CHICAGO – A new agent under consideration for approval by the Food and Drug Administration to treat moderately to severely active ulcerative colitis (UC) has an “acceptable” safety profile, new evidence reveals.

Etrasimod (Arena Pharma/Pfizer) is an oral sphingosine-1-phosphate (S1P) receptor that binds with high affinity to receptors 1, 4, and 5. If approved by the FDA, etrasimod could become the second agent in the S1P class approved for ulcerative colitis in the United States. The other agent, ozanimod (Zeposia), received FDA approval for treating moderately to severely active UC in May 2021.

The updated safety profile of etrasimod, presented at the annual Digestive Disease Week® (DDW), is based on data from multiple clinical trials, including OASIS phase 2 and the ELEVATE phase 3, placebo-controlled trials, as well as an ongoing, open-label extension study.

“Etrasimod was well tolerated in patients with moderately to severely active UC and had an acceptable safety profile that did not appear to change with longer-term treatment up to 2.5 years,” said OASIS lead author Séverine Vermeire, MD, PhD, an expert on translational research in gastrointestinal disorders and professor of medicine at KU Leuven (Belgium), while presenting the findings at DDW.

Dr. Vermeire noted that data show an elevated risk for atrioventricular (AV) block or bradycardia in a minority of people treated with the agent during this time period. However, most of the heart-related risk was during induction, and the risks could be minimized by ordering an electrocardiogram before prescribing, she said.
 

Cumulative safety data

Researchers separated the trial participants into two cohorts. The all-UC cohort consisted of 956 patients who took at least one dose of etrasimod. The placebo-controlled cohort consisted of 629 patients taking etrasimod and 314 patients who took a placebo. Some patients participated in more than one study, the researchers noted.

In both cohorts, mean duration of disease was about 7 years, about 42% of all participants were female, and mean age was about 41 years.

The investigators looked at the frequency of adverse events and exposure-adjusted incidence rates from the OASIS phase 2 and the ELEVATE phase 3 placebo-controlled trials, as well as an ongoing, open-label extension study. They also assessed safety in placebo and 1 mg or 2 mg etrasimod in the phase 2 NCT02447302 or two phase 3 trials, NCT03945188 and NCT03996369, reported up until Jan. 31, 2022.

There were 770 patient-years of etrasimod exposure in the all-UC cohort, while exposure in the placebo-controlled cohort was 288 patient-years in the etrasimod group and 115 patient-years in the placebo group. Mean exposure to etrasimod was 42 weeks in the all-UC cohort. Mean exposure in the placebo-controlled cohort was 24 weeks in the etrasimod group and 19 weeks in the placebo group.

Because of the mechanism of action of etrasimod, Dr. Vermeire and colleagues focused on cardiovascular events, macular edema, severe or opportunistic infections, herpes zoster infections, and malignancies.

Eleven patients (1.8%) treated with etrasimod reported bradycardia or sinus bradycardia in the placebo-controlled research, and 9 of 11 were asymptomatic. No bradycardia was associated with taking a placebo. In the all-UC cohort, bradycardia or sinus bradycardia was reported in 14 patients (1.5%).

“Bradycardia is something you need to tell patients may occur,” Dr. Vermeire said. “Most of the bradycardia occurred on day one or day two, mostly on day one.”

Four people taking etrasimod in the placebo-controlled cohort and 7 people in the all-UC cohort had AV block of the first or second degree. No reports of AV block occurred in the placebo group.

“Other adverse events of special interest, including hypertension and macular edema, were all rare and similar between the treatment arms,” Dr. Vermeire said.

Herpes zoster infections were reported in two patients taking etrasimod and two taking placebo in the placebo-controlled cohort. Seven cases were reported in the all-UC cohort. Dr. Vermeire said she advocates vaccinating patients against herpes zoster soon after UC diagnosis, if possible.

In the placebo-controlled cohort, 11 patients taking etrasimod and two patients taking placebo experienced elevated ALT. This was fewer than 2% of patients. One patient taking etrasimod and one receiving placebo discontinued the study for this reason. In the all-UC cohort, 27 people experienced elevated ALT.

In the placebo-controlled cohort, 13 people treated with etrasimod and two taking placebo developed elevated gamma-glutamyltransferase. This adverse event was reported in 32 patients in the all-UC cohort.

There were no deaths reported in the placebo-controlled cohort of patients. One patient in the all-UC cohort developed a neuroendocrine tumor and died. The person received etrasimod 2 mg daily for about 6 months before the event’s onset. “This was assessed as unlikely related to the study treatment as judged by investigators,” Dr. Vermeire said.

Limitations of the study include a relatively short average duration of exposure to etrasimod.

“As the study continues, we will continue collecting and reporting the safety data,” Dr. Vermeire said.
 

A well-tolerated therapy

“The important take-home message is that patients tolerated therapy very well,” said session comoderator Jordan E. Axelrad, MD, MPH, when asked to comment.

There were very few adverse events, and of these, they were mostly minor, with patients being able to continue on therapy in large part, added Dr. Axelrad, a gastroenterologist at the Inflammatory Bowel Disease Center at NYU Langone Health, New York.

Physicians will “need to get comfortable” with ordering an ECG to screen patients before prescribing etrasimod, he noted.

“Once we can get past that hurdle [of ordering an ECG], we should be integrating it into our practice,” Dr. Axelrad said.

The study was funded by Arena Pharmaceuticals, which was acquired by Pfizer; Pfizer completed the acquisition in March 2022. Dr. Vermeire reported receiving consulting and speaking fees from Arena Pharmaceuticals and grant and research support from Pfizer. Dr. Axelrad reported no relevant financial relationships.

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.

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

CHICAGO – A new agent under consideration for approval by the Food and Drug Administration to treat moderately to severely active ulcerative colitis (UC) has an “acceptable” safety profile, new evidence reveals.

Etrasimod (Arena Pharma/Pfizer) is an oral sphingosine-1-phosphate (S1P) receptor that binds with high affinity to receptors 1, 4, and 5. If approved by the FDA, etrasimod could become the second agent in the S1P class approved for ulcerative colitis in the United States. The other agent, ozanimod (Zeposia), received FDA approval for treating moderately to severely active UC in May 2021.

The updated safety profile of etrasimod, presented at the annual Digestive Disease Week® (DDW), is based on data from multiple clinical trials, including OASIS phase 2 and the ELEVATE phase 3, placebo-controlled trials, as well as an ongoing, open-label extension study.

“Etrasimod was well tolerated in patients with moderately to severely active UC and had an acceptable safety profile that did not appear to change with longer-term treatment up to 2.5 years,” said OASIS lead author Séverine Vermeire, MD, PhD, an expert on translational research in gastrointestinal disorders and professor of medicine at KU Leuven (Belgium), while presenting the findings at DDW.

Dr. Vermeire noted that data show an elevated risk for atrioventricular (AV) block or bradycardia in a minority of people treated with the agent during this time period. However, most of the heart-related risk was during induction, and the risks could be minimized by ordering an electrocardiogram before prescribing, she said.
 

Cumulative safety data

Researchers separated the trial participants into two cohorts. The all-UC cohort consisted of 956 patients who took at least one dose of etrasimod. The placebo-controlled cohort consisted of 629 patients taking etrasimod and 314 patients who took a placebo. Some patients participated in more than one study, the researchers noted.

In both cohorts, mean duration of disease was about 7 years, about 42% of all participants were female, and mean age was about 41 years.

The investigators looked at the frequency of adverse events and exposure-adjusted incidence rates from the OASIS phase 2 and the ELEVATE phase 3 placebo-controlled trials, as well as an ongoing, open-label extension study. They also assessed safety in placebo and 1 mg or 2 mg etrasimod in the phase 2 NCT02447302 or two phase 3 trials, NCT03945188 and NCT03996369, reported up until Jan. 31, 2022.

There were 770 patient-years of etrasimod exposure in the all-UC cohort, while exposure in the placebo-controlled cohort was 288 patient-years in the etrasimod group and 115 patient-years in the placebo group. Mean exposure to etrasimod was 42 weeks in the all-UC cohort. Mean exposure in the placebo-controlled cohort was 24 weeks in the etrasimod group and 19 weeks in the placebo group.

Because of the mechanism of action of etrasimod, Dr. Vermeire and colleagues focused on cardiovascular events, macular edema, severe or opportunistic infections, herpes zoster infections, and malignancies.

Eleven patients (1.8%) treated with etrasimod reported bradycardia or sinus bradycardia in the placebo-controlled research, and 9 of 11 were asymptomatic. No bradycardia was associated with taking a placebo. In the all-UC cohort, bradycardia or sinus bradycardia was reported in 14 patients (1.5%).

“Bradycardia is something you need to tell patients may occur,” Dr. Vermeire said. “Most of the bradycardia occurred on day one or day two, mostly on day one.”

Four people taking etrasimod in the placebo-controlled cohort and 7 people in the all-UC cohort had AV block of the first or second degree. No reports of AV block occurred in the placebo group.

“Other adverse events of special interest, including hypertension and macular edema, were all rare and similar between the treatment arms,” Dr. Vermeire said.

Herpes zoster infections were reported in two patients taking etrasimod and two taking placebo in the placebo-controlled cohort. Seven cases were reported in the all-UC cohort. Dr. Vermeire said she advocates vaccinating patients against herpes zoster soon after UC diagnosis, if possible.

In the placebo-controlled cohort, 11 patients taking etrasimod and two patients taking placebo experienced elevated ALT. This was fewer than 2% of patients. One patient taking etrasimod and one receiving placebo discontinued the study for this reason. In the all-UC cohort, 27 people experienced elevated ALT.

In the placebo-controlled cohort, 13 people treated with etrasimod and two taking placebo developed elevated gamma-glutamyltransferase. This adverse event was reported in 32 patients in the all-UC cohort.

There were no deaths reported in the placebo-controlled cohort of patients. One patient in the all-UC cohort developed a neuroendocrine tumor and died. The person received etrasimod 2 mg daily for about 6 months before the event’s onset. “This was assessed as unlikely related to the study treatment as judged by investigators,” Dr. Vermeire said.

Limitations of the study include a relatively short average duration of exposure to etrasimod.

“As the study continues, we will continue collecting and reporting the safety data,” Dr. Vermeire said.
 

A well-tolerated therapy

“The important take-home message is that patients tolerated therapy very well,” said session comoderator Jordan E. Axelrad, MD, MPH, when asked to comment.

There were very few adverse events, and of these, they were mostly minor, with patients being able to continue on therapy in large part, added Dr. Axelrad, a gastroenterologist at the Inflammatory Bowel Disease Center at NYU Langone Health, New York.

Physicians will “need to get comfortable” with ordering an ECG to screen patients before prescribing etrasimod, he noted.

“Once we can get past that hurdle [of ordering an ECG], we should be integrating it into our practice,” Dr. Axelrad said.

The study was funded by Arena Pharmaceuticals, which was acquired by Pfizer; Pfizer completed the acquisition in March 2022. Dr. Vermeire reported receiving consulting and speaking fees from Arena Pharmaceuticals and grant and research support from Pfizer. Dr. Axelrad reported no relevant financial relationships.

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.

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

CHICAGO – A new agent under consideration for approval by the Food and Drug Administration to treat moderately to severely active ulcerative colitis (UC) has an “acceptable” safety profile, new evidence reveals.

Etrasimod (Arena Pharma/Pfizer) is an oral sphingosine-1-phosphate (S1P) receptor that binds with high affinity to receptors 1, 4, and 5. If approved by the FDA, etrasimod could become the second agent in the S1P class approved for ulcerative colitis in the United States. The other agent, ozanimod (Zeposia), received FDA approval for treating moderately to severely active UC in May 2021.

The updated safety profile of etrasimod, presented at the annual Digestive Disease Week® (DDW), is based on data from multiple clinical trials, including OASIS phase 2 and the ELEVATE phase 3, placebo-controlled trials, as well as an ongoing, open-label extension study.

“Etrasimod was well tolerated in patients with moderately to severely active UC and had an acceptable safety profile that did not appear to change with longer-term treatment up to 2.5 years,” said OASIS lead author Séverine Vermeire, MD, PhD, an expert on translational research in gastrointestinal disorders and professor of medicine at KU Leuven (Belgium), while presenting the findings at DDW.

Dr. Vermeire noted that data show an elevated risk for atrioventricular (AV) block or bradycardia in a minority of people treated with the agent during this time period. However, most of the heart-related risk was during induction, and the risks could be minimized by ordering an electrocardiogram before prescribing, she said.
 

Cumulative safety data

Researchers separated the trial participants into two cohorts. The all-UC cohort consisted of 956 patients who took at least one dose of etrasimod. The placebo-controlled cohort consisted of 629 patients taking etrasimod and 314 patients who took a placebo. Some patients participated in more than one study, the researchers noted.

In both cohorts, mean duration of disease was about 7 years, about 42% of all participants were female, and mean age was about 41 years.

The investigators looked at the frequency of adverse events and exposure-adjusted incidence rates from the OASIS phase 2 and the ELEVATE phase 3 placebo-controlled trials, as well as an ongoing, open-label extension study. They also assessed safety in placebo and 1 mg or 2 mg etrasimod in the phase 2 NCT02447302 or two phase 3 trials, NCT03945188 and NCT03996369, reported up until Jan. 31, 2022.

There were 770 patient-years of etrasimod exposure in the all-UC cohort, while exposure in the placebo-controlled cohort was 288 patient-years in the etrasimod group and 115 patient-years in the placebo group. Mean exposure to etrasimod was 42 weeks in the all-UC cohort. Mean exposure in the placebo-controlled cohort was 24 weeks in the etrasimod group and 19 weeks in the placebo group.

Because of the mechanism of action of etrasimod, Dr. Vermeire and colleagues focused on cardiovascular events, macular edema, severe or opportunistic infections, herpes zoster infections, and malignancies.

Eleven patients (1.8%) treated with etrasimod reported bradycardia or sinus bradycardia in the placebo-controlled research, and 9 of 11 were asymptomatic. No bradycardia was associated with taking a placebo. In the all-UC cohort, bradycardia or sinus bradycardia was reported in 14 patients (1.5%).

“Bradycardia is something you need to tell patients may occur,” Dr. Vermeire said. “Most of the bradycardia occurred on day one or day two, mostly on day one.”

Four people taking etrasimod in the placebo-controlled cohort and 7 people in the all-UC cohort had AV block of the first or second degree. No reports of AV block occurred in the placebo group.

“Other adverse events of special interest, including hypertension and macular edema, were all rare and similar between the treatment arms,” Dr. Vermeire said.

Herpes zoster infections were reported in two patients taking etrasimod and two taking placebo in the placebo-controlled cohort. Seven cases were reported in the all-UC cohort. Dr. Vermeire said she advocates vaccinating patients against herpes zoster soon after UC diagnosis, if possible.

In the placebo-controlled cohort, 11 patients taking etrasimod and two patients taking placebo experienced elevated ALT. This was fewer than 2% of patients. One patient taking etrasimod and one receiving placebo discontinued the study for this reason. In the all-UC cohort, 27 people experienced elevated ALT.

In the placebo-controlled cohort, 13 people treated with etrasimod and two taking placebo developed elevated gamma-glutamyltransferase. This adverse event was reported in 32 patients in the all-UC cohort.

There were no deaths reported in the placebo-controlled cohort of patients. One patient in the all-UC cohort developed a neuroendocrine tumor and died. The person received etrasimod 2 mg daily for about 6 months before the event’s onset. “This was assessed as unlikely related to the study treatment as judged by investigators,” Dr. Vermeire said.

Limitations of the study include a relatively short average duration of exposure to etrasimod.

“As the study continues, we will continue collecting and reporting the safety data,” Dr. Vermeire said.
 

A well-tolerated therapy

“The important take-home message is that patients tolerated therapy very well,” said session comoderator Jordan E. Axelrad, MD, MPH, when asked to comment.

There were very few adverse events, and of these, they were mostly minor, with patients being able to continue on therapy in large part, added Dr. Axelrad, a gastroenterologist at the Inflammatory Bowel Disease Center at NYU Langone Health, New York.

Physicians will “need to get comfortable” with ordering an ECG to screen patients before prescribing etrasimod, he noted.

“Once we can get past that hurdle [of ordering an ECG], we should be integrating it into our practice,” Dr. Axelrad said.

The study was funded by Arena Pharmaceuticals, which was acquired by Pfizer; Pfizer completed the acquisition in March 2022. Dr. Vermeire reported receiving consulting and speaking fees from Arena Pharmaceuticals and grant and research support from Pfizer. Dr. Axelrad reported no relevant financial relationships.

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.

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

In 2022, the most significant advances in the treatment of gynecologic cancers were achieved for patients with ovarian cancer. While ovarian cancer continues to carry the worst prognosis of all gynecologic cancers, 5-year relative survival has gradually increased, from 34.4% in 1975 to 52.4% in 2014.¹

In this Update, we highlight the recent advances in our understanding of targeted therapy in ovarian cancer. We review SORAYA, a trial that demonstrated that mirvetuximab soravtansine, an antibody-drug conjugate, has promising efficacy in platinum-resistant ovarian cancers that overexpress folate receptor α. We also spotlight progress in the treatment of low-grade serous ovarian cancer, another notoriously chemotherapy-resistant disease, in GOG 281/LOGS, a phase 2 study of the MEK inhibitor trametinib. Finally, we discuss emerging long-term follow-up data on poly(ADP-ribose) polymerase (PARP) inhibitors, which are helping to refine the role of these groundbreaking drugs.

New drug approved for platinum-resistant epithelial ovarian cancer—the first since 2014

Matulonis UA, Lorusso D, Oaknin A, et al. Efficacy and safety of mirvetuximab soravtansine in patients with platinum-resistant ovarian cancer with high folate receptor alpha expression: results from the SORAYA study. J Clin Oncol. 2023;41:2436-2445. doi:10.1200/JCO.22.01900.

While most patients diagnosed with advanced ovarian cancer will respond to platinum-based chemotherapy, those whose disease recurs eventually develop resistance to platinum agents. Treatment options for platinum-resistant ovarian cancer are limited and prognosis is poor. Most regimens have a response rate of only 10%. Since the approval of bevacizumab combined with chemotherapy in 2014, no new agents have been approved by the US Food and Drug Administration (FDA) for use in platinum-resistant ovarian cancer.

Efficacy shown with mirvetuximab

Recently, Matulonis and colleagues published results of the SORAYA study, a single-arm,phase 2 trial, that examined the efficacy and safety of mirvetuximab soravtansine-gynx among women with platinum-resistant ovarian cancer.² Mirvetuximab is an antibody-drug conjugate composed of an antibody directed at the folate receptor α attached to a cytotoxic microtubule inhibitor.

The study included 106 patients with platinum-resistant ovarian cancer whose tumors expressed folate receptor α at a high level—a feature of approximately 50% of patients screened for the study. Twenty-nine patients experienced a partial response and 5 had a complete response, corresponding to a remarkable objective response rate of 32.4%. The median progression-free survival was 4.3 months.

Like other antibody-drug conjugates, ocular toxicities, including blurred vision (41%) and keratopathy (29%), were common. However, toxicity was manageable and rarely led to drug discontinuation.

