Preoperative nivolumab plus ipilimumab appears safe and feasible for patients with early-stage colon cancer, according to researchers.

The combination produced few grade 3/4 toxicities in a phase 2 trial. It also produced pathological responