t certified often remain in salaried positions until they can make partnership and earn a portion of the practice’s profits, “which could easily change your annual compensation by six digits,” Dr. Dover said.

According to the team’s study, annual compensation typically increases by $30,000-$50,000 after board certification, with some reporting an increase of over $100,000. That salary hike also impacts physicians’ ability to pay off medical school loans, make financial investments, and afford the cost of childcare.

In other words, when it comes to family planning, there’s often no good option.
 

Change on the horizon

When the pandemic struck, the American Board of Radiology quickly went into triage mode, postponing in-person board certification exams scheduled in 2020 and brainstorming solutions.

By June, the organization announced that the exams would switch to a virtual format in 2021. Each test would be offered twice – once early in the year for candidates like Dover whose postponed 2020 exams had ultimately been canceled, and then again for those already planning to take their tests in 2021.

The shift to remote testing was a boon. Taking the tests from home not only allowed candidates to forgo the cost, stress, and time of travel, it also mitigated the burden of juggling pregnancy and parenting needs.

For example, Courtney Hentz, MD, a pediatric radiation oncologist at Loyola University Chicago, Maywood, Ill., and a study coauthor, was given the choice to take a virtual exam in one day with two breastfeeding breaks or to spread the exam over 2 days with one breastfeeding break each day.

“Transitioning exams to a virtual format has been a really big achievement that the American Board of Radiology should be applauded for,” Dr. Dover said.

Not only that, offering the exams multiple times a year has “significantly increased flexibility for candidates as they juggle completing residency, starting at their first practice, and balancing time with their family,” Dr. Goodman added.

Brent Wagner, MD, MBA, executive director of the American Board of Radiology, Tucson, Ariz., said in an interviewthat remote exams are here to stay. “I don’t foresee us ever going back to in-person board exams,” said Dr. Wagner, a diagnostic radiologist. “Administering exams remotely last year worked better than I could have expected.”

Dr. Wagner said the American Board of Radiology also plans to keep two dates for the oral certifying exam for the foreseeable future, though will revert to one date for the written qualifying exams.

“In a perfect world, we’d offer an exam every quarter,” he said. However, providing multiple dates for the written exams “is not practical with a cohort of a few hundred people,” given the staff resources needed to create and score twice the number of items each year. The board did not rule out reassessing this decision in the future, “as examination development software improves and more resources become available.”

Another big change, proposed by Dr. Dover, Dr. Goodman, and others, would be to combine the four exams into fewer tests, such as consolidating the three written exams into one. Such a shift would allow physicians to launch their careers sooner and begin focusing on other career-advancing endeavors such as research and publishing. It would also significantly improve radiation oncologists’ quality of life.

“The amount of time that you spend studying for these very high-level, high-stakes exams really puts a toll on your mental health,” Dr. Dover said. “The longer it’s dragged out, the longer you’re dealing with that, and it contributes tremendously to poor job satisfaction and work-life balance.” 

The American Board of Radiology said it is discussing options for consolidating the exams, but the challenge with combining the three written exams into one comes down to scoring. “We need to get a statistically valid result in all three categories,” Dr. Wagner said.

Another recent change: The American Board of Radiology is now allowing residents flexibility on the sequence of the written exams.

“In the past, we said you had to pass the physics exam before moving on to clinical radiology, but now we’re letting residents decide the order for themselves,” Dr. Wagner said. “This change may introduce more flexibility for someone who missed their first opportunity to take the physics exam but is ready to take the clinical exam.”

Dr. Wagner added: “We’re learning as we go, and I tell our staff that there’s no reason we should think we’re done making improvements. It’s going to keep getting better.”

The recent changes have already made a difference to radiation oncologists. And many hope to build on this new foundation to move the specialty toward a more family-friendly, equitable culture.

“I think as people in a caregiver profession, it’s hard to prioritize doing things for yourself or your own family sometimes; it’s hard to speak up and say: ‘We need something different,’ ” Dr. Masters said. “I think we have [an opportunity] to capitalize on the momentum we have now.”