Continue to: A novel agent for recurrent low-grade serous ovarian carcinoma...

A novel agent for recurrent low-grade serous ovarian carcinoma

Gershenson DM, Miller A, Brady WE, et al. Trametinib versus standard of care in patients with recurrent low-grade serous ovarian cancer (GOG 281/LOGS): an international, randomised, open-label, multicentre, phase 2/3 trial. Lancet. 2022;399:541-553. doi:10.1016/S0140-6736(21)02175-9.

Low-grade serous carcinoma is a histologic subtype that makes up approximately 5% of all epithelial ovarian cancers.³ Patients with low-grade serous carcinoma are often younger and, because of the indolent nature of the histology, generally have a longer overall survival compared with patients with high-grade serous carcinoma. Unlike high-grade disease, however, low-grade serous carcinoma usually is resistant to chemotherapy, making treatment options limited for patients with advanced and recurrent disease.

Trametinib: A potential option

In an international, randomized, open-label trial (GOG 281/LOGS), Gershenson and colleagues investigated the efficacy of trametinib compared with standard-of-care chemotherapy in patients with recurrent low-grade serous ovarian cancer.⁴ Trametinib, a mitogen-activated protein kinase MEK inhibitor, is a targeted agent that is FDA approved for treatment in BRAF-mutated melanoma, lung, and thyroid cancers.

Patients with recurrent low-grade serous ovarian cancer were randomly assigned to trametinib (n = 130) or 1 of 5 standard-of-care treatment options (n = 130), including both chemotherapy and hormonal treatments. Those assigned to trametinib were significantly less likely to have disease progression (78% vs 89%), with a median progression-free survival of 13 months, compared with7.2 months in controls (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.36–0.64). Additionally, patients who had a radiographic response to trametinib experienced a longer duration of response compared with those who responded to standard-of-care treatment (13.6 months vs 5.9 months).

While there was no statistically significant difference in overall survival (HR, 0.76; 95% CI, 0.51–1.12), crossover to trametinib from the standard-of-care group was allowed and occurred among 68% of patients, which limits the study’s ability to measure differences in overall survival.

Trametinib was well tolerated by patients, but skin rash and anemia followed by hypertension were the most common adverse effects. In the standard-of-care group, the most common toxicities were abdominal pain, nausea, and anemia. A slightly higher proportion of patients in the trametinib group discontinued the drug due to toxicity compared with the standard-of-care group (36% vs 30%), but the there was no difference between the 2 groups in scores on quality-of-life assessments.

Continue to: PARP inhibitors benefit many women with ovarian cancer, but they may hurt others...

PARP inhibitors benefit many women with ovarian cancer, but they may hurt others

Monk BJ, Parkinson C, Lim MC, et al. A randomized, phase III trial to evaluate rucaparib monotherapy as maintenance treatment in patients with newly diagnosed ovarian cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45). J Clin Oncol. 2022;40:3952-3964. doi:10.1200/JCO.22.01003.

Poly(ADP-ribose) polymerase (PARP) inhibitors are a class of oral anticancer agents that target DNA repair. Since the initial FDA approval in 2014 of olaparib for the treatment of patients with recurrent BRCA-mutated ovarian cancer, PARP inhibitors have been approved for maintenance in both the frontline setting and after platinum-sensitive recurrence, and as single-agenttreatment for ovarian cancer with BRCA mutations or evidence of homologous repair deficiency (HRD), a BRCA-like molecular phenotype.⁵ The expanding role for PARP inhibitors in ovarian cancer seemed inexorable.

Restricted prescribing advised

In 2022, we learned that in certain settings, PARP inhibitors may be the wrong choice. Several “Dear Health Care Provider” letters were issued by AstraZeneca, Clovis, and GSK to advise physicians to restrict the prescribing of olaparib, rucaparib, and niraparib.^6,7

AstraZeneca and Clovis issued letters spurred by the final analysis of ARIEL4 and SOLO3 studies, 2 randomized trials that investigated, respectively, rucaparib and olaparib monotherapy compared with chemotherapy in recurrent ovarian cancer.^8,9 In both cases patients randomized to PARP inhibitors may have experienced an overall survival decrement compared with those who received chemotherapy.

At the FDA’s request, Clovis has withdrawn rucaparib as a treatment for patients with recurrent BRCA-mutant ovarian cancer who had received 2 or more lines of chemotherapy, and AstraZeneca withdrew olaparib monotherapy in germline BRCA-mutant patients with recurrent ovarian cancer. Shortly after these withdrawals, GSK also withdrew its indication for niraparib as a treatment for women with HRD, platinum-sensitive ovarian cancer who have received 3 or more prior chemotherapies. Furthermore, based on the final overall survival analysis of the NOVA study, GSK also restricted its indication for niraparib maintenance for recurrent ovarian cancer to patients with germline BRCA mutations, due to evidence of an overall survival detriment in this setting.¹⁰

Positive study results

Fortunately, 2022 was not all bad news for PARP inhibitors in ovarian cancer. In June 2022, the ATHENA-MONO trial, a phase 3 double-blind randomized controlled trial, demonstrated that rucaparib maintenance in patients with newly diagnosed epithelial ovarian cancer was associated with a significantly longer progression-free survival compared with placebo.¹¹ The effect was most pronounced in the BRCA-mutant/HRD population, with a median progression-free survival of 28.7 months in the rucaparib group compared with 11.3 months in the placebo group (HR, 0.47; 95% CI, 0.31–0.72). Thus, rucaparib was added to the list of PARP inhibitors approved for upfront maintenance therapy in epithelial ovarian cancer.

Similarly, the long-term overall survival analysis from the upfront trials SOLO-1 and PAOLA-1 showed an overall survival advantage of PARP inhibitor, compared with placebo, maintenance in patients with BRCA mutations or HRD tumors.^12,13 ●

In 2022, the most significant advances in the treatment of gynecologic cancers were achieved for patients with ovarian cancer. While ovarian cancer continues to carry the worst prognosis of all gynecologic cancers, 5-year relative survival has gradually increased, from 34.4% in 1975 to 52.4% in 2014.¹

In this Update, we highlight the recent advances in our understanding of targeted therapy in ovarian cancer. We review SORAYA, a trial that demonstrated that mirvetuximab soravtansine, an antibody-drug conjugate, has promising efficacy in platinum-resistant ovarian cancers that overexpress folate receptor α. We also spotlight progress in the treatment of low-grade serous ovarian cancer, another notoriously chemotherapy-resistant disease, in GOG 281/LOGS, a phase 2 study of the MEK inhibitor trametinib. Finally, we discuss emerging long-term follow-up data on poly(ADP-ribose) polymerase (PARP) inhibitors, which are helping to refine the role of these groundbreaking drugs.

New drug approved for platinum-resistant epithelial ovarian cancer—the first since 2014

Matulonis UA, Lorusso D, Oaknin A, et al. Efficacy and safety of mirvetuximab soravtansine in patients with platinum-resistant ovarian cancer with high folate receptor alpha expression: results from the SORAYA study. J Clin Oncol. 2023;41:2436-2445. doi:10.1200/JCO.22.01900.

While most patients diagnosed with advanced ovarian cancer will respond to platinum-based chemotherapy, those whose disease recurs eventually develop resistance to platinum agents. Treatment options for platinum-resistant ovarian cancer are limited and prognosis is poor. Most regimens have a response rate of only 10%. Since the approval of bevacizumab combined with chemotherapy in 2014, no new agents have been approved by the US Food and Drug Administration (FDA) for use in platinum-resistant ovarian cancer.

Efficacy shown with mirvetuximab

Recently, Matulonis and colleagues published results of the SORAYA study, a single-arm,phase 2 trial, that examined the efficacy and safety of mirvetuximab soravtansine-gynx among women with platinum-resistant ovarian cancer.² Mirvetuximab is an antibody-drug conjugate composed of an antibody directed at the folate receptor α attached to a cytotoxic microtubule inhibitor.

The study included 106 patients with platinum-resistant ovarian cancer whose tumors expressed folate receptor α at a high level—a feature of approximately 50% of patients screened for the study. Twenty-nine patients experienced a partial response and 5 had a complete response, corresponding to a remarkable objective response rate of 32.4%. The median progression-free survival was 4.3 months.

Like other antibody-drug conjugates, ocular toxicities, including blurred vision (41%) and keratopathy (29%), were common. However, toxicity was manageable and rarely led to drug discontinuation.

Continue to: A novel agent for recurrent low-grade serous ovarian carcinoma...

A novel agent for recurrent low-grade serous ovarian carcinoma

Gershenson DM, Miller A, Brady WE, et al. Trametinib versus standard of care in patients with recurrent low-grade serous ovarian cancer (GOG 281/LOGS): an international, randomised, open-label, multicentre, phase 2/3 trial. Lancet. 2022;399:541-553. doi:10.1016/S0140-6736(21)02175-9.

Low-grade serous carcinoma is a histologic subtype that makes up approximately 5% of all epithelial ovarian cancers.³ Patients with low-grade serous carcinoma are often younger and, because of the indolent nature of the histology, generally have a longer overall survival compared with patients with high-grade serous carcinoma. Unlike high-grade disease, however, low-grade serous carcinoma usually is resistant to chemotherapy, making treatment options limited for patients with advanced and recurrent disease.

Trametinib: A potential option

In an international, randomized, open-label trial (GOG 281/LOGS), Gershenson and colleagues investigated the efficacy of trametinib compared with standard-of-care chemotherapy in patients with recurrent low-grade serous ovarian cancer.⁴ Trametinib, a mitogen-activated protein kinase MEK inhibitor, is a targeted agent that is FDA approved for treatment in BRAF-mutated melanoma, lung, and thyroid cancers.

Patients with recurrent low-grade serous ovarian cancer were randomly assigned to trametinib (n = 130) or 1 of 5 standard-of-care treatment options (n = 130), including both chemotherapy and hormonal treatments. Those assigned to trametinib were significantly less likely to have disease progression (78% vs 89%), with a median progression-free survival of 13 months, compared with7.2 months in controls (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.36–0.64). Additionally, patients who had a radiographic response to trametinib experienced a longer duration of response compared with those who responded to standard-of-care treatment (13.6 months vs 5.9 months).

While there was no statistically significant difference in overall survival (HR, 0.76; 95% CI, 0.51–1.12), crossover to trametinib from the standard-of-care group was allowed and occurred among 68% of patients, which limits the study’s ability to measure differences in overall survival.

Trametinib was well tolerated by patients, but skin rash and anemia followed by hypertension were the most common adverse effects. In the standard-of-care group, the most common toxicities were abdominal pain, nausea, and anemia. A slightly higher proportion of patients in the trametinib group discontinued the drug due to toxicity compared with the standard-of-care group (36% vs 30%), but the there was no difference between the 2 groups in scores on quality-of-life assessments.

Continue to: PARP inhibitors benefit many women with ovarian cancer, but they may hurt others...

PARP inhibitors benefit many women with ovarian cancer, but they may hurt others

Monk BJ, Parkinson C, Lim MC, et al. A randomized, phase III trial to evaluate rucaparib monotherapy as maintenance treatment in patients with newly diagnosed ovarian cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45). J Clin Oncol. 2022;40:3952-3964. doi:10.1200/JCO.22.01003.

Poly(ADP-ribose) polymerase (PARP) inhibitors are a class of oral anticancer agents that target DNA repair. Since the initial FDA approval in 2014 of olaparib for the treatment of patients with recurrent BRCA-mutated ovarian cancer, PARP inhibitors have been approved for maintenance in both the frontline setting and after platinum-sensitive recurrence, and as single-agenttreatment for ovarian cancer with BRCA mutations or evidence of homologous repair deficiency (HRD), a BRCA-like molecular phenotype.⁵ The expanding role for PARP inhibitors in ovarian cancer seemed inexorable.

Restricted prescribing advised

In 2022, we learned that in certain settings, PARP inhibitors may be the wrong choice. Several “Dear Health Care Provider” letters were issued by AstraZeneca, Clovis, and GSK to advise physicians to restrict the prescribing of olaparib, rucaparib, and niraparib.^6,7

AstraZeneca and Clovis issued letters spurred by the final analysis of ARIEL4 and SOLO3 studies, 2 randomized trials that investigated, respectively, rucaparib and olaparib monotherapy compared with chemotherapy in recurrent ovarian cancer.^8,9 In both cases patients randomized to PARP inhibitors may have experienced an overall survival decrement compared with those who received chemotherapy.

At the FDA’s request, Clovis has withdrawn rucaparib as a treatment for patients with recurrent BRCA-mutant ovarian cancer who had received 2 or more lines of chemotherapy, and AstraZeneca withdrew olaparib monotherapy in germline BRCA-mutant patients with recurrent ovarian cancer. Shortly after these withdrawals, GSK also withdrew its indication for niraparib as a treatment for women with HRD, platinum-sensitive ovarian cancer who have received 3 or more prior chemotherapies. Furthermore, based on the final overall survival analysis of the NOVA study, GSK also restricted its indication for niraparib maintenance for recurrent ovarian cancer to patients with germline BRCA mutations, due to evidence of an overall survival detriment in this setting.¹⁰

Positive study results

Fortunately, 2022 was not all bad news for PARP inhibitors in ovarian cancer. In June 2022, the ATHENA-MONO trial, a phase 3 double-blind randomized controlled trial, demonstrated that rucaparib maintenance in patients with newly diagnosed epithelial ovarian cancer was associated with a significantly longer progression-free survival compared with placebo.¹¹ The effect was most pronounced in the BRCA-mutant/HRD population, with a median progression-free survival of 28.7 months in the rucaparib group compared with 11.3 months in the placebo group (HR, 0.47; 95% CI, 0.31–0.72). Thus, rucaparib was added to the list of PARP inhibitors approved for upfront maintenance therapy in epithelial ovarian cancer.

Similarly, the long-term overall survival analysis from the upfront trials SOLO-1 and PAOLA-1 showed an overall survival advantage of PARP inhibitor, compared with placebo, maintenance in patients with BRCA mutations or HRD tumors.^12,13 ●

In 2022, the most significant advances in the treatment of gynecologic cancers were achieved for patients with ovarian cancer. While ovarian cancer continues to carry the worst prognosis of all gynecologic cancers, 5-year relative survival has gradually increased, from 34.4% in 1975 to 52.4% in 2014.¹

In this Update, we highlight the recent advances in our understanding of targeted therapy in ovarian cancer. We review SORAYA, a trial that demonstrated that mirvetuximab soravtansine, an antibody-drug conjugate, has promising efficacy in platinum-resistant ovarian cancers that overexpress folate receptor α. We also spotlight progress in the treatment of low-grade serous ovarian cancer, another notoriously chemotherapy-resistant disease, in GOG 281/LOGS, a phase 2 study of the MEK inhibitor trametinib. Finally, we discuss emerging long-term follow-up data on poly(ADP-ribose) polymerase (PARP) inhibitors, which are helping to refine the role of these groundbreaking drugs.

New drug approved for platinum-resistant epithelial ovarian cancer—the first since 2014

Matulonis UA, Lorusso D, Oaknin A, et al. Efficacy and safety of mirvetuximab soravtansine in patients with platinum-resistant ovarian cancer with high folate receptor alpha expression: results from the SORAYA study. J Clin Oncol. 2023;41:2436-2445. doi:10.1200/JCO.22.01900.

While most patients diagnosed with advanced ovarian cancer will respond to platinum-based chemotherapy, those whose disease recurs eventually develop resistance to platinum agents. Treatment options for platinum-resistant ovarian cancer are limited and prognosis is poor. Most regimens have a response rate of only 10%. Since the approval of bevacizumab combined with chemotherapy in 2014, no new agents have been approved by the US Food and Drug Administration (FDA) for use in platinum-resistant ovarian cancer.

Efficacy shown with mirvetuximab

Recently, Matulonis and colleagues published results of the SORAYA study, a single-arm,phase 2 trial, that examined the efficacy and safety of mirvetuximab soravtansine-gynx among women with platinum-resistant ovarian cancer.² Mirvetuximab is an antibody-drug conjugate composed of an antibody directed at the folate receptor α attached to a cytotoxic microtubule inhibitor.

The study included 106 patients with platinum-resistant ovarian cancer whose tumors expressed folate receptor α at a high level—a feature of approximately 50% of patients screened for the study. Twenty-nine patients experienced a partial response and 5 had a complete response, corresponding to a remarkable objective response rate of 32.4%. The median progression-free survival was 4.3 months.

Like other antibody-drug conjugates, ocular toxicities, including blurred vision (41%) and keratopathy (29%), were common. However, toxicity was manageable and rarely led to drug discontinuation.

Continue to: A novel agent for recurrent low-grade serous ovarian carcinoma...

A novel agent for recurrent low-grade serous ovarian carcinoma

Gershenson DM, Miller A, Brady WE, et al. Trametinib versus standard of care in patients with recurrent low-grade serous ovarian cancer (GOG 281/LOGS): an international, randomised, open-label, multicentre, phase 2/3 trial. Lancet. 2022;399:541-553. doi:10.1016/S0140-6736(21)02175-9.

Low-grade serous carcinoma is a histologic subtype that makes up approximately 5% of all epithelial ovarian cancers.³ Patients with low-grade serous carcinoma are often younger and, because of the indolent nature of the histology, generally have a longer overall survival compared with patients with high-grade serous carcinoma. Unlike high-grade disease, however, low-grade serous carcinoma usually is resistant to chemotherapy, making treatment options limited for patients with advanced and recurrent disease.

Trametinib: A potential option

In an international, randomized, open-label trial (GOG 281/LOGS), Gershenson and colleagues investigated the efficacy of trametinib compared with standard-of-care chemotherapy in patients with recurrent low-grade serous ovarian cancer.⁴ Trametinib, a mitogen-activated protein kinase MEK inhibitor, is a targeted agent that is FDA approved for treatment in BRAF-mutated melanoma, lung, and thyroid cancers.

Patients with recurrent low-grade serous ovarian cancer were randomly assigned to trametinib (n = 130) or 1 of 5 standard-of-care treatment options (n = 130), including both chemotherapy and hormonal treatments. Those assigned to trametinib were significantly less likely to have disease progression (78% vs 89%), with a median progression-free survival of 13 months, compared with7.2 months in controls (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.36–0.64). Additionally, patients who had a radiographic response to trametinib experienced a longer duration of response compared with those who responded to standard-of-care treatment (13.6 months vs 5.9 months).

While there was no statistically significant difference in overall survival (HR, 0.76; 95% CI, 0.51–1.12), crossover to trametinib from the standard-of-care group was allowed and occurred among 68% of patients, which limits the study’s ability to measure differences in overall survival.

Trametinib was well tolerated by patients, but skin rash and anemia followed by hypertension were the most common adverse effects. In the standard-of-care group, the most common toxicities were abdominal pain, nausea, and anemia. A slightly higher proportion of patients in the trametinib group discontinued the drug due to toxicity compared with the standard-of-care group (36% vs 30%), but the there was no difference between the 2 groups in scores on quality-of-life assessments.

Continue to: PARP inhibitors benefit many women with ovarian cancer, but they may hurt others...

