Practice Gap

Basal cell carcinoma (BCC) is the most common cancer, and its incidence is on the rise.¹ The risk of this skin cancer is increased when there is a history of squamous cell carcinoma (SCC) or BCC.² Basal cell carcinoma often is found in sun-exposed areas, most commonly due to a history of intense sunburn.³ Other risk factors include male gender and increased age.⁴

Eighty percent to 85% of BCCs present on the head and neck⁵; however, BCC also can occur in unusual locations. When BCC presents in areas such as the perianal region, it is found to be larger than when found in more common areas,⁶ likely because neoplasms in this sensitive area often are overlooked. Literature on BCC of the intergluteal crease is limited.⁷ Being educated on the existence of BCC in this sensitive area can aid proper diagnosis.

The Technique and Case

An 83-year-old woman presented to the dermatology clinic for a suspicious lesion in the intergluteal crease that was tender to palpation with drainage. She first noticed this lesion and reported it to her primary care physician at a visit 6 months prior. The primary care physician did not pursue investigation of the lesion. One month later, the patient was seen by a gastroenterologist for the lesion and was referred to dermatology. The patient’s medical history included SCC and BCC on the face, both treated successfully with Mohs micrographic surgery.

Physical examination revealed a 2.6×1.1-cm, erythematous, nodular plaque in the coccygeal area of the intergluteal crease (Figure 1). A shave biopsy disclosed BCC, nodular type, ulcerated. Microscopically, there were nodular aggregates of basaloid cells with hyperchromatic nuclei and peripheral palisading, separated from mucinous stromal surroundings by artefactual clefts.

Practical Implications

Without thorough examination, this cancerous lesion would not have been seen (Figure 2). Therefore, it is important to practice thorough physical examination skills to avoid missing these cancers, particularly when examining a patient with a history of SCC or BCC. Furthermore, biopsy is recommended for suspicious lesions to rule out BCC.

Be careful not to get caught up in epidemiological or demographic considerations when making a diagnosis of this kind or when assessing the severity of a lesion. This patient, for instance, was female, which makes her less likely to present with BCC.⁸ Moreover, the cancer presented in a highly unlikely location for BCC, where there had not been significant sunburn.⁹ Patients and physicians should be educated about the incidence of BCC in unexpected areas; without a second and close look, this BCC could have been missed.

Final Thoughts

The literature continuously demonstrates the rarity of BCC in the intergluteal crease.¹⁰ However, when perianal BCC is properly identified and treated with local excision, prognosis is good.¹¹ Basal cell carcinoma has been seen to arise in other sensitive locations; vulvar, nipple, and scrotal BCC neoplasms are among the uncommon locations where BCC has appeared.¹² These areas are frequently—and easily—ignored. A total-body skin examination should be performed to ensure that these insidious-onset carcinomas are not overlooked to protect patients from the adverse consequences of untreated cancer.¹³

Practice Gap

Basal cell carcinoma (BCC) is the most common cancer, and its incidence is on the rise.¹ The risk of this skin cancer is increased when there is a history of squamous cell carcinoma (SCC) or BCC.² Basal cell carcinoma often is found in sun-exposed areas, most commonly due to a history of intense sunburn.³ Other risk factors include male gender and increased age.⁴

Eighty percent to 85% of BCCs present on the head and neck⁵; however, BCC also can occur in unusual locations. When BCC presents in areas such as the perianal region, it is found to be larger than when found in more common areas,⁶ likely because neoplasms in this sensitive area often are overlooked. Literature on BCC of the intergluteal crease is limited.⁷ Being educated on the existence of BCC in this sensitive area can aid proper diagnosis.

The Technique and Case

An 83-year-old woman presented to the dermatology clinic for a suspicious lesion in the intergluteal crease that was tender to palpation with drainage. She first noticed this lesion and reported it to her primary care physician at a visit 6 months prior. The primary care physician did not pursue investigation of the lesion. One month later, the patient was seen by a gastroenterologist for the lesion and was referred to dermatology. The patient’s medical history included SCC and BCC on the face, both treated successfully with Mohs micrographic surgery.

Physical examination revealed a 2.6×1.1-cm, erythematous, nodular plaque in the coccygeal area of the intergluteal crease (Figure 1). A shave biopsy disclosed BCC, nodular type, ulcerated. Microscopically, there were nodular aggregates of basaloid cells with hyperchromatic nuclei and peripheral palisading, separated from mucinous stromal surroundings by artefactual clefts.

Practical Implications

Without thorough examination, this cancerous lesion would not have been seen (Figure 2). Therefore, it is important to practice thorough physical examination skills to avoid missing these cancers, particularly when examining a patient with a history of SCC or BCC. Furthermore, biopsy is recommended for suspicious lesions to rule out BCC.

Be careful not to get caught up in epidemiological or demographic considerations when making a diagnosis of this kind or when assessing the severity of a lesion. This patient, for instance, was female, which makes her less likely to present with BCC.⁸ Moreover, the cancer presented in a highly unlikely location for BCC, where there had not been significant sunburn.⁹ Patients and physicians should be educated about the incidence of BCC in unexpected areas; without a second and close look, this BCC could have been missed.

Final Thoughts

The literature continuously demonstrates the rarity of BCC in the intergluteal crease.¹⁰ However, when perianal BCC is properly identified and treated with local excision, prognosis is good.¹¹ Basal cell carcinoma has been seen to arise in other sensitive locations; vulvar, nipple, and scrotal BCC neoplasms are among the uncommon locations where BCC has appeared.¹² These areas are frequently—and easily—ignored. A total-body skin examination should be performed to ensure that these insidious-onset carcinomas are not overlooked to protect patients from the adverse consequences of untreated cancer.¹³

Practice Gap

Basal cell carcinoma (BCC) is the most common cancer, and its incidence is on the rise.¹ The risk of this skin cancer is increased when there is a history of squamous cell carcinoma (SCC) or BCC.² Basal cell carcinoma often is found in sun-exposed areas, most commonly due to a history of intense sunburn.³ Other risk factors include male gender and increased age.⁴

Eighty percent to 85% of BCCs present on the head and neck⁵; however, BCC also can occur in unusual locations. When BCC presents in areas such as the perianal region, it is found to be larger than when found in more common areas,⁶ likely because neoplasms in this sensitive area often are overlooked. Literature on BCC of the intergluteal crease is limited.⁷ Being educated on the existence of BCC in this sensitive area can aid proper diagnosis.

The Technique and Case

An 83-year-old woman presented to the dermatology clinic for a suspicious lesion in the intergluteal crease that was tender to palpation with drainage. She first noticed this lesion and reported it to her primary care physician at a visit 6 months prior. The primary care physician did not pursue investigation of the lesion. One month later, the patient was seen by a gastroenterologist for the lesion and was referred to dermatology. The patient’s medical history included SCC and BCC on the face, both treated successfully with Mohs micrographic surgery.

Physical examination revealed a 2.6×1.1-cm, erythematous, nodular plaque in the coccygeal area of the intergluteal crease (Figure 1). A shave biopsy disclosed BCC, nodular type, ulcerated. Microscopically, there were nodular aggregates of basaloid cells with hyperchromatic nuclei and peripheral palisading, separated from mucinous stromal surroundings by artefactual clefts.

Practical Implications

Without thorough examination, this cancerous lesion would not have been seen (Figure 2). Therefore, it is important to practice thorough physical examination skills to avoid missing these cancers, particularly when examining a patient with a history of SCC or BCC. Furthermore, biopsy is recommended for suspicious lesions to rule out BCC.

Be careful not to get caught up in epidemiological or demographic considerations when making a diagnosis of this kind or when assessing the severity of a lesion. This patient, for instance, was female, which makes her less likely to present with BCC.⁸ Moreover, the cancer presented in a highly unlikely location for BCC, where there had not been significant sunburn.⁹ Patients and physicians should be educated about the incidence of BCC in unexpected areas; without a second and close look, this BCC could have been missed.

Final Thoughts

The literature continuously demonstrates the rarity of BCC in the intergluteal crease.¹⁰ However, when perianal BCC is properly identified and treated with local excision, prognosis is good.¹¹ Basal cell carcinoma has been seen to arise in other sensitive locations; vulvar, nipple, and scrotal BCC neoplasms are among the uncommon locations where BCC has appeared.¹² These areas are frequently—and easily—ignored. A total-body skin examination should be performed to ensure that these insidious-onset carcinomas are not overlooked to protect patients from the adverse consequences of untreated cancer.¹³

Women at risk of preterm birth who took daily low-dose aspirin did not have significantly lower rates of preterm birth than those who did not take aspirin, according to preliminary findings from a small randomized controlled trial. There was a trend toward lower rates, especially among those with the highest compliance, but the study was underpowered to detect a difference with statistical significance, said Anadeijda Landman, MD, of the Amsterdam University Medical Center. Dr. Landman presented the findings Jan. 28 at a meeting sponsored by the Society for Maternal-Fetal Medicine.

Preterm birth accounts for a third of all neonatal mortality, she told attendees. Among 15 million preterm births worldwide each year, 65% are spontaneous, indicating the need for effective preventive interventions. Dr. Landman reviewed several mechanisms by which aspirin may help reduce preterm birth via different pathways.

The researchers’ multicenter, placebo-controlled trial involved 8 tertiary care and 26 secondary care hospitals in the Netherlands between May 2016 and June 2019. Starting between 8 and 15 weeks’ gestation, women took either 80 mg of aspirin or a placebo daily until 36 weeks’ gestation or delivery. Women also received progesterone, cerclage, or pessary as indicated according to local protocols.

The study enrolled 406 women with singleton pregnancy and a history of preterm birth delivered between 22 and 37 weeks’ gestation. The final analysis, after exclusions for pregnancy termination, congenital anomalies, multiples pregnancy, or similar reasons, included 193 women in the intervention group and 194 in the placebo group. The women had similar baseline characteristics across both groups except a higher number of past mid-trimester fetal deaths in the aspirin group.

“It’s important to realize these women had multiple preterm births, as one of our inclusion criteria was previous spontaneous preterm birth later than 22 weeks’ gestation, so this particular group is very high risk for cervical insufficiency as a probable cause,” Dr. Landman told attendees.

Among women in the aspirin group, 21.2% delivered before 37 weeks, compared with 25.4% in the placebo group (P = .323). The rate of spontaneous birth was 20.1% in the aspirin group and 23.8% in the placebo group (P = .376). Though still not statistically significant, the difference between the groups was larger when the researchers limited their analysis to the 245 women with at least 80% compliance: 18.5% of women in the aspirin group had a preterm birth, compared with 24.8% of women in the placebo group (P = .238).

There were no significant differences between the groups in composite poor neonatal outcomes or in a range of prespecified newborn complications. The aspirin group did have two stillbirths, two mid-trimester fetal losses, and two extremely preterm newborns (at 24+2 weeks and 25+2 weeks). The placebo group had two mid-trimester fetal losses.

“These deaths are inherent to the study population, and it seems unlikely they are related to the use of aspirin,” Dr. Landman said. “Moreover other aspirin studies have not found an increased perinatal mortality rate, and some large studies indicated the neonatal mortality rate is even reduced.”

Although preterm birth only trended lower in the aspirin group, Dr. Landman said the researchers believe they cannot rule out an effect from aspirin.

“It’s also important to note that our study was underpowered as the recurrence risk of preterm birth in our study was lower than expected, so it’s possible a small treatment effect of aspirin could not be demonstrated in our study,” she said. “And, despite the proper randomization procedure, many more women in the aspirin group had a previous mid-trimester fetal loss. This indicates that the aspirin group might be more at risk for preterm birth than the placebo group, and this imbalance could also have diminished a small protective effect of aspirin.”

In response to an audience question, Dr. Landman acknowledged that more recent studies on aspirin have used 100- to 150-mg dosages, but that evidence was not as clear when their study began in 2015. She added that her research team does not advise changing clinical care currently and believes it is too soon to recommend aspirin to this population.

Tracy Manuck, MD, MS, an associate professor of ob.gyn. at the University of North Carolina in Chapel Hill, agreed that it is premature to begin prescribing aspirin for preterm birth prevention, but she noted that most of the patients she cares for clinically already meet criteria for aspirin based on their risk factors for preeclampsia.

“Additional research is needed in the form of a well-designed and large [randomized, controlled trial],” Dr Manuck, who moderated the session, said in an interview. “However, such a trial is becoming increasingly difficult to conduct because so many pregnant women qualify to receive aspirin for the prevention of preeclampsia due to their weight, medical comorbidities, or prior pregnancy history.”

She said she anticipates seeing patient-level data meta-analyses in the coming months as more data on aspirin for preterm birth prevention are published.

“Given that these data are supportive of the overall trends seen in prior publications, I do think that low-dose aspirin will eventually bear out as a helpful preventative measure to prevent recurrent preterm birth. Aspirin is low risk, readily available, and is inexpensive,” Dr. Manuck said. “I hope that meta-analysis data will provide additional information regarding the benefit of low-dose aspirin for prematurity prevention.”

The research was funded by the Dutch Organization for Health Care Research and the Dutch Consortium for Research in Women’s Health. Dr. Landman and Dr. Manuck had no disclosures.

Women at risk of preterm birth who took daily low-dose aspirin did not have significantly lower rates of preterm birth than those who did not take aspirin, according to preliminary findings from a small randomized controlled trial. There was a trend toward lower rates, especially among those with the highest compliance, but the study was underpowered to detect a difference with statistical significance, said Anadeijda Landman, MD, of the Amsterdam University Medical Center. Dr. Landman presented the findings Jan. 28 at a meeting sponsored by the Society for Maternal-Fetal Medicine.

Preterm birth accounts for a third of all neonatal mortality, she told attendees. Among 15 million preterm births worldwide each year, 65% are spontaneous, indicating the need for effective preventive interventions. Dr. Landman reviewed several mechanisms by which aspirin may help reduce preterm birth via different pathways.

The researchers’ multicenter, placebo-controlled trial involved 8 tertiary care and 26 secondary care hospitals in the Netherlands between May 2016 and June 2019. Starting between 8 and 15 weeks’ gestation, women took either 80 mg of aspirin or a placebo daily until 36 weeks’ gestation or delivery. Women also received progesterone, cerclage, or pessary as indicated according to local protocols.

The study enrolled 406 women with singleton pregnancy and a history of preterm birth delivered between 22 and 37 weeks’ gestation. The final analysis, after exclusions for pregnancy termination, congenital anomalies, multiples pregnancy, or similar reasons, included 193 women in the intervention group and 194 in the placebo group. The women had similar baseline characteristics across both groups except a higher number of past mid-trimester fetal deaths in the aspirin group.

“It’s important to realize these women had multiple preterm births, as one of our inclusion criteria was previous spontaneous preterm birth later than 22 weeks’ gestation, so this particular group is very high risk for cervical insufficiency as a probable cause,” Dr. Landman told attendees.

Among women in the aspirin group, 21.2% delivered before 37 weeks, compared with 25.4% in the placebo group (P = .323). The rate of spontaneous birth was 20.1% in the aspirin group and 23.8% in the placebo group (P = .376). Though still not statistically significant, the difference between the groups was larger when the researchers limited their analysis to the 245 women with at least 80% compliance: 18.5% of women in the aspirin group had a preterm birth, compared with 24.8% of women in the placebo group (P = .238).

There were no significant differences between the groups in composite poor neonatal outcomes or in a range of prespecified newborn complications. The aspirin group did have two stillbirths, two mid-trimester fetal losses, and two extremely preterm newborns (at 24+2 weeks and 25+2 weeks). The placebo group had two mid-trimester fetal losses.

“These deaths are inherent to the study population, and it seems unlikely they are related to the use of aspirin,” Dr. Landman said. “Moreover other aspirin studies have not found an increased perinatal mortality rate, and some large studies indicated the neonatal mortality rate is even reduced.”

Although preterm birth only trended lower in the aspirin group, Dr. Landman said the researchers believe they cannot rule out an effect from aspirin.

“It’s also important to note that our study was underpowered as the recurrence risk of preterm birth in our study was lower than expected, so it’s possible a small treatment effect of aspirin could not be demonstrated in our study,” she said. “And, despite the proper randomization procedure, many more women in the aspirin group had a previous mid-trimester fetal loss. This indicates that the aspirin group might be more at risk for preterm birth than the placebo group, and this imbalance could also have diminished a small protective effect of aspirin.”

In response to an audience question, Dr. Landman acknowledged that more recent studies on aspirin have used 100- to 150-mg dosages, but that evidence was not as clear when their study began in 2015. She added that her research team does not advise changing clinical care currently and believes it is too soon to recommend aspirin to this population.

Tracy Manuck, MD, MS, an associate professor of ob.gyn. at the University of North Carolina in Chapel Hill, agreed that it is premature to begin prescribing aspirin for preterm birth prevention, but she noted that most of the patients she cares for clinically already meet criteria for aspirin based on their risk factors for preeclampsia.

“Additional research is needed in the form of a well-designed and large [randomized, controlled trial],” Dr Manuck, who moderated the session, said in an interview. “However, such a trial is becoming increasingly difficult to conduct because so many pregnant women qualify to receive aspirin for the prevention of preeclampsia due to their weight, medical comorbidities, or prior pregnancy history.”