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

The volume of prescription opioids dispensed at retail pharmacies in the United States dropped by 21% in recent years amid efforts to reduce unnecessary use of the painkillers, but the rate of decline varied greatly among types of patients and by type of clinician, a study found.

In a brief report published by Annals of Internal Medicine, researchers from the nonprofit RAND Corp reported an analysis of opioid prescriptions from two periods, 2008-2009 and 2017-2018.

The researchers sought to assess total opioid use rather than simply track the number of pills dispensed. So they used days’ supply and total daily dose to calculate per capita morphine milligram equivalents (MME) for opioid prescriptions, write Bradley D. Stein, MD, PhD, MPH, the study’s lead author and a senior physician researcher at RAND Corp, and his coauthors in their paper.

For the study, the researchers used data from the consulting firm IQVIA, which they say covers about 90% of U.S. prescriptions. Total opioid volume per capita by prescriptions filled in retail pharmacies decreased from 951.4 MME in 2008-2009 to 749.3 MME in 2017-2018, Dr. Stein’s group found.

(In 2020, IQVIA separately said that prescription opioid use per adult in this country rose from an average of 16 pills, or 134 MMEs, in 1992 to a peak of about 55 pills a person, or 790 MMEs, in 2011. By 2019, opioid use per adult had declined to 29 pills and 366 MMEs per capita.)

The RAND report found substantial variation in opioid volume by type of insurance, including a 41.5% decline (636.5 MME to 372.6 MME) among people covered by commercial health plans. That exceeded the 27.7% drop seen for people enrolled in Medicaid (646.8 MME to 467.7 MME). The decline was smaller (17.5%; 2,780.2 MME to 2,294.2 MME) for those on Medicare, who as a group used the most opioids.

‘Almost functions as a Rorschach test’

The causes of the decline are easy to guess, although definitive conclusions are impossible, Dr. Stein told this news organization.

Significant work has been done in recent years to change attitudes about opioid prescriptions by physicians, researchers, and lawmakers. Aggressive promotion of prescription painkillers, particularly Purdue Pharma’s OxyContin, in the 1990s, is widely cited as the triggering event for the national opioid crisis.

In response, states created databases known as prescription drug monitoring programs. The Centers for Disease Control and Prevention in 2016 issued guidelines intended to curb unnecessary use of opioids. The guidelines noted that other medicines could treat chronic pain without raising the risk of addiction. The Choosing Wisely campaign, run by a foundation of the American Board of Internal Medicine, also offered recommendations about limiting use of opioids. And insurers have restricted access to opioids through the prior authorization process. As a result, researchers will make their own guesses at the causes of the decline in opioid prescriptions, based on their own experiences and research interests, Dr. Stein said.

“It almost functions as a Rorschach test,” he said.

Dr. Stein’s group also looked at trends among medical specialties. They found the largest reduction between 2008-2009 and 2017-2018 among emergency physicians (70.5% drop from 99,254.5 MME to 29,234.3 MME), psychiatrists (67.2% drop from 50,464.3 MME to 16,533.0 MME) and oncologists (59.5% drop from 51,731.2 MME to 20,941.4).

Among surgeons, the RAND researchers found a drop of 49.3% from 220,764.6 to 111,904.4. Among dentists, they found a drop of 41.3% from 22,345.3 to 13,126.1.

Among pain specialists, they found a drop of 15.4% from 1,020,808.4 MME to 863,140.7 MME.

Among adult primary care clinicians, Dr. Stein and his colleagues found a drop of 40% from 651,489.4 MME in 2008-2009 to 390,841.0 MME in 2017-2018.

However, one of the groups tracked in the study increased the volume of opioid prescriptions written: advanced practice providers, among whom scripts for the drugs rose 22.7%, from 112,873.9 MME to 138,459.3 MME.