PARP inhibitors benefit many women with ovarian cancer, but they may hurt others

Monk BJ, Parkinson C, Lim MC, et al. A randomized, phase III trial to evaluate rucaparib monotherapy as maintenance treatment in patients with newly diagnosed ovarian cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45). J Clin Oncol. 2022;40:3952-3964. doi:10.1200/JCO.22.01003.

Poly(ADP-ribose) polymerase (PARP) inhibitors are a class of oral anticancer agents that target DNA repair. Since the initial FDA approval in 2014 of olaparib for the treatment of patients with recurrent BRCA-mutated ovarian cancer, PARP inhibitors have been approved for maintenance in both the frontline setting and after platinum-sensitive recurrence, and as single-agenttreatment for ovarian cancer with BRCA mutations or evidence of homologous repair deficiency (HRD), a BRCA-like molecular phenotype.⁵ The expanding role for PARP inhibitors in ovarian cancer seemed inexorable.

Restricted prescribing advised

In 2022, we learned that in certain settings, PARP inhibitors may be the wrong choice. Several “Dear Health Care Provider” letters were issued by AstraZeneca, Clovis, and GSK to advise physicians to restrict the prescribing of olaparib, rucaparib, and niraparib.^6,7

AstraZeneca and Clovis issued letters spurred by the final analysis of ARIEL4 and SOLO3 studies, 2 randomized trials that investigated, respectively, rucaparib and olaparib monotherapy compared with chemotherapy in recurrent ovarian cancer.^8,9 In both cases patients randomized to PARP inhibitors may have experienced an overall survival decrement compared with those who received chemotherapy.

At the FDA’s request, Clovis has withdrawn rucaparib as a treatment for patients with recurrent BRCA-mutant ovarian cancer who had received 2 or more lines of chemotherapy, and AstraZeneca withdrew olaparib monotherapy in germline BRCA-mutant patients with recurrent ovarian cancer. Shortly after these withdrawals, GSK also withdrew its indication for niraparib as a treatment for women with HRD, platinum-sensitive ovarian cancer who have received 3 or more prior chemotherapies. Furthermore, based on the final overall survival analysis of the NOVA study, GSK also restricted its indication for niraparib maintenance for recurrent ovarian cancer to patients with germline BRCA mutations, due to evidence of an overall survival detriment in this setting.¹⁰

Positive study results

Fortunately, 2022 was not all bad news for PARP inhibitors in ovarian cancer. In June 2022, the ATHENA-MONO trial, a phase 3 double-blind randomized controlled trial, demonstrated that rucaparib maintenance in patients with newly diagnosed epithelial ovarian cancer was associated with a significantly longer progression-free survival compared with placebo.¹¹ The effect was most pronounced in the BRCA-mutant/HRD population, with a median progression-free survival of 28.7 months in the rucaparib group compared with 11.3 months in the placebo group (HR, 0.47; 95% CI, 0.31–0.72). Thus, rucaparib was added to the list of PARP inhibitors approved for upfront maintenance therapy in epithelial ovarian cancer.

Similarly, the long-term overall survival analysis from the upfront trials SOLO-1 and PAOLA-1 showed an overall survival advantage of PARP inhibitor, compared with placebo, maintenance in patients with BRCA mutations or HRD tumors.^12,13 ●

A multicenter randomized controlled trial has provided more evidence that acupuncture and doxylamine-pyridoxine (Diclegis/Diclectin) are modestly effective for the nausea and vomiting of pregnancy (NVP). While the benefit of either agent was clinically small for moderate to severe symptoms, the combination showed numerically larger and potentially more meaningful benefit, according to a team led by Xiao-Ke Wu, MD, PhD, of the department of obstetrics and gynecology at First Affiliated Hospital, Heilongjiang University of Chinese Medicine, and Heilongjiang Provincial Hospital in Harbin, China.

The treatments found small reductions in symptoms of less than one point to 1.6 points on an emesis scale. Nevertheless, Dr. Wu’s group wrote online June 19 in Annals of Internal Medicine that the finding “is especially significant because there is a pressing need to establish a pregnancy-safe treatment regimen and an integrative guideline for managing severe NVP.”

NVP affects as many as 85% of pregnant women, 80%-90% of whom have only mild symptoms, the authors noted. However, severe NVP and hyperemesis gravidarum, or HG, develop in about 10%. “Unfortunately, as many as 10% of wanted pregnancies with severe NVP or HG are terminated because of intolerable and untreatable symptoms and complications,” Dr. Wu told this news organization. And antiemetics may be underprescribed by general practitioners because of concerns about potential teratogenic effects, he said.

“Our findings suggest that either acupuncture or doxylamine-pyridoxine alone is a suitable for treating moderate to severe NVP, and a combination of both can be used to treat severe NVP and HG,” Dr. Wu said.

Commenting on the study but not involved in it, Catherine S. Stika, MD, a clinical professor of ob.gyn. at Northwestern University in Chicago, said the results suggest these two therapies are more suited to mild than severe symptoms. “But an RCT is important to do in order to support the use of these therapies since they’re not as widely accepted as they ought to be,” she said in an interview.

Design

The randomized, double-blind, placebo-controled 2x2 factorial trial was conducted at 13 tertiary-care hospitals in mainland China from June 2020 to February 2022. The researchers recruited 352 women in early pregnancy with moderate to severe NVP. The mean age of participants was about 29 years and the mean gestational age was about 9 weeks.

Participants were randomized into four 14-day treatment groups: active acupuncture for 30 minutes a day plus the antihistamine-vitamin B6 agent doxylamine-pyridoxine; sham acupuncture for 30 minutes daily plus doxylamine-pyridoxine; active acupuncture plus placebo; and sham acupuncture plus placebo.

The primary outcome was the reduction in Pregnancy-Unique Quantification of Emesis (PUQE) score at day 15 relative to baseline with a score of less than 6 indicating mild NVP, 6-12 indicating moderate NVP, and 13 or higher indicating severe NVP. Secondary outcomes ranged from quality of life and adverse events to maternal and perinatal complications. Acupuncture and combined treatment yielded larger though still small reductions in PUQE score, compared with control treatments. The mean differences were as follows: acupuncture, –.07; 95% confidence interval, 1.3-0.1); doxylamine-pyridoxine, –1.0: 95% CI, 1.6-0.4); combination of both, –1.6; 95% CI, 2.2-0.9). No significant interaction was detected between the interventions (P = .69).Compared with placebo treatments, pharmaceutical therapy resulted in more somnolence, while active acupuncture led to more frequent dyspnea, bruising, itching, and pain. A higher risk of babies born small for gestational age was observed in mothers who took doxylamine-pyridoxine versus placebo: odds ratio, 3.8; 95% CI, 1-14.1). Neither the placebo effects of the sham interventions nor the natural regression of symptoms experienced by many women were evaluated.
 

Suited to milder symptoms?

Dr. Stika called the study well-designed and well-written but cited several limitations, including the small cohort, the minor symptom improvement, and the lack of a comparator group receiving neither sham nor active treatment.

“Compared with sham combination treatments, the active combination arm was only about a point and a half better,” she said. “And would some women have got better over the 2 weeks anyway with no intervention at all? A large percentage of women with NVP do improve on their own.”

And in terms of acceptability to U.S. women, she cautioned, “The study cohort was entirely Chinese, and this is a population that already accepts acupuncture treatment.”

Countered Dr. Wu, “Medical care provided by licensed acupuncturists is approved in many countries. Certainly, it is ready to be prescribed by physicians when a pregnant patient is seeking NVP treatment.”

Dr. Stika stressed that these therapies are suited to milder NV, and would “barely take edge off severe symptoms,” for which a patient might have to “go up to a big gun like the antiemetic Zofran” (ondansetron). She is currently involved in a National Institutes of Health–funded clinical trial of the antidepressant mirtazapine (Remeron) for NVP.

Matthew Carroll, MD, a professor of obstetrics and gynecology at Baylor College of Medicine and Texas Children’s Hospital in Houston, noted that doxylamine-pyridoxine is already an effective treatment for NVP, but in his experience it is often "not enough" to help patients deal with symptoms.

"Many patients are hesitant to take additional medications," he said. "If acupuncture can be safely done in pregnancy, then it seems a reasonable option as an adjuvant treatment for NVP. I think there is a cohort of pregnant people in the US who would be excited to try a complementary and nonpharmaceutical treatment option. Unfortunately, complementary therapies are rarely evaluated at a systems level for safety and so they are hard to recommend for obstetricians in the US," he added.

Dr. Carroll, who was not involved in the study. noted that "studies like this can help us counsel patients who may be seeking these treatments even if not approved or recommended by ACOG."

This study was funded by the National Key R&D Program of China and the Project of Heilongjiang Province “TouYan” Innovation Team. Support also came from the National Clinical Research Base of Chinese Medicine, the Heilongjiang Provincial Clinical Research Centre for Ovary Diseases, and the 2023 Capability Improvement Project for Evidence-based Assessment of Traditional Chinese Medicine.

Study coauthor Ben Willem J. Mol, MD, PhD, reported consulting fees from ObsEva and Merck and travel fees from Merck.

Dr. Stika and Dr. Carroll had no competing interests to disclose.

A multicenter randomized controlled trial has provided more evidence that acupuncture and doxylamine-pyridoxine (Diclegis/Diclectin) are modestly effective for the nausea and vomiting of pregnancy (NVP). While the benefit of either agent was clinically small for moderate to severe symptoms, the combination showed numerically larger and potentially more meaningful benefit, according to a team led by Xiao-Ke Wu, MD, PhD, of the department of obstetrics and gynecology at First Affiliated Hospital, Heilongjiang University of Chinese Medicine, and Heilongjiang Provincial Hospital in Harbin, China.

The treatments found small reductions in symptoms of less than one point to 1.6 points on an emesis scale. Nevertheless, Dr. Wu’s group wrote online June 19 in Annals of Internal Medicine that the finding “is especially significant because there is a pressing need to establish a pregnancy-safe treatment regimen and an integrative guideline for managing severe NVP.”

NVP affects as many as 85% of pregnant women, 80%-90% of whom have only mild symptoms, the authors noted. However, severe NVP and hyperemesis gravidarum, or HG, develop in about 10%. “Unfortunately, as many as 10% of wanted pregnancies with severe NVP or HG are terminated because of intolerable and untreatable symptoms and complications,” Dr. Wu told this news organization. And antiemetics may be underprescribed by general practitioners because of concerns about potential teratogenic effects, he said.

“Our findings suggest that either acupuncture or doxylamine-pyridoxine alone is a suitable for treating moderate to severe NVP, and a combination of both can be used to treat severe NVP and HG,” Dr. Wu said.

Commenting on the study but not involved in it, Catherine S. Stika, MD, a clinical professor of ob.gyn. at Northwestern University in Chicago, said the results suggest these two therapies are more suited to mild than severe symptoms. “But an RCT is important to do in order to support the use of these therapies since they’re not as widely accepted as they ought to be,” she said in an interview.

Design

The randomized, double-blind, placebo-controled 2x2 factorial trial was conducted at 13 tertiary-care hospitals in mainland China from June 2020 to February 2022. The researchers recruited 352 women in early pregnancy with moderate to severe NVP. The mean age of participants was about 29 years and the mean gestational age was about 9 weeks.

Participants were randomized into four 14-day treatment groups: active acupuncture for 30 minutes a day plus the antihistamine-vitamin B6 agent doxylamine-pyridoxine; sham acupuncture for 30 minutes daily plus doxylamine-pyridoxine; active acupuncture plus placebo; and sham acupuncture plus placebo.

The primary outcome was the reduction in Pregnancy-Unique Quantification of Emesis (PUQE) score at day 15 relative to baseline with a score of less than 6 indicating mild NVP, 6-12 indicating moderate NVP, and 13 or higher indicating severe NVP. Secondary outcomes ranged from quality of life and adverse events to maternal and perinatal complications. Acupuncture and combined treatment yielded larger though still small reductions in PUQE score, compared with control treatments. The mean differences were as follows: acupuncture, –.07; 95% confidence interval, 1.3-0.1); doxylamine-pyridoxine, –1.0: 95% CI, 1.6-0.4); combination of both, –1.6; 95% CI, 2.2-0.9). No significant interaction was detected between the interventions (P = .69).Compared with placebo treatments, pharmaceutical therapy resulted in more somnolence, while active acupuncture led to more frequent dyspnea, bruising, itching, and pain. A higher risk of babies born small for gestational age was observed in mothers who took doxylamine-pyridoxine versus placebo: odds ratio, 3.8; 95% CI, 1-14.1). Neither the placebo effects of the sham interventions nor the natural regression of symptoms experienced by many women were evaluated.
 

Suited to milder symptoms?

Dr. Stika called the study well-designed and well-written but cited several limitations, including the small cohort, the minor symptom improvement, and the lack of a comparator group receiving neither sham nor active treatment.

“Compared with sham combination treatments, the active combination arm was only about a point and a half better,” she said. “And would some women have got better over the 2 weeks anyway with no intervention at all? A large percentage of women with NVP do improve on their own.”

And in terms of acceptability to U.S. women, she cautioned, “The study cohort was entirely Chinese, and this is a population that already accepts acupuncture treatment.”

Countered Dr. Wu, “Medical care provided by licensed acupuncturists is approved in many countries. Certainly, it is ready to be prescribed by physicians when a pregnant patient is seeking NVP treatment.”

Dr. Stika stressed that these therapies are suited to milder NV, and would “barely take edge off severe symptoms,” for which a patient might have to “go up to a big gun like the antiemetic Zofran” (ondansetron). She is currently involved in a National Institutes of Health–funded clinical trial of the antidepressant mirtazapine (Remeron) for NVP.

Matthew Carroll, MD, a professor of obstetrics and gynecology at Baylor College of Medicine and Texas Children’s Hospital in Houston, noted that doxylamine-pyridoxine is already an effective treatment for NVP, but in his experience it is often "not enough" to help patients deal with symptoms.

"Many patients are hesitant to take additional medications," he said. "If acupuncture can be safely done in pregnancy, then it seems a reasonable option as an adjuvant treatment for NVP. I think there is a cohort of pregnant people in the US who would be excited to try a complementary and nonpharmaceutical treatment option. Unfortunately, complementary therapies are rarely evaluated at a systems level for safety and so they are hard to recommend for obstetricians in the US," he added.

Dr. Carroll, who was not involved in the study. noted that "studies like this can help us counsel patients who may be seeking these treatments even if not approved or recommended by ACOG."

This study was funded by the National Key R&D Program of China and the Project of Heilongjiang Province “TouYan” Innovation Team. Support also came from the National Clinical Research Base of Chinese Medicine, the Heilongjiang Provincial Clinical Research Centre for Ovary Diseases, and the 2023 Capability Improvement Project for Evidence-based Assessment of Traditional Chinese Medicine.

Study coauthor Ben Willem J. Mol, MD, PhD, reported consulting fees from ObsEva and Merck and travel fees from Merck.

Dr. Stika and Dr. Carroll had no competing interests to disclose.

A multicenter randomized controlled trial has provided more evidence that acupuncture and doxylamine-pyridoxine (Diclegis/Diclectin) are modestly effective for the nausea and vomiting of pregnancy (NVP). While the benefit of either agent was clinically small for moderate to severe symptoms, the combination showed numerically larger and potentially more meaningful benefit, according to a team led by Xiao-Ke Wu, MD, PhD, of the department of obstetrics and gynecology at First Affiliated Hospital, Heilongjiang University of Chinese Medicine, and Heilongjiang Provincial Hospital in Harbin, China.

The treatments found small reductions in symptoms of less than one point to 1.6 points on an emesis scale. Nevertheless, Dr. Wu’s group wrote online June 19 in Annals of Internal Medicine that the finding “is especially significant because there is a pressing need to establish a pregnancy-safe treatment regimen and an integrative guideline for managing severe NVP.”

NVP affects as many as 85% of pregnant women, 80%-90% of whom have only mild symptoms, the authors noted. However, severe NVP and hyperemesis gravidarum, or HG, develop in about 10%. “Unfortunately, as many as 10% of wanted pregnancies with severe NVP or HG are terminated because of intolerable and untreatable symptoms and complications,” Dr. Wu told this news organization. And antiemetics may be underprescribed by general practitioners because of concerns about potential teratogenic effects, he said.

“Our findings suggest that either acupuncture or doxylamine-pyridoxine alone is a suitable for treating moderate to severe NVP, and a combination of both can be used to treat severe NVP and HG,” Dr. Wu said.

Commenting on the study but not involved in it, Catherine S. Stika, MD, a clinical professor of ob.gyn. at Northwestern University in Chicago, said the results suggest these two therapies are more suited to mild than severe symptoms. “But an RCT is important to do in order to support the use of these therapies since they’re not as widely accepted as they ought to be,” she said in an interview.

Design

The randomized, double-blind, placebo-controled 2x2 factorial trial was conducted at 13 tertiary-care hospitals in mainland China from June 2020 to February 2022. The researchers recruited 352 women in early pregnancy with moderate to severe NVP. The mean age of participants was about 29 years and the mean gestational age was about 9 weeks.

Participants were randomized into four 14-day treatment groups: active acupuncture for 30 minutes a day plus the antihistamine-vitamin B6 agent doxylamine-pyridoxine; sham acupuncture for 30 minutes daily plus doxylamine-pyridoxine; active acupuncture plus placebo; and sham acupuncture plus placebo.

The primary outcome was the reduction in Pregnancy-Unique Quantification of Emesis (PUQE) score at day 15 relative to baseline with a score of less than 6 indicating mild NVP, 6-12 indicating moderate NVP, and 13 or higher indicating severe NVP. Secondary outcomes ranged from quality of life and adverse events to maternal and perinatal complications. Acupuncture and combined treatment yielded larger though still small reductions in PUQE score, compared with control treatments. The mean differences were as follows: acupuncture, –.07; 95% confidence interval, 1.3-0.1); doxylamine-pyridoxine, –1.0: 95% CI, 1.6-0.4); combination of both, –1.6; 95% CI, 2.2-0.9). No significant interaction was detected between the interventions (P = .69).Compared with placebo treatments, pharmaceutical therapy resulted in more somnolence, while active acupuncture led to more frequent dyspnea, bruising, itching, and pain. A higher risk of babies born small for gestational age was observed in mothers who took doxylamine-pyridoxine versus placebo: odds ratio, 3.8; 95% CI, 1-14.1). Neither the placebo effects of the sham interventions nor the natural regression of symptoms experienced by many women were evaluated.
 

Suited to milder symptoms?

Dr. Stika called the study well-designed and well-written but cited several limitations, including the small cohort, the minor symptom improvement, and the lack of a comparator group receiving neither sham nor active treatment.

“Compared with sham combination treatments, the active combination arm was only about a point and a half better,” she said. “And would some women have got better over the 2 weeks anyway with no intervention at all? A large percentage of women with NVP do improve on their own.”

And in terms of acceptability to U.S. women, she cautioned, “The study cohort was entirely Chinese, and this is a population that already accepts acupuncture treatment.”

Countered Dr. Wu, “Medical care provided by licensed acupuncturists is approved in many countries. Certainly, it is ready to be prescribed by physicians when a pregnant patient is seeking NVP treatment.”