She said she anticipates seeing patient-level data meta-analyses in the coming months as more data on aspirin for preterm birth prevention are published.

“Given that these data are supportive of the overall trends seen in prior publications, I do think that low-dose aspirin will eventually bear out as a helpful preventative measure to prevent recurrent preterm birth. Aspirin is low risk, readily available, and is inexpensive,” Dr. Manuck said. “I hope that meta-analysis data will provide additional information regarding the benefit of low-dose aspirin for prematurity prevention.”

The research was funded by the Dutch Organization for Health Care Research and the Dutch Consortium for Research in Women’s Health. Dr. Landman and Dr. Manuck had no disclosures.

Women at risk of preterm birth who took daily low-dose aspirin did not have significantly lower rates of preterm birth than those who did not take aspirin, according to preliminary findings from a small randomized controlled trial. There was a trend toward lower rates, especially among those with the highest compliance, but the study was underpowered to detect a difference with statistical significance, said Anadeijda Landman, MD, of the Amsterdam University Medical Center. Dr. Landman presented the findings Jan. 28 at a meeting sponsored by the Society for Maternal-Fetal Medicine.

Preterm birth accounts for a third of all neonatal mortality, she told attendees. Among 15 million preterm births worldwide each year, 65% are spontaneous, indicating the need for effective preventive interventions. Dr. Landman reviewed several mechanisms by which aspirin may help reduce preterm birth via different pathways.

The researchers’ multicenter, placebo-controlled trial involved 8 tertiary care and 26 secondary care hospitals in the Netherlands between May 2016 and June 2019. Starting between 8 and 15 weeks’ gestation, women took either 80 mg of aspirin or a placebo daily until 36 weeks’ gestation or delivery. Women also received progesterone, cerclage, or pessary as indicated according to local protocols.

The study enrolled 406 women with singleton pregnancy and a history of preterm birth delivered between 22 and 37 weeks’ gestation. The final analysis, after exclusions for pregnancy termination, congenital anomalies, multiples pregnancy, or similar reasons, included 193 women in the intervention group and 194 in the placebo group. The women had similar baseline characteristics across both groups except a higher number of past mid-trimester fetal deaths in the aspirin group.

“It’s important to realize these women had multiple preterm births, as one of our inclusion criteria was previous spontaneous preterm birth later than 22 weeks’ gestation, so this particular group is very high risk for cervical insufficiency as a probable cause,” Dr. Landman told attendees.

Among women in the aspirin group, 21.2% delivered before 37 weeks, compared with 25.4% in the placebo group (P = .323). The rate of spontaneous birth was 20.1% in the aspirin group and 23.8% in the placebo group (P = .376). Though still not statistically significant, the difference between the groups was larger when the researchers limited their analysis to the 245 women with at least 80% compliance: 18.5% of women in the aspirin group had a preterm birth, compared with 24.8% of women in the placebo group (P = .238).

There were no significant differences between the groups in composite poor neonatal outcomes or in a range of prespecified newborn complications. The aspirin group did have two stillbirths, two mid-trimester fetal losses, and two extremely preterm newborns (at 24+2 weeks and 25+2 weeks). The placebo group had two mid-trimester fetal losses.

“These deaths are inherent to the study population, and it seems unlikely they are related to the use of aspirin,” Dr. Landman said. “Moreover other aspirin studies have not found an increased perinatal mortality rate, and some large studies indicated the neonatal mortality rate is even reduced.”

Although preterm birth only trended lower in the aspirin group, Dr. Landman said the researchers believe they cannot rule out an effect from aspirin.

“It’s also important to note that our study was underpowered as the recurrence risk of preterm birth in our study was lower than expected, so it’s possible a small treatment effect of aspirin could not be demonstrated in our study,” she said. “And, despite the proper randomization procedure, many more women in the aspirin group had a previous mid-trimester fetal loss. This indicates that the aspirin group might be more at risk for preterm birth than the placebo group, and this imbalance could also have diminished a small protective effect of aspirin.”

In response to an audience question, Dr. Landman acknowledged that more recent studies on aspirin have used 100- to 150-mg dosages, but that evidence was not as clear when their study began in 2015. She added that her research team does not advise changing clinical care currently and believes it is too soon to recommend aspirin to this population.

Tracy Manuck, MD, MS, an associate professor of ob.gyn. at the University of North Carolina in Chapel Hill, agreed that it is premature to begin prescribing aspirin for preterm birth prevention, but she noted that most of the patients she cares for clinically already meet criteria for aspirin based on their risk factors for preeclampsia.

“Additional research is needed in the form of a well-designed and large [randomized, controlled trial],” Dr Manuck, who moderated the session, said in an interview. “However, such a trial is becoming increasingly difficult to conduct because so many pregnant women qualify to receive aspirin for the prevention of preeclampsia due to their weight, medical comorbidities, or prior pregnancy history.”

She said she anticipates seeing patient-level data meta-analyses in the coming months as more data on aspirin for preterm birth prevention are published.

“Given that these data are supportive of the overall trends seen in prior publications, I do think that low-dose aspirin will eventually bear out as a helpful preventative measure to prevent recurrent preterm birth. Aspirin is low risk, readily available, and is inexpensive,” Dr. Manuck said. “I hope that meta-analysis data will provide additional information regarding the benefit of low-dose aspirin for prematurity prevention.”

The research was funded by the Dutch Organization for Health Care Research and the Dutch Consortium for Research in Women’s Health. Dr. Landman and Dr. Manuck had no disclosures.

On Jan. 13, 2 days after a drive-through vaccination “superstation” opened in San Diego, six people were treated for anaphylaxis after they received the Moderna vaccine, leading the California state epidemiologist to recommend pausing the administration of that particular lot.
 

A group of allergy and immunology experts and public health officials reviewed the cases, as well as an incident that occurred the day before, and concluded that at least some of the responses were angioedema, or swelling — a serious allergic reaction — but none were actually anaphylaxis. No similar clusters had occurred with the same vaccine lot in other states, and California resumed using the doses.

Yet questions remain about the reactions and the mechanisms for them. Some might have been triggered by an allergy to a vaccine component, most likely the polyethylene glycol (PEG) that stabilizes the lipid surrounding the mRNA, the key vaccine component in both the Moderna and Pfizer vaccines. Another possible explanation is that some could be pseudoallergic reactions to a blood protein known as complement, a little-understood process that resembles an antigen-based reaction but doesn’t leave an immune memory and might not recur.

Cases of complement-activation-related pseudoallergy look like a severe allergic reaction but occur through a different mechanism and don’t require previous exposure to an allergen.

“It has the same signs and symptoms and is treated the same way, but it occurs through a different pathway,” explained Neal Halsey, MD, director emeritus of the Institute for Vaccine Safety and emeritus professor at the Johns Hopkins Bloomberg School of Public Health in Baltimore.

Pseudoallergies are not well understood, but they have been associated with reactions to the contrast media used in imaging, such as with MRI. “If people have had an anaphylaxis-type reaction following the injection of contrast-dye material, that is a strong signal that it might be a complement-activation-related pseudoallergy,” said Dr. Halsey, a member of the Clinical Immunization Safety Assessment Network. “Those are the people who definitely need to consider seeing an allergist before getting the COVID vaccines.”

When Aleena Banerji, MD, clinical director of the allergy and clinical immunology unit at Massachusetts General Hospital in Boston, talks to patients about vaccine reactions, she addresses the risk for COVID-19 infection. All of the people who developed allergies after the Pfizer and Moderna vaccines recovered, but more than 445,000 Americans have died from COVID-19.

Most people with common allergies, such as to food or oral medications, don’t need to worry about reactions, said Dr. Banerji, lead author of a review that assessed the risk for allergic reactions to the Pfizer and Moderna vaccines.
 

Investigating reactions

As investigators search for the answers to what causes reactions, transparency is crucial to trust, said Kathryn Edwards, MD, principal investigator of the Clinical Immunization Safety Assessment Project, a vaccine safety network funded by the Centers for Disease Control and Prevention.

“Unless the public knows that we’re really investigating and we’re taking this seriously, then I think the vaccine hesitancy is going to increase,” said Dr. Edwards, professor of pediatrics at Vanderbilt University Medical Center and scientific director of the Vanderbilt Vaccine Research Program in Nashville, Tenn.

First reports of anaphylaxis came quickly after COVID-19 vaccinations began. In the 2 weeks before the holidays, almost 2 million health care workers received the Pfizer vaccine, and 21 of them developed anaphylaxis, according to CDC researchers who reviewed case reports from the Vaccine Adverse Event Reporting System (VAERS). That rate of about 1 in 100,000 is 10 times higher than the occurrence with other vaccines. No deaths from anaphylaxis were reported.

As the vaccinations ramped up, the rate declined. As of Jan. 18, 50 cases of anaphylaxis were reported to VAERS after the administration of 9,943,247 Pfizer doses, for a rate of 5.0 per million, according to data presented at the Jan. 27 meeting of the CDC Advisory Committee on Immunization Practices. And 21 cases of anaphylaxis were reported to VAERS after the administration of 7,581,429 Moderna doses, for a rate of 2.8 per million.

The anaphylaxis occurred almost exclusively in women; only three of the VAERS anaphylaxis reports were from men. Only 24% had a history of anaphylaxis.

The earlier CDC report explored the potential link to allergies. One person with anaphylaxis had a history of allergy to iodinated contrast media, and others had allergies to various medications, vaccines, foods, and animals. The researchers reported 86 nonanaphylaxis allergic reactions and 61 nonallergic adverse events among the 175 case reports they reviewed as possible cases of severe allergic reaction.

Of 1,266 reports that VAERS received from Dec. 21 to Jan. 10, the CDC identified 108 possible cases of severe allergic reaction after the Moderna vaccine. Only 10 met the case definition of anaphylaxis put forward by the Brighton Collaboration, a vaccine safety organization. All but one case involved a history of allergies or allergic reactions; only five had a previously experienced anaphylaxis.

There were 47 nonanaphylaxis allergic reactions.

The San Diego cluster also met the Brighton case definition for anaphylaxis, Dr. Edwards reported. This discrepancy highlights the difficulties in characterizing vaccine reactions.

Measuring a pseudoallergic reaction is a challenge. It requires that a blood sample be drawn soon after the incident and then frozen to protect heat-sensitive blood markers, Dr. Edwards explained.

And as vaccinations rise, so do adverse-event reports. But unlike in clinical trials, there is no control group for comparison. That is why vaccine safety experts urge caution when evaluating events and, where possible, advise looking at background rates.

“A major way to determine whether the adverse event is causally related is to assess the incidence of the adverse event in vaccines versus nonvaccines,” said Walter Orenstein, MD, who directed the U.S. Immunization Program from 1988 to 2004 and is now associate director of the Emory Vaccine Center and professor of infectious diseases at Emory University in Atlanta. Public health officials could then identify vaccine risk factors, he said.

When a reaction occurs almost immediately after vaccination, vaccine safety investigators look for probable triggers. If allergy to PEG is the culprit in anaphylactic reactions, then the individuals would have had a previous exposure, perhaps from injectable medications, Dr. Edwards said.

It might be feasible to perform a skin test for allergy to PEG. “If the skin testing is negative, that doesn’t completely rule out allergy, but it can be used in the decision-making about giving the first or second vaccine dose,” Dr. Banerji said.

Other vaccines, such as childhood vaccines, contain polysorbate as a stabilizer, which has a similar chemical structure, and it’s not clear why someone would react to PEG but not to polysorbate, Dr. Edwards said.

Meanwhile, other illnesses and even deaths sometimes occur in the days after vaccination, but that doesn’t mean the vaccine caused them, cautioned Steve Black, MD, emeritus professor of pediatrics at Cincinnati Children’s Hospital and cofounder of the Global Vaccine Data Network, an international vaccine safety collaboration.

“Different events and clusters of events will occur by chance alone, as these events can occur without vaccines. We need to not immediately assume that they’re due to the vaccine,” he said. “You don’t want to undermine the whole vaccine program every time something comes up and assume that it’s associated with the vaccine.”

The CDC only has three contraindications for the vaccines:

• Severe allergic reaction (such as anaphylaxis) after a previous dose of an mRNA COVID-19 vaccine or any of its components.
• Immediate allergic reaction of any severity to a previous dose of an mRNA COVID-19 vaccine or any of its components (including PEG).
• Immediate allergic reaction of any severity to polysorbate (due to potential cross-reactive hypersensitivity with PEG).

People who have had an immediate allergic reaction to other vaccines or injectable therapies should consider consulting with an allergist or immunologist before getting the Pfizer or Moderna vaccines, the CDC advises.

The CDC also says that people with a history of anaphylaxis from any cause should be observed for 30 minutes after vaccination. Vaccination protocol calls for everyone else to wait on site for 15 minutes after vaccination.

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

On Jan. 13, 2 days after a drive-through vaccination “superstation” opened in San Diego, six people were treated for anaphylaxis after they received the Moderna vaccine, leading the California state epidemiologist to recommend pausing the administration of that particular lot.
 

A group of allergy and immunology experts and public health officials reviewed the cases, as well as an incident that occurred the day before, and concluded that at least some of the responses were angioedema, or swelling — a serious allergic reaction — but none were actually anaphylaxis. No similar clusters had occurred with the same vaccine lot in other states, and California resumed using the doses.

Yet questions remain about the reactions and the mechanisms for them. Some might have been triggered by an allergy to a vaccine component, most likely the polyethylene glycol (PEG) that stabilizes the lipid surrounding the mRNA, the key vaccine component in both the Moderna and Pfizer vaccines. Another possible explanation is that some could be pseudoallergic reactions to a blood protein known as complement, a little-understood process that resembles an antigen-based reaction but doesn’t leave an immune memory and might not recur.

Cases of complement-activation-related pseudoallergy look like a severe allergic reaction but occur through a different mechanism and don’t require previous exposure to an allergen.

“It has the same signs and symptoms and is treated the same way, but it occurs through a different pathway,” explained Neal Halsey, MD, director emeritus of the Institute for Vaccine Safety and emeritus professor at the Johns Hopkins Bloomberg School of Public Health in Baltimore.

Pseudoallergies are not well understood, but they have been associated with reactions to the contrast media used in imaging, such as with MRI. “If people have had an anaphylaxis-type reaction following the injection of contrast-dye material, that is a strong signal that it might be a complement-activation-related pseudoallergy,” said Dr. Halsey, a member of the Clinical Immunization Safety Assessment Network. “Those are the people who definitely need to consider seeing an allergist before getting the COVID vaccines.”

When Aleena Banerji, MD, clinical director of the allergy and clinical immunology unit at Massachusetts General Hospital in Boston, talks to patients about vaccine reactions, she addresses the risk for COVID-19 infection. All of the people who developed allergies after the Pfizer and Moderna vaccines recovered, but more than 445,000 Americans have died from COVID-19.

Most people with common allergies, such as to food or oral medications, don’t need to worry about reactions, said Dr. Banerji, lead author of a review that assessed the risk for allergic reactions to the Pfizer and Moderna vaccines.
 

Investigating reactions

As investigators search for the answers to what causes reactions, transparency is crucial to trust, said Kathryn Edwards, MD, principal investigator of the Clinical Immunization Safety Assessment Project, a vaccine safety network funded by the Centers for Disease Control and Prevention.

“Unless the public knows that we’re really investigating and we’re taking this seriously, then I think the vaccine hesitancy is going to increase,” said Dr. Edwards, professor of pediatrics at Vanderbilt University Medical Center and scientific director of the Vanderbilt Vaccine Research Program in Nashville, Tenn.

First reports of anaphylaxis came quickly after COVID-19 vaccinations began. In the 2 weeks before the holidays, almost 2 million health care workers received the Pfizer vaccine, and 21 of them developed anaphylaxis, according to CDC researchers who reviewed case reports from the Vaccine Adverse Event Reporting System (VAERS). That rate of about 1 in 100,000 is 10 times higher than the occurrence with other vaccines. No deaths from anaphylaxis were reported.

As the vaccinations ramped up, the rate declined. As of Jan. 18, 50 cases of anaphylaxis were reported to VAERS after the administration of 9,943,247 Pfizer doses, for a rate of 5.0 per million, according to data presented at the Jan. 27 meeting of the CDC Advisory Committee on Immunization Practices. And 21 cases of anaphylaxis were reported to VAERS after the administration of 7,581,429 Moderna doses, for a rate of 2.8 per million.

The anaphylaxis occurred almost exclusively in women; only three of the VAERS anaphylaxis reports were from men. Only 24% had a history of anaphylaxis.

The earlier CDC report explored the potential link to allergies. One person with anaphylaxis had a history of allergy to iodinated contrast media, and others had allergies to various medications, vaccines, foods, and animals. The researchers reported 86 nonanaphylaxis allergic reactions and 61 nonallergic adverse events among the 175 case reports they reviewed as possible cases of severe allergic reaction.