Dr. Stein said he suspects that this gain reflects a change in the nature of the practice of primary care, with nurse practitioners and physician assistants taking more active roles in treatment of patients. Some of the reduction seen among primary care clinicians who treat adults may reflect a shift in which medical personnel in a practice write the opioid prescriptions.

Still, the trends in general seen by Dr. Stein and coauthors are encouraging, even if further study of these patterns is needed, he said.

“This is one of those papers that I think potentially raises as many questions as it provides answers for,” he said.

What’s missing

Maya Hambright, MD, a family medicine physician in New York’s Hudson Valley, who has been working mainly in addiction in response to the opioid overdose crisis, observed that the drop in total prescribed volume of prescription painkillers does not necessarily translate into a reduction in use of opioids

“No one is taking fewer opioids,” Dr. Hambright told this news organization. “I can say that comfortably. They are just getting them from other sources.”

CDC data support Dr. Hambright’s view.

An estimated 100,306 people in the United States died of a drug overdose in the 12 months that ended in April 2021, an increase of 28.5% from the 78,056 deaths during the same period the year before, according to the CDC.

Dr. Hambright said more physicians need to be involved in prescribing medication-assisted treatment (MAT).

The federal government has in the past year loosened restrictions on a requirement, known as an X waiver. Certain clinicians have been exempted from training requirements, as explained in the frequently asked questions page on the Substance Abuse and Mental Health Services Administration website.

SAMHSA says legislation is required to eliminate the waiver. As of Dec. 30, 2021, more than half of the members of the U.S. House of Representatives were listed as sponsors of the Mainstreaming Addiction Treatment (MAT) Act (HR 1384), which would end the need for X waivers. The bill has the backing of 187 Democrats and 43 Republicans.

At this time, too many physicians shy away from offering MAT, Dr. Hambright said.

“People are still scared of it,” she said. “People don’t want to deal with addicts.”

But Dr. Hambright said it’s well worth the initial time invested in having the needed conversations with patients about MAT.

“Afterwards, it’s so straightforward. People feel better. They’re healthier. It’s amazing,” she said. “You’re changing lives.”

The research was supported by grants from the National Institutes of Health. Dr. Stein and coauthors reported no relevant financial relationships.

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

The volume of prescription opioids dispensed at retail pharmacies in the United States dropped by 21% in recent years amid efforts to reduce unnecessary use of the painkillers, but the rate of decline varied greatly among types of patients and by type of clinician, a study found.

In a brief report published by Annals of Internal Medicine, researchers from the nonprofit RAND Corp reported an analysis of opioid prescriptions from two periods, 2008-2009 and 2017-2018.

The researchers sought to assess total opioid use rather than simply track the number of pills dispensed. So they used days’ supply and total daily dose to calculate per capita morphine milligram equivalents (MME) for opioid prescriptions, write Bradley D. Stein, MD, PhD, MPH, the study’s lead author and a senior physician researcher at RAND Corp, and his coauthors in their paper.

For the study, the researchers used data from the consulting firm IQVIA, which they say covers about 90% of U.S. prescriptions. Total opioid volume per capita by prescriptions filled in retail pharmacies decreased from 951.4 MME in 2008-2009 to 749.3 MME in 2017-2018, Dr. Stein’s group found.

(In 2020, IQVIA separately said that prescription opioid use per adult in this country rose from an average of 16 pills, or 134 MMEs, in 1992 to a peak of about 55 pills a person, or 790 MMEs, in 2011. By 2019, opioid use per adult had declined to 29 pills and 366 MMEs per capita.)

The RAND report found substantial variation in opioid volume by type of insurance, including a 41.5% decline (636.5 MME to 372.6 MME) among people covered by commercial health plans. That exceeded the 27.7% drop seen for people enrolled in Medicaid (646.8 MME to 467.7 MME). The decline was smaller (17.5%; 2,780.2 MME to 2,294.2 MME) for those on Medicare, who as a group used the most opioids.