Dr. Stika stressed that these therapies are suited to milder NV, and would “barely take edge off severe symptoms,” for which a patient might have to “go up to a big gun like the antiemetic Zofran” (ondansetron). She is currently involved in a National Institutes of Health–funded clinical trial of the antidepressant mirtazapine (Remeron) for NVP.

Matthew Carroll, MD, a professor of obstetrics and gynecology at Baylor College of Medicine and Texas Children’s Hospital in Houston, noted that doxylamine-pyridoxine is already an effective treatment for NVP, but in his experience it is often "not enough" to help patients deal with symptoms.

"Many patients are hesitant to take additional medications," he said. "If acupuncture can be safely done in pregnancy, then it seems a reasonable option as an adjuvant treatment for NVP. I think there is a cohort of pregnant people in the US who would be excited to try a complementary and nonpharmaceutical treatment option. Unfortunately, complementary therapies are rarely evaluated at a systems level for safety and so they are hard to recommend for obstetricians in the US," he added.

Dr. Carroll, who was not involved in the study. noted that "studies like this can help us counsel patients who may be seeking these treatments even if not approved or recommended by ACOG."

This study was funded by the National Key R&D Program of China and the Project of Heilongjiang Province “TouYan” Innovation Team. Support also came from the National Clinical Research Base of Chinese Medicine, the Heilongjiang Provincial Clinical Research Centre for Ovary Diseases, and the 2023 Capability Improvement Project for Evidence-based Assessment of Traditional Chinese Medicine.

Study coauthor Ben Willem J. Mol, MD, PhD, reported consulting fees from ObsEva and Merck and travel fees from Merck.

Dr. Stika and Dr. Carroll had no competing interests to disclose.

Elephantiasis nostras verrucosa (ENV) is a chronic, uncommon and progressively disfiguring disease most commonly presenting on the bilateral lower extremities in the setting of chronic nonfilarial lymphedema resulting in secondary dermatologic sequelae.¹ Clinically, ENV presents as verrucous, hyperkeratotic, cobblestone-like patches, plaques, and nodules with associated nonpitting edema of the affected body area.¹ Secondary bacterial infections are common and often worsen the clinical course. The etiology of ENV involves chronic lymphatic obstruction and venous insufficiency, with additional risk factors including obesity, chronic lymphedema, bacterial infection, surgery or trauma, neoplasia, radiation, congestive heart failure, or scleroderma.^2,3 While most commonly presenting on the lower extremities, cases have been reported involving the abdomen, sacrum, ears, buttocks, and penoscrotal area.^1,2

Regardless of location, the pathogenesis of ENV remains the same. Chronic lymphatic obstruction results in accumulation and lymphostasis of protein-rich dermal fluid, which subsequently precipitates fibroblast proliferation and activation, suppression of the local immune response and development of recurrent lymphangitis, chronic inflammation, and potential secondary bacterial infection.^2,4

There is no standard of care for the treatment and management of ENV and recurrence is common. Interventions often involve those used for chronic lymphedema – including leg elevation, compression stockings or devices, skin hygiene, and lymphatic pumping.^2,3 Medical management with topical and oral retinoids has been reported, as well as emphasis on weight loss and infection control.^1,4 Surgical intervention is often reserved for refractory cases that fail to respond to more conservative management, or severe presentations resulting in extensive functional and aesthetic impairment. Less commonly reported treatment modalities include lymphaticovenular anastomosis and ablative carbon dioxide laser use, although this latter intervention demonstrated minimal improvement in this patient.^5,6

Penoscrotal ENV is a rare form of ENV affecting the genital region of males, often resulting in significant disfigurement, functional impairment, and psychosocial distress. Penoscrotal elephantiasis can be idiopathic, due to filarial infections, scleroinflammatory stricture of the urethra, Chlamydia trachomatis infection, and lymphostasis secondary to chronic inflammatory conditions such as streptococcal infections, radiotherapy, surgery, chronic venous stasis, or Kaposi sarcoma.⁷

In addition, hidradenitis suppurativa (HS) has been documented multiple times in the literature in association with the development of ENV, detailing lymphatic scarring secondary to chronic inguinal HS as the main pathogenic factor.^8,9

Surgery is the mainstay of treatment for penoscrotal ENV, which not only improves functionality and cosmesis, but also aids in prevention of rare malignant sequelae, such as lymphangiosarcoma.¹⁰ Such interventions can involve lymphangioplasty to aid in lymphatic drainage or excision of the mass and subcutaneous tissue with full-thickness skin grafting for reconstruction.⁷ Collaboration between urology, plastic surgery, and dermatology is often essential to obtain adequate care with satisfactory outcomes and minimal recurrence for patients with this uncommon condition.

This case and photo were submitted by Marlee Hill, a medical student at the University of Oklahoma, Oklahoma City; and Michael Franzetti, MD, and Jeffrey McBride, MD, department of dermatology, University of Oklahoma Health Sciences Center. The column was edited by Donna Bilu Martin, MD.
 

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

References

1. Hadian Y et al. Dermatol Online J. 2019 Dec 15;25(12):13030/qt6rn1s8ff.

2. Judge N and Kilic A. J Dermatol Case Rep. 2016 Nov 13;10(2):32-4.

3. Dean SM et al. J Am Acad Dermatol. 2011 Jun;64(6):1104-10.

4. Sisto K and Khachemoune A. Am J Clin Dermatol. 2008;9(3):141-6.

5. Motegi S et al. Dermatology. 2007;215(2):147-51.

6. Robinson CG et al. J Cutan Med Surg. 2018;22(6):611-3.

7. Koualla S et al. Ann Chir Plast Esthet. 2023 Apr 10;S0294-1260(23)00035-3.

8. Lelonek E et al. Acta Derm Venereol. 2021 Feb 11;101(2):adv00389.

9. Good LM et al. J Am Acad Dermatol. 2011 May;64(5):993-4.

10. Cerri A et al. Eur J Dermatol. 1998 Oct-Nov;8(7):511-4.

Elephantiasis nostras verrucosa (ENV) is a chronic, uncommon and progressively disfiguring disease most commonly presenting on the bilateral lower extremities in the setting of chronic nonfilarial lymphedema resulting in secondary dermatologic sequelae.¹ Clinically, ENV presents as verrucous, hyperkeratotic, cobblestone-like patches, plaques, and nodules with associated nonpitting edema of the affected body area.¹ Secondary bacterial infections are common and often worsen the clinical course. The etiology of ENV involves chronic lymphatic obstruction and venous insufficiency, with additional risk factors including obesity, chronic lymphedema, bacterial infection, surgery or trauma, neoplasia, radiation, congestive heart failure, or scleroderma.^2,3 While most commonly presenting on the lower extremities, cases have been reported involving the abdomen, sacrum, ears, buttocks, and penoscrotal area.^1,2

Regardless of location, the pathogenesis of ENV remains the same. Chronic lymphatic obstruction results in accumulation and lymphostasis of protein-rich dermal fluid, which subsequently precipitates fibroblast proliferation and activation, suppression of the local immune response and development of recurrent lymphangitis, chronic inflammation, and potential secondary bacterial infection.^2,4

There is no standard of care for the treatment and management of ENV and recurrence is common. Interventions often involve those used for chronic lymphedema – including leg elevation, compression stockings or devices, skin hygiene, and lymphatic pumping.^2,3 Medical management with topical and oral retinoids has been reported, as well as emphasis on weight loss and infection control.^1,4 Surgical intervention is often reserved for refractory cases that fail to respond to more conservative management, or severe presentations resulting in extensive functional and aesthetic impairment. Less commonly reported treatment modalities include lymphaticovenular anastomosis and ablative carbon dioxide laser use, although this latter intervention demonstrated minimal improvement in this patient.^5,6

Penoscrotal ENV is a rare form of ENV affecting the genital region of males, often resulting in significant disfigurement, functional impairment, and psychosocial distress. Penoscrotal elephantiasis can be idiopathic, due to filarial infections, scleroinflammatory stricture of the urethra, Chlamydia trachomatis infection, and lymphostasis secondary to chronic inflammatory conditions such as streptococcal infections, radiotherapy, surgery, chronic venous stasis, or Kaposi sarcoma.⁷

In addition, hidradenitis suppurativa (HS) has been documented multiple times in the literature in association with the development of ENV, detailing lymphatic scarring secondary to chronic inguinal HS as the main pathogenic factor.^8,9

Surgery is the mainstay of treatment for penoscrotal ENV, which not only improves functionality and cosmesis, but also aids in prevention of rare malignant sequelae, such as lymphangiosarcoma.¹⁰ Such interventions can involve lymphangioplasty to aid in lymphatic drainage or excision of the mass and subcutaneous tissue with full-thickness skin grafting for reconstruction.⁷ Collaboration between urology, plastic surgery, and dermatology is often essential to obtain adequate care with satisfactory outcomes and minimal recurrence for patients with this uncommon condition.

This case and photo were submitted by Marlee Hill, a medical student at the University of Oklahoma, Oklahoma City; and Michael Franzetti, MD, and Jeffrey McBride, MD, department of dermatology, University of Oklahoma Health Sciences Center. The column was edited by Donna Bilu Martin, MD.
 

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

References

1. Hadian Y et al. Dermatol Online J. 2019 Dec 15;25(12):13030/qt6rn1s8ff.

2. Judge N and Kilic A. J Dermatol Case Rep. 2016 Nov 13;10(2):32-4.

3. Dean SM et al. J Am Acad Dermatol. 2011 Jun;64(6):1104-10.

4. Sisto K and Khachemoune A. Am J Clin Dermatol. 2008;9(3):141-6.

5. Motegi S et al. Dermatology. 2007;215(2):147-51.

6. Robinson CG et al. J Cutan Med Surg. 2018;22(6):611-3.

7. Koualla S et al. Ann Chir Plast Esthet. 2023 Apr 10;S0294-1260(23)00035-3.

8. Lelonek E et al. Acta Derm Venereol. 2021 Feb 11;101(2):adv00389.

9. Good LM et al. J Am Acad Dermatol. 2011 May;64(5):993-4.

10. Cerri A et al. Eur J Dermatol. 1998 Oct-Nov;8(7):511-4.

Elephantiasis nostras verrucosa (ENV) is a chronic, uncommon and progressively disfiguring disease most commonly presenting on the bilateral lower extremities in the setting of chronic nonfilarial lymphedema resulting in secondary dermatologic sequelae.¹ Clinically, ENV presents as verrucous, hyperkeratotic, cobblestone-like patches, plaques, and nodules with associated nonpitting edema of the affected body area.¹ Secondary bacterial infections are common and often worsen the clinical course. The etiology of ENV involves chronic lymphatic obstruction and venous insufficiency, with additional risk factors including obesity, chronic lymphedema, bacterial infection, surgery or trauma, neoplasia, radiation, congestive heart failure, or scleroderma.^2,3 While most commonly presenting on the lower extremities, cases have been reported involving the abdomen, sacrum, ears, buttocks, and penoscrotal area.^1,2

Regardless of location, the pathogenesis of ENV remains the same. Chronic lymphatic obstruction results in accumulation and lymphostasis of protein-rich dermal fluid, which subsequently precipitates fibroblast proliferation and activation, suppression of the local immune response and development of recurrent lymphangitis, chronic inflammation, and potential secondary bacterial infection.^2,4

There is no standard of care for the treatment and management of ENV and recurrence is common. Interventions often involve those used for chronic lymphedema – including leg elevation, compression stockings or devices, skin hygiene, and lymphatic pumping.^2,3 Medical management with topical and oral retinoids has been reported, as well as emphasis on weight loss and infection control.^1,4 Surgical intervention is often reserved for refractory cases that fail to respond to more conservative management, or severe presentations resulting in extensive functional and aesthetic impairment. Less commonly reported treatment modalities include lymphaticovenular anastomosis and ablative carbon dioxide laser use, although this latter intervention demonstrated minimal improvement in this patient.^5,6

Penoscrotal ENV is a rare form of ENV affecting the genital region of males, often resulting in significant disfigurement, functional impairment, and psychosocial distress. Penoscrotal elephantiasis can be idiopathic, due to filarial infections, scleroinflammatory stricture of the urethra, Chlamydia trachomatis infection, and lymphostasis secondary to chronic inflammatory conditions such as streptococcal infections, radiotherapy, surgery, chronic venous stasis, or Kaposi sarcoma.⁷

In addition, hidradenitis suppurativa (HS) has been documented multiple times in the literature in association with the development of ENV, detailing lymphatic scarring secondary to chronic inguinal HS as the main pathogenic factor.^8,9

Surgery is the mainstay of treatment for penoscrotal ENV, which not only improves functionality and cosmesis, but also aids in prevention of rare malignant sequelae, such as lymphangiosarcoma.¹⁰ Such interventions can involve lymphangioplasty to aid in lymphatic drainage or excision of the mass and subcutaneous tissue with full-thickness skin grafting for reconstruction.⁷ Collaboration between urology, plastic surgery, and dermatology is often essential to obtain adequate care with satisfactory outcomes and minimal recurrence for patients with this uncommon condition.

This case and photo were submitted by Marlee Hill, a medical student at the University of Oklahoma, Oklahoma City; and Michael Franzetti, MD, and Jeffrey McBride, MD, department of dermatology, University of Oklahoma Health Sciences Center. The column was edited by Donna Bilu Martin, MD.
 

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

References

1. Hadian Y et al. Dermatol Online J. 2019 Dec 15;25(12):13030/qt6rn1s8ff.

2. Judge N and Kilic A. J Dermatol Case Rep. 2016 Nov 13;10(2):32-4.

3. Dean SM et al. J Am Acad Dermatol. 2011 Jun;64(6):1104-10.

4. Sisto K and Khachemoune A. Am J Clin Dermatol. 2008;9(3):141-6.

5. Motegi S et al. Dermatology. 2007;215(2):147-51.

6. Robinson CG et al. J Cutan Med Surg. 2018;22(6):611-3.

7. Koualla S et al. Ann Chir Plast Esthet. 2023 Apr 10;S0294-1260(23)00035-3.

8. Lelonek E et al. Acta Derm Venereol. 2021 Feb 11;101(2):adv00389.

9. Good LM et al. J Am Acad Dermatol. 2011 May;64(5):993-4.

10. Cerri A et al. Eur J Dermatol. 1998 Oct-Nov;8(7):511-4.

Infants of fathers who want their child to breastfeed are more likely to be part of a family unit that starts and continues breastfeeding, and fathers informed of safe sleep practices are more likely to follow those sleeping recommendations for their infant, according to the results of a recent survey published in Pediatrics.

The results suggest that including fathers in conversations about breastfeeding and infant sleep practices could help improve adherence, the researchers said.

“Our findings underscore that new fathers are a critical audience to promote breastfeeding and safe infant sleep,” John James Parker, MD, instructor of pediatrics at Northwestern University, Chicago, stated in a press release. “Many families do not gain the health benefits from breastfeeding because they are not provided the support to breastfeed successfully. Fathers need to be directly engaged in breastfeeding discussions, and providers need to describe the important role fathers play in breastfeeding success.”
 

Population-based survey results

Dr. Parker and colleagues used the Pregnancy Risk Assessment Monitoring System (PRAMS) for Dads population-based survey to evaluate the rate of adherence to breastfeeding and infant sleep practices recommended by the American Academy of Pediatrics. In total, 250 fathers in Georgia were surveyed between October 2018 and July 2019 about whether their infants were breastfeeding and if they were breastfeeding at 8 weeks. The fathers were also asked how often the infant slept in a back sleeping position, on an approved sleep surface, and sleeping with no soft objects or soft bedding.

In addition to surveying fathers on their attitudes on breastfeeding and whether they followed safe infant sleep practices, the researchers collected information on paternal sociodemographic characteristics such as age, race and ethnicity, education, health insurance status, and marital status. Overall, a majority fathers who responded to the survey were between 25 years and 34 years old (56.5%), non-Hispanic White (44.7%), had a high school diploma or less (43.7%) or completed college (37.1%), and were married (65.2%).

Dr. Parker and colleagues found fathers surveyed said 86.1% of infants were ever breastfed, which decreased to 63.4% at 8 weeks. Compared with fathers who did not want their infant to breastfeed or expressed no opinion, fathers who wanted to have the infant’s mother breastfeed had a higher likelihood of reporting breastfeeding initiation (adjusted prevalence ratio, 1.39; 95% confidence interval, 1.15-1.68) and breastfeeding at 8 weeks (aPR, 2.33; 95% CI, 1.59-3.42). Having a college degree was also associated with the infant breastfeeding (93.6% vs. 75.1%; aPR, 1.25; 95% CI, 1.06-1.46) and breastfeeding at 8 weeks (74.7% vs. 52.0%; aPR, 1.44; 95% CI, 1.08-1.91), compared with fathers who graduated from high school or less.

Regarding safe infant sleeping practices, 81.18% of fathers said they placed their infants on their back to sleep, but 44.1% said they did not use soft bedding, and 31.9% said they used an approved sleep surface. In total, 99.4% of fathers put their infant to sleep, and 68.4% said they received information on all three infant safe sleeping practices, while 15.7% said they followed all three sleeping recommendations. A health care provider was the most common person giving advice to the father on placing the infant to sleep on their back (84.7%); to use a safe sleep surface such as a crib, bassinet, or pack-and-play (78.7%); and receiving information about what not to place in the infant’s bed (79.1%).

The survey found non-Hispanic Black fathers reported they were less likely to put the infant to sleep on their back (62.5% vs. 89.5%; aPR, 0.70; 95% CI, 0.54-0.90) and not use soft bedding (28.1% vs. 54.1%; aPR, 0.52; 95% CI, 0.30-0.89), compared with non-Hispanic White fathers. College graduates were more likely to not use soft bedding (61.4% vs. 31.9%; aPR, 1.92; 95% CI, 1.25-2.95), more likely to get advice on placing the infant on their back for sleep (94.3% vs. 73.6%; aPR, 1.28; 95% CI, 1.09-1.51), and more likely to receive advice on what not to place in the infant’s bed (88.1% vs. 68.5%; aPR, 1.29; 95% CI, 1.06-1.57), compared with fathers with a high school diploma or less.

“Fathers need to receive counseling on all the safe sleep practices for their infants,” Dr. Parker said. “To reduce racial disparities in sudden unexpected infant death, we need tailored strategies to increase safe infant sleep practices in the Black community, including public campaigns to increase awareness and home visiting programs. These interventions must involve both parents to be most effective.”
 

Educational efforts should recognize father’s contributions

In an interview, Deborah E. Campbell, MD, chief of neonatology at the Children’s Hospital at Montefiore, New York, said the survey “adds further important information on the role of fathers both in the care of their infants and young children, but also in terms of supporting the birth parent and a number of the parenting decisions, whether it’s breastfeeding as well as safe sleep practices for the infant.”

The benefits of breastfeeding are important for the infant but also for the health of the family and the community, Dr. Campbell explained, noting that breastfeeding can aid in preventing chronic disease and cancer. Promoting safe sleep practices for infants, on the other hand, helps reduce factors such as infant mortality and sudden unexpected infant death.

While PRAMS has existed for decades, PRAMS for Dads is relatively new and localized as a pilot program in Georgia, Dr. Campbell noted. The pilot program “really shows that you can get helpful information, and it would be wonderful to see that model expanded to begin to look at the father’s role in other states as well.”