Of 1,266 reports that VAERS received from Dec. 21 to Jan. 10, the CDC identified 108 possible cases of severe allergic reaction after the Moderna vaccine. Only 10 met the case definition of anaphylaxis put forward by the Brighton Collaboration, a vaccine safety organization. All but one case involved a history of allergies or allergic reactions; only five had a previously experienced anaphylaxis.

There were 47 nonanaphylaxis allergic reactions.

The San Diego cluster also met the Brighton case definition for anaphylaxis, Dr. Edwards reported. This discrepancy highlights the difficulties in characterizing vaccine reactions.

Measuring a pseudoallergic reaction is a challenge. It requires that a blood sample be drawn soon after the incident and then frozen to protect heat-sensitive blood markers, Dr. Edwards explained.

And as vaccinations rise, so do adverse-event reports. But unlike in clinical trials, there is no control group for comparison. That is why vaccine safety experts urge caution when evaluating events and, where possible, advise looking at background rates.

“A major way to determine whether the adverse event is causally related is to assess the incidence of the adverse event in vaccines versus nonvaccines,” said Walter Orenstein, MD, who directed the U.S. Immunization Program from 1988 to 2004 and is now associate director of the Emory Vaccine Center and professor of infectious diseases at Emory University in Atlanta. Public health officials could then identify vaccine risk factors, he said.

When a reaction occurs almost immediately after vaccination, vaccine safety investigators look for probable triggers. If allergy to PEG is the culprit in anaphylactic reactions, then the individuals would have had a previous exposure, perhaps from injectable medications, Dr. Edwards said.

It might be feasible to perform a skin test for allergy to PEG. “If the skin testing is negative, that doesn’t completely rule out allergy, but it can be used in the decision-making about giving the first or second vaccine dose,” Dr. Banerji said.

Other vaccines, such as childhood vaccines, contain polysorbate as a stabilizer, which has a similar chemical structure, and it’s not clear why someone would react to PEG but not to polysorbate, Dr. Edwards said.

Meanwhile, other illnesses and even deaths sometimes occur in the days after vaccination, but that doesn’t mean the vaccine caused them, cautioned Steve Black, MD, emeritus professor of pediatrics at Cincinnati Children’s Hospital and cofounder of the Global Vaccine Data Network, an international vaccine safety collaboration.

“Different events and clusters of events will occur by chance alone, as these events can occur without vaccines. We need to not immediately assume that they’re due to the vaccine,” he said. “You don’t want to undermine the whole vaccine program every time something comes up and assume that it’s associated with the vaccine.”

The CDC only has three contraindications for the vaccines:

• Severe allergic reaction (such as anaphylaxis) after a previous dose of an mRNA COVID-19 vaccine or any of its components.
• Immediate allergic reaction of any severity to a previous dose of an mRNA COVID-19 vaccine or any of its components (including PEG).
• Immediate allergic reaction of any severity to polysorbate (due to potential cross-reactive hypersensitivity with PEG).

People who have had an immediate allergic reaction to other vaccines or injectable therapies should consider consulting with an allergist or immunologist before getting the Pfizer or Moderna vaccines, the CDC advises.

The CDC also says that people with a history of anaphylaxis from any cause should be observed for 30 minutes after vaccination. Vaccination protocol calls for everyone else to wait on site for 15 minutes after vaccination.

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

On Jan. 13, 2 days after a drive-through vaccination “superstation” opened in San Diego, six people were treated for anaphylaxis after they received the Moderna vaccine, leading the California state epidemiologist to recommend pausing the administration of that particular lot.
 

A group of allergy and immunology experts and public health officials reviewed the cases, as well as an incident that occurred the day before, and concluded that at least some of the responses were angioedema, or swelling — a serious allergic reaction — but none were actually anaphylaxis. No similar clusters had occurred with the same vaccine lot in other states, and California resumed using the doses.

Yet questions remain about the reactions and the mechanisms for them. Some might have been triggered by an allergy to a vaccine component, most likely the polyethylene glycol (PEG) that stabilizes the lipid surrounding the mRNA, the key vaccine component in both the Moderna and Pfizer vaccines. Another possible explanation is that some could be pseudoallergic reactions to a blood protein known as complement, a little-understood process that resembles an antigen-based reaction but doesn’t leave an immune memory and might not recur.

Cases of complement-activation-related pseudoallergy look like a severe allergic reaction but occur through a different mechanism and don’t require previous exposure to an allergen.

“It has the same signs and symptoms and is treated the same way, but it occurs through a different pathway,” explained Neal Halsey, MD, director emeritus of the Institute for Vaccine Safety and emeritus professor at the Johns Hopkins Bloomberg School of Public Health in Baltimore.

Pseudoallergies are not well understood, but they have been associated with reactions to the contrast media used in imaging, such as with MRI. “If people have had an anaphylaxis-type reaction following the injection of contrast-dye material, that is a strong signal that it might be a complement-activation-related pseudoallergy,” said Dr. Halsey, a member of the Clinical Immunization Safety Assessment Network. “Those are the people who definitely need to consider seeing an allergist before getting the COVID vaccines.”

When Aleena Banerji, MD, clinical director of the allergy and clinical immunology unit at Massachusetts General Hospital in Boston, talks to patients about vaccine reactions, she addresses the risk for COVID-19 infection. All of the people who developed allergies after the Pfizer and Moderna vaccines recovered, but more than 445,000 Americans have died from COVID-19.

Most people with common allergies, such as to food or oral medications, don’t need to worry about reactions, said Dr. Banerji, lead author of a review that assessed the risk for allergic reactions to the Pfizer and Moderna vaccines.
 

Investigating reactions

As investigators search for the answers to what causes reactions, transparency is crucial to trust, said Kathryn Edwards, MD, principal investigator of the Clinical Immunization Safety Assessment Project, a vaccine safety network funded by the Centers for Disease Control and Prevention.

“Unless the public knows that we’re really investigating and we’re taking this seriously, then I think the vaccine hesitancy is going to increase,” said Dr. Edwards, professor of pediatrics at Vanderbilt University Medical Center and scientific director of the Vanderbilt Vaccine Research Program in Nashville, Tenn.

First reports of anaphylaxis came quickly after COVID-19 vaccinations began. In the 2 weeks before the holidays, almost 2 million health care workers received the Pfizer vaccine, and 21 of them developed anaphylaxis, according to CDC researchers who reviewed case reports from the Vaccine Adverse Event Reporting System (VAERS). That rate of about 1 in 100,000 is 10 times higher than the occurrence with other vaccines. No deaths from anaphylaxis were reported.

As the vaccinations ramped up, the rate declined. As of Jan. 18, 50 cases of anaphylaxis were reported to VAERS after the administration of 9,943,247 Pfizer doses, for a rate of 5.0 per million, according to data presented at the Jan. 27 meeting of the CDC Advisory Committee on Immunization Practices. And 21 cases of anaphylaxis were reported to VAERS after the administration of 7,581,429 Moderna doses, for a rate of 2.8 per million.

The anaphylaxis occurred almost exclusively in women; only three of the VAERS anaphylaxis reports were from men. Only 24% had a history of anaphylaxis.

The earlier CDC report explored the potential link to allergies. One person with anaphylaxis had a history of allergy to iodinated contrast media, and others had allergies to various medications, vaccines, foods, and animals. The researchers reported 86 nonanaphylaxis allergic reactions and 61 nonallergic adverse events among the 175 case reports they reviewed as possible cases of severe allergic reaction.

Of 1,266 reports that VAERS received from Dec. 21 to Jan. 10, the CDC identified 108 possible cases of severe allergic reaction after the Moderna vaccine. Only 10 met the case definition of anaphylaxis put forward by the Brighton Collaboration, a vaccine safety organization. All but one case involved a history of allergies or allergic reactions; only five had a previously experienced anaphylaxis.

There were 47 nonanaphylaxis allergic reactions.

The San Diego cluster also met the Brighton case definition for anaphylaxis, Dr. Edwards reported. This discrepancy highlights the difficulties in characterizing vaccine reactions.

Measuring a pseudoallergic reaction is a challenge. It requires that a blood sample be drawn soon after the incident and then frozen to protect heat-sensitive blood markers, Dr. Edwards explained.

And as vaccinations rise, so do adverse-event reports. But unlike in clinical trials, there is no control group for comparison. That is why vaccine safety experts urge caution when evaluating events and, where possible, advise looking at background rates.

“A major way to determine whether the adverse event is causally related is to assess the incidence of the adverse event in vaccines versus nonvaccines,” said Walter Orenstein, MD, who directed the U.S. Immunization Program from 1988 to 2004 and is now associate director of the Emory Vaccine Center and professor of infectious diseases at Emory University in Atlanta. Public health officials could then identify vaccine risk factors, he said.

When a reaction occurs almost immediately after vaccination, vaccine safety investigators look for probable triggers. If allergy to PEG is the culprit in anaphylactic reactions, then the individuals would have had a previous exposure, perhaps from injectable medications, Dr. Edwards said.

It might be feasible to perform a skin test for allergy to PEG. “If the skin testing is negative, that doesn’t completely rule out allergy, but it can be used in the decision-making about giving the first or second vaccine dose,” Dr. Banerji said.

Other vaccines, such as childhood vaccines, contain polysorbate as a stabilizer, which has a similar chemical structure, and it’s not clear why someone would react to PEG but not to polysorbate, Dr. Edwards said.

Meanwhile, other illnesses and even deaths sometimes occur in the days after vaccination, but that doesn’t mean the vaccine caused them, cautioned Steve Black, MD, emeritus professor of pediatrics at Cincinnati Children’s Hospital and cofounder of the Global Vaccine Data Network, an international vaccine safety collaboration.

“Different events and clusters of events will occur by chance alone, as these events can occur without vaccines. We need to not immediately assume that they’re due to the vaccine,” he said. “You don’t want to undermine the whole vaccine program every time something comes up and assume that it’s associated with the vaccine.”

The CDC only has three contraindications for the vaccines:

• Severe allergic reaction (such as anaphylaxis) after a previous dose of an mRNA COVID-19 vaccine or any of its components.
• Immediate allergic reaction of any severity to a previous dose of an mRNA COVID-19 vaccine or any of its components (including PEG).
• Immediate allergic reaction of any severity to polysorbate (due to potential cross-reactive hypersensitivity with PEG).

People who have had an immediate allergic reaction to other vaccines or injectable therapies should consider consulting with an allergist or immunologist before getting the Pfizer or Moderna vaccines, the CDC advises.

The CDC also says that people with a history of anaphylaxis from any cause should be observed for 30 minutes after vaccination. Vaccination protocol calls for everyone else to wait on site for 15 minutes after vaccination.

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

Aerosolized high-molecular-weight hyaluronan (HMW-HA) may improve acute exacerbations of chronic obstructive pulmonary disease (COPD), findings of a new study suggest.

HMW-HA was associated with a significantly shorter duration of noninvasive positive-pressure ventilation (NIPPV), lower systemic inflammatory markers, and lower measured peak airway pressure, compared with placebo, reported lead author Flavia Galdi, MD, of Campus Bio-Medico University Hospital, Rome, and colleagues.

“HMW-HA is a naturally occurring sugar that is abundant in the extracellular matrix, including in the lung,” the investigators wrote in Respiratory Research. “[It] has been used routinely, together with hypertonic saline, in cystic fibrosis patients [for several years] with no reported side effects; rather, it improves tolerability and decreases the need for bronchodilators in these patients.”

According to Robert A. Sandhaus, MD, PhD, FCCP, of National Jewish Health, Denver, the role of hyaluronan in lung disease was first recognized decades ago.

“Data stretching back into the 1970s has identified decreases in hyaluronan content in emphysematous lung tissue, protection of lung connective tissue from proteolysis by hyaluronan, and potential therapeutic roles for hyaluronan in a variety of disease, especially of the lungs,” he said in an interview.

For patients with COPD, treatment with HMW-HA may provide benefit by counteracting an imbalance in diseased lung tissue, wrote Dr. Galdi and colleagues.

“Emerging evidence suggests that imbalance between declining HMW-HA levels, and increasing smaller fragments of hyaluronan may contribute to chronic airway disease pathogenesis,” they wrote. “This has led to the hypothesis that exogenous supplementation of HMW-HA may restore hyaluronan homeostasis in favor of undegraded molecules, inhibit inflammation and loss of lung function, and ameliorate COPD progression.”

To test this hypothesis, the investigators screened 44 patients with a history of acute exacerbations of COPD necessitating NIPPV, ultimately excluding 3 patients because of heart failure. Following 1:1 randomization, 20 patients received HMW-HA while 21 received placebo, each twice daily, in conjunction with NIPPV and standard medical therapy. Treatment continued until NIPPV failure or liberation from NIPPV. Most patients received NIPPV in the hospital; however, home/chronic NIPPV was given to four patients in the placebo group and three patients in the HMW-HA group.

The primary outcome was duration of NIPPV. Secondary outcomes included markers of systemic inflammation associated with acute exacerbations of COPD and respiratory physiology parameters. Adverse events were also reported.

Results showed that patients treated with HMW-HA were liberated sooner from NIPPV than were those who received placebo (mean, 5.2 vs 6.4 days; P < .037). Similarly, patients in the HMW-HA group had significantly shorter hospital stay, on average, than those in the placebo group (mean, 7.2 vs 10.2 days; P = .039). Median values followed a similar pattern.

“These data suggest that HMW-HA shortened the duration of acute respiratory failure, need for NIPPV and, consequently, hospital length of stay in these patients,” the investigators wrote.

Secondary outcomes further supported these therapeutic benefits. Compared with placebo, HMW-HA was associated with significantly lower peak pressure and greater improvements in both pCO2/FiO2 ratio and inflammatory markers. No adverse events were reported.

Further analyses involving human bronchial epithelial cell cultures offered some mechanistic insight. Using micro-optical coherence tomography imaging, the investigators found that HMW-HA treatment was associated with “a prominent effect on mucociliary transport” in cell cultures derived from COPD patients and in healthy nonsmoker cell cultures exposed to cigarette smoke extract.

“Our study shows for the first time the therapeutic potential of an extracellular matrix molecule in acute exacerbation of human lung disease,” the investigators concluded, noting a “clinically meaningful salutary effect” on duration of NIPPV.

Dr. Galdi and colleagues went on to predict that benefits in a real-world patient population could be even more meaningful.

“Since the serum samples were collected at the end of NIPPV, HMW-HA–treated patients were on average sampled a day earlier than placebo-treated patients (because they were liberated from NIPPV a day earlier on average),” the investigators wrote. “Thus, HMW-HA treatment effects may have been underestimated in our study.”

According to Dr. Sandhaus, “The current report, while a relatively small single-center study, is well controlled and the results suggest that inhaled hyaluronan decreased time on noninvasive ventilation, decreased hospital stay duration, and decreased some mediators of inflammation.”

He also suggested that HMW-HA may have a role in the prophylactic setting.

“The limitations of this pilot study are appropriately explored by the authors but do not dampen the exciting possibility that this therapeutic approach may hold promise not only in severe exacerbations of COPD but potentially for the prevention of such exacerbations,” Dr. Sandhaus said.

Jerome O. Cantor, MD, FCCP, of St. John’s University, New York, who previously conducted a pilot study for using lower molecular weight hyaluronan in COPD and published a review on the subject, said that more studies are necessary.

“Further clinical trials are needed to better determine the role of hyaluronan as an adjunct to existing therapies for COPD exacerbations,” he said.

The study was supported by the National Institutes of Health. The investigators and Dr. Sandhaus declared no conflicts of interest. Dr. Cantor disclosed a relationship with MatRx Therapeutics.

Aerosolized high-molecular-weight hyaluronan (HMW-HA) may improve acute exacerbations of chronic obstructive pulmonary disease (COPD), findings of a new study suggest.

HMW-HA was associated with a significantly shorter duration of noninvasive positive-pressure ventilation (NIPPV), lower systemic inflammatory markers, and lower measured peak airway pressure, compared with placebo, reported lead author Flavia Galdi, MD, of Campus Bio-Medico University Hospital, Rome, and colleagues.

“HMW-HA is a naturally occurring sugar that is abundant in the extracellular matrix, including in the lung,” the investigators wrote in Respiratory Research. “[It] has been used routinely, together with hypertonic saline, in cystic fibrosis patients [for several years] with no reported side effects; rather, it improves tolerability and decreases the need for bronchodilators in these patients.”

According to Robert A. Sandhaus, MD, PhD, FCCP, of National Jewish Health, Denver, the role of hyaluronan in lung disease was first recognized decades ago.

“Data stretching back into the 1970s has identified decreases in hyaluronan content in emphysematous lung tissue, protection of lung connective tissue from proteolysis by hyaluronan, and potential therapeutic roles for hyaluronan in a variety of disease, especially of the lungs,” he said in an interview.

For patients with COPD, treatment with HMW-HA may provide benefit by counteracting an imbalance in diseased lung tissue, wrote Dr. Galdi and colleagues.