‘Almost functions as a Rorschach test’

The causes of the decline are easy to guess, although definitive conclusions are impossible, Dr. Stein told this news organization.

Significant work has been done in recent years to change attitudes about opioid prescriptions by physicians, researchers, and lawmakers. Aggressive promotion of prescription painkillers, particularly Purdue Pharma’s OxyContin, in the 1990s, is widely cited as the triggering event for the national opioid crisis.

In response, states created databases known as prescription drug monitoring programs. The Centers for Disease Control and Prevention in 2016 issued guidelines intended to curb unnecessary use of opioids. The guidelines noted that other medicines could treat chronic pain without raising the risk of addiction. The Choosing Wisely campaign, run by a foundation of the American Board of Internal Medicine, also offered recommendations about limiting use of opioids. And insurers have restricted access to opioids through the prior authorization process. As a result, researchers will make their own guesses at the causes of the decline in opioid prescriptions, based on their own experiences and research interests, Dr. Stein said.

“It almost functions as a Rorschach test,” he said.

Dr. Stein’s group also looked at trends among medical specialties. They found the largest reduction between 2008-2009 and 2017-2018 among emergency physicians (70.5% drop from 99,254.5 MME to 29,234.3 MME), psychiatrists (67.2% drop from 50,464.3 MME to 16,533.0 MME) and oncologists (59.5% drop from 51,731.2 MME to 20,941.4).

Among surgeons, the RAND researchers found a drop of 49.3% from 220,764.6 to 111,904.4. Among dentists, they found a drop of 41.3% from 22,345.3 to 13,126.1.

Among pain specialists, they found a drop of 15.4% from 1,020,808.4 MME to 863,140.7 MME.

Among adult primary care clinicians, Dr. Stein and his colleagues found a drop of 40% from 651,489.4 MME in 2008-2009 to 390,841.0 MME in 2017-2018.

However, one of the groups tracked in the study increased the volume of opioid prescriptions written: advanced practice providers, among whom scripts for the drugs rose 22.7%, from 112,873.9 MME to 138,459.3 MME.

Dr. Stein said he suspects that this gain reflects a change in the nature of the practice of primary care, with nurse practitioners and physician assistants taking more active roles in treatment of patients. Some of the reduction seen among primary care clinicians who treat adults may reflect a shift in which medical personnel in a practice write the opioid prescriptions.

Still, the trends in general seen by Dr. Stein and coauthors are encouraging, even if further study of these patterns is needed, he said.

“This is one of those papers that I think potentially raises as many questions as it provides answers for,” he said.

What’s missing

Maya Hambright, MD, a family medicine physician in New York’s Hudson Valley, who has been working mainly in addiction in response to the opioid overdose crisis, observed that the drop in total prescribed volume of prescription painkillers does not necessarily translate into a reduction in use of opioids

“No one is taking fewer opioids,” Dr. Hambright told this news organization. “I can say that comfortably. They are just getting them from other sources.”

CDC data support Dr. Hambright’s view.

An estimated 100,306 people in the United States died of a drug overdose in the 12 months that ended in April 2021, an increase of 28.5% from the 78,056 deaths during the same period the year before, according to the CDC.

Dr. Hambright said more physicians need to be involved in prescribing medication-assisted treatment (MAT).

The federal government has in the past year loosened restrictions on a requirement, known as an X waiver. Certain clinicians have been exempted from training requirements, as explained in the frequently asked questions page on the Substance Abuse and Mental Health Services Administration website.

SAMHSA says legislation is required to eliminate the waiver. As of Dec. 30, 2021, more than half of the members of the U.S. House of Representatives were listed as sponsors of the Mainstreaming Addiction Treatment (MAT) Act (HR 1384), which would end the need for X waivers. The bill has the backing of 187 Democrats and 43 Republicans.

At this time, too many physicians shy away from offering MAT, Dr. Hambright said.