To improve adherence to breastfeeding and infant safe sleeping practices, creating broadly educational efforts that include and recognize the contributions of the father are important, especially as fathers today are generally more involved and engaged than in past generations, Dr. Campbell said. For instance, pediatric or family practice offices could be structured in a way that welcomes fathers and appreciates them, rather than focusing solely on the birth mother or the baby.

“I think certainly as we have greater diversity among our families, greater diversity within our communities, just more varied family constellations, recognizing and valuing each member of the family becomes important and then providing them with the information and the tools,” she said.

While health literacy is important, structural inequalities in care provision in health care settings mean that “it’s honestly much more likely that an educated parent is going to have an opportunity to hear more of those messages,” Dr. Campbell said. “They are much more likely to be able to go to childbirth classes, go to the pediatrician visits, take off from work, have leaves so that they can spend time in the hospital during the infant’s stay and the birth parent’s initial recoveries so that they have greater opportunity to get those messages.”

Fathers with lower educational attainment may have good health literacy, but may be unable to be around for these conversations. “Education is really a proxy for a lot of other structural issues,” she said.

Educational messages around safe sleeping practices for the infant should acknowledge that many families might not have the space to have a dedicated room with a crib for an infant, and offer assurances that other safe sleeping options exist, such as a pack-and-play or Moses basket. The most important message to get across to parents is that the baby is “sleeping alone” in a firm, noninclined surface and does not have bedding or other objects around them.

It is not just the infant’s bed that should follow the AAP recommendations: the family bed should also be a firm surface free of soft objects and bedding for breastfeeding, Dr. Campbell noted. If a parent falls asleep while breastfeeding in bed, the AAP’s most recent guidance notes the parent should move the infant to a separate sleep space as soon as they wake up, but the Academy also acknowledges how that can be challenging in early months with sleep deprivation.

“I think it’s dealing with the realities of having a new baby and trying to create the safest environment for that baby, one that supports and promotes breastfeeding as well as safe sleep,” she said.

In families where there are “strong cultural beliefs and traditions” about the baby sleeping with the parents, it is important to “convey the messages in a way that, that honors and values, family traditions and customs, but also assures the safety of the infant,” Dr. Campbell said.

This study was supported by the Centers for Disease Control and Prevention and CDC Innovation Fund. The authors reported no relevant conflicts of interest. Dr. Campbell reported no relevant conflicts of interest.

Infants of fathers who want their child to breastfeed are more likely to be part of a family unit that starts and continues breastfeeding, and fathers informed of safe sleep practices are more likely to follow those sleeping recommendations for their infant, according to the results of a recent survey published in Pediatrics.

The results suggest that including fathers in conversations about breastfeeding and infant sleep practices could help improve adherence, the researchers said.

“Our findings underscore that new fathers are a critical audience to promote breastfeeding and safe infant sleep,” John James Parker, MD, instructor of pediatrics at Northwestern University, Chicago, stated in a press release. “Many families do not gain the health benefits from breastfeeding because they are not provided the support to breastfeed successfully. Fathers need to be directly engaged in breastfeeding discussions, and providers need to describe the important role fathers play in breastfeeding success.”
 

Population-based survey results

Dr. Parker and colleagues used the Pregnancy Risk Assessment Monitoring System (PRAMS) for Dads population-based survey to evaluate the rate of adherence to breastfeeding and infant sleep practices recommended by the American Academy of Pediatrics. In total, 250 fathers in Georgia were surveyed between October 2018 and July 2019 about whether their infants were breastfeeding and if they were breastfeeding at 8 weeks. The fathers were also asked how often the infant slept in a back sleeping position, on an approved sleep surface, and sleeping with no soft objects or soft bedding.

In addition to surveying fathers on their attitudes on breastfeeding and whether they followed safe infant sleep practices, the researchers collected information on paternal sociodemographic characteristics such as age, race and ethnicity, education, health insurance status, and marital status. Overall, a majority fathers who responded to the survey were between 25 years and 34 years old (56.5%), non-Hispanic White (44.7%), had a high school diploma or less (43.7%) or completed college (37.1%), and were married (65.2%).

Dr. Parker and colleagues found fathers surveyed said 86.1% of infants were ever breastfed, which decreased to 63.4% at 8 weeks. Compared with fathers who did not want their infant to breastfeed or expressed no opinion, fathers who wanted to have the infant’s mother breastfeed had a higher likelihood of reporting breastfeeding initiation (adjusted prevalence ratio, 1.39; 95% confidence interval, 1.15-1.68) and breastfeeding at 8 weeks (aPR, 2.33; 95% CI, 1.59-3.42). Having a college degree was also associated with the infant breastfeeding (93.6% vs. 75.1%; aPR, 1.25; 95% CI, 1.06-1.46) and breastfeeding at 8 weeks (74.7% vs. 52.0%; aPR, 1.44; 95% CI, 1.08-1.91), compared with fathers who graduated from high school or less.

Regarding safe infant sleeping practices, 81.18% of fathers said they placed their infants on their back to sleep, but 44.1% said they did not use soft bedding, and 31.9% said they used an approved sleep surface. In total, 99.4% of fathers put their infant to sleep, and 68.4% said they received information on all three infant safe sleeping practices, while 15.7% said they followed all three sleeping recommendations. A health care provider was the most common person giving advice to the father on placing the infant to sleep on their back (84.7%); to use a safe sleep surface such as a crib, bassinet, or pack-and-play (78.7%); and receiving information about what not to place in the infant’s bed (79.1%).

The survey found non-Hispanic Black fathers reported they were less likely to put the infant to sleep on their back (62.5% vs. 89.5%; aPR, 0.70; 95% CI, 0.54-0.90) and not use soft bedding (28.1% vs. 54.1%; aPR, 0.52; 95% CI, 0.30-0.89), compared with non-Hispanic White fathers. College graduates were more likely to not use soft bedding (61.4% vs. 31.9%; aPR, 1.92; 95% CI, 1.25-2.95), more likely to get advice on placing the infant on their back for sleep (94.3% vs. 73.6%; aPR, 1.28; 95% CI, 1.09-1.51), and more likely to receive advice on what not to place in the infant’s bed (88.1% vs. 68.5%; aPR, 1.29; 95% CI, 1.06-1.57), compared with fathers with a high school diploma or less.

“Fathers need to receive counseling on all the safe sleep practices for their infants,” Dr. Parker said. “To reduce racial disparities in sudden unexpected infant death, we need tailored strategies to increase safe infant sleep practices in the Black community, including public campaigns to increase awareness and home visiting programs. These interventions must involve both parents to be most effective.”
 

Educational efforts should recognize father’s contributions

In an interview, Deborah E. Campbell, MD, chief of neonatology at the Children’s Hospital at Montefiore, New York, said the survey “adds further important information on the role of fathers both in the care of their infants and young children, but also in terms of supporting the birth parent and a number of the parenting decisions, whether it’s breastfeeding as well as safe sleep practices for the infant.”

The benefits of breastfeeding are important for the infant but also for the health of the family and the community, Dr. Campbell explained, noting that breastfeeding can aid in preventing chronic disease and cancer. Promoting safe sleep practices for infants, on the other hand, helps reduce factors such as infant mortality and sudden unexpected infant death.

While PRAMS has existed for decades, PRAMS for Dads is relatively new and localized as a pilot program in Georgia, Dr. Campbell noted. The pilot program “really shows that you can get helpful information, and it would be wonderful to see that model expanded to begin to look at the father’s role in other states as well.”

To improve adherence to breastfeeding and infant safe sleeping practices, creating broadly educational efforts that include and recognize the contributions of the father are important, especially as fathers today are generally more involved and engaged than in past generations, Dr. Campbell said. For instance, pediatric or family practice offices could be structured in a way that welcomes fathers and appreciates them, rather than focusing solely on the birth mother or the baby.

“I think certainly as we have greater diversity among our families, greater diversity within our communities, just more varied family constellations, recognizing and valuing each member of the family becomes important and then providing them with the information and the tools,” she said.

While health literacy is important, structural inequalities in care provision in health care settings mean that “it’s honestly much more likely that an educated parent is going to have an opportunity to hear more of those messages,” Dr. Campbell said. “They are much more likely to be able to go to childbirth classes, go to the pediatrician visits, take off from work, have leaves so that they can spend time in the hospital during the infant’s stay and the birth parent’s initial recoveries so that they have greater opportunity to get those messages.”

Fathers with lower educational attainment may have good health literacy, but may be unable to be around for these conversations. “Education is really a proxy for a lot of other structural issues,” she said.

Educational messages around safe sleeping practices for the infant should acknowledge that many families might not have the space to have a dedicated room with a crib for an infant, and offer assurances that other safe sleeping options exist, such as a pack-and-play or Moses basket. The most important message to get across to parents is that the baby is “sleeping alone” in a firm, noninclined surface and does not have bedding or other objects around them.

It is not just the infant’s bed that should follow the AAP recommendations: the family bed should also be a firm surface free of soft objects and bedding for breastfeeding, Dr. Campbell noted. If a parent falls asleep while breastfeeding in bed, the AAP’s most recent guidance notes the parent should move the infant to a separate sleep space as soon as they wake up, but the Academy also acknowledges how that can be challenging in early months with sleep deprivation.

“I think it’s dealing with the realities of having a new baby and trying to create the safest environment for that baby, one that supports and promotes breastfeeding as well as safe sleep,” she said.

In families where there are “strong cultural beliefs and traditions” about the baby sleeping with the parents, it is important to “convey the messages in a way that, that honors and values, family traditions and customs, but also assures the safety of the infant,” Dr. Campbell said.

This study was supported by the Centers for Disease Control and Prevention and CDC Innovation Fund. The authors reported no relevant conflicts of interest. Dr. Campbell reported no relevant conflicts of interest.

Infants of fathers who want their child to breastfeed are more likely to be part of a family unit that starts and continues breastfeeding, and fathers informed of safe sleep practices are more likely to follow those sleeping recommendations for their infant, according to the results of a recent survey published in Pediatrics.

The results suggest that including fathers in conversations about breastfeeding and infant sleep practices could help improve adherence, the researchers said.

“Our findings underscore that new fathers are a critical audience to promote breastfeeding and safe infant sleep,” John James Parker, MD, instructor of pediatrics at Northwestern University, Chicago, stated in a press release. “Many families do not gain the health benefits from breastfeeding because they are not provided the support to breastfeed successfully. Fathers need to be directly engaged in breastfeeding discussions, and providers need to describe the important role fathers play in breastfeeding success.”
 

Population-based survey results

Dr. Parker and colleagues used the Pregnancy Risk Assessment Monitoring System (PRAMS) for Dads population-based survey to evaluate the rate of adherence to breastfeeding and infant sleep practices recommended by the American Academy of Pediatrics. In total, 250 fathers in Georgia were surveyed between October 2018 and July 2019 about whether their infants were breastfeeding and if they were breastfeeding at 8 weeks. The fathers were also asked how often the infant slept in a back sleeping position, on an approved sleep surface, and sleeping with no soft objects or soft bedding.

In addition to surveying fathers on their attitudes on breastfeeding and whether they followed safe infant sleep practices, the researchers collected information on paternal sociodemographic characteristics such as age, race and ethnicity, education, health insurance status, and marital status. Overall, a majority fathers who responded to the survey were between 25 years and 34 years old (56.5%), non-Hispanic White (44.7%), had a high school diploma or less (43.7%) or completed college (37.1%), and were married (65.2%).

Dr. Parker and colleagues found fathers surveyed said 86.1% of infants were ever breastfed, which decreased to 63.4% at 8 weeks. Compared with fathers who did not want their infant to breastfeed or expressed no opinion, fathers who wanted to have the infant’s mother breastfeed had a higher likelihood of reporting breastfeeding initiation (adjusted prevalence ratio, 1.39; 95% confidence interval, 1.15-1.68) and breastfeeding at 8 weeks (aPR, 2.33; 95% CI, 1.59-3.42). Having a college degree was also associated with the infant breastfeeding (93.6% vs. 75.1%; aPR, 1.25; 95% CI, 1.06-1.46) and breastfeeding at 8 weeks (74.7% vs. 52.0%; aPR, 1.44; 95% CI, 1.08-1.91), compared with fathers who graduated from high school or less.

Regarding safe infant sleeping practices, 81.18% of fathers said they placed their infants on their back to sleep, but 44.1% said they did not use soft bedding, and 31.9% said they used an approved sleep surface. In total, 99.4% of fathers put their infant to sleep, and 68.4% said they received information on all three infant safe sleeping practices, while 15.7% said they followed all three sleeping recommendations. A health care provider was the most common person giving advice to the father on placing the infant to sleep on their back (84.7%); to use a safe sleep surface such as a crib, bassinet, or pack-and-play (78.7%); and receiving information about what not to place in the infant’s bed (79.1%).

The survey found non-Hispanic Black fathers reported they were less likely to put the infant to sleep on their back (62.5% vs. 89.5%; aPR, 0.70; 95% CI, 0.54-0.90) and not use soft bedding (28.1% vs. 54.1%; aPR, 0.52; 95% CI, 0.30-0.89), compared with non-Hispanic White fathers. College graduates were more likely to not use soft bedding (61.4% vs. 31.9%; aPR, 1.92; 95% CI, 1.25-2.95), more likely to get advice on placing the infant on their back for sleep (94.3% vs. 73.6%; aPR, 1.28; 95% CI, 1.09-1.51), and more likely to receive advice on what not to place in the infant’s bed (88.1% vs. 68.5%; aPR, 1.29; 95% CI, 1.06-1.57), compared with fathers with a high school diploma or less.

“Fathers need to receive counseling on all the safe sleep practices for their infants,” Dr. Parker said. “To reduce racial disparities in sudden unexpected infant death, we need tailored strategies to increase safe infant sleep practices in the Black community, including public campaigns to increase awareness and home visiting programs. These interventions must involve both parents to be most effective.”
 

Educational efforts should recognize father’s contributions

In an interview, Deborah E. Campbell, MD, chief of neonatology at the Children’s Hospital at Montefiore, New York, said the survey “adds further important information on the role of fathers both in the care of their infants and young children, but also in terms of supporting the birth parent and a number of the parenting decisions, whether it’s breastfeeding as well as safe sleep practices for the infant.”

The benefits of breastfeeding are important for the infant but also for the health of the family and the community, Dr. Campbell explained, noting that breastfeeding can aid in preventing chronic disease and cancer. Promoting safe sleep practices for infants, on the other hand, helps reduce factors such as infant mortality and sudden unexpected infant death.

While PRAMS has existed for decades, PRAMS for Dads is relatively new and localized as a pilot program in Georgia, Dr. Campbell noted. The pilot program “really shows that you can get helpful information, and it would be wonderful to see that model expanded to begin to look at the father’s role in other states as well.”

To improve adherence to breastfeeding and infant safe sleeping practices, creating broadly educational efforts that include and recognize the contributions of the father are important, especially as fathers today are generally more involved and engaged than in past generations, Dr. Campbell said. For instance, pediatric or family practice offices could be structured in a way that welcomes fathers and appreciates them, rather than focusing solely on the birth mother or the baby.

“I think certainly as we have greater diversity among our families, greater diversity within our communities, just more varied family constellations, recognizing and valuing each member of the family becomes important and then providing them with the information and the tools,” she said.

While health literacy is important, structural inequalities in care provision in health care settings mean that “it’s honestly much more likely that an educated parent is going to have an opportunity to hear more of those messages,” Dr. Campbell said. “They are much more likely to be able to go to childbirth classes, go to the pediatrician visits, take off from work, have leaves so that they can spend time in the hospital during the infant’s stay and the birth parent’s initial recoveries so that they have greater opportunity to get those messages.”

Fathers with lower educational attainment may have good health literacy, but may be unable to be around for these conversations. “Education is really a proxy for a lot of other structural issues,” she said.

Educational messages around safe sleeping practices for the infant should acknowledge that many families might not have the space to have a dedicated room with a crib for an infant, and offer assurances that other safe sleeping options exist, such as a pack-and-play or Moses basket. The most important message to get across to parents is that the baby is “sleeping alone” in a firm, noninclined surface and does not have bedding or other objects around them.

It is not just the infant’s bed that should follow the AAP recommendations: the family bed should also be a firm surface free of soft objects and bedding for breastfeeding, Dr. Campbell noted. If a parent falls asleep while breastfeeding in bed, the AAP’s most recent guidance notes the parent should move the infant to a separate sleep space as soon as they wake up, but the Academy also acknowledges how that can be challenging in early months with sleep deprivation.

“I think it’s dealing with the realities of having a new baby and trying to create the safest environment for that baby, one that supports and promotes breastfeeding as well as safe sleep,” she said.

In families where there are “strong cultural beliefs and traditions” about the baby sleeping with the parents, it is important to “convey the messages in a way that, that honors and values, family traditions and customs, but also assures the safety of the infant,” Dr. Campbell said.

This study was supported by the Centers for Disease Control and Prevention and CDC Innovation Fund. The authors reported no relevant conflicts of interest. Dr. Campbell reported no relevant conflicts of interest.

A 4-year-old male presented to an urgent care center with a 2-week history of runny nose and cough. The treating clinician suspected a postviral cough, but the child’s mother was unconvinced. Testing for SARS-CoV-2, influenza, and respiratory syncytial virus performed earlier in the week at the pediatrician’s office was negative. At the mother’s insistence, an expanded respiratory panel was ordered and revealed a surprising result: Bordetella parapertussis.

Just like B. pertussis, B. parapertussis can cause a prolonged cough illness characterized by coughing paroxysms, whoop, and posttussive emesis. Testing is the only way to reliably distinguish between the two infections. In general, disease due to B. parapertussis tends to be milder than typical pertussis and symptoms usually don’t last as long. In one study, 40% of people with B. parapertussis had no symptoms. B. parapertussis does not produce pertussis toxin and this may affect disease severity. Rarely, children can be coinfected with both B. pertussis and B. parapertussis.

The burden of B. parapertussis in the United States is not well described because only pertussis cases caused by B. pertussis are reportable to the Centers for Disease Control and Prevention. Nevertheless, some states include cases in public reporting and outbreaks have been reported. Historically, disease has been cyclical, with peaks in cases every 4 years and no seasonality.

This year, some communities are currently seeing an increase in B. parapertussis cases. Through June 11 of this year, 40 cases of B. parapertussis and no cases of B. pertussis have been identified at Norton Healthcare in Louisville, Ky. For comparison, one case of B. parapertussis was reported in 2022 and no cases were reported in 2021. Chatter on infectious diseases listservs suggests that clinicians in other communities are also seeing an increase in cases.

According to Andi Shane, MD, MPH, chief of the division of pediatric infectious diseases at Emory University and Children’s Healthcare of Atlanta, an unusually high number of children with B. parapertussis were identified in the Atlanta area this spring. “Fortunately, most children had mild illness and of these, only a few required admission to the hospital,” Dr. Shane said.

Back at the urgent care center, the clinician on duty called the patient’s mom to discuss the diagnosis of B. parapertussis. By the time the test result was available, the patient was asymptomatic. The clinician advised that antibiotic therapy was not indicated.