“Emerging evidence suggests that imbalance between declining HMW-HA levels, and increasing smaller fragments of hyaluronan may contribute to chronic airway disease pathogenesis,” they wrote. “This has led to the hypothesis that exogenous supplementation of HMW-HA may restore hyaluronan homeostasis in favor of undegraded molecules, inhibit inflammation and loss of lung function, and ameliorate COPD progression.”

To test this hypothesis, the investigators screened 44 patients with a history of acute exacerbations of COPD necessitating NIPPV, ultimately excluding 3 patients because of heart failure. Following 1:1 randomization, 20 patients received HMW-HA while 21 received placebo, each twice daily, in conjunction with NIPPV and standard medical therapy. Treatment continued until NIPPV failure or liberation from NIPPV. Most patients received NIPPV in the hospital; however, home/chronic NIPPV was given to four patients in the placebo group and three patients in the HMW-HA group.

The primary outcome was duration of NIPPV. Secondary outcomes included markers of systemic inflammation associated with acute exacerbations of COPD and respiratory physiology parameters. Adverse events were also reported.

Results showed that patients treated with HMW-HA were liberated sooner from NIPPV than were those who received placebo (mean, 5.2 vs 6.4 days; P < .037). Similarly, patients in the HMW-HA group had significantly shorter hospital stay, on average, than those in the placebo group (mean, 7.2 vs 10.2 days; P = .039). Median values followed a similar pattern.

“These data suggest that HMW-HA shortened the duration of acute respiratory failure, need for NIPPV and, consequently, hospital length of stay in these patients,” the investigators wrote.

Secondary outcomes further supported these therapeutic benefits. Compared with placebo, HMW-HA was associated with significantly lower peak pressure and greater improvements in both pCO2/FiO2 ratio and inflammatory markers. No adverse events were reported.

Further analyses involving human bronchial epithelial cell cultures offered some mechanistic insight. Using micro-optical coherence tomography imaging, the investigators found that HMW-HA treatment was associated with “a prominent effect on mucociliary transport” in cell cultures derived from COPD patients and in healthy nonsmoker cell cultures exposed to cigarette smoke extract.

“Our study shows for the first time the therapeutic potential of an extracellular matrix molecule in acute exacerbation of human lung disease,” the investigators concluded, noting a “clinically meaningful salutary effect” on duration of NIPPV.

Dr. Galdi and colleagues went on to predict that benefits in a real-world patient population could be even more meaningful.

“Since the serum samples were collected at the end of NIPPV, HMW-HA–treated patients were on average sampled a day earlier than placebo-treated patients (because they were liberated from NIPPV a day earlier on average),” the investigators wrote. “Thus, HMW-HA treatment effects may have been underestimated in our study.”

According to Dr. Sandhaus, “The current report, while a relatively small single-center study, is well controlled and the results suggest that inhaled hyaluronan decreased time on noninvasive ventilation, decreased hospital stay duration, and decreased some mediators of inflammation.”

He also suggested that HMW-HA may have a role in the prophylactic setting.

“The limitations of this pilot study are appropriately explored by the authors but do not dampen the exciting possibility that this therapeutic approach may hold promise not only in severe exacerbations of COPD but potentially for the prevention of such exacerbations,” Dr. Sandhaus said.

Jerome O. Cantor, MD, FCCP, of St. John’s University, New York, who previously conducted a pilot study for using lower molecular weight hyaluronan in COPD and published a review on the subject, said that more studies are necessary.

“Further clinical trials are needed to better determine the role of hyaluronan as an adjunct to existing therapies for COPD exacerbations,” he said.

The study was supported by the National Institutes of Health. The investigators and Dr. Sandhaus declared no conflicts of interest. Dr. Cantor disclosed a relationship with MatRx Therapeutics.

Aerosolized high-molecular-weight hyaluronan (HMW-HA) may improve acute exacerbations of chronic obstructive pulmonary disease (COPD), findings of a new study suggest.

HMW-HA was associated with a significantly shorter duration of noninvasive positive-pressure ventilation (NIPPV), lower systemic inflammatory markers, and lower measured peak airway pressure, compared with placebo, reported lead author Flavia Galdi, MD, of Campus Bio-Medico University Hospital, Rome, and colleagues.

“HMW-HA is a naturally occurring sugar that is abundant in the extracellular matrix, including in the lung,” the investigators wrote in Respiratory Research. “[It] has been used routinely, together with hypertonic saline, in cystic fibrosis patients [for several years] with no reported side effects; rather, it improves tolerability and decreases the need for bronchodilators in these patients.”

According to Robert A. Sandhaus, MD, PhD, FCCP, of National Jewish Health, Denver, the role of hyaluronan in lung disease was first recognized decades ago.

“Data stretching back into the 1970s has identified decreases in hyaluronan content in emphysematous lung tissue, protection of lung connective tissue from proteolysis by hyaluronan, and potential therapeutic roles for hyaluronan in a variety of disease, especially of the lungs,” he said in an interview.

For patients with COPD, treatment with HMW-HA may provide benefit by counteracting an imbalance in diseased lung tissue, wrote Dr. Galdi and colleagues.

“Emerging evidence suggests that imbalance between declining HMW-HA levels, and increasing smaller fragments of hyaluronan may contribute to chronic airway disease pathogenesis,” they wrote. “This has led to the hypothesis that exogenous supplementation of HMW-HA may restore hyaluronan homeostasis in favor of undegraded molecules, inhibit inflammation and loss of lung function, and ameliorate COPD progression.”

To test this hypothesis, the investigators screened 44 patients with a history of acute exacerbations of COPD necessitating NIPPV, ultimately excluding 3 patients because of heart failure. Following 1:1 randomization, 20 patients received HMW-HA while 21 received placebo, each twice daily, in conjunction with NIPPV and standard medical therapy. Treatment continued until NIPPV failure or liberation from NIPPV. Most patients received NIPPV in the hospital; however, home/chronic NIPPV was given to four patients in the placebo group and three patients in the HMW-HA group.

The primary outcome was duration of NIPPV. Secondary outcomes included markers of systemic inflammation associated with acute exacerbations of COPD and respiratory physiology parameters. Adverse events were also reported.

Results showed that patients treated with HMW-HA were liberated sooner from NIPPV than were those who received placebo (mean, 5.2 vs 6.4 days; P < .037). Similarly, patients in the HMW-HA group had significantly shorter hospital stay, on average, than those in the placebo group (mean, 7.2 vs 10.2 days; P = .039). Median values followed a similar pattern.

“These data suggest that HMW-HA shortened the duration of acute respiratory failure, need for NIPPV and, consequently, hospital length of stay in these patients,” the investigators wrote.

Secondary outcomes further supported these therapeutic benefits. Compared with placebo, HMW-HA was associated with significantly lower peak pressure and greater improvements in both pCO2/FiO2 ratio and inflammatory markers. No adverse events were reported.

Further analyses involving human bronchial epithelial cell cultures offered some mechanistic insight. Using micro-optical coherence tomography imaging, the investigators found that HMW-HA treatment was associated with “a prominent effect on mucociliary transport” in cell cultures derived from COPD patients and in healthy nonsmoker cell cultures exposed to cigarette smoke extract.

“Our study shows for the first time the therapeutic potential of an extracellular matrix molecule in acute exacerbation of human lung disease,” the investigators concluded, noting a “clinically meaningful salutary effect” on duration of NIPPV.

Dr. Galdi and colleagues went on to predict that benefits in a real-world patient population could be even more meaningful.

“Since the serum samples were collected at the end of NIPPV, HMW-HA–treated patients were on average sampled a day earlier than placebo-treated patients (because they were liberated from NIPPV a day earlier on average),” the investigators wrote. “Thus, HMW-HA treatment effects may have been underestimated in our study.”

According to Dr. Sandhaus, “The current report, while a relatively small single-center study, is well controlled and the results suggest that inhaled hyaluronan decreased time on noninvasive ventilation, decreased hospital stay duration, and decreased some mediators of inflammation.”

He also suggested that HMW-HA may have a role in the prophylactic setting.

“The limitations of this pilot study are appropriately explored by the authors but do not dampen the exciting possibility that this therapeutic approach may hold promise not only in severe exacerbations of COPD but potentially for the prevention of such exacerbations,” Dr. Sandhaus said.

Jerome O. Cantor, MD, FCCP, of St. John’s University, New York, who previously conducted a pilot study for using lower molecular weight hyaluronan in COPD and published a review on the subject, said that more studies are necessary.

“Further clinical trials are needed to better determine the role of hyaluronan as an adjunct to existing therapies for COPD exacerbations,” he said.

The study was supported by the National Institutes of Health. The investigators and Dr. Sandhaus declared no conflicts of interest. Dr. Cantor disclosed a relationship with MatRx Therapeutics.

When 42-year-old Danielle Simone Brand started having hormonal migraines, she first turned to cannabidiol (CBD) oil, eventually adding an occasional pull on a prefilled tetrahydrocannabinol (THC) vape for nighttime use. She was careful to avoid THC during work hours. A parenting and cannabis writer, Ms. Brand had more than a cursory background in cannabinoid medicine and had spent time at her local California dispensary discussing various cannabinoid components that might help alleviate her pain.

Anatoliy Sizov/Getty Images

A self-professed “do-it-yourselfer,” Ms. Brand continues to use cannabinoids for her monthly headaches, forgoing any other pain medication. “There are times for conventional medicine in partnership with your doctor, but when it comes to health and wellness, women should be empowered to make decisions and self-experiment,” she said in an interview.

Ms. Brand is not alone. Significant numbers of women are replacing or supplementing prescription medications with cannabinoids, often without consulting their primary care physician, ob.gyn., or other specialist. At times, women have tried to have these conversations, only to be met with silence or worse.

Take Linda Fuller, a 58-year-old yoga instructor from Long Island who says that she uses CBD and THC for chronic sacroiliac pain after a car accident and to alleviate stress-triggered eczema flares. “I’ve had doctors turn their backs on me; I’ve had nurse practitioners walk out on me in the middle of a sentence,” she said in an interview.

Ms. Fuller said her conversion to cannabinoid medicine is relatively new; she never used cannabis recreationally before her accident but now considers it a gift. She doesn’t keep aspirin in the house and refused pain medication immediately after she injured her back.

Diana Krach, a 34-year-old writer from Maryland, says she’s encountered roadblocks about her decision to use cannabinoids for endometriosis and for pain from Crohn’s disease. When she tried to discuss her CBD use with a gastroenterologist, he interrupted her: “Whatever pot you’re smoking isn’t going to work, you’re going on biologics.”

Ms. Krach had not been smoking anything but had turned to a CBD tincture for symptom relief after prescription pain medications failed to help.

Ms. Brand, Ms. Fuller, and Ms. Krach are the tip of the iceberg when it comes to women seeking symptom relief outside the medicine cabinet. A recent survey in the Journal of Women’s Health of almost 1,000 women show that 90% (most between the ages of 35 and 44) had used cannabis and would consider using it to treat gynecologic pain. Roughly 80% said they would consider using it for procedure-related pain or other conditions. Additionally, women have reported using cannabinoids for PTSD, sleep disturbances or insomnia, anxiety, and migraine headaches.

Observational survey data have likewise shown that 80% of women with advanced or recurrent gynecologic malignancies who were prescribed cannabis reported that it was equivalent or superior to other medications for relieving pain, neuropathy, nausea, insomnia, decreased appetite, and anxiety.

In another survey, almost half (45%) of women with gynecologic malignancies who used nonprescribed cannabis for the same symptoms reported that they had reduced their use of prescription narcotics after initiating use of cannabis.
 

The gray zone

There has been a surge in self-reported cannabis use among pregnant women in particular. The National Survey on Drug Use and Health findings for the periods 2002-2003 and 2016-2017 highlight increases in adjusted prevalence rates from 3.4% to 7% in past-month use among pregnant women overall and from 5.7% to 12.1% during the first trimester alone.

“The more that you talk to pregnant women, the more that you realize that a lot are using cannabinoids for something that is basically medicinal, for sleep, for anxiety, or for nausea,” Katrina Mark, MD, an ob.gyn. and associate professor of medicine at the University of Maryland, College Park, said in an interview. “I’m not saying it’s fine to use drugs in pregnancy, but it is a grayer conversation than a lot of colleagues want to believe. Telling women to quit seems foolish since the alternative is to be anxious, don’t sleep, don’t eat, or use a medication that also has risks to it.”

One observational study shows that pregnant women themselves are conflicted. Although the majority believe that cannabis is “natural” and “safe,” compared with prescription drugs, they aren’t entirely in the dark about potential risks. They often express frustration with practitioners’ responses when these topics are broached during office visits. An observational survey among women and practitioners published in 2020 highlights that only half of doctors openly discouraged perinatal cannabis use and that others opted out of the discussion entirely.

This is the experience of many of the women that this news organization spoke with. Ms. Krach pointed out that “there’s a big deficit in listening; the doctor is supposed to be working for our behalf, especially when it comes to reproductive health.”

Dr. Mark believed that a lot of the conversation has been clouded by the illegality of the substance but that cannabinoids deserve as much of a fair chance for discussion and consideration as other medicines, which also carry risks in pregnancy. “There’s literally no evidence that it will work in pregnancy [for these symptoms], but there’s no evidence that it doesn’t, either,” she said in an interview. “When I have this conversation with colleagues who do not share my views, I try to encourage them to look at the actual risks versus the benefits versus the alternatives.”

The ‘entourage effect’

Data supporting cannabinoids have been mostly laboratory based, case based, or observational. However, several well-designed (albeit small) trials have demonstrated efficacy for chronic pain conditions, including neuropathic and headache pain, as well as in Crohn’s disease. Most investigators have concluded that dosage is important and that there is a synergistic interaction between compounds (known as the “entourage effect”) that relates to cannabinoid efficacy or lack thereof, as well as possible adverse effects.

In addition to legality issues, the entourage effect is one of the most important factors related to the medical use of cannabinoids. “There are literally thousands of cultivars of cannabis, each with their own phytocannabinoid and terpenic profiles that may produce distinct therapeutic effects, [so] it is misguided to speak of cannabis in monolithic terms. It is like making broad claims about soup,” wrote coauthor Samoon Ahmad, MD, in Medical Marijuana: A Clinical Handbook.

Additionally, the role that reproductive hormones play is not entirely understood. Reproductive-aged women appear to be more susceptible to a “telescoping” (gender-related progression to dependence) effect in comparison with men. Ziva Cooper, PhD, director of the Cannabis Research Initiative at the University of California, Los Angeles, said in an interview. She explained that research has shown that factors such as the degree of exposure, frequency of use, and menses confound this susceptibility.
 

It’s the data

Frustration over cannabinoid therapeutics abound, especially when it comes to data, legal issues, and lack of training. “The feedback that I hear from providers is that there isn’t enough information; we just don’t know enough about it,” Dr. Mark said, “but there is information that we do have, and ignoring it is not beneficial.”

Dr. Cooper concurred. Although she readily acknowledges that data from randomized, placebo-controlled trials are mostly lacking, she says, “There are signals in the literature providing evidence for the utility of cannabis and cannabinoids for pain and some other effects.”

Other practitioners said in an interview that some patients admit to using cannabinoids but that they lack the ample information to guide these patients. By and large, many women equate “natural” with “safe,” and some will experiment on their own to see what works.

Those experiments are not without risk, which is why “it’s just as important for physicians to talk to their patients about cannabis use as it is for patients to be forthcoming about that use,” said Dr. Cooper. “It could have implications on their overall health as well as interactions with other drugs that they’re using.”

That balance from a clinical perspective on cannabis is crucial, wrote coauthor Kenneth Hill, MD, in Medical Marijuana: A Clinical Handbook. “Without it,” he wrote, “the window of opportunity for a patient to accept treatment that she needs may not be open very long.”

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

When 42-year-old Danielle Simone Brand started having hormonal migraines, she first turned to cannabidiol (CBD) oil, eventually adding an occasional pull on a prefilled tetrahydrocannabinol (THC) vape for nighttime use. She was careful to avoid THC during work hours. A parenting and cannabis writer, Ms. Brand had more than a cursory background in cannabinoid medicine and had spent time at her local California dispensary discussing various cannabinoid components that might help alleviate her pain.

Anatoliy Sizov/Getty Images

A self-professed “do-it-yourselfer,” Ms. Brand continues to use cannabinoids for her monthly headaches, forgoing any other pain medication. “There are times for conventional medicine in partnership with your doctor, but when it comes to health and wellness, women should be empowered to make decisions and self-experiment,” she said in an interview.

Ms. Brand is not alone. Significant numbers of women are replacing or supplementing prescription medications with cannabinoids, often without consulting their primary care physician, ob.gyn., or other specialist. At times, women have tried to have these conversations, only to be met with silence or worse.

Take Linda Fuller, a 58-year-old yoga instructor from Long Island who says that she uses CBD and THC for chronic sacroiliac pain after a car accident and to alleviate stress-triggered eczema flares. “I’ve had doctors turn their backs on me; I’ve had nurse practitioners walk out on me in the middle of a sentence,” she said in an interview.

Ms. Fuller said her conversion to cannabinoid medicine is relatively new; she never used cannabis recreationally before her accident but now considers it a gift. She doesn’t keep aspirin in the house and refused pain medication immediately after she injured her back.