“People are still scared of it,” she said. “People don’t want to deal with addicts.”

But Dr. Hambright said it’s well worth the initial time invested in having the needed conversations with patients about MAT.

“Afterwards, it’s so straightforward. People feel better. They’re healthier. It’s amazing,” she said. “You’re changing lives.”

The research was supported by grants from the National Institutes of Health. Dr. Stein and coauthors reported no relevant financial relationships.

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

The volume of prescription opioids dispensed at retail pharmacies in the United States dropped by 21% in recent years amid efforts to reduce unnecessary use of the painkillers, but the rate of decline varied greatly among types of patients and by type of clinician, a study found.

In a brief report published by Annals of Internal Medicine, researchers from the nonprofit RAND Corp reported an analysis of opioid prescriptions from two periods, 2008-2009 and 2017-2018.

The researchers sought to assess total opioid use rather than simply track the number of pills dispensed. So they used days’ supply and total daily dose to calculate per capita morphine milligram equivalents (MME) for opioid prescriptions, write Bradley D. Stein, MD, PhD, MPH, the study’s lead author and a senior physician researcher at RAND Corp, and his coauthors in their paper.

For the study, the researchers used data from the consulting firm IQVIA, which they say covers about 90% of U.S. prescriptions. Total opioid volume per capita by prescriptions filled in retail pharmacies decreased from 951.4 MME in 2008-2009 to 749.3 MME in 2017-2018, Dr. Stein’s group found.

(In 2020, IQVIA separately said that prescription opioid use per adult in this country rose from an average of 16 pills, or 134 MMEs, in 1992 to a peak of about 55 pills a person, or 790 MMEs, in 2011. By 2019, opioid use per adult had declined to 29 pills and 366 MMEs per capita.)

The RAND report found substantial variation in opioid volume by type of insurance, including a 41.5% decline (636.5 MME to 372.6 MME) among people covered by commercial health plans. That exceeded the 27.7% drop seen for people enrolled in Medicaid (646.8 MME to 467.7 MME). The decline was smaller (17.5%; 2,780.2 MME to 2,294.2 MME) for those on Medicare, who as a group used the most opioids.

‘Almost functions as a Rorschach test’

The causes of the decline are easy to guess, although definitive conclusions are impossible, Dr. Stein told this news organization.

Significant work has been done in recent years to change attitudes about opioid prescriptions by physicians, researchers, and lawmakers. Aggressive promotion of prescription painkillers, particularly Purdue Pharma’s OxyContin, in the 1990s, is widely cited as the triggering event for the national opioid crisis.

In response, states created databases known as prescription drug monitoring programs. The Centers for Disease Control and Prevention in 2016 issued guidelines intended to curb unnecessary use of opioids. The guidelines noted that other medicines could treat chronic pain without raising the risk of addiction. The Choosing Wisely campaign, run by a foundation of the American Board of Internal Medicine, also offered recommendations about limiting use of opioids. And insurers have restricted access to opioids through the prior authorization process. As a result, researchers will make their own guesses at the causes of the decline in opioid prescriptions, based on their own experiences and research interests, Dr. Stein said.

“It almost functions as a Rorschach test,” he said.

Dr. Stein’s group also looked at trends among medical specialties. They found the largest reduction between 2008-2009 and 2017-2018 among emergency physicians (70.5% drop from 99,254.5 MME to 29,234.3 MME), psychiatrists (67.2% drop from 50,464.3 MME to 16,533.0 MME) and oncologists (59.5% drop from 51,731.2 MME to 20,941.4).

Among surgeons, the RAND researchers found a drop of 49.3% from 220,764.6 to 111,904.4. Among dentists, they found a drop of 41.3% from 22,345.3 to 13,126.1.

Among pain specialists, they found a drop of 15.4% from 1,020,808.4 MME to 863,140.7 MME.

Among adult primary care clinicians, Dr. Stein and his colleagues found a drop of 40% from 651,489.4 MME in 2008-2009 to 390,841.0 MME in 2017-2018.