Treatment recommendations diverge for B. pertussis and B. parapertussis and this is a point of emphasis for clinicians. Treatment of B. pertussis during the catarrhal phase may ameliorate disease. Treatment initiated after the catarrhal phase has little impact on symptoms but may reduce spread to others. In most cases, treatment isn’t recommended for B. parapertussis. It is not clear how well antibiotics work against this organism. Macrolides such as erythromycin and azithromycin that are used to treat pertussis may have some activity, along with trimethoprim-sulfamethoxazole and ciprofloxacin. According to the American Academy of Pediatrics, treatment is usually reserved for individuals at risk for more severe disease, including infants, especially those less than 6 months of age, the elderly, and immunocompromised persons. Prophylactic antibiotic therapy is not recommended for most persons exposed to B. parapertussis, although some public health experts also recommend treatment of B. parapertussis-infected people in contact with young infants and others are risk for severe disease.

In recent epidemiologic reports, patients with B. parapertussis infection had received age-appropriate vaccination for pertussis, suggesting that available pertussis vaccines offer little to no protection against this disease. The best prevention strategies are similar to those that are effective against other illness spread by respiratory droplets. Sick people should stay at home and cover their coughs when around others. Everyone should practice good hand hygiene.

Are you seeing increased cases of B. parapertussis in your community? Email me at [email protected].

Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She is a member of the AAP’s Committee on Infectious Diseases and one of the lead authors of the AAP’s Recommendations for Prevention and Control of Influenza in Children, 2022-2023. The opinions expressed in this article are her own. Dr. Bryant discloses that she has served as an investigator on clinical trials funded by Pfizer, Enanta and Gilead. Email her at [email protected].

A 4-year-old male presented to an urgent care center with a 2-week history of runny nose and cough. The treating clinician suspected a postviral cough, but the child’s mother was unconvinced. Testing for SARS-CoV-2, influenza, and respiratory syncytial virus performed earlier in the week at the pediatrician’s office was negative. At the mother’s insistence, an expanded respiratory panel was ordered and revealed a surprising result: Bordetella parapertussis.

Just like B. pertussis, B. parapertussis can cause a prolonged cough illness characterized by coughing paroxysms, whoop, and posttussive emesis. Testing is the only way to reliably distinguish between the two infections. In general, disease due to B. parapertussis tends to be milder than typical pertussis and symptoms usually don’t last as long. In one study, 40% of people with B. parapertussis had no symptoms. B. parapertussis does not produce pertussis toxin and this may affect disease severity. Rarely, children can be coinfected with both B. pertussis and B. parapertussis.

The burden of B. parapertussis in the United States is not well described because only pertussis cases caused by B. pertussis are reportable to the Centers for Disease Control and Prevention. Nevertheless, some states include cases in public reporting and outbreaks have been reported. Historically, disease has been cyclical, with peaks in cases every 4 years and no seasonality.

This year, some communities are currently seeing an increase in B. parapertussis cases. Through June 11 of this year, 40 cases of B. parapertussis and no cases of B. pertussis have been identified at Norton Healthcare in Louisville, Ky. For comparison, one case of B. parapertussis was reported in 2022 and no cases were reported in 2021. Chatter on infectious diseases listservs suggests that clinicians in other communities are also seeing an increase in cases.

According to Andi Shane, MD, MPH, chief of the division of pediatric infectious diseases at Emory University and Children’s Healthcare of Atlanta, an unusually high number of children with B. parapertussis were identified in the Atlanta area this spring. “Fortunately, most children had mild illness and of these, only a few required admission to the hospital,” Dr. Shane said.

Back at the urgent care center, the clinician on duty called the patient’s mom to discuss the diagnosis of B. parapertussis. By the time the test result was available, the patient was asymptomatic. The clinician advised that antibiotic therapy was not indicated.

Treatment recommendations diverge for B. pertussis and B. parapertussis and this is a point of emphasis for clinicians. Treatment of B. pertussis during the catarrhal phase may ameliorate disease. Treatment initiated after the catarrhal phase has little impact on symptoms but may reduce spread to others. In most cases, treatment isn’t recommended for B. parapertussis. It is not clear how well antibiotics work against this organism. Macrolides such as erythromycin and azithromycin that are used to treat pertussis may have some activity, along with trimethoprim-sulfamethoxazole and ciprofloxacin. According to the American Academy of Pediatrics, treatment is usually reserved for individuals at risk for more severe disease, including infants, especially those less than 6 months of age, the elderly, and immunocompromised persons. Prophylactic antibiotic therapy is not recommended for most persons exposed to B. parapertussis, although some public health experts also recommend treatment of B. parapertussis-infected people in contact with young infants and others are risk for severe disease.

In recent epidemiologic reports, patients with B. parapertussis infection had received age-appropriate vaccination for pertussis, suggesting that available pertussis vaccines offer little to no protection against this disease. The best prevention strategies are similar to those that are effective against other illness spread by respiratory droplets. Sick people should stay at home and cover their coughs when around others. Everyone should practice good hand hygiene.

Are you seeing increased cases of B. parapertussis in your community? Email me at [email protected].

Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She is a member of the AAP’s Committee on Infectious Diseases and one of the lead authors of the AAP’s Recommendations for Prevention and Control of Influenza in Children, 2022-2023. The opinions expressed in this article are her own. Dr. Bryant discloses that she has served as an investigator on clinical trials funded by Pfizer, Enanta and Gilead. Email her at [email protected].

A 4-year-old male presented to an urgent care center with a 2-week history of runny nose and cough. The treating clinician suspected a postviral cough, but the child’s mother was unconvinced. Testing for SARS-CoV-2, influenza, and respiratory syncytial virus performed earlier in the week at the pediatrician’s office was negative. At the mother’s insistence, an expanded respiratory panel was ordered and revealed a surprising result: Bordetella parapertussis.

Just like B. pertussis, B. parapertussis can cause a prolonged cough illness characterized by coughing paroxysms, whoop, and posttussive emesis. Testing is the only way to reliably distinguish between the two infections. In general, disease due to B. parapertussis tends to be milder than typical pertussis and symptoms usually don’t last as long. In one study, 40% of people with B. parapertussis had no symptoms. B. parapertussis does not produce pertussis toxin and this may affect disease severity. Rarely, children can be coinfected with both B. pertussis and B. parapertussis.

The burden of B. parapertussis in the United States is not well described because only pertussis cases caused by B. pertussis are reportable to the Centers for Disease Control and Prevention. Nevertheless, some states include cases in public reporting and outbreaks have been reported. Historically, disease has been cyclical, with peaks in cases every 4 years and no seasonality.

This year, some communities are currently seeing an increase in B. parapertussis cases. Through June 11 of this year, 40 cases of B. parapertussis and no cases of B. pertussis have been identified at Norton Healthcare in Louisville, Ky. For comparison, one case of B. parapertussis was reported in 2022 and no cases were reported in 2021. Chatter on infectious diseases listservs suggests that clinicians in other communities are also seeing an increase in cases.

According to Andi Shane, MD, MPH, chief of the division of pediatric infectious diseases at Emory University and Children’s Healthcare of Atlanta, an unusually high number of children with B. parapertussis were identified in the Atlanta area this spring. “Fortunately, most children had mild illness and of these, only a few required admission to the hospital,” Dr. Shane said.

Back at the urgent care center, the clinician on duty called the patient’s mom to discuss the diagnosis of B. parapertussis. By the time the test result was available, the patient was asymptomatic. The clinician advised that antibiotic therapy was not indicated.

Treatment recommendations diverge for B. pertussis and B. parapertussis and this is a point of emphasis for clinicians. Treatment of B. pertussis during the catarrhal phase may ameliorate disease. Treatment initiated after the catarrhal phase has little impact on symptoms but may reduce spread to others. In most cases, treatment isn’t recommended for B. parapertussis. It is not clear how well antibiotics work against this organism. Macrolides such as erythromycin and azithromycin that are used to treat pertussis may have some activity, along with trimethoprim-sulfamethoxazole and ciprofloxacin. According to the American Academy of Pediatrics, treatment is usually reserved for individuals at risk for more severe disease, including infants, especially those less than 6 months of age, the elderly, and immunocompromised persons. Prophylactic antibiotic therapy is not recommended for most persons exposed to B. parapertussis, although some public health experts also recommend treatment of B. parapertussis-infected people in contact with young infants and others are risk for severe disease.

In recent epidemiologic reports, patients with B. parapertussis infection had received age-appropriate vaccination for pertussis, suggesting that available pertussis vaccines offer little to no protection against this disease. The best prevention strategies are similar to those that are effective against other illness spread by respiratory droplets. Sick people should stay at home and cover their coughs when around others. Everyone should practice good hand hygiene.

Are you seeing increased cases of B. parapertussis in your community? Email me at [email protected].

Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She is a member of the AAP’s Committee on Infectious Diseases and one of the lead authors of the AAP’s Recommendations for Prevention and Control of Influenza in Children, 2022-2023. The opinions expressed in this article are her own. Dr. Bryant discloses that she has served as an investigator on clinical trials funded by Pfizer, Enanta and Gilead. Email her at [email protected].

Maintaining a slightly elevated CO₂ level (hypercapnia) for the first 24 hours in comatose patients who had been resuscitated after out-of-hospital cardiac arrest did not improve outcomes in a large randomized controlled trial.

The Targeted Therapeutic Mild Hypercapnia After Resuscitated Cardiac Arrest (TAME) study showed that the intervention failed to improve neurologic or functional outcomes or quality of life at 6 months. However, the researchers also found that slightly elevated CO₂ levels were not associated with worse outcomes.

“I think these results show that our hypothesis – that raising CO₂ levels as applied in this trial may be beneficial for these patients – was not effective, even though previous work suggested that it would be,” co–lead investigator Alistair Nichol, MD, said in an interview.

“This was a rigorous trial; the intervention was well delivered, and the results are pretty clear. Unfortunately, we have proved a null hypothesis – that this approach doesn’t seem to work,” Dr. Nichol, who is professor of critical care medicine at University College Dublin, said.

“However, we did find that hypercapnia was safe. This is an important finding, as sometimes in very sick patients such as those who develop pneumonia, we have to drive the ventilator less hard to minimize injury to the lungs, and this can lead to higher CO₂ levels,” he added. “Our results show that this practice should not be harmful, which is reassuring.”

The TAME study was presented at the Critical Care Reviews 2023 Meeting (CCR23) held in Belfast, Northern Ireland.

It was simultaneously published online in the New England Journal of Medicine.

The researchers explain that after the return of spontaneous circulation, brain hypoperfusion may contribute to cerebral hypoxia, exacerbate brain damage, and lead to poor neurologic outcomes. The partial pressure of arterial carbon dioxide (PaCO₂) is the major physiologic regulator of cerebrovascular tone, and increasing CO₂ levels increases cerebral blood flow.

Two previous observational studies showed that exposure to hypercapnia was associated with an increase in the likelihood of being discharged home and better neurologic outcomes at 12 months, compared with hypocapnia or normocapnia.

In addition, a physiologic study showed that deliberate increases in PaCO₂ induced higher cerebral oxygen saturations, compared with normocapnia. A phase 2 randomized trial showed that hypercapnia significantly attenuated the release of neuron-specific enolase, a biomarker of brain injury, and also suggested better 6-month neurologic recovery with hypercapnia compared with normocapnia.

The current TAME trial was conducted to try to confirm these results in a larger, more definitive study.

For the trial, 1,700 adults with coma who had been resuscitated after out-of-hospital cardiac arrest were randomly assigned to receive either 24 hours of mild hypercapnia (target PaCO₂, 50-55 mm Hg) or normocapnia (target PaCO₂, 35-45 mm Hg).

The primary outcome – a favorable neurologic outcome, defined as a score of 5 or higher on the Glasgow Outcome Scale–Extended at 6 months – occurred in 43.5% in the mild hypercapnia group and in 44.6% in the normocapnia group (relative risk, 0.98; P = .76).

By 6 months, 48.2% of those in the mild hypercapnia group and 45.9% in the normocapnia group had died (relative risk with mild hypercapnia, 1.05; 95% confidence interval, 0.94-1.16). In the mild hypercapnia group, 53.4% had a poor functional outcome, defined as a Modified Rankin Scale score of 4-6, compared with 51.3% in the normocapnia group.

Health-related quality of life, as assessed by the EQ Visual Analogue Scale component of the EuroQol-5D-5L, was similar in the two groups.

In terms of safety, results showed that mild hypercapnia did not increase the incidence of prespecified adverse events.

The authors note that there is concern that mild hypercapnia may worsen cerebral edema and elevate intracranial pressure; however, elevated intracranial pressure is uncommon in the first 72 hours after the return of spontaneous circulation.

In the TAME trial, there was one case of cerebral edema in the hypercapnia group. “This is a very low rate and would be expected in a group this size, so this does not indicate a safety concern,” Dr. Nichol commented.

The researchers are planning further analyses of biological samples to look for possible prognostic markers.

“These out-of-hospital cardiac arrest patients are a very diverse group, and it may be possible that some patients could have benefited from hypercapnia while others may have been harmed,” Dr. Nichol noted.

“Raising CO₂ levels does improve overall delivery of oxygen to the brain, but this might not have occurred in the right areas. It may be possible that some patients benefited, and analysis of biological samples will help us look more closely at this.”

He added that other ongoing trials are investigating hypercapnia in patients with traumatic brain injury.

“These patients are managed differently and often have probes in their brain to measure the response to CO₂, so more of a precision medicine approach is possible,” he explained.

He also noted that the TAME study, which was conducted in conjunction with the TTM-2 study investigating hypothermia in out-of-hospital cardiac arrest patients, has established a network of ICU teams around the world, providing an infrastructure for further trials to be performed in this patient population in the future.

The TAME trial was funded by the National Health and Medical Research Council of Australia, the Health Research Board of Ireland, and the Health Research Council of New Zealand.

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

Maintaining a slightly elevated CO₂ level (hypercapnia) for the first 24 hours in comatose patients who had been resuscitated after out-of-hospital cardiac arrest did not improve outcomes in a large randomized controlled trial.

The Targeted Therapeutic Mild Hypercapnia After Resuscitated Cardiac Arrest (TAME) study showed that the intervention failed to improve neurologic or functional outcomes or quality of life at 6 months. However, the researchers also found that slightly elevated CO₂ levels were not associated with worse outcomes.

“I think these results show that our hypothesis – that raising CO₂ levels as applied in this trial may be beneficial for these patients – was not effective, even though previous work suggested that it would be,” co–lead investigator Alistair Nichol, MD, said in an interview.

“This was a rigorous trial; the intervention was well delivered, and the results are pretty clear. Unfortunately, we have proved a null hypothesis – that this approach doesn’t seem to work,” Dr. Nichol, who is professor of critical care medicine at University College Dublin, said.

“However, we did find that hypercapnia was safe. This is an important finding, as sometimes in very sick patients such as those who develop pneumonia, we have to drive the ventilator less hard to minimize injury to the lungs, and this can lead to higher CO₂ levels,” he added. “Our results show that this practice should not be harmful, which is reassuring.”

The TAME study was presented at the Critical Care Reviews 2023 Meeting (CCR23) held in Belfast, Northern Ireland.

It was simultaneously published online in the New England Journal of Medicine.

The researchers explain that after the return of spontaneous circulation, brain hypoperfusion may contribute to cerebral hypoxia, exacerbate brain damage, and lead to poor neurologic outcomes. The partial pressure of arterial carbon dioxide (PaCO₂) is the major physiologic regulator of cerebrovascular tone, and increasing CO₂ levels increases cerebral blood flow.

Two previous observational studies showed that exposure to hypercapnia was associated with an increase in the likelihood of being discharged home and better neurologic outcomes at 12 months, compared with hypocapnia or normocapnia.

In addition, a physiologic study showed that deliberate increases in PaCO₂ induced higher cerebral oxygen saturations, compared with normocapnia. A phase 2 randomized trial showed that hypercapnia significantly attenuated the release of neuron-specific enolase, a biomarker of brain injury, and also suggested better 6-month neurologic recovery with hypercapnia compared with normocapnia.

The current TAME trial was conducted to try to confirm these results in a larger, more definitive study.

For the trial, 1,700 adults with coma who had been resuscitated after out-of-hospital cardiac arrest were randomly assigned to receive either 24 hours of mild hypercapnia (target PaCO₂, 50-55 mm Hg) or normocapnia (target PaCO₂, 35-45 mm Hg).

The primary outcome – a favorable neurologic outcome, defined as a score of 5 or higher on the Glasgow Outcome Scale–Extended at 6 months – occurred in 43.5% in the mild hypercapnia group and in 44.6% in the normocapnia group (relative risk, 0.98; P = .76).

By 6 months, 48.2% of those in the mild hypercapnia group and 45.9% in the normocapnia group had died (relative risk with mild hypercapnia, 1.05; 95% confidence interval, 0.94-1.16). In the mild hypercapnia group, 53.4% had a poor functional outcome, defined as a Modified Rankin Scale score of 4-6, compared with 51.3% in the normocapnia group.

Health-related quality of life, as assessed by the EQ Visual Analogue Scale component of the EuroQol-5D-5L, was similar in the two groups.

In terms of safety, results showed that mild hypercapnia did not increase the incidence of prespecified adverse events.

The authors note that there is concern that mild hypercapnia may worsen cerebral edema and elevate intracranial pressure; however, elevated intracranial pressure is uncommon in the first 72 hours after the return of spontaneous circulation.

In the TAME trial, there was one case of cerebral edema in the hypercapnia group. “This is a very low rate and would be expected in a group this size, so this does not indicate a safety concern,” Dr. Nichol commented.

The researchers are planning further analyses of biological samples to look for possible prognostic markers.

“These out-of-hospital cardiac arrest patients are a very diverse group, and it may be possible that some patients could have benefited from hypercapnia while others may have been harmed,” Dr. Nichol noted.

“Raising CO₂ levels does improve overall delivery of oxygen to the brain, but this might not have occurred in the right areas. It may be possible that some patients benefited, and analysis of biological samples will help us look more closely at this.”

He added that other ongoing trials are investigating hypercapnia in patients with traumatic brain injury.

“These patients are managed differently and often have probes in their brain to measure the response to CO₂, so more of a precision medicine approach is possible,” he explained.

He also noted that the TAME study, which was conducted in conjunction with the TTM-2 study investigating hypothermia in out-of-hospital cardiac arrest patients, has established a network of ICU teams around the world, providing an infrastructure for further trials to be performed in this patient population in the future.

The TAME trial was funded by the National Health and Medical Research Council of Australia, the Health Research Board of Ireland, and the Health Research Council of New Zealand.

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

Maintaining a slightly elevated CO₂ level (hypercapnia) for the first 24 hours in comatose patients who had been resuscitated after out-of-hospital cardiac arrest did not improve outcomes in a large randomized controlled trial.

The Targeted Therapeutic Mild Hypercapnia After Resuscitated Cardiac Arrest (TAME) study showed that the intervention failed to improve neurologic or functional outcomes or quality of life at 6 months. However, the researchers also found that slightly elevated CO₂ levels were not associated with worse outcomes.

“I think these results show that our hypothesis – that raising CO₂ levels as applied in this trial may be beneficial for these patients – was not effective, even though previous work suggested that it would be,” co–lead investigator Alistair Nichol, MD, said in an interview.