Diana Krach, a 34-year-old writer from Maryland, says she’s encountered roadblocks about her decision to use cannabinoids for endometriosis and for pain from Crohn’s disease. When she tried to discuss her CBD use with a gastroenterologist, he interrupted her: “Whatever pot you’re smoking isn’t going to work, you’re going on biologics.”

Ms. Krach had not been smoking anything but had turned to a CBD tincture for symptom relief after prescription pain medications failed to help.

Ms. Brand, Ms. Fuller, and Ms. Krach are the tip of the iceberg when it comes to women seeking symptom relief outside the medicine cabinet. A recent survey in the Journal of Women’s Health of almost 1,000 women show that 90% (most between the ages of 35 and 44) had used cannabis and would consider using it to treat gynecologic pain. Roughly 80% said they would consider using it for procedure-related pain or other conditions. Additionally, women have reported using cannabinoids for PTSD, sleep disturbances or insomnia, anxiety, and migraine headaches.

Observational survey data have likewise shown that 80% of women with advanced or recurrent gynecologic malignancies who were prescribed cannabis reported that it was equivalent or superior to other medications for relieving pain, neuropathy, nausea, insomnia, decreased appetite, and anxiety.

In another survey, almost half (45%) of women with gynecologic malignancies who used nonprescribed cannabis for the same symptoms reported that they had reduced their use of prescription narcotics after initiating use of cannabis.
 

The gray zone

There has been a surge in self-reported cannabis use among pregnant women in particular. The National Survey on Drug Use and Health findings for the periods 2002-2003 and 2016-2017 highlight increases in adjusted prevalence rates from 3.4% to 7% in past-month use among pregnant women overall and from 5.7% to 12.1% during the first trimester alone.

“The more that you talk to pregnant women, the more that you realize that a lot are using cannabinoids for something that is basically medicinal, for sleep, for anxiety, or for nausea,” Katrina Mark, MD, an ob.gyn. and associate professor of medicine at the University of Maryland, College Park, said in an interview. “I’m not saying it’s fine to use drugs in pregnancy, but it is a grayer conversation than a lot of colleagues want to believe. Telling women to quit seems foolish since the alternative is to be anxious, don’t sleep, don’t eat, or use a medication that also has risks to it.”

One observational study shows that pregnant women themselves are conflicted. Although the majority believe that cannabis is “natural” and “safe,” compared with prescription drugs, they aren’t entirely in the dark about potential risks. They often express frustration with practitioners’ responses when these topics are broached during office visits. An observational survey among women and practitioners published in 2020 highlights that only half of doctors openly discouraged perinatal cannabis use and that others opted out of the discussion entirely.

This is the experience of many of the women that this news organization spoke with. Ms. Krach pointed out that “there’s a big deficit in listening; the doctor is supposed to be working for our behalf, especially when it comes to reproductive health.”

Dr. Mark believed that a lot of the conversation has been clouded by the illegality of the substance but that cannabinoids deserve as much of a fair chance for discussion and consideration as other medicines, which also carry risks in pregnancy. “There’s literally no evidence that it will work in pregnancy [for these symptoms], but there’s no evidence that it doesn’t, either,” she said in an interview. “When I have this conversation with colleagues who do not share my views, I try to encourage them to look at the actual risks versus the benefits versus the alternatives.”

The ‘entourage effect’

Data supporting cannabinoids have been mostly laboratory based, case based, or observational. However, several well-designed (albeit small) trials have demonstrated efficacy for chronic pain conditions, including neuropathic and headache pain, as well as in Crohn’s disease. Most investigators have concluded that dosage is important and that there is a synergistic interaction between compounds (known as the “entourage effect”) that relates to cannabinoid efficacy or lack thereof, as well as possible adverse effects.

In addition to legality issues, the entourage effect is one of the most important factors related to the medical use of cannabinoids. “There are literally thousands of cultivars of cannabis, each with their own phytocannabinoid and terpenic profiles that may produce distinct therapeutic effects, [so] it is misguided to speak of cannabis in monolithic terms. It is like making broad claims about soup,” wrote coauthor Samoon Ahmad, MD, in Medical Marijuana: A Clinical Handbook.

Additionally, the role that reproductive hormones play is not entirely understood. Reproductive-aged women appear to be more susceptible to a “telescoping” (gender-related progression to dependence) effect in comparison with men. Ziva Cooper, PhD, director of the Cannabis Research Initiative at the University of California, Los Angeles, said in an interview. She explained that research has shown that factors such as the degree of exposure, frequency of use, and menses confound this susceptibility.
 

It’s the data

Frustration over cannabinoid therapeutics abound, especially when it comes to data, legal issues, and lack of training. “The feedback that I hear from providers is that there isn’t enough information; we just don’t know enough about it,” Dr. Mark said, “but there is information that we do have, and ignoring it is not beneficial.”

Dr. Cooper concurred. Although she readily acknowledges that data from randomized, placebo-controlled trials are mostly lacking, she says, “There are signals in the literature providing evidence for the utility of cannabis and cannabinoids for pain and some other effects.”

Other practitioners said in an interview that some patients admit to using cannabinoids but that they lack the ample information to guide these patients. By and large, many women equate “natural” with “safe,” and some will experiment on their own to see what works.

Those experiments are not without risk, which is why “it’s just as important for physicians to talk to their patients about cannabis use as it is for patients to be forthcoming about that use,” said Dr. Cooper. “It could have implications on their overall health as well as interactions with other drugs that they’re using.”

That balance from a clinical perspective on cannabis is crucial, wrote coauthor Kenneth Hill, MD, in Medical Marijuana: A Clinical Handbook. “Without it,” he wrote, “the window of opportunity for a patient to accept treatment that she needs may not be open very long.”

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

When 42-year-old Danielle Simone Brand started having hormonal migraines, she first turned to cannabidiol (CBD) oil, eventually adding an occasional pull on a prefilled tetrahydrocannabinol (THC) vape for nighttime use. She was careful to avoid THC during work hours. A parenting and cannabis writer, Ms. Brand had more than a cursory background in cannabinoid medicine and had spent time at her local California dispensary discussing various cannabinoid components that might help alleviate her pain.

Anatoliy Sizov/Getty Images

A self-professed “do-it-yourselfer,” Ms. Brand continues to use cannabinoids for her monthly headaches, forgoing any other pain medication. “There are times for conventional medicine in partnership with your doctor, but when it comes to health and wellness, women should be empowered to make decisions and self-experiment,” she said in an interview.

Ms. Brand is not alone. Significant numbers of women are replacing or supplementing prescription medications with cannabinoids, often without consulting their primary care physician, ob.gyn., or other specialist. At times, women have tried to have these conversations, only to be met with silence or worse.

Take Linda Fuller, a 58-year-old yoga instructor from Long Island who says that she uses CBD and THC for chronic sacroiliac pain after a car accident and to alleviate stress-triggered eczema flares. “I’ve had doctors turn their backs on me; I’ve had nurse practitioners walk out on me in the middle of a sentence,” she said in an interview.

Ms. Fuller said her conversion to cannabinoid medicine is relatively new; she never used cannabis recreationally before her accident but now considers it a gift. She doesn’t keep aspirin in the house and refused pain medication immediately after she injured her back.

Diana Krach, a 34-year-old writer from Maryland, says she’s encountered roadblocks about her decision to use cannabinoids for endometriosis and for pain from Crohn’s disease. When she tried to discuss her CBD use with a gastroenterologist, he interrupted her: “Whatever pot you’re smoking isn’t going to work, you’re going on biologics.”

Ms. Krach had not been smoking anything but had turned to a CBD tincture for symptom relief after prescription pain medications failed to help.

Ms. Brand, Ms. Fuller, and Ms. Krach are the tip of the iceberg when it comes to women seeking symptom relief outside the medicine cabinet. A recent survey in the Journal of Women’s Health of almost 1,000 women show that 90% (most between the ages of 35 and 44) had used cannabis and would consider using it to treat gynecologic pain. Roughly 80% said they would consider using it for procedure-related pain or other conditions. Additionally, women have reported using cannabinoids for PTSD, sleep disturbances or insomnia, anxiety, and migraine headaches.

Observational survey data have likewise shown that 80% of women with advanced or recurrent gynecologic malignancies who were prescribed cannabis reported that it was equivalent or superior to other medications for relieving pain, neuropathy, nausea, insomnia, decreased appetite, and anxiety.

In another survey, almost half (45%) of women with gynecologic malignancies who used nonprescribed cannabis for the same symptoms reported that they had reduced their use of prescription narcotics after initiating use of cannabis.
 

The gray zone

There has been a surge in self-reported cannabis use among pregnant women in particular. The National Survey on Drug Use and Health findings for the periods 2002-2003 and 2016-2017 highlight increases in adjusted prevalence rates from 3.4% to 7% in past-month use among pregnant women overall and from 5.7% to 12.1% during the first trimester alone.

“The more that you talk to pregnant women, the more that you realize that a lot are using cannabinoids for something that is basically medicinal, for sleep, for anxiety, or for nausea,” Katrina Mark, MD, an ob.gyn. and associate professor of medicine at the University of Maryland, College Park, said in an interview. “I’m not saying it’s fine to use drugs in pregnancy, but it is a grayer conversation than a lot of colleagues want to believe. Telling women to quit seems foolish since the alternative is to be anxious, don’t sleep, don’t eat, or use a medication that also has risks to it.”

One observational study shows that pregnant women themselves are conflicted. Although the majority believe that cannabis is “natural” and “safe,” compared with prescription drugs, they aren’t entirely in the dark about potential risks. They often express frustration with practitioners’ responses when these topics are broached during office visits. An observational survey among women and practitioners published in 2020 highlights that only half of doctors openly discouraged perinatal cannabis use and that others opted out of the discussion entirely.

This is the experience of many of the women that this news organization spoke with. Ms. Krach pointed out that “there’s a big deficit in listening; the doctor is supposed to be working for our behalf, especially when it comes to reproductive health.”

Dr. Mark believed that a lot of the conversation has been clouded by the illegality of the substance but that cannabinoids deserve as much of a fair chance for discussion and consideration as other medicines, which also carry risks in pregnancy. “There’s literally no evidence that it will work in pregnancy [for these symptoms], but there’s no evidence that it doesn’t, either,” she said in an interview. “When I have this conversation with colleagues who do not share my views, I try to encourage them to look at the actual risks versus the benefits versus the alternatives.”

The ‘entourage effect’

Data supporting cannabinoids have been mostly laboratory based, case based, or observational. However, several well-designed (albeit small) trials have demonstrated efficacy for chronic pain conditions, including neuropathic and headache pain, as well as in Crohn’s disease. Most investigators have concluded that dosage is important and that there is a synergistic interaction between compounds (known as the “entourage effect”) that relates to cannabinoid efficacy or lack thereof, as well as possible adverse effects.

In addition to legality issues, the entourage effect is one of the most important factors related to the medical use of cannabinoids. “There are literally thousands of cultivars of cannabis, each with their own phytocannabinoid and terpenic profiles that may produce distinct therapeutic effects, [so] it is misguided to speak of cannabis in monolithic terms. It is like making broad claims about soup,” wrote coauthor Samoon Ahmad, MD, in Medical Marijuana: A Clinical Handbook.

Additionally, the role that reproductive hormones play is not entirely understood. Reproductive-aged women appear to be more susceptible to a “telescoping” (gender-related progression to dependence) effect in comparison with men. Ziva Cooper, PhD, director of the Cannabis Research Initiative at the University of California, Los Angeles, said in an interview. She explained that research has shown that factors such as the degree of exposure, frequency of use, and menses confound this susceptibility.
 

It’s the data

Frustration over cannabinoid therapeutics abound, especially when it comes to data, legal issues, and lack of training. “The feedback that I hear from providers is that there isn’t enough information; we just don’t know enough about it,” Dr. Mark said, “but there is information that we do have, and ignoring it is not beneficial.”

Dr. Cooper concurred. Although she readily acknowledges that data from randomized, placebo-controlled trials are mostly lacking, she says, “There are signals in the literature providing evidence for the utility of cannabis and cannabinoids for pain and some other effects.”

Other practitioners said in an interview that some patients admit to using cannabinoids but that they lack the ample information to guide these patients. By and large, many women equate “natural” with “safe,” and some will experiment on their own to see what works.

Those experiments are not without risk, which is why “it’s just as important for physicians to talk to their patients about cannabis use as it is for patients to be forthcoming about that use,” said Dr. Cooper. “It could have implications on their overall health as well as interactions with other drugs that they’re using.”

That balance from a clinical perspective on cannabis is crucial, wrote coauthor Kenneth Hill, MD, in Medical Marijuana: A Clinical Handbook. “Without it,” he wrote, “the window of opportunity for a patient to accept treatment that she needs may not be open very long.”

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

Every day, around 1.5 million doses of the COVID-19 vaccine are being delivered across the United States, but oncologists and patient advocates say that patients with cancer are missing out.

While official bodies recommend that patients with cancer are given priority, only 16 states currently prioritize them in the vaccine rollout. The other 34 states have thus far not singled out patients with cancer for earlier vaccination.

This flies in the face of recommendations from heavy hitters such as the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices, the National Comprehensive Cancer Network, and the American Association for Cancer Research.

All are in agreement: Patients on active cancer treatment should be prioritized for available vaccine because of their greater risk of death or complications from SARS-CoV-2 infection.

“All municipalities, states, cities, and even individual hospitals have so far been left to their own devices to try to figure out what the best way to do this is and that often conflicts with other recommendations or guidelines,” said E. John Wherry, PhD, chair of the department of systems pharmacology and translational therapeutics at the University of Pennsylvania, Philadelphia.

Dr. Wherry was on a panel at an AACR conference last week that discussed the failings of vaccine delivery to cancer patients.

During the meeting, lung cancer advocate Jill Feldman commented on the situation in Chicago, one of the jurisdictions that has not prioritized patients with cancer: “People don’t know what to do. ‘Do I need to sign up myself somewhere? Is my doctor’s office going to contact me?’ ”

Ms. Feldman said many people have called their cancer centers, “but cancer centers aren’t really providing updates directly to us. And they aren’t because they don’t have the information [either].”

Even in the 16 states that have ushered patients with cancer to the front of the line, the process for flagging these individuals is often unclear or nonexistent.

“Everyone that registers is basically on the same playing field ... because there’s no verification process. That’s very unfortunate,” said patient advocate Grace Cordovano, PhD, describing the vaccine sign-up process in New Jersey.

“It’s an easy fix,” said Dr. Cordovano. “Adding a few more fields [in the form] could really make a difference.”

COVID-19 fatality rates are twice as high in people with cancer than in people without cancer, according to a review published in December 2020 by the AACR’s COVID-19 and Cancer Task Force in the journal Cancer Discovery. Hematologic malignancies conferred an especially high risk.

“Any delay in vaccine access will result in loss of life that could be prevented with earlier access to vaccination,” AACR President Antoni Ribas, MD, told this news organization at the time.

There are also sound epidemiologic reasons to prioritize high-risk cancer patients for the COVID-19 vaccine, Dr. Wherry said in an interview. “What we do in infectious disease is to think about where your transmission and your risks are highest,” he said, citing cancer treatment centers as examples.

People with hematologic malignancies also tend to be long-term viral shedders, he said, putting caregivers and health care staff at increased risk. “There’s a big, big impact [in vaccinating cancer patients] and the numbers are not small.”

The CDC’s Jan. 1 recommendation is that patients with cancer should be assigned to priority group 1c, along with other “persons aged 16-64 with other high-risk medical conditions.”

However, more recent guidance from the NCCN hastened the urgency, advising that “patients with cancer should be assigned to the [CDC] priority group 1b/c.”

Out of 16 states that currently prioritize patients with cancer, 3 states have exceeded official advice, placing patients with cancer in priority group 1a. They opened their first batches of vaccine to everyone “deemed extremely vulnerable to COVID-19 by hospital providers” (Florida), or to “16-64 years old with a chronic health condition” (Mississippi) and to “persons aged 16-64 with high-risk conditions” (Pennsylvania, some jurisdictions).

However, despite these heroic intentions, no jurisdiction appears to have specifically tackled the thorny issue of subgroups of cancer that are more urgent than others, and this worries oncologists.

“Not all cancer patients are the same,” said Marina Garassino, MD, a medical oncologist at the National Tumor Institute of Milan. She shared registry data with the AACR panelists indicating that COVID-19 mortality in thoracic and hematologic malignancies rises to 30%-40%, compared with 13% for cancer overall.

At the AACR meeting, Dr. Ribas summed up his feelings on the issue: “It’s clear to me that patients with cancer should be prioritized. We have to then start defining this population and it should be the patient with an active cancer diagnosis undergoing treatment, in particular patients with lung cancers or hematologic malignancies.”

Since patients with cancer as a whole have problems getting timely vaccination – let alone someone with lung cancer or leukemia – the AACR meeting panelists grappled with solutions.

Dr. Cordovano said it was a “no brainer” to start with cancer centers. “Patients there are already registered, they have an account in the electronic health record system, they have insurance information, the care team knows them.”