However, one of the groups tracked in the study increased the volume of opioid prescriptions written: advanced practice providers, among whom scripts for the drugs rose 22.7%, from 112,873.9 MME to 138,459.3 MME.

Dr. Stein said he suspects that this gain reflects a change in the nature of the practice of primary care, with nurse practitioners and physician assistants taking more active roles in treatment of patients. Some of the reduction seen among primary care clinicians who treat adults may reflect a shift in which medical personnel in a practice write the opioid prescriptions.

Still, the trends in general seen by Dr. Stein and coauthors are encouraging, even if further study of these patterns is needed, he said.

“This is one of those papers that I think potentially raises as many questions as it provides answers for,” he said.

What’s missing

Maya Hambright, MD, a family medicine physician in New York’s Hudson Valley, who has been working mainly in addiction in response to the opioid overdose crisis, observed that the drop in total prescribed volume of prescription painkillers does not necessarily translate into a reduction in use of opioids

“No one is taking fewer opioids,” Dr. Hambright told this news organization. “I can say that comfortably. They are just getting them from other sources.”

CDC data support Dr. Hambright’s view.

An estimated 100,306 people in the United States died of a drug overdose in the 12 months that ended in April 2021, an increase of 28.5% from the 78,056 deaths during the same period the year before, according to the CDC.

Dr. Hambright said more physicians need to be involved in prescribing medication-assisted treatment (MAT).

The federal government has in the past year loosened restrictions on a requirement, known as an X waiver. Certain clinicians have been exempted from training requirements, as explained in the frequently asked questions page on the Substance Abuse and Mental Health Services Administration website.

SAMHSA says legislation is required to eliminate the waiver. As of Dec. 30, 2021, more than half of the members of the U.S. House of Representatives were listed as sponsors of the Mainstreaming Addiction Treatment (MAT) Act (HR 1384), which would end the need for X waivers. The bill has the backing of 187 Democrats and 43 Republicans.

At this time, too many physicians shy away from offering MAT, Dr. Hambright said.

“People are still scared of it,” she said. “People don’t want to deal with addicts.”

But Dr. Hambright said it’s well worth the initial time invested in having the needed conversations with patients about MAT.

“Afterwards, it’s so straightforward. People feel better. They’re healthier. It’s amazing,” she said. “You’re changing lives.”

The research was supported by grants from the National Institutes of Health. Dr. Stein and coauthors reported no relevant financial relationships.

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

The Centers for Disease Control and Prevention’s recently updated guidance on isolating and testing were tied to the public’s increased interest in testing, Director Rochelle Walenksy, MD, said during a White House briefing Jan. 5.

Health officials recently shortened the recommended COVID-19 isolation and quarantine period from 10 days to 5, creating confusion amid an outbreak of the highly transmissible Omicron variant, which now accounts for 95% of cases in the United States.

Then, in slightly updated guidance, the CDC recommended using an at-home antigen test after 5 days of isolation if possible, even though these tests having aren’t as sensitive to the Omicron variant, according to the FDA.

“After we released our recs early last week, it became very clear people were interested in using the rapid test, though not authorized for this purpose after the end of their isolation period,” Dr. Walensky said. “We then provided guidance on how they should be used.”

“If that test is negative, people really do need to understand they must continue to wear their mask for those 5 days,” Dr. Walensky said.

But for many, the CDC guidelines are murky and seem to always change.

“Nearly 2 years into this pandemic, with Omicron cases surging across the country, the American people should be able to count on the Centers for Disease Control and Prevention for timely, accurate, clear guidance to protect themselves, their loved ones, and their communities,” American Medical Association president Gerald Harmon, MD, said in a statement. “Instead, the new recommendations on quarantine and isolation are not only confusing, but are risking further spread of the virus.”

About 31% of people remain infectious 5 days after a positive COVID-19 test, Dr. Harmon said, quoting the CDC’s own rationale for changing its guidance.