“This was a rigorous trial; the intervention was well delivered, and the results are pretty clear. Unfortunately, we have proved a null hypothesis – that this approach doesn’t seem to work,” Dr. Nichol, who is professor of critical care medicine at University College Dublin, said.

“However, we did find that hypercapnia was safe. This is an important finding, as sometimes in very sick patients such as those who develop pneumonia, we have to drive the ventilator less hard to minimize injury to the lungs, and this can lead to higher CO₂ levels,” he added. “Our results show that this practice should not be harmful, which is reassuring.”

The TAME study was presented at the Critical Care Reviews 2023 Meeting (CCR23) held in Belfast, Northern Ireland.

It was simultaneously published online in the New England Journal of Medicine.

The researchers explain that after the return of spontaneous circulation, brain hypoperfusion may contribute to cerebral hypoxia, exacerbate brain damage, and lead to poor neurologic outcomes. The partial pressure of arterial carbon dioxide (PaCO₂) is the major physiologic regulator of cerebrovascular tone, and increasing CO₂ levels increases cerebral blood flow.

Two previous observational studies showed that exposure to hypercapnia was associated with an increase in the likelihood of being discharged home and better neurologic outcomes at 12 months, compared with hypocapnia or normocapnia.

In addition, a physiologic study showed that deliberate increases in PaCO₂ induced higher cerebral oxygen saturations, compared with normocapnia. A phase 2 randomized trial showed that hypercapnia significantly attenuated the release of neuron-specific enolase, a biomarker of brain injury, and also suggested better 6-month neurologic recovery with hypercapnia compared with normocapnia.

The current TAME trial was conducted to try to confirm these results in a larger, more definitive study.

For the trial, 1,700 adults with coma who had been resuscitated after out-of-hospital cardiac arrest were randomly assigned to receive either 24 hours of mild hypercapnia (target PaCO₂, 50-55 mm Hg) or normocapnia (target PaCO₂, 35-45 mm Hg).

The primary outcome – a favorable neurologic outcome, defined as a score of 5 or higher on the Glasgow Outcome Scale–Extended at 6 months – occurred in 43.5% in the mild hypercapnia group and in 44.6% in the normocapnia group (relative risk, 0.98; P = .76).

By 6 months, 48.2% of those in the mild hypercapnia group and 45.9% in the normocapnia group had died (relative risk with mild hypercapnia, 1.05; 95% confidence interval, 0.94-1.16). In the mild hypercapnia group, 53.4% had a poor functional outcome, defined as a Modified Rankin Scale score of 4-6, compared with 51.3% in the normocapnia group.

Health-related quality of life, as assessed by the EQ Visual Analogue Scale component of the EuroQol-5D-5L, was similar in the two groups.

In terms of safety, results showed that mild hypercapnia did not increase the incidence of prespecified adverse events.

The authors note that there is concern that mild hypercapnia may worsen cerebral edema and elevate intracranial pressure; however, elevated intracranial pressure is uncommon in the first 72 hours after the return of spontaneous circulation.

In the TAME trial, there was one case of cerebral edema in the hypercapnia group. “This is a very low rate and would be expected in a group this size, so this does not indicate a safety concern,” Dr. Nichol commented.

The researchers are planning further analyses of biological samples to look for possible prognostic markers.

“These out-of-hospital cardiac arrest patients are a very diverse group, and it may be possible that some patients could have benefited from hypercapnia while others may have been harmed,” Dr. Nichol noted.

“Raising CO₂ levels does improve overall delivery of oxygen to the brain, but this might not have occurred in the right areas. It may be possible that some patients benefited, and analysis of biological samples will help us look more closely at this.”

He added that other ongoing trials are investigating hypercapnia in patients with traumatic brain injury.

“These patients are managed differently and often have probes in their brain to measure the response to CO₂, so more of a precision medicine approach is possible,” he explained.

He also noted that the TAME study, which was conducted in conjunction with the TTM-2 study investigating hypothermia in out-of-hospital cardiac arrest patients, has established a network of ICU teams around the world, providing an infrastructure for further trials to be performed in this patient population in the future.

The TAME trial was funded by the National Health and Medical Research Council of Australia, the Health Research Board of Ireland, and the Health Research Council of New Zealand.

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

Primary care providers (PCPs) are addressing an increasing number of mental health visits, requiring collaborative and innovative approaches to providing psychiatric care.

This growth in the number of patients needing behavioral health–related care is likely driven by multiple factors, including a shortage of mental health care providers, an increasing incidence of psychiatric illness, and destigmatization of mental health in general, suggested Swetha P. Iruku, MD, MPH, associate professor of family medicine and community health at the University of Pennsylvania and Penn Medicine family physician in Philadelphia.

The Centers for Disease Control and Prevention noted that “the COVID-19 pandemic has been associated with mental health challenges related to the morbidity and mortality caused by the disease and to mitigation activities, including the impact of physical distancing and stay-at-home orders,” in a Morbidity and Mortality Weekly Report.

From June 24 to 30, 2020, U.S. adults reported considerably elevated adverse mental health conditions associated with COVID-19, and symptoms of anxiety disorder and depressive disorder climbed during the months of April through June of the same year, compared with the same period in 2019, they wrote.

Even before the pandemic got underway, multiple studies of national data published this year suggested mental issues were on the rise in the United States. For example, the proportion of adult patient visits to primary care providers that addressed mental health concerns rose from 10.7% to 15.9% from 2006 to 2018, according to research published in Health Affairs. Plus, the number and proportion of pediatric acute care hospitalizations because of mental health diagnoses increased significantly between 2009 and 2019, according to a paper published in JAMA.

“I truly believe that we can’t, as primary care physicians, take care of someone’s physical health without also taking care of their mental health,” Dr. Iruku said in an interview. “It’s all intertwined.”

To rise to this challenge, PCPs first need a collaborative mindset, she suggested, as well as familiarity with available resources, both locally and virtually.

This article examines strategies for managing mental illness in primary care, outlines clinical resources, and reviews related educational opportunities.

In addition, clinical pearls are shared by Dr. Iruku and five other clinicians who provide or have provided mental health care to primary care patients or work in close collaboration with a primary care practice, including a clinical psychologist, a nurse practitioner licensed in psychiatric health, a pediatrician, and a licensed clinical social worker.
 

Build a network

Most of the providers interviewed cited the importance of collaboration in mental health care, particularly for complex cases.

“I would recommend [that primary care providers get] to know the psychiatric providers [in their area],” said Jessica Viton, DNP, FNP, PMHNP, who delivers mental health care through a community-based primary care practice in Colorado which she requested remain anonymous.

Dr. Iruku suggested making an in-person connection first, if possible.

“So much of what we do is ‘see one, do one, teach one,’ so learn a little bit, then go off and trial,” she said. “[It can be valuable] having someone in your back pocket that you can contact in the case of an emergency, or in a situation where you just don’t know how to tackle it.”
 

Screen for depression and anxiety

William J. Sieber, PhD, a clinical psychologist, director of integrated behavioral health, and professor in the department of family medicine and public health and the department of psychiatry at the University of California, San Diego, said primary care providers should screen all adult patients for depression and anxiety with the Patient Health Questionnaire (PHQ-9) and General Anxiety Disorder Assessment (GAD-7), respectively.

To save time, he suggested a cascading approach.

“In primary care, everybody’s in a hurry,” Dr. Sieber said. “[With the cascading approach,] the first two items [from each questionnaire] are given, and if a person endorses either of those items … then they are asked to complete the other items.”

Jennifer Mullally, MD, a pediatrician at Sanford Health in Fargo, N.D., uses this cascading approach to depression and anxiety screening with all her patients aged 13-18. For younger kids, she screens only those who present with signs or symptoms of mental health issues, or if the parent shares a concern.

This approach differs slightly from U.S. Preventive Services Task Force recommendations, which suggest screening for anxiety in patients aged 8-18 years and depression in patients aged 12-18 years.
 

Use other screening tools only as needed

Dr. Sieber, the research director for the division of family medicine at UC San Diego, collaborates regularly with primary care providers via hallway consultations, by sharing cases, and through providing oversight of psychiatric care at 13 primary care practices within the UC San Diego network. He recommended against routine screening beyond depression and anxiety in the primary care setting.

“There are a lot of screening tools,” Dr. Sieber said. “It depends on what you’re presented with. The challenge in primary care is you’re going to see all kinds of things. It’s not like running a depression clinic.”

Other than the PHQ-9 and GAD-7, he suggested primary care providers establish familiarity with screening tools for posttraumatic stress disorder and attention-deficit/hyperactivity disorder, noting again that these should be used only when one of the conditions is already suspected.

Dr. Mullally follows a similar approach with her pediatric population. In addition to the GAD-7, she investigates whether a patient has anxiety with the Screen for Child Anxiety Related Disorders (SCARED). For depression, she couples the PHQ-9 with the Columbia Suicide Severity Rating Scale.

While additional screening tools like these are readily available online, Dr. Viton suggested that they should be employed only if the provider is trained to interpret and respond to those findings, and only if they know which tool to use, and when.

For example, she has recently observed PCPs diagnosing adults with ADHD using a three-question test, when in fact a full-length, standardized instrument should be administered by a provider with necessary training.

She also pointed out that bipolar disorder continues to be underdiagnosed, possibly because of providers detecting depression using a questionnaire like the PHQ-9, while failing to inquire about manic episodes.
 

Leverage online resources

If depression is confirmed, Dr. Iruku often directs the patient to the Mayo Clinic Depression Medication Choice Decision Aid. This website steers patients through medication options based on their answers to a questionnaire. Choices are listed alongside possible adverse effects.

For clinician use, Dr. Iruku recommended The Waco Guide to Psychopharmacology in Primary Care, which aids clinical decision-making for mental illness and substance abuse. The app processes case details to suggest first-, second-, and third-line pharmacotherapies, as well as modifications based on patient needs.

Even with tools like these, however, a referral may be needed.

“[Primary care providers] may not be the best fit for what the patient is looking for, from a mental health or behavioral standpoint,” Dr. Sieber said.

In this case, he encourages patients to visit Psychology Today, a “quite popular portal” that helps patients locate a suitable provider based on location, insurance, driving radius, and mental health concern. This usually generates 10-20 options, Dr. Sieber said, although results can vary.

“It may be discouraging, because maybe only three [providers] pop up based on your criteria, and the closest one is miles away,” he said.
 

Consider virtual support

If no local psychiatric help is available, Dr. Sieber suggested virtual support, highlighting that “it’s much easier now than it was 3 or 4 years ago” to connect patients with external mental health care.

But this strategy should be reserved for cases of actual need instead of pure convenience, cautioned Dr. Viton, who noted that virtual visits may fail to capture the nuance of an in-person meeting, as body language, mode of dress, and other clues can provide insights into mental health status.

“Occasionally, I think you do have to have an in-person visit, especially when you’re developing a rapport with someone,” Dr. Viton said.

Claire McArdle, a licensed clinical social worker in Fort Collins, Colo., noted that virtual care from an outside provider may also impede the collaboration needed to effectively address mental illness.

In her 11 years in primary care at Associates in Family Medicine, Ms. McArdle had countless interactions with colleagues seeking support when managing a complex case. “I’m coaching providers, front desk staff, and nursing staff on how to interact with patients [with] behavioral health needs,” she said, citing the multitude of nonmedical factors that need to be considered, such as family relationships and patient preferences.

These unscheduled conversations with colleagues throughout the day are impossible to have when sharing a case with an unknown, remote peer.

Ms. McArdle speaks from experience. She recently resigned from Associates in Family Medicine to start her own private therapy practice after her former employer was acquired by VillageMD, a national provider that terminated employment of most other social workers in the practice and began outsourcing mental health care to Mindoula Health, a virtual provider.

Dr. Sieber offered a similar perspective on in-person collaboration as the psychiatric specialist at his center. He routinely offers on-site support for both providers and patients, serving as “another set of eyes and ears” when there is a concern about patient safety or directly managing care when a patient is hospitalized for mental illness.

While virtual solutions may fall short of in-person management, they can offer care at a scale and cost impossible through traditional practice.

This could even be free. Zero-cost, automated software now allows individuals who are uninsured or unable to afford care at least one avenue to manage their mental health concerns.

For example, Bliss is a free, 8-session, interactive online therapy program for depression that was created by the Centre for Interactive Mental Health Solutions. The program offers a tool for monitoring mood and quizzes to test understanding of personal mental health management, among other features.

More advanced programs are emerging as artificial intelligence (AI) enables dialogues between humans and machines. This is the case with Woebot, an app that asks the user about their mood throughout the day, and responds with evidence-based strategies for managing concerns, all for free at press time.
 

Keep learning

A range of educational options and professional resources are available for primary care providers who would like to improve their knowledge of mental health care. These include formal fellowships in primary care psychiatry/behavioral health integration, free mental health webinars, and various other opportunities.

Eric Eschweiler, DNP, APRN, FNP-C, PHN, completed the University of California, Irvine, Train New Trainers (TNT) Primary Care Psychiatry (PCP) Fellowship in 2016, when he was working as a solo nurse practitioner.

“I was drowning in practice,” said Dr. Eschweiler, director of nursing and public health outreach services at Riverside-San Bernardino County Indian Health, Grand Terrace, Calif., in an interview. “I was a solo NP. There was no physician on site. We were seeing a lot of [individuals with] schizoaffective [disorder] in downtown San Bernardino, the homeless, unhoused – a lot of substance use. I felt I needed to have the skills to be able to treat them effectively. That’s what the fellowship did.”

The skills Dr. Eschweiler learned from participating in his fellowship allowed him to manage more cases of mental illness without need for referral. When a referral was needed for a complex or severe case, he had the confidence to bridge care and collaborate more effectively with psychiatric specialists.

“It was awesome, because we were able to communicate using the same language,” Dr. Eschweiler said of these collaborations. “It’s [about] talking that same language, starting those initial treatments, and then moving forward with specialty care, and vice versa. [Psychiatric specialists] would send me patients that needed medical care because of the types of medications they were taking. And I was then very well aware of those side effects and other issues that might come up from those treatments. So it’s a two-way street.”

Dr. Eschweiler was so impressed by his fellowship that he has since ushered multiple providers through the program since transitioning to an administrative role as director of nursing.

In Fargo, where psychiatric care is sparse and wait times for referral can be months long, Dr. Mullally, like Dr. Eschweiler, knew that she needed more training in mental health.

“I don’t feel like we get enough training in residency,” Dr. Mullally said. “So you do need to look at your options for further CME.”

Out of several CME courses she has taken to further her understanding of pediatric psychiatry, Dr. Mullally recommended The Reach Institute above all others, as their courses involve in-depth discussions and valuable handouts, particularly for medication selection.

“I think that a lot of the other CMEs tend to involve a lot more PowerPoint presentations,” Dr. Mullally said. “And you don’t necessarily leave with a lot of good documents. I still use my Reach handouts. I have them sitting right next to me. I use them every single day.”

Providers interested in The Reach Institute, however, should be prepared to invest both time and money, she added, citing a 2-3 day commitment, and calling it “not cheap.” To overcome these barriers, she suggested that providers get their institution to support their attendance.

For a lighter commitment, Dr. Iruku recommended the American Academy of Family Physicians CME portal, as this offers 13 online, accredited courses covering a range of topics, from adolescent health to substance abuse disorders.

Dr. Sieber suggested that primary care providers join the Collaborative Family Healthcare Association, which aims to integrate physical and behavioral health in routine practice. CFHA, of which he is a member, offers a “bevy of different resources” for interested providers, including a conference in Phoenix this October.

The interviewees disclosed no conflicts of interest.

Primary care providers (PCPs) are addressing an increasing number of mental health visits, requiring collaborative and innovative approaches to providing psychiatric care.

This growth in the number of patients needing behavioral health–related care is likely driven by multiple factors, including a shortage of mental health care providers, an increasing incidence of psychiatric illness, and destigmatization of mental health in general, suggested Swetha P. Iruku, MD, MPH, associate professor of family medicine and community health at the University of Pennsylvania and Penn Medicine family physician in Philadelphia.

The Centers for Disease Control and Prevention noted that “the COVID-19 pandemic has been associated with mental health challenges related to the morbidity and mortality caused by the disease and to mitigation activities, including the impact of physical distancing and stay-at-home orders,” in a Morbidity and Mortality Weekly Report.

From June 24 to 30, 2020, U.S. adults reported considerably elevated adverse mental health conditions associated with COVID-19, and symptoms of anxiety disorder and depressive disorder climbed during the months of April through June of the same year, compared with the same period in 2019, they wrote.

Even before the pandemic got underway, multiple studies of national data published this year suggested mental issues were on the rise in the United States. For example, the proportion of adult patient visits to primary care providers that addressed mental health concerns rose from 10.7% to 15.9% from 2006 to 2018, according to research published in Health Affairs. Plus, the number and proportion of pediatric acute care hospitalizations because of mental health diagnoses increased significantly between 2009 and 2019, according to a paper published in JAMA.

“I truly believe that we can’t, as primary care physicians, take care of someone’s physical health without also taking care of their mental health,” Dr. Iruku said in an interview. “It’s all intertwined.”

To rise to this challenge, PCPs first need a collaborative mindset, she suggested, as well as familiarity with available resources, both locally and virtually.

This article examines strategies for managing mental illness in primary care, outlines clinical resources, and reviews related educational opportunities.

In addition, clinical pearls are shared by Dr. Iruku and five other clinicians who provide or have provided mental health care to primary care patients or work in close collaboration with a primary care practice, including a clinical psychologist, a nurse practitioner licensed in psychiatric health, a pediatrician, and a licensed clinical social worker.
 

Build a network

Most of the providers interviewed cited the importance of collaboration in mental health care, particularly for complex cases.

“I would recommend [that primary care providers get] to know the psychiatric providers [in their area],” said Jessica Viton, DNP, FNP, PMHNP, who delivers mental health care through a community-based primary care practice in Colorado which she requested remain anonymous.

Dr. Iruku suggested making an in-person connection first, if possible.

“So much of what we do is ‘see one, do one, teach one,’ so learn a little bit, then go off and trial,” she said. “[It can be valuable] having someone in your back pocket that you can contact in the case of an emergency, or in a situation where you just don’t know how to tackle it.”
 

Screen for depression and anxiety

William J. Sieber, PhD, a clinical psychologist, director of integrated behavioral health, and professor in the department of family medicine and public health and the department of psychiatry at the University of California, San Diego, said primary care providers should screen all adult patients for depression and anxiety with the Patient Health Questionnaire (PHQ-9) and General Anxiety Disorder Assessment (GAD-7), respectively.

To save time, he suggested a cascading approach.

“In primary care, everybody’s in a hurry,” Dr. Sieber said. “[With the cascading approach,] the first two items [from each questionnaire] are given, and if a person endorses either of those items … then they are asked to complete the other items.”

Jennifer Mullally, MD, a pediatrician at Sanford Health in Fargo, N.D., uses this cascading approach to depression and anxiety screening with all her patients aged 13-18. For younger kids, she screens only those who present with signs or symptoms of mental health issues, or if the parent shares a concern.

This approach differs slightly from U.S. Preventive Services Task Force recommendations, which suggest screening for anxiety in patients aged 8-18 years and depression in patients aged 12-18 years.
 