Vaccination referrals sent directly from oncology centers would eliminate the need for the patient to provide verification or any additional documentation, she pointed out.

However, in New Jersey, cancer centers “have been completely excluded from the process,” she said.  

Florida and New Hampshire have somewhat adopted the mechanism suggested by Dr. Cordovano. These states require health care providers to verify that a patient is “especially vulnerable” (Florida) or “medically vulnerable” (New Hampshire) in order for the patient to receive priority vaccine access. In New Hampshire, patients must have at least one other medical condition in addition to cancer to get on the list.

Jia Luo, MD, a medical oncology fellow at Memorial Sloan Kettering Cancer Center, New York, told the meeting that MSKCC has set up a proactive task force that sends “daily emails” to clinic staff highlighting patients eligible for the vaccine. “My sense is, it’s being prioritized to active cancer treatment,” said Dr. Luo. “All of our physicians are currently discussing [it] at each appointment and ... all of our nurses and staff have been talking to our patients on the phone.”

Dr. Cordovano, while advocating hard for cancer patients today, retained optimism about tomorrow: “This isn’t a long-term thing. This is just until things catch up. We knew we were going to have this problem.” Her hope is that, within 6 months, COVID-19 vaccination will become a standard of care in cancer.

Dr. Wherry agreed: “It’s going to take time to catch up with how far behind we are on certain things. ... What we’re seeing is a healthy debate rather than something that we should be concerned about – as long as that debate leads to rapid action.”

“We have to follow the science,” concluded Cordovano. “We can do better than this.”

Dr. Cordovano, Ms. Feldman, and Dr. Wherry have disclosed no relevant financial relationships. Dr. Luo declared a financial relationship with Targeted Oncology. Dr. Ribas declared financial relationships with 4C Biomed, Advaxis, Agilent, Amgen, AstraZeneca, Arcus, Bristol-Myers Squibb, and Kite-Gilead.

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

Every day, around 1.5 million doses of the COVID-19 vaccine are being delivered across the United States, but oncologists and patient advocates say that patients with cancer are missing out.

While official bodies recommend that patients with cancer are given priority, only 16 states currently prioritize them in the vaccine rollout. The other 34 states have thus far not singled out patients with cancer for earlier vaccination.

This flies in the face of recommendations from heavy hitters such as the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices, the National Comprehensive Cancer Network, and the American Association for Cancer Research.

All are in agreement: Patients on active cancer treatment should be prioritized for available vaccine because of their greater risk of death or complications from SARS-CoV-2 infection.

“All municipalities, states, cities, and even individual hospitals have so far been left to their own devices to try to figure out what the best way to do this is and that often conflicts with other recommendations or guidelines,” said E. John Wherry, PhD, chair of the department of systems pharmacology and translational therapeutics at the University of Pennsylvania, Philadelphia.

Dr. Wherry was on a panel at an AACR conference last week that discussed the failings of vaccine delivery to cancer patients.

During the meeting, lung cancer advocate Jill Feldman commented on the situation in Chicago, one of the jurisdictions that has not prioritized patients with cancer: “People don’t know what to do. ‘Do I need to sign up myself somewhere? Is my doctor’s office going to contact me?’ ”

Ms. Feldman said many people have called their cancer centers, “but cancer centers aren’t really providing updates directly to us. And they aren’t because they don’t have the information [either].”

Even in the 16 states that have ushered patients with cancer to the front of the line, the process for flagging these individuals is often unclear or nonexistent.

“Everyone that registers is basically on the same playing field ... because there’s no verification process. That’s very unfortunate,” said patient advocate Grace Cordovano, PhD, describing the vaccine sign-up process in New Jersey.

“It’s an easy fix,” said Dr. Cordovano. “Adding a few more fields [in the form] could really make a difference.”

COVID-19 fatality rates are twice as high in people with cancer than in people without cancer, according to a review published in December 2020 by the AACR’s COVID-19 and Cancer Task Force in the journal Cancer Discovery. Hematologic malignancies conferred an especially high risk.

“Any delay in vaccine access will result in loss of life that could be prevented with earlier access to vaccination,” AACR President Antoni Ribas, MD, told this news organization at the time.

There are also sound epidemiologic reasons to prioritize high-risk cancer patients for the COVID-19 vaccine, Dr. Wherry said in an interview. “What we do in infectious disease is to think about where your transmission and your risks are highest,” he said, citing cancer treatment centers as examples.

People with hematologic malignancies also tend to be long-term viral shedders, he said, putting caregivers and health care staff at increased risk. “There’s a big, big impact [in vaccinating cancer patients] and the numbers are not small.”

The CDC’s Jan. 1 recommendation is that patients with cancer should be assigned to priority group 1c, along with other “persons aged 16-64 with other high-risk medical conditions.”

However, more recent guidance from the NCCN hastened the urgency, advising that “patients with cancer should be assigned to the [CDC] priority group 1b/c.”

Out of 16 states that currently prioritize patients with cancer, 3 states have exceeded official advice, placing patients with cancer in priority group 1a. They opened their first batches of vaccine to everyone “deemed extremely vulnerable to COVID-19 by hospital providers” (Florida), or to “16-64 years old with a chronic health condition” (Mississippi) and to “persons aged 16-64 with high-risk conditions” (Pennsylvania, some jurisdictions).

However, despite these heroic intentions, no jurisdiction appears to have specifically tackled the thorny issue of subgroups of cancer that are more urgent than others, and this worries oncologists.

“Not all cancer patients are the same,” said Marina Garassino, MD, a medical oncologist at the National Tumor Institute of Milan. She shared registry data with the AACR panelists indicating that COVID-19 mortality in thoracic and hematologic malignancies rises to 30%-40%, compared with 13% for cancer overall.

At the AACR meeting, Dr. Ribas summed up his feelings on the issue: “It’s clear to me that patients with cancer should be prioritized. We have to then start defining this population and it should be the patient with an active cancer diagnosis undergoing treatment, in particular patients with lung cancers or hematologic malignancies.”

Since patients with cancer as a whole have problems getting timely vaccination – let alone someone with lung cancer or leukemia – the AACR meeting panelists grappled with solutions.

Dr. Cordovano said it was a “no brainer” to start with cancer centers. “Patients there are already registered, they have an account in the electronic health record system, they have insurance information, the care team knows them.”

Vaccination referrals sent directly from oncology centers would eliminate the need for the patient to provide verification or any additional documentation, she pointed out.

However, in New Jersey, cancer centers “have been completely excluded from the process,” she said.  

Florida and New Hampshire have somewhat adopted the mechanism suggested by Dr. Cordovano. These states require health care providers to verify that a patient is “especially vulnerable” (Florida) or “medically vulnerable” (New Hampshire) in order for the patient to receive priority vaccine access. In New Hampshire, patients must have at least one other medical condition in addition to cancer to get on the list.

Jia Luo, MD, a medical oncology fellow at Memorial Sloan Kettering Cancer Center, New York, told the meeting that MSKCC has set up a proactive task force that sends “daily emails” to clinic staff highlighting patients eligible for the vaccine. “My sense is, it’s being prioritized to active cancer treatment,” said Dr. Luo. “All of our physicians are currently discussing [it] at each appointment and ... all of our nurses and staff have been talking to our patients on the phone.”

Dr. Cordovano, while advocating hard for cancer patients today, retained optimism about tomorrow: “This isn’t a long-term thing. This is just until things catch up. We knew we were going to have this problem.” Her hope is that, within 6 months, COVID-19 vaccination will become a standard of care in cancer.

Dr. Wherry agreed: “It’s going to take time to catch up with how far behind we are on certain things. ... What we’re seeing is a healthy debate rather than something that we should be concerned about – as long as that debate leads to rapid action.”

“We have to follow the science,” concluded Cordovano. “We can do better than this.”

Dr. Cordovano, Ms. Feldman, and Dr. Wherry have disclosed no relevant financial relationships. Dr. Luo declared a financial relationship with Targeted Oncology. Dr. Ribas declared financial relationships with 4C Biomed, Advaxis, Agilent, Amgen, AstraZeneca, Arcus, Bristol-Myers Squibb, and Kite-Gilead.

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

Every day, around 1.5 million doses of the COVID-19 vaccine are being delivered across the United States, but oncologists and patient advocates say that patients with cancer are missing out.

While official bodies recommend that patients with cancer are given priority, only 16 states currently prioritize them in the vaccine rollout. The other 34 states have thus far not singled out patients with cancer for earlier vaccination.

This flies in the face of recommendations from heavy hitters such as the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices, the National Comprehensive Cancer Network, and the American Association for Cancer Research.

All are in agreement: Patients on active cancer treatment should be prioritized for available vaccine because of their greater risk of death or complications from SARS-CoV-2 infection.

“All municipalities, states, cities, and even individual hospitals have so far been left to their own devices to try to figure out what the best way to do this is and that often conflicts with other recommendations or guidelines,” said E. John Wherry, PhD, chair of the department of systems pharmacology and translational therapeutics at the University of Pennsylvania, Philadelphia.

Dr. Wherry was on a panel at an AACR conference last week that discussed the failings of vaccine delivery to cancer patients.

During the meeting, lung cancer advocate Jill Feldman commented on the situation in Chicago, one of the jurisdictions that has not prioritized patients with cancer: “People don’t know what to do. ‘Do I need to sign up myself somewhere? Is my doctor’s office going to contact me?’ ”

Ms. Feldman said many people have called their cancer centers, “but cancer centers aren’t really providing updates directly to us. And they aren’t because they don’t have the information [either].”

Even in the 16 states that have ushered patients with cancer to the front of the line, the process for flagging these individuals is often unclear or nonexistent.

“Everyone that registers is basically on the same playing field ... because there’s no verification process. That’s very unfortunate,” said patient advocate Grace Cordovano, PhD, describing the vaccine sign-up process in New Jersey.

“It’s an easy fix,” said Dr. Cordovano. “Adding a few more fields [in the form] could really make a difference.”

COVID-19 fatality rates are twice as high in people with cancer than in people without cancer, according to a review published in December 2020 by the AACR’s COVID-19 and Cancer Task Force in the journal Cancer Discovery. Hematologic malignancies conferred an especially high risk.

“Any delay in vaccine access will result in loss of life that could be prevented with earlier access to vaccination,” AACR President Antoni Ribas, MD, told this news organization at the time.

There are also sound epidemiologic reasons to prioritize high-risk cancer patients for the COVID-19 vaccine, Dr. Wherry said in an interview. “What we do in infectious disease is to think about where your transmission and your risks are highest,” he said, citing cancer treatment centers as examples.

People with hematologic malignancies also tend to be long-term viral shedders, he said, putting caregivers and health care staff at increased risk. “There’s a big, big impact [in vaccinating cancer patients] and the numbers are not small.”

The CDC’s Jan. 1 recommendation is that patients with cancer should be assigned to priority group 1c, along with other “persons aged 16-64 with other high-risk medical conditions.”

However, more recent guidance from the NCCN hastened the urgency, advising that “patients with cancer should be assigned to the [CDC] priority group 1b/c.”

Out of 16 states that currently prioritize patients with cancer, 3 states have exceeded official advice, placing patients with cancer in priority group 1a. They opened their first batches of vaccine to everyone “deemed extremely vulnerable to COVID-19 by hospital providers” (Florida), or to “16-64 years old with a chronic health condition” (Mississippi) and to “persons aged 16-64 with high-risk conditions” (Pennsylvania, some jurisdictions).

However, despite these heroic intentions, no jurisdiction appears to have specifically tackled the thorny issue of subgroups of cancer that are more urgent than others, and this worries oncologists.

“Not all cancer patients are the same,” said Marina Garassino, MD, a medical oncologist at the National Tumor Institute of Milan. She shared registry data with the AACR panelists indicating that COVID-19 mortality in thoracic and hematologic malignancies rises to 30%-40%, compared with 13% for cancer overall.

At the AACR meeting, Dr. Ribas summed up his feelings on the issue: “It’s clear to me that patients with cancer should be prioritized. We have to then start defining this population and it should be the patient with an active cancer diagnosis undergoing treatment, in particular patients with lung cancers or hematologic malignancies.”

Since patients with cancer as a whole have problems getting timely vaccination – let alone someone with lung cancer or leukemia – the AACR meeting panelists grappled with solutions.

Dr. Cordovano said it was a “no brainer” to start with cancer centers. “Patients there are already registered, they have an account in the electronic health record system, they have insurance information, the care team knows them.”

Vaccination referrals sent directly from oncology centers would eliminate the need for the patient to provide verification or any additional documentation, she pointed out.

However, in New Jersey, cancer centers “have been completely excluded from the process,” she said.  

Florida and New Hampshire have somewhat adopted the mechanism suggested by Dr. Cordovano. These states require health care providers to verify that a patient is “especially vulnerable” (Florida) or “medically vulnerable” (New Hampshire) in order for the patient to receive priority vaccine access. In New Hampshire, patients must have at least one other medical condition in addition to cancer to get on the list.

Jia Luo, MD, a medical oncology fellow at Memorial Sloan Kettering Cancer Center, New York, told the meeting that MSKCC has set up a proactive task force that sends “daily emails” to clinic staff highlighting patients eligible for the vaccine. “My sense is, it’s being prioritized to active cancer treatment,” said Dr. Luo. “All of our physicians are currently discussing [it] at each appointment and ... all of our nurses and staff have been talking to our patients on the phone.”

Dr. Cordovano, while advocating hard for cancer patients today, retained optimism about tomorrow: “This isn’t a long-term thing. This is just until things catch up. We knew we were going to have this problem.” Her hope is that, within 6 months, COVID-19 vaccination will become a standard of care in cancer.

Dr. Wherry agreed: “It’s going to take time to catch up with how far behind we are on certain things. ... What we’re seeing is a healthy debate rather than something that we should be concerned about – as long as that debate leads to rapid action.”

“We have to follow the science,” concluded Cordovano. “We can do better than this.”

Dr. Cordovano, Ms. Feldman, and Dr. Wherry have disclosed no relevant financial relationships. Dr. Luo declared a financial relationship with Targeted Oncology. Dr. Ribas declared financial relationships with 4C Biomed, Advaxis, Agilent, Amgen, AstraZeneca, Arcus, Bristol-Myers Squibb, and Kite-Gilead.

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

When the pandemic hit, health officials in Montana’s Beaverhead County had barely begun to fill a hole left by the 2017 closure of the local public assistance office, mental health clinic, chemical dependency center and job placement office after the state’s last budget shortfall.

Now, those health officials worry more cuts are coming, even as they brace for a spike in demand for substance abuse and mental health services. That would be no small challenge in a poor farming and ranching region where stigma often prevents people from admitting they need help, said Katherine Buckley-Patton, who chairs the county’s Mental Health Local Advisory Council.

“I find it very challenging to find the words that will not make one of my hard-nosed cowboys turn around and walk away,” Ms. Buckley-Patton said. “They’re lonely, they’re isolated, they’re depressed, but they’re not going to call a suicide hotline.”

States across the U.S. are still stinging after businesses closed and millions of people lost jobs because of COVID-related shutdowns and restrictions. Meanwhile, the pandemic has led to a dramatic increase in the number of people who say their mental health has suffered, rising from one in three people in March to more than half of people polled by KFF in July. (KHN is an editorially independent program of KFF.)

The full extent of the mental health crisis and the demand for behavioral health services may not be known until after the pandemic is over, mental health experts said. That could add costs that budget writers haven’t anticipated.

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

When the pandemic hit, health officials in Montana’s Beaverhead County had barely begun to fill a hole left by the 2017 closure of the local public assistance office, mental health clinic, chemical dependency center and job placement office after the state’s last budget shortfall.

Now, those health officials worry more cuts are coming, even as they brace for a spike in demand for substance abuse and mental health services. That would be no small challenge in a poor farming and ranching region where stigma often prevents people from admitting they need help, said Katherine Buckley-Patton, who chairs the county’s Mental Health Local Advisory Council.

“I find it very challenging to find the words that will not make one of my hard-nosed cowboys turn around and walk away,” Ms. Buckley-Patton said. “They’re lonely, they’re isolated, they’re depressed, but they’re not going to call a suicide hotline.”

States across the U.S. are still stinging after businesses closed and millions of people lost jobs because of COVID-related shutdowns and restrictions. Meanwhile, the pandemic has led to a dramatic increase in the number of people who say their mental health has suffered, rising from one in three people in March to more than half of people polled by KFF in July. (KHN is an editorially independent program of KFF.)

The full extent of the mental health crisis and the demand for behavioral health services may not be known until after the pandemic is over, mental health experts said. That could add costs that budget writers haven’t anticipated.

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

When the pandemic hit, health officials in Montana’s Beaverhead County had barely begun to fill a hole left by the 2017 closure of the local public assistance office, mental health clinic, chemical dependency center and job placement office after the state’s last budget shortfall.

Now, those health officials worry more cuts are coming, even as they brace for a spike in demand for substance abuse and mental health services. That would be no small challenge in a poor farming and ranching region where stigma often prevents people from admitting they need help, said Katherine Buckley-Patton, who chairs the county’s Mental Health Local Advisory Council.