“With hundreds of thousands of new cases daily and more than a million positive reported cases on January 3, tens of thousands – potentially hundreds of thousands of people – could return to work and school infectious if they follow the CDC’s new guidance on ending isolation after 5 days without a negative test,” he said. “Physicians are concerned that these recommendations put our patients at risk and could further overwhelm our health care system.”

Instead, Dr. Harmon said a negative test should be required for ending isolation.

“Reemerging without knowing one’s status unnecessarily risks further transmission of the virus,” he said.

Meanwhile, also during the White House briefing, officials said that early data continue to show that Omicron infections are less severe than those from other variants, but skyrocketing cases will still put a strain on the health care system.

“The big caveat is we should not be complacent,” presidential Chief Medical Adviser Anthony Fauci, MD, said a White House briefing Jan. 5.

He added that Omicron “could still stress our hospital system because a certain proportion of a large volume of cases, no matter what, are going to be severe.”

Cases continue to increase greatly. This week’s 7-day daily average of infections is 491,700 -- an increase of 98% over last week, Dr. Walensky said. Hospitalizations, while lagging behind case numbers, are still rising significantly: The daily average is 14,800 admissions, up 63% from last week. Daily deaths this week are 1,200, an increase of only 5%.

Dr. Walensky continues to encourage vaccinations, boosters, and other precautions.

“Vaccines and boosters are protecting people from the severe and tragic outcomes that can occur from COVID-19 infection,” she said. “Get vaccinated and get boosted if eligible, wear a mask, stay home when you’re sick, and take a test if you have symptoms or are looking for greater reassurance before you gather with others.”

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

The Centers for Disease Control and Prevention’s recently updated guidance on isolating and testing were tied to the public’s increased interest in testing, Director Rochelle Walenksy, MD, said during a White House briefing Jan. 5.

Health officials recently shortened the recommended COVID-19 isolation and quarantine period from 10 days to 5, creating confusion amid an outbreak of the highly transmissible Omicron variant, which now accounts for 95% of cases in the United States.

Then, in slightly updated guidance, the CDC recommended using an at-home antigen test after 5 days of isolation if possible, even though these tests having aren’t as sensitive to the Omicron variant, according to the FDA.

“After we released our recs early last week, it became very clear people were interested in using the rapid test, though not authorized for this purpose after the end of their isolation period,” Dr. Walensky said. “We then provided guidance on how they should be used.”

“If that test is negative, people really do need to understand they must continue to wear their mask for those 5 days,” Dr. Walensky said.

But for many, the CDC guidelines are murky and seem to always change.

“Nearly 2 years into this pandemic, with Omicron cases surging across the country, the American people should be able to count on the Centers for Disease Control and Prevention for timely, accurate, clear guidance to protect themselves, their loved ones, and their communities,” American Medical Association president Gerald Harmon, MD, said in a statement. “Instead, the new recommendations on quarantine and isolation are not only confusing, but are risking further spread of the virus.”

About 31% of people remain infectious 5 days after a positive COVID-19 test, Dr. Harmon said, quoting the CDC’s own rationale for changing its guidance.

“With hundreds of thousands of new cases daily and more than a million positive reported cases on January 3, tens of thousands – potentially hundreds of thousands of people – could return to work and school infectious if they follow the CDC’s new guidance on ending isolation after 5 days without a negative test,” he said. “Physicians are concerned that these recommendations put our patients at risk and could further overwhelm our health care system.”

Instead, Dr. Harmon said a negative test should be required for ending isolation.

“Reemerging without knowing one’s status unnecessarily risks further transmission of the virus,” he said.

Meanwhile, also during the White House briefing, officials said that early data continue to show that Omicron infections are less severe than those from other variants, but skyrocketing cases will still put a strain on the health care system.

“The big caveat is we should not be complacent,” presidential Chief Medical Adviser Anthony Fauci, MD, said a White House briefing Jan. 5.