Use other screening tools only as needed

Dr. Sieber, the research director for the division of family medicine at UC San Diego, collaborates regularly with primary care providers via hallway consultations, by sharing cases, and through providing oversight of psychiatric care at 13 primary care practices within the UC San Diego network. He recommended against routine screening beyond depression and anxiety in the primary care setting.

“There are a lot of screening tools,” Dr. Sieber said. “It depends on what you’re presented with. The challenge in primary care is you’re going to see all kinds of things. It’s not like running a depression clinic.”

Other than the PHQ-9 and GAD-7, he suggested primary care providers establish familiarity with screening tools for posttraumatic stress disorder and attention-deficit/hyperactivity disorder, noting again that these should be used only when one of the conditions is already suspected.

Dr. Mullally follows a similar approach with her pediatric population. In addition to the GAD-7, she investigates whether a patient has anxiety with the Screen for Child Anxiety Related Disorders (SCARED). For depression, she couples the PHQ-9 with the Columbia Suicide Severity Rating Scale.

While additional screening tools like these are readily available online, Dr. Viton suggested that they should be employed only if the provider is trained to interpret and respond to those findings, and only if they know which tool to use, and when.

For example, she has recently observed PCPs diagnosing adults with ADHD using a three-question test, when in fact a full-length, standardized instrument should be administered by a provider with necessary training.

She also pointed out that bipolar disorder continues to be underdiagnosed, possibly because of providers detecting depression using a questionnaire like the PHQ-9, while failing to inquire about manic episodes.
 

Leverage online resources

If depression is confirmed, Dr. Iruku often directs the patient to the Mayo Clinic Depression Medication Choice Decision Aid. This website steers patients through medication options based on their answers to a questionnaire. Choices are listed alongside possible adverse effects.

For clinician use, Dr. Iruku recommended The Waco Guide to Psychopharmacology in Primary Care, which aids clinical decision-making for mental illness and substance abuse. The app processes case details to suggest first-, second-, and third-line pharmacotherapies, as well as modifications based on patient needs.

Even with tools like these, however, a referral may be needed.

“[Primary care providers] may not be the best fit for what the patient is looking for, from a mental health or behavioral standpoint,” Dr. Sieber said.

In this case, he encourages patients to visit Psychology Today, a “quite popular portal” that helps patients locate a suitable provider based on location, insurance, driving radius, and mental health concern. This usually generates 10-20 options, Dr. Sieber said, although results can vary.

“It may be discouraging, because maybe only three [providers] pop up based on your criteria, and the closest one is miles away,” he said.
 

Consider virtual support

If no local psychiatric help is available, Dr. Sieber suggested virtual support, highlighting that “it’s much easier now than it was 3 or 4 years ago” to connect patients with external mental health care.

But this strategy should be reserved for cases of actual need instead of pure convenience, cautioned Dr. Viton, who noted that virtual visits may fail to capture the nuance of an in-person meeting, as body language, mode of dress, and other clues can provide insights into mental health status.

“Occasionally, I think you do have to have an in-person visit, especially when you’re developing a rapport with someone,” Dr. Viton said.

Claire McArdle, a licensed clinical social worker in Fort Collins, Colo., noted that virtual care from an outside provider may also impede the collaboration needed to effectively address mental illness.

In her 11 years in primary care at Associates in Family Medicine, Ms. McArdle had countless interactions with colleagues seeking support when managing a complex case. “I’m coaching providers, front desk staff, and nursing staff on how to interact with patients [with] behavioral health needs,” she said, citing the multitude of nonmedical factors that need to be considered, such as family relationships and patient preferences.

These unscheduled conversations with colleagues throughout the day are impossible to have when sharing a case with an unknown, remote peer.

Ms. McArdle speaks from experience. She recently resigned from Associates in Family Medicine to start her own private therapy practice after her former employer was acquired by VillageMD, a national provider that terminated employment of most other social workers in the practice and began outsourcing mental health care to Mindoula Health, a virtual provider.

Dr. Sieber offered a similar perspective on in-person collaboration as the psychiatric specialist at his center. He routinely offers on-site support for both providers and patients, serving as “another set of eyes and ears” when there is a concern about patient safety or directly managing care when a patient is hospitalized for mental illness.

While virtual solutions may fall short of in-person management, they can offer care at a scale and cost impossible through traditional practice.

This could even be free. Zero-cost, automated software now allows individuals who are uninsured or unable to afford care at least one avenue to manage their mental health concerns.

For example, Bliss is a free, 8-session, interactive online therapy program for depression that was created by the Centre for Interactive Mental Health Solutions. The program offers a tool for monitoring mood and quizzes to test understanding of personal mental health management, among other features.

More advanced programs are emerging as artificial intelligence (AI) enables dialogues between humans and machines. This is the case with Woebot, an app that asks the user about their mood throughout the day, and responds with evidence-based strategies for managing concerns, all for free at press time.
 

Keep learning

A range of educational options and professional resources are available for primary care providers who would like to improve their knowledge of mental health care. These include formal fellowships in primary care psychiatry/behavioral health integration, free mental health webinars, and various other opportunities.

Eric Eschweiler, DNP, APRN, FNP-C, PHN, completed the University of California, Irvine, Train New Trainers (TNT) Primary Care Psychiatry (PCP) Fellowship in 2016, when he was working as a solo nurse practitioner.

“I was drowning in practice,” said Dr. Eschweiler, director of nursing and public health outreach services at Riverside-San Bernardino County Indian Health, Grand Terrace, Calif., in an interview. “I was a solo NP. There was no physician on site. We were seeing a lot of [individuals with] schizoaffective [disorder] in downtown San Bernardino, the homeless, unhoused – a lot of substance use. I felt I needed to have the skills to be able to treat them effectively. That’s what the fellowship did.”

The skills Dr. Eschweiler learned from participating in his fellowship allowed him to manage more cases of mental illness without need for referral. When a referral was needed for a complex or severe case, he had the confidence to bridge care and collaborate more effectively with psychiatric specialists.

“It was awesome, because we were able to communicate using the same language,” Dr. Eschweiler said of these collaborations. “It’s [about] talking that same language, starting those initial treatments, and then moving forward with specialty care, and vice versa. [Psychiatric specialists] would send me patients that needed medical care because of the types of medications they were taking. And I was then very well aware of those side effects and other issues that might come up from those treatments. So it’s a two-way street.”

Dr. Eschweiler was so impressed by his fellowship that he has since ushered multiple providers through the program since transitioning to an administrative role as director of nursing.

In Fargo, where psychiatric care is sparse and wait times for referral can be months long, Dr. Mullally, like Dr. Eschweiler, knew that she needed more training in mental health.

“I don’t feel like we get enough training in residency,” Dr. Mullally said. “So you do need to look at your options for further CME.”

Out of several CME courses she has taken to further her understanding of pediatric psychiatry, Dr. Mullally recommended The Reach Institute above all others, as their courses involve in-depth discussions and valuable handouts, particularly for medication selection.

“I think that a lot of the other CMEs tend to involve a lot more PowerPoint presentations,” Dr. Mullally said. “And you don’t necessarily leave with a lot of good documents. I still use my Reach handouts. I have them sitting right next to me. I use them every single day.”

Providers interested in The Reach Institute, however, should be prepared to invest both time and money, she added, citing a 2-3 day commitment, and calling it “not cheap.” To overcome these barriers, she suggested that providers get their institution to support their attendance.

For a lighter commitment, Dr. Iruku recommended the American Academy of Family Physicians CME portal, as this offers 13 online, accredited courses covering a range of topics, from adolescent health to substance abuse disorders.

Dr. Sieber suggested that primary care providers join the Collaborative Family Healthcare Association, which aims to integrate physical and behavioral health in routine practice. CFHA, of which he is a member, offers a “bevy of different resources” for interested providers, including a conference in Phoenix this October.

The interviewees disclosed no conflicts of interest.

Primary care providers (PCPs) are addressing an increasing number of mental health visits, requiring collaborative and innovative approaches to providing psychiatric care.

This growth in the number of patients needing behavioral health–related care is likely driven by multiple factors, including a shortage of mental health care providers, an increasing incidence of psychiatric illness, and destigmatization of mental health in general, suggested Swetha P. Iruku, MD, MPH, associate professor of family medicine and community health at the University of Pennsylvania and Penn Medicine family physician in Philadelphia.

The Centers for Disease Control and Prevention noted that “the COVID-19 pandemic has been associated with mental health challenges related to the morbidity and mortality caused by the disease and to mitigation activities, including the impact of physical distancing and stay-at-home orders,” in a Morbidity and Mortality Weekly Report.

From June 24 to 30, 2020, U.S. adults reported considerably elevated adverse mental health conditions associated with COVID-19, and symptoms of anxiety disorder and depressive disorder climbed during the months of April through June of the same year, compared with the same period in 2019, they wrote.

Even before the pandemic got underway, multiple studies of national data published this year suggested mental issues were on the rise in the United States. For example, the proportion of adult patient visits to primary care providers that addressed mental health concerns rose from 10.7% to 15.9% from 2006 to 2018, according to research published in Health Affairs. Plus, the number and proportion of pediatric acute care hospitalizations because of mental health diagnoses increased significantly between 2009 and 2019, according to a paper published in JAMA.

“I truly believe that we can’t, as primary care physicians, take care of someone’s physical health without also taking care of their mental health,” Dr. Iruku said in an interview. “It’s all intertwined.”

To rise to this challenge, PCPs first need a collaborative mindset, she suggested, as well as familiarity with available resources, both locally and virtually.

This article examines strategies for managing mental illness in primary care, outlines clinical resources, and reviews related educational opportunities.

In addition, clinical pearls are shared by Dr. Iruku and five other clinicians who provide or have provided mental health care to primary care patients or work in close collaboration with a primary care practice, including a clinical psychologist, a nurse practitioner licensed in psychiatric health, a pediatrician, and a licensed clinical social worker.
 

Build a network

Most of the providers interviewed cited the importance of collaboration in mental health care, particularly for complex cases.

“I would recommend [that primary care providers get] to know the psychiatric providers [in their area],” said Jessica Viton, DNP, FNP, PMHNP, who delivers mental health care through a community-based primary care practice in Colorado which she requested remain anonymous.

Dr. Iruku suggested making an in-person connection first, if possible.

“So much of what we do is ‘see one, do one, teach one,’ so learn a little bit, then go off and trial,” she said. “[It can be valuable] having someone in your back pocket that you can contact in the case of an emergency, or in a situation where you just don’t know how to tackle it.”
 

Screen for depression and anxiety

William J. Sieber, PhD, a clinical psychologist, director of integrated behavioral health, and professor in the department of family medicine and public health and the department of psychiatry at the University of California, San Diego, said primary care providers should screen all adult patients for depression and anxiety with the Patient Health Questionnaire (PHQ-9) and General Anxiety Disorder Assessment (GAD-7), respectively.

To save time, he suggested a cascading approach.

“In primary care, everybody’s in a hurry,” Dr. Sieber said. “[With the cascading approach,] the first two items [from each questionnaire] are given, and if a person endorses either of those items … then they are asked to complete the other items.”

Jennifer Mullally, MD, a pediatrician at Sanford Health in Fargo, N.D., uses this cascading approach to depression and anxiety screening with all her patients aged 13-18. For younger kids, she screens only those who present with signs or symptoms of mental health issues, or if the parent shares a concern.

This approach differs slightly from U.S. Preventive Services Task Force recommendations, which suggest screening for anxiety in patients aged 8-18 years and depression in patients aged 12-18 years.
 

Use other screening tools only as needed

Dr. Sieber, the research director for the division of family medicine at UC San Diego, collaborates regularly with primary care providers via hallway consultations, by sharing cases, and through providing oversight of psychiatric care at 13 primary care practices within the UC San Diego network. He recommended against routine screening beyond depression and anxiety in the primary care setting.

“There are a lot of screening tools,” Dr. Sieber said. “It depends on what you’re presented with. The challenge in primary care is you’re going to see all kinds of things. It’s not like running a depression clinic.”

Other than the PHQ-9 and GAD-7, he suggested primary care providers establish familiarity with screening tools for posttraumatic stress disorder and attention-deficit/hyperactivity disorder, noting again that these should be used only when one of the conditions is already suspected.

Dr. Mullally follows a similar approach with her pediatric population. In addition to the GAD-7, she investigates whether a patient has anxiety with the Screen for Child Anxiety Related Disorders (SCARED). For depression, she couples the PHQ-9 with the Columbia Suicide Severity Rating Scale.

While additional screening tools like these are readily available online, Dr. Viton suggested that they should be employed only if the provider is trained to interpret and respond to those findings, and only if they know which tool to use, and when.

For example, she has recently observed PCPs diagnosing adults with ADHD using a three-question test, when in fact a full-length, standardized instrument should be administered by a provider with necessary training.

She also pointed out that bipolar disorder continues to be underdiagnosed, possibly because of providers detecting depression using a questionnaire like the PHQ-9, while failing to inquire about manic episodes.
 

Leverage online resources

If depression is confirmed, Dr. Iruku often directs the patient to the Mayo Clinic Depression Medication Choice Decision Aid. This website steers patients through medication options based on their answers to a questionnaire. Choices are listed alongside possible adverse effects.

For clinician use, Dr. Iruku recommended The Waco Guide to Psychopharmacology in Primary Care, which aids clinical decision-making for mental illness and substance abuse. The app processes case details to suggest first-, second-, and third-line pharmacotherapies, as well as modifications based on patient needs.

Even with tools like these, however, a referral may be needed.

“[Primary care providers] may not be the best fit for what the patient is looking for, from a mental health or behavioral standpoint,” Dr. Sieber said.

In this case, he encourages patients to visit Psychology Today, a “quite popular portal” that helps patients locate a suitable provider based on location, insurance, driving radius, and mental health concern. This usually generates 10-20 options, Dr. Sieber said, although results can vary.

“It may be discouraging, because maybe only three [providers] pop up based on your criteria, and the closest one is miles away,” he said.
 

Consider virtual support

If no local psychiatric help is available, Dr. Sieber suggested virtual support, highlighting that “it’s much easier now than it was 3 or 4 years ago” to connect patients with external mental health care.

But this strategy should be reserved for cases of actual need instead of pure convenience, cautioned Dr. Viton, who noted that virtual visits may fail to capture the nuance of an in-person meeting, as body language, mode of dress, and other clues can provide insights into mental health status.

“Occasionally, I think you do have to have an in-person visit, especially when you’re developing a rapport with someone,” Dr. Viton said.

Claire McArdle, a licensed clinical social worker in Fort Collins, Colo., noted that virtual care from an outside provider may also impede the collaboration needed to effectively address mental illness.

In her 11 years in primary care at Associates in Family Medicine, Ms. McArdle had countless interactions with colleagues seeking support when managing a complex case. “I’m coaching providers, front desk staff, and nursing staff on how to interact with patients [with] behavioral health needs,” she said, citing the multitude of nonmedical factors that need to be considered, such as family relationships and patient preferences.

These unscheduled conversations with colleagues throughout the day are impossible to have when sharing a case with an unknown, remote peer.

Ms. McArdle speaks from experience. She recently resigned from Associates in Family Medicine to start her own private therapy practice after her former employer was acquired by VillageMD, a national provider that terminated employment of most other social workers in the practice and began outsourcing mental health care to Mindoula Health, a virtual provider.

Dr. Sieber offered a similar perspective on in-person collaboration as the psychiatric specialist at his center. He routinely offers on-site support for both providers and patients, serving as “another set of eyes and ears” when there is a concern about patient safety or directly managing care when a patient is hospitalized for mental illness.

While virtual solutions may fall short of in-person management, they can offer care at a scale and cost impossible through traditional practice.

This could even be free. Zero-cost, automated software now allows individuals who are uninsured or unable to afford care at least one avenue to manage their mental health concerns.

For example, Bliss is a free, 8-session, interactive online therapy program for depression that was created by the Centre for Interactive Mental Health Solutions. The program offers a tool for monitoring mood and quizzes to test understanding of personal mental health management, among other features.

More advanced programs are emerging as artificial intelligence (AI) enables dialogues between humans and machines. This is the case with Woebot, an app that asks the user about their mood throughout the day, and responds with evidence-based strategies for managing concerns, all for free at press time.
 

Keep learning

A range of educational options and professional resources are available for primary care providers who would like to improve their knowledge of mental health care. These include formal fellowships in primary care psychiatry/behavioral health integration, free mental health webinars, and various other opportunities.

Eric Eschweiler, DNP, APRN, FNP-C, PHN, completed the University of California, Irvine, Train New Trainers (TNT) Primary Care Psychiatry (PCP) Fellowship in 2016, when he was working as a solo nurse practitioner.

“I was drowning in practice,” said Dr. Eschweiler, director of nursing and public health outreach services at Riverside-San Bernardino County Indian Health, Grand Terrace, Calif., in an interview. “I was a solo NP. There was no physician on site. We were seeing a lot of [individuals with] schizoaffective [disorder] in downtown San Bernardino, the homeless, unhoused – a lot of substance use. I felt I needed to have the skills to be able to treat them effectively. That’s what the fellowship did.”

The skills Dr. Eschweiler learned from participating in his fellowship allowed him to manage more cases of mental illness without need for referral. When a referral was needed for a complex or severe case, he had the confidence to bridge care and collaborate more effectively with psychiatric specialists.

“It was awesome, because we were able to communicate using the same language,” Dr. Eschweiler said of these collaborations. “It’s [about] talking that same language, starting those initial treatments, and then moving forward with specialty care, and vice versa. [Psychiatric specialists] would send me patients that needed medical care because of the types of medications they were taking. And I was then very well aware of those side effects and other issues that might come up from those treatments. So it’s a two-way street.”

Dr. Eschweiler was so impressed by his fellowship that he has since ushered multiple providers through the program since transitioning to an administrative role as director of nursing.

In Fargo, where psychiatric care is sparse and wait times for referral can be months long, Dr. Mullally, like Dr. Eschweiler, knew that she needed more training in mental health.

“I don’t feel like we get enough training in residency,” Dr. Mullally said. “So you do need to look at your options for further CME.”

Out of several CME courses she has taken to further her understanding of pediatric psychiatry, Dr. Mullally recommended The Reach Institute above all others, as their courses involve in-depth discussions and valuable handouts, particularly for medication selection.

“I think that a lot of the other CMEs tend to involve a lot more PowerPoint presentations,” Dr. Mullally said. “And you don’t necessarily leave with a lot of good documents. I still use my Reach handouts. I have them sitting right next to me. I use them every single day.”

Providers interested in The Reach Institute, however, should be prepared to invest both time and money, she added, citing a 2-3 day commitment, and calling it “not cheap.” To overcome these barriers, she suggested that providers get their institution to support their attendance.

For a lighter commitment, Dr. Iruku recommended the American Academy of Family Physicians CME portal, as this offers 13 online, accredited courses covering a range of topics, from adolescent health to substance abuse disorders.

Dr. Sieber suggested that primary care providers join the Collaborative Family Healthcare Association, which aims to integrate physical and behavioral health in routine practice. CFHA, of which he is a member, offers a “bevy of different resources” for interested providers, including a conference in Phoenix this October.

The interviewees disclosed no conflicts of interest.