“I find it very challenging to find the words that will not make one of my hard-nosed cowboys turn around and walk away,” Ms. Buckley-Patton said. “They’re lonely, they’re isolated, they’re depressed, but they’re not going to call a suicide hotline.”

States across the U.S. are still stinging after businesses closed and millions of people lost jobs because of COVID-related shutdowns and restrictions. Meanwhile, the pandemic has led to a dramatic increase in the number of people who say their mental health has suffered, rising from one in three people in March to more than half of people polled by KFF in July. (KHN is an editorially independent program of KFF.)

The full extent of the mental health crisis and the demand for behavioral health services may not be known until after the pandemic is over, mental health experts said. That could add costs that budget writers haven’t anticipated.

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

The Food and Drug Administration has approved cemiplimab-rwlc (Libtayo) as the first immunotherapy to treat patients with locally advanced or metastatic basal cell carcinoma (BCC) previously treated with a hedgehog pathway inhibitor or in whom an HHI is inappropriate.

The FDA granted full approval for the locally advanced BCC indication and accelerated approval for the metastatic BCC indication, according to a press release from Regeneron and Sanofi, the companies jointly developing cemiplimab.

Cemiplimab is a programmed death–1 inhibitor that was first FDA approved in 2018 for locally advanced or metastatic cutaneous squamous cell carcinoma not eligible for curative surgery or radiation.

The new approval “will change the treatment paradigm for patients with advanced basal cell carcinoma,” according to Karl Lewis, MD, a professor at the University of Colorado at Denver, Aurora, and an investigator on the phase 2 trial of cemiplimab.

“While the primary systemic treatment options are hedgehog inhibitors, many patients will eventually progress on or become intolerant to this therapy,” Dr. Lewis said in the press release. “With Libtayo [cemiplimab], these patients now have a new immunotherapy option.”

The approval of cemiplimab in BCC was based on an open-label, phase 2 trial of 132 patients with advanced BCC. Patients could not tolerate, had progressed on, or had not responded to HHIs after 9 months of treatment.

Cemiplimab was given at 350 mg every 3 weeks. The study was not placebo controlled and has not been published, a Regeneron spokesperson said.

There were 112 patients in the efficacy analysis. The overall response rate was 21% (6/28) in metastatic BCC patients, with no complete responders. In locally advanced BCC patients, the objective response rate was 29% (24/84), with five complete responders.

The median duration of response was not reached in either group but was at least 6 months long in all metastatic patients and in 79% (19/84) of the locally advanced BCC patients.

The most common adverse events among the 132 subjects evaluable for safety were fatigue (49%), musculoskeletal pain (33%), diarrhea (25%), rash (22%), pruritus (20%), and upper respiratory tract infection (15%).

Serious adverse events occurred in 32% of patients, including colitis, acute kidney injury, adrenal insufficiency, and anemia. Adverse events led to discontinuation in 13% of patients, most often for colitis and general physical health deterioration.

For more details on cemiplimab, see the full prescribing information.

[email protected]

The Food and Drug Administration has approved cemiplimab-rwlc (Libtayo) as the first immunotherapy to treat patients with locally advanced or metastatic basal cell carcinoma (BCC) previously treated with a hedgehog pathway inhibitor or in whom an HHI is inappropriate.

The FDA granted full approval for the locally advanced BCC indication and accelerated approval for the metastatic BCC indication, according to a press release from Regeneron and Sanofi, the companies jointly developing cemiplimab.

Cemiplimab is a programmed death–1 inhibitor that was first FDA approved in 2018 for locally advanced or metastatic cutaneous squamous cell carcinoma not eligible for curative surgery or radiation.

The new approval “will change the treatment paradigm for patients with advanced basal cell carcinoma,” according to Karl Lewis, MD, a professor at the University of Colorado at Denver, Aurora, and an investigator on the phase 2 trial of cemiplimab.

“While the primary systemic treatment options are hedgehog inhibitors, many patients will eventually progress on or become intolerant to this therapy,” Dr. Lewis said in the press release. “With Libtayo [cemiplimab], these patients now have a new immunotherapy option.”

The approval of cemiplimab in BCC was based on an open-label, phase 2 trial of 132 patients with advanced BCC. Patients could not tolerate, had progressed on, or had not responded to HHIs after 9 months of treatment.

Cemiplimab was given at 350 mg every 3 weeks. The study was not placebo controlled and has not been published, a Regeneron spokesperson said.

There were 112 patients in the efficacy analysis. The overall response rate was 21% (6/28) in metastatic BCC patients, with no complete responders. In locally advanced BCC patients, the objective response rate was 29% (24/84), with five complete responders.

The median duration of response was not reached in either group but was at least 6 months long in all metastatic patients and in 79% (19/84) of the locally advanced BCC patients.

The most common adverse events among the 132 subjects evaluable for safety were fatigue (49%), musculoskeletal pain (33%), diarrhea (25%), rash (22%), pruritus (20%), and upper respiratory tract infection (15%).

Serious adverse events occurred in 32% of patients, including colitis, acute kidney injury, adrenal insufficiency, and anemia. Adverse events led to discontinuation in 13% of patients, most often for colitis and general physical health deterioration.

For more details on cemiplimab, see the full prescribing information.

[email protected]

The Food and Drug Administration has approved cemiplimab-rwlc (Libtayo) as the first immunotherapy to treat patients with locally advanced or metastatic basal cell carcinoma (BCC) previously treated with a hedgehog pathway inhibitor or in whom an HHI is inappropriate.

The FDA granted full approval for the locally advanced BCC indication and accelerated approval for the metastatic BCC indication, according to a press release from Regeneron and Sanofi, the companies jointly developing cemiplimab.

Cemiplimab is a programmed death–1 inhibitor that was first FDA approved in 2018 for locally advanced or metastatic cutaneous squamous cell carcinoma not eligible for curative surgery or radiation.

The new approval “will change the treatment paradigm for patients with advanced basal cell carcinoma,” according to Karl Lewis, MD, a professor at the University of Colorado at Denver, Aurora, and an investigator on the phase 2 trial of cemiplimab.

“While the primary systemic treatment options are hedgehog inhibitors, many patients will eventually progress on or become intolerant to this therapy,” Dr. Lewis said in the press release. “With Libtayo [cemiplimab], these patients now have a new immunotherapy option.”

The approval of cemiplimab in BCC was based on an open-label, phase 2 trial of 132 patients with advanced BCC. Patients could not tolerate, had progressed on, or had not responded to HHIs after 9 months of treatment.

Cemiplimab was given at 350 mg every 3 weeks. The study was not placebo controlled and has not been published, a Regeneron spokesperson said.

There were 112 patients in the efficacy analysis. The overall response rate was 21% (6/28) in metastatic BCC patients, with no complete responders. In locally advanced BCC patients, the objective response rate was 29% (24/84), with five complete responders.

The median duration of response was not reached in either group but was at least 6 months long in all metastatic patients and in 79% (19/84) of the locally advanced BCC patients.

The most common adverse events among the 132 subjects evaluable for safety were fatigue (49%), musculoskeletal pain (33%), diarrhea (25%), rash (22%), pruritus (20%), and upper respiratory tract infection (15%).

Serious adverse events occurred in 32% of patients, including colitis, acute kidney injury, adrenal insufficiency, and anemia. Adverse events led to discontinuation in 13% of patients, most often for colitis and general physical health deterioration.

For more details on cemiplimab, see the full prescribing information.

[email protected]

New COVID-19 cases in children dropped for the third consecutive week, even as children continue to make up a larger share of all cases, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

New child cases totaled almost 118,000 for the week of Jan. 29-Feb. 4, continuing the decline that began right after the United States topped 200,000 cases for the only time Jan. 8-14, the AAP and the CHA said in their weekly COVID-19 report.

For the latest week, however, children represented 16.0% of all new COVID-19 cases, continuing a 5-week increase that began in early December 2020, after the proportion had dropped to 12.6%, based on data collected from the health departments of 49 states (excluding New York), the District of Columbia, New York City, Puerto Rico, and Guam. During the week of Sept. 11-17, children made up 16.9% of all cases, the highest level seen during the pandemic.

The 2.93 million cases that have been reported in children make up 12.9% of all cases since the pandemic began, and the overall rate of pediatric coronavirus infection is 3,899 cases per 100,000 children in the population. Taking a step down from the national level, 30 states are above that rate and 18 are below it, along with D.C., New York City, Puerto Rico, and Guam (New York and Texas are excluded), the AAP and CHA reported.

There were 12 new COVID-19–related child deaths in the 43 states, along with New York City and Guam, that are reporting such data, bringing the total to 227. Nationally, 0.06% of all deaths have occurred in children, with rates ranging from 0.00% (11 states) to 0.26% (Nebraska) in the 45 jurisdictions, the AAP/CHA report shows.

Child hospitalizations rose to 1.9% of all hospitalizations after holding at 1.8% since mid-November in 25 reporting jurisdictions (24 states and New York City), but the hospitalization rate among children with COVID held at 0.8%, where it has been for the last 4 weeks. Hospitalization rates as high as 3.8% were recorded early in the pandemic, the AAP and CHA noted.

[email protected]

New COVID-19 cases in children dropped for the third consecutive week, even as children continue to make up a larger share of all cases, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

New child cases totaled almost 118,000 for the week of Jan. 29-Feb. 4, continuing the decline that began right after the United States topped 200,000 cases for the only time Jan. 8-14, the AAP and the CHA said in their weekly COVID-19 report.

For the latest week, however, children represented 16.0% of all new COVID-19 cases, continuing a 5-week increase that began in early December 2020, after the proportion had dropped to 12.6%, based on data collected from the health departments of 49 states (excluding New York), the District of Columbia, New York City, Puerto Rico, and Guam. During the week of Sept. 11-17, children made up 16.9% of all cases, the highest level seen during the pandemic.

The 2.93 million cases that have been reported in children make up 12.9% of all cases since the pandemic began, and the overall rate of pediatric coronavirus infection is 3,899 cases per 100,000 children in the population. Taking a step down from the national level, 30 states are above that rate and 18 are below it, along with D.C., New York City, Puerto Rico, and Guam (New York and Texas are excluded), the AAP and CHA reported.

There were 12 new COVID-19–related child deaths in the 43 states, along with New York City and Guam, that are reporting such data, bringing the total to 227. Nationally, 0.06% of all deaths have occurred in children, with rates ranging from 0.00% (11 states) to 0.26% (Nebraska) in the 45 jurisdictions, the AAP/CHA report shows.

Child hospitalizations rose to 1.9% of all hospitalizations after holding at 1.8% since mid-November in 25 reporting jurisdictions (24 states and New York City), but the hospitalization rate among children with COVID held at 0.8%, where it has been for the last 4 weeks. Hospitalization rates as high as 3.8% were recorded early in the pandemic, the AAP and CHA noted.

[email protected]

New COVID-19 cases in children dropped for the third consecutive week, even as children continue to make up a larger share of all cases, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

New child cases totaled almost 118,000 for the week of Jan. 29-Feb. 4, continuing the decline that began right after the United States topped 200,000 cases for the only time Jan. 8-14, the AAP and the CHA said in their weekly COVID-19 report.

For the latest week, however, children represented 16.0% of all new COVID-19 cases, continuing a 5-week increase that began in early December 2020, after the proportion had dropped to 12.6%, based on data collected from the health departments of 49 states (excluding New York), the District of Columbia, New York City, Puerto Rico, and Guam. During the week of Sept. 11-17, children made up 16.9% of all cases, the highest level seen during the pandemic.

The 2.93 million cases that have been reported in children make up 12.9% of all cases since the pandemic began, and the overall rate of pediatric coronavirus infection is 3,899 cases per 100,000 children in the population. Taking a step down from the national level, 30 states are above that rate and 18 are below it, along with D.C., New York City, Puerto Rico, and Guam (New York and Texas are excluded), the AAP and CHA reported.

There were 12 new COVID-19–related child deaths in the 43 states, along with New York City and Guam, that are reporting such data, bringing the total to 227. Nationally, 0.06% of all deaths have occurred in children, with rates ranging from 0.00% (11 states) to 0.26% (Nebraska) in the 45 jurisdictions, the AAP/CHA report shows.

Child hospitalizations rose to 1.9% of all hospitalizations after holding at 1.8% since mid-November in 25 reporting jurisdictions (24 states and New York City), but the hospitalization rate among children with COVID held at 0.8%, where it has been for the last 4 weeks. Hospitalization rates as high as 3.8% were recorded early in the pandemic, the AAP and CHA noted.

[email protected]

To improve autism screening rates, researchers in Utah tried a range of interventions.

They added automatic reminders to the electronic health record (EHR). They started using a shorter, more sensitive screening instrument. And they trained clinicians to perform autism-specific evaluations in a primary care clinic.

Three phases

They examined more than 12,000 well-child visits for children aged 16-30 months between July 2017 and June 2019.

In all, 4,155 visits occurred at the 2 intervention clinics, and 8,078 visits occurred at the 27 community clinics in the University of Utah health care system.

From baseline through the interventions, the proportion of visits with screening increased by 51% in the intervention clinics (from 58.6% to 88.8%), and by 21% in the community clinics (from 43.4% to 52.4%). The proportion of referrals increased 1.5-fold in intervention clinics, from 1.3% to 3.3%, the authors said.

The American Academy of Pediatrics (AAP) supports screening for autism in all children starting at age 18 months, but “only 44% of children with autism have had a comprehensive autism evaluation before age 36 months,” Dr. Campbell and colleagues wrote.

In their system, about half of the children were being screened for autism, and 0.5% had autism diagnosed.

In an effort to increase the proportion of visits with screening for autism and the proportion of visits with referrals for autism evaluation, Dr. Campbell and colleagues designed a quality improvement study.

Following a baseline period, they implemented interventions in three phases.

Initially, all clinics used the Modified Checklist for Autism in Toddlers, Revised (M-CHAT-R) for autism screening. For the first phase starting in July 2018, the researchers changed the screening instrument at the two intervention clinics to the Parent’s Observation of Social Interaction (POSI). This instrument “is embedded in a broadband developmental screen, is shorter than the M-CHAT-R, and includes questions about the consistency of the child’s behavior,” the authors said. “The POSI has greater sensitivity than the M-CHAT-R ... and similar, although somewhat lower, specificity.”

In intervention phase 2 starting in November 2018, the researchers “added an automatic reminder for autism screening to the EHR health maintenance screen.” Both the intervention clinics and the community clinics received the automatic reminders.

In intervention phase 3 starting in February 2019, they “added a referral option that clinicians could use for rapid access to autism-specific evaluation ... for children who had a POSI result suggestive of autism and for whom the clinician had sufficient concerns about autism that would indicate the need for referral for autism evaluation,” the researchers said.

“Using an online tutorial, we trained three clinicians in the intervention clinics to administer an observational assessment known as the Screening Tool for Autism in Toddlers (STAT),” which requires a 30-minute visit, they said. “Children who had a STAT result suggestive of autism were referred for expedited autism diagnostic evaluation, which was performed by a multidisciplinary team in our university-based developmental assessment clinic. Children who had a STAT result that did not suggest autism did not receive further autism evaluations unless the clinician felt they still needed further evaluation at the developmental clinic.”

After the switch to POSI, the percentage of visits with a positive screen result increased from 4.7% to 13.5% in the intervention clinics.

Furthermore, referrals were 3.4 times more frequent for visits during phase 3 in the intervention clinics, relative to the baseline period.
 

Potential to overwhelm

“The change to a more sensitive screening instrument increased the frequency of screening results suggestive of autism and informed our improvement team of the need to implement autism evaluation in primary care to avoid overwhelming our referral system,” Dr. Campbell and coauthors reported.

Future studies may assess whether increased screening and referrals speed the time to diagnosis and treatment and improve long-term functional abilities of children with autism. Some children in the study have received an autism diagnosis, while others have not yet been evaluated.

The use of STAT in primary care may be limited by “the barriers of training providers and purchasing materials,” the authors noted. “However, the time-based billing for lengthier appointments and billing for developmental testing help to cover cost.”

The intervention clinics and community clinics were staffed by pediatric providers, including residents and attendings, said Dr. Campbell.

“The staffing is similar at the community and intervention clinics, with mostly pediatricians and some nurse practitioners,” Dr. Campbell said. “One difference is that there are a few family medicine physicians in the community clinics, but we did not study whether that made a difference in screening. At the beginning of the study the approach to screening was the same.”

From the start, the community clinics were screening for autism and referring for further autism evaluation less often than the intervention clinics. “I don’t know why they were screening less, but they did improve with the automatic reminders,” said Dr. Campbell. “We didn’t examine type of provider or type of practice in this study, but the literature suggests that family physicians do not screen for autism as often as pediatricians.”
 

Payment and referral challenges

In theory, the approach in the study is a great idea, but it may not be feasible to implement for many private practices, said Herschel Lessin, MD. Dr. Lessin is a senior partner of the Children’s Medical Group in New York.