He added that Omicron “could still stress our hospital system because a certain proportion of a large volume of cases, no matter what, are going to be severe.”

Cases continue to increase greatly. This week’s 7-day daily average of infections is 491,700 -- an increase of 98% over last week, Dr. Walensky said. Hospitalizations, while lagging behind case numbers, are still rising significantly: The daily average is 14,800 admissions, up 63% from last week. Daily deaths this week are 1,200, an increase of only 5%.

Dr. Walensky continues to encourage vaccinations, boosters, and other precautions.

“Vaccines and boosters are protecting people from the severe and tragic outcomes that can occur from COVID-19 infection,” she said. “Get vaccinated and get boosted if eligible, wear a mask, stay home when you’re sick, and take a test if you have symptoms or are looking for greater reassurance before you gather with others.”

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

The Centers for Disease Control and Prevention’s recently updated guidance on isolating and testing were tied to the public’s increased interest in testing, Director Rochelle Walenksy, MD, said during a White House briefing Jan. 5.

Health officials recently shortened the recommended COVID-19 isolation and quarantine period from 10 days to 5, creating confusion amid an outbreak of the highly transmissible Omicron variant, which now accounts for 95% of cases in the United States.

Then, in slightly updated guidance, the CDC recommended using an at-home antigen test after 5 days of isolation if possible, even though these tests having aren’t as sensitive to the Omicron variant, according to the FDA.

“After we released our recs early last week, it became very clear people were interested in using the rapid test, though not authorized for this purpose after the end of their isolation period,” Dr. Walensky said. “We then provided guidance on how they should be used.”

“If that test is negative, people really do need to understand they must continue to wear their mask for those 5 days,” Dr. Walensky said.

But for many, the CDC guidelines are murky and seem to always change.

“Nearly 2 years into this pandemic, with Omicron cases surging across the country, the American people should be able to count on the Centers for Disease Control and Prevention for timely, accurate, clear guidance to protect themselves, their loved ones, and their communities,” American Medical Association president Gerald Harmon, MD, said in a statement. “Instead, the new recommendations on quarantine and isolation are not only confusing, but are risking further spread of the virus.”

About 31% of people remain infectious 5 days after a positive COVID-19 test, Dr. Harmon said, quoting the CDC’s own rationale for changing its guidance.

“With hundreds of thousands of new cases daily and more than a million positive reported cases on January 3, tens of thousands – potentially hundreds of thousands of people – could return to work and school infectious if they follow the CDC’s new guidance on ending isolation after 5 days without a negative test,” he said. “Physicians are concerned that these recommendations put our patients at risk and could further overwhelm our health care system.”

Instead, Dr. Harmon said a negative test should be required for ending isolation.

“Reemerging without knowing one’s status unnecessarily risks further transmission of the virus,” he said.

Meanwhile, also during the White House briefing, officials said that early data continue to show that Omicron infections are less severe than those from other variants, but skyrocketing cases will still put a strain on the health care system.

“The big caveat is we should not be complacent,” presidential Chief Medical Adviser Anthony Fauci, MD, said a White House briefing Jan. 5.

He added that Omicron “could still stress our hospital system because a certain proportion of a large volume of cases, no matter what, are going to be severe.”

Cases continue to increase greatly. This week’s 7-day daily average of infections is 491,700 -- an increase of 98% over last week, Dr. Walensky said. Hospitalizations, while lagging behind case numbers, are still rising significantly: The daily average is 14,800 admissions, up 63% from last week. Daily deaths this week are 1,200, an increase of only 5%.

Dr. Walensky continues to encourage vaccinations, boosters, and other precautions.

“Vaccines and boosters are protecting people from the severe and tragic outcomes that can occur from COVID-19 infection,” she said. “Get vaccinated and get boosted if eligible, wear a mask, stay home when you’re sick, and take a test if you have symptoms or are looking for greater reassurance before you gather with others.”

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