“We desperately need autism screening in a primary care setting,” Dr. Lessin said. “These authors found that wasn’t being done as recommended by the AAP Bright Futures, which is a problem.”

However, the researchers incorporated the interventions in a health care system with “far more resources than most people in practice would ever have” and substituted a less familiar screening tool.

In addition, the ability to use confirmatory STAT for primary care evaluations may be limited. “Unless you can find pediatricians willing to commit 30 to 45 minutes on one of these evaluations ... few are going to do that,” he said.

“The whole problem is that there are no referrals available or very few referrals available, and that insurance payments so underpay for developmental screening and evaluation that it does not justify the time doing it, so a lot of doctors are unable to do it,” said Dr. Lessin. When a referral is warranted, developmental pediatricians may have 6- to 12-month waiting lists, he said.

“For people in clinical practice, this is not news,” Dr. Lessin said. “We know we should screen for autism. The problem is it’s time consuming. Nobody pays for it. We have no place to send them even when we are suspicious.”
 

From screening to diagnosis to treatment

“Autism screen approaches vary but with educational efforts on the part of the AAP, CDC, and family organizations the rates for autism screening have dramatically improved,” said Susan L. Hyman, MD, professor of pediatrics at the University of Rochester in New York. “I do not know if screening rates have been impacted by COVID.”

Dr. Hyman and coauthors wrote an AAP clinical report on the identification, evaluation, and management of children with autism spectrum disorder. The report was published in the January 2020 issue of Pediatrics.

After screening and diagnostic testing, patients most importantly need to be able to access “timely and equitable evidence-based intervention,” which should be available, said Dr. Hyman.

Although researchers have proposed training primary care providers in autism diagnostics, “older, more complex patients with co-occurring behavioral health or other developmental disorders may need more specialized diagnostic assessment than could be accomplished in a primary care setting,” Dr. Hyman added.

“However, it is very important to identify children with therapeutic needs as early as possible and move them through the continuum from screening to diagnosis to treatment in a timely fashion. It would be wonderful if symptoms could be addressed without the need for diagnosis in the very youngest children,” Dr. Hyman said. “Early symptoms, even if not autism, are likely to be appropriate for intervention – whether it is speech therapy, attention to food selectivity, sleep problems – things that impact quality of life and potential future symptoms.”

The research was supported by the Utah Stimulating Access to Research in Residency Transition Scholar award, which is funded by the National Institutes of Health.

Dr. Campbell is an inventor on a patent related to screening for autism. The study authors otherwise had no disclosures. Dr. Lessin is on the editorial advisory board for Pediatric News and is on an advisory board for Cognoa, which is developing a medical device to diagnose autism and he is also the co-editor of the AAP's current ADHD Toolkit. Dr. Hyman had no relevant financial disclosures.

[email protected]

*This story was updated on Feb. 11, 2021.

To improve autism screening rates, researchers in Utah tried a range of interventions.

They added automatic reminders to the electronic health record (EHR). They started using a shorter, more sensitive screening instrument. And they trained clinicians to perform autism-specific evaluations in a primary care clinic.

Three phases

They examined more than 12,000 well-child visits for children aged 16-30 months between July 2017 and June 2019.

In all, 4,155 visits occurred at the 2 intervention clinics, and 8,078 visits occurred at the 27 community clinics in the University of Utah health care system.

From baseline through the interventions, the proportion of visits with screening increased by 51% in the intervention clinics (from 58.6% to 88.8%), and by 21% in the community clinics (from 43.4% to 52.4%). The proportion of referrals increased 1.5-fold in intervention clinics, from 1.3% to 3.3%, the authors said.

The American Academy of Pediatrics (AAP) supports screening for autism in all children starting at age 18 months, but “only 44% of children with autism have had a comprehensive autism evaluation before age 36 months,” Dr. Campbell and colleagues wrote.

In their system, about half of the children were being screened for autism, and 0.5% had autism diagnosed.

In an effort to increase the proportion of visits with screening for autism and the proportion of visits with referrals for autism evaluation, Dr. Campbell and colleagues designed a quality improvement study.

Following a baseline period, they implemented interventions in three phases.

Initially, all clinics used the Modified Checklist for Autism in Toddlers, Revised (M-CHAT-R) for autism screening. For the first phase starting in July 2018, the researchers changed the screening instrument at the two intervention clinics to the Parent’s Observation of Social Interaction (POSI). This instrument “is embedded in a broadband developmental screen, is shorter than the M-CHAT-R, and includes questions about the consistency of the child’s behavior,” the authors said. “The POSI has greater sensitivity than the M-CHAT-R ... and similar, although somewhat lower, specificity.”

In intervention phase 2 starting in November 2018, the researchers “added an automatic reminder for autism screening to the EHR health maintenance screen.” Both the intervention clinics and the community clinics received the automatic reminders.

In intervention phase 3 starting in February 2019, they “added a referral option that clinicians could use for rapid access to autism-specific evaluation ... for children who had a POSI result suggestive of autism and for whom the clinician had sufficient concerns about autism that would indicate the need for referral for autism evaluation,” the researchers said.

“Using an online tutorial, we trained three clinicians in the intervention clinics to administer an observational assessment known as the Screening Tool for Autism in Toddlers (STAT),” which requires a 30-minute visit, they said. “Children who had a STAT result suggestive of autism were referred for expedited autism diagnostic evaluation, which was performed by a multidisciplinary team in our university-based developmental assessment clinic. Children who had a STAT result that did not suggest autism did not receive further autism evaluations unless the clinician felt they still needed further evaluation at the developmental clinic.”

After the switch to POSI, the percentage of visits with a positive screen result increased from 4.7% to 13.5% in the intervention clinics.

Furthermore, referrals were 3.4 times more frequent for visits during phase 3 in the intervention clinics, relative to the baseline period.
 

Potential to overwhelm

“The change to a more sensitive screening instrument increased the frequency of screening results suggestive of autism and informed our improvement team of the need to implement autism evaluation in primary care to avoid overwhelming our referral system,” Dr. Campbell and coauthors reported.

Future studies may assess whether increased screening and referrals speed the time to diagnosis and treatment and improve long-term functional abilities of children with autism. Some children in the study have received an autism diagnosis, while others have not yet been evaluated.

The use of STAT in primary care may be limited by “the barriers of training providers and purchasing materials,” the authors noted. “However, the time-based billing for lengthier appointments and billing for developmental testing help to cover cost.”

The intervention clinics and community clinics were staffed by pediatric providers, including residents and attendings, said Dr. Campbell.

“The staffing is similar at the community and intervention clinics, with mostly pediatricians and some nurse practitioners,” Dr. Campbell said. “One difference is that there are a few family medicine physicians in the community clinics, but we did not study whether that made a difference in screening. At the beginning of the study the approach to screening was the same.”

From the start, the community clinics were screening for autism and referring for further autism evaluation less often than the intervention clinics. “I don’t know why they were screening less, but they did improve with the automatic reminders,” said Dr. Campbell. “We didn’t examine type of provider or type of practice in this study, but the literature suggests that family physicians do not screen for autism as often as pediatricians.”
 

Payment and referral challenges

In theory, the approach in the study is a great idea, but it may not be feasible to implement for many private practices, said Herschel Lessin, MD. Dr. Lessin is a senior partner of the Children’s Medical Group in New York.

“We desperately need autism screening in a primary care setting,” Dr. Lessin said. “These authors found that wasn’t being done as recommended by the AAP Bright Futures, which is a problem.”

However, the researchers incorporated the interventions in a health care system with “far more resources than most people in practice would ever have” and substituted a less familiar screening tool.

In addition, the ability to use confirmatory STAT for primary care evaluations may be limited. “Unless you can find pediatricians willing to commit 30 to 45 minutes on one of these evaluations ... few are going to do that,” he said.

“The whole problem is that there are no referrals available or very few referrals available, and that insurance payments so underpay for developmental screening and evaluation that it does not justify the time doing it, so a lot of doctors are unable to do it,” said Dr. Lessin. When a referral is warranted, developmental pediatricians may have 6- to 12-month waiting lists, he said.

“For people in clinical practice, this is not news,” Dr. Lessin said. “We know we should screen for autism. The problem is it’s time consuming. Nobody pays for it. We have no place to send them even when we are suspicious.”
 

From screening to diagnosis to treatment

“Autism screen approaches vary but with educational efforts on the part of the AAP, CDC, and family organizations the rates for autism screening have dramatically improved,” said Susan L. Hyman, MD, professor of pediatrics at the University of Rochester in New York. “I do not know if screening rates have been impacted by COVID.”

Dr. Hyman and coauthors wrote an AAP clinical report on the identification, evaluation, and management of children with autism spectrum disorder. The report was published in the January 2020 issue of Pediatrics.

After screening and diagnostic testing, patients most importantly need to be able to access “timely and equitable evidence-based intervention,” which should be available, said Dr. Hyman.

Although researchers have proposed training primary care providers in autism diagnostics, “older, more complex patients with co-occurring behavioral health or other developmental disorders may need more specialized diagnostic assessment than could be accomplished in a primary care setting,” Dr. Hyman added.

“However, it is very important to identify children with therapeutic needs as early as possible and move them through the continuum from screening to diagnosis to treatment in a timely fashion. It would be wonderful if symptoms could be addressed without the need for diagnosis in the very youngest children,” Dr. Hyman said. “Early symptoms, even if not autism, are likely to be appropriate for intervention – whether it is speech therapy, attention to food selectivity, sleep problems – things that impact quality of life and potential future symptoms.”

The research was supported by the Utah Stimulating Access to Research in Residency Transition Scholar award, which is funded by the National Institutes of Health.

Dr. Campbell is an inventor on a patent related to screening for autism. The study authors otherwise had no disclosures. Dr. Lessin is on the editorial advisory board for Pediatric News and is on an advisory board for Cognoa, which is developing a medical device to diagnose autism and he is also the co-editor of the AAP's current ADHD Toolkit. Dr. Hyman had no relevant financial disclosures.

[email protected]

*This story was updated on Feb. 11, 2021.

To improve autism screening rates, researchers in Utah tried a range of interventions.

They added automatic reminders to the electronic health record (EHR). They started using a shorter, more sensitive screening instrument. And they trained clinicians to perform autism-specific evaluations in a primary care clinic.

Three phases

They examined more than 12,000 well-child visits for children aged 16-30 months between July 2017 and June 2019.

In all, 4,155 visits occurred at the 2 intervention clinics, and 8,078 visits occurred at the 27 community clinics in the University of Utah health care system.

From baseline through the interventions, the proportion of visits with screening increased by 51% in the intervention clinics (from 58.6% to 88.8%), and by 21% in the community clinics (from 43.4% to 52.4%). The proportion of referrals increased 1.5-fold in intervention clinics, from 1.3% to 3.3%, the authors said.

The American Academy of Pediatrics (AAP) supports screening for autism in all children starting at age 18 months, but “only 44% of children with autism have had a comprehensive autism evaluation before age 36 months,” Dr. Campbell and colleagues wrote.

In their system, about half of the children were being screened for autism, and 0.5% had autism diagnosed.

In an effort to increase the proportion of visits with screening for autism and the proportion of visits with referrals for autism evaluation, Dr. Campbell and colleagues designed a quality improvement study.

Following a baseline period, they implemented interventions in three phases.

Initially, all clinics used the Modified Checklist for Autism in Toddlers, Revised (M-CHAT-R) for autism screening. For the first phase starting in July 2018, the researchers changed the screening instrument at the two intervention clinics to the Parent’s Observation of Social Interaction (POSI). This instrument “is embedded in a broadband developmental screen, is shorter than the M-CHAT-R, and includes questions about the consistency of the child’s behavior,” the authors said. “The POSI has greater sensitivity than the M-CHAT-R ... and similar, although somewhat lower, specificity.”

In intervention phase 2 starting in November 2018, the researchers “added an automatic reminder for autism screening to the EHR health maintenance screen.” Both the intervention clinics and the community clinics received the automatic reminders.

In intervention phase 3 starting in February 2019, they “added a referral option that clinicians could use for rapid access to autism-specific evaluation ... for children who had a POSI result suggestive of autism and for whom the clinician had sufficient concerns about autism that would indicate the need for referral for autism evaluation,” the researchers said.

“Using an online tutorial, we trained three clinicians in the intervention clinics to administer an observational assessment known as the Screening Tool for Autism in Toddlers (STAT),” which requires a 30-minute visit, they said. “Children who had a STAT result suggestive of autism were referred for expedited autism diagnostic evaluation, which was performed by a multidisciplinary team in our university-based developmental assessment clinic. Children who had a STAT result that did not suggest autism did not receive further autism evaluations unless the clinician felt they still needed further evaluation at the developmental clinic.”

After the switch to POSI, the percentage of visits with a positive screen result increased from 4.7% to 13.5% in the intervention clinics.

Furthermore, referrals were 3.4 times more frequent for visits during phase 3 in the intervention clinics, relative to the baseline period.
 

Potential to overwhelm

“The change to a more sensitive screening instrument increased the frequency of screening results suggestive of autism and informed our improvement team of the need to implement autism evaluation in primary care to avoid overwhelming our referral system,” Dr. Campbell and coauthors reported.

Future studies may assess whether increased screening and referrals speed the time to diagnosis and treatment and improve long-term functional abilities of children with autism. Some children in the study have received an autism diagnosis, while others have not yet been evaluated.

The use of STAT in primary care may be limited by “the barriers of training providers and purchasing materials,” the authors noted. “However, the time-based billing for lengthier appointments and billing for developmental testing help to cover cost.”

The intervention clinics and community clinics were staffed by pediatric providers, including residents and attendings, said Dr. Campbell.

“The staffing is similar at the community and intervention clinics, with mostly pediatricians and some nurse practitioners,” Dr. Campbell said. “One difference is that there are a few family medicine physicians in the community clinics, but we did not study whether that made a difference in screening. At the beginning of the study the approach to screening was the same.”

From the start, the community clinics were screening for autism and referring for further autism evaluation less often than the intervention clinics. “I don’t know why they were screening less, but they did improve with the automatic reminders,” said Dr. Campbell. “We didn’t examine type of provider or type of practice in this study, but the literature suggests that family physicians do not screen for autism as often as pediatricians.”
 

Payment and referral challenges

In theory, the approach in the study is a great idea, but it may not be feasible to implement for many private practices, said Herschel Lessin, MD. Dr. Lessin is a senior partner of the Children’s Medical Group in New York.

“We desperately need autism screening in a primary care setting,” Dr. Lessin said. “These authors found that wasn’t being done as recommended by the AAP Bright Futures, which is a problem.”

However, the researchers incorporated the interventions in a health care system with “far more resources than most people in practice would ever have” and substituted a less familiar screening tool.

In addition, the ability to use confirmatory STAT for primary care evaluations may be limited. “Unless you can find pediatricians willing to commit 30 to 45 minutes on one of these evaluations ... few are going to do that,” he said.

“The whole problem is that there are no referrals available or very few referrals available, and that insurance payments so underpay for developmental screening and evaluation that it does not justify the time doing it, so a lot of doctors are unable to do it,” said Dr. Lessin. When a referral is warranted, developmental pediatricians may have 6- to 12-month waiting lists, he said.

“For people in clinical practice, this is not news,” Dr. Lessin said. “We know we should screen for autism. The problem is it’s time consuming. Nobody pays for it. We have no place to send them even when we are suspicious.”
 

From screening to diagnosis to treatment

“Autism screen approaches vary but with educational efforts on the part of the AAP, CDC, and family organizations the rates for autism screening have dramatically improved,” said Susan L. Hyman, MD, professor of pediatrics at the University of Rochester in New York. “I do not know if screening rates have been impacted by COVID.”

Dr. Hyman and coauthors wrote an AAP clinical report on the identification, evaluation, and management of children with autism spectrum disorder. The report was published in the January 2020 issue of Pediatrics.

After screening and diagnostic testing, patients most importantly need to be able to access “timely and equitable evidence-based intervention,” which should be available, said Dr. Hyman.

Although researchers have proposed training primary care providers in autism diagnostics, “older, more complex patients with co-occurring behavioral health or other developmental disorders may need more specialized diagnostic assessment than could be accomplished in a primary care setting,” Dr. Hyman added.

“However, it is very important to identify children with therapeutic needs as early as possible and move them through the continuum from screening to diagnosis to treatment in a timely fashion. It would be wonderful if symptoms could be addressed without the need for diagnosis in the very youngest children,” Dr. Hyman said. “Early symptoms, even if not autism, are likely to be appropriate for intervention – whether it is speech therapy, attention to food selectivity, sleep problems – things that impact quality of life and potential future symptoms.”

The research was supported by the Utah Stimulating Access to Research in Residency Transition Scholar award, which is funded by the National Institutes of Health.

Dr. Campbell is an inventor on a patent related to screening for autism. The study authors otherwise had no disclosures. Dr. Lessin is on the editorial advisory board for Pediatric News and is on an advisory board for Cognoa, which is developing a medical device to diagnose autism and he is also the co-editor of the AAP's current ADHD Toolkit. Dr. Hyman had no relevant financial disclosures.

[email protected]

*This story was updated on Feb. 11, 2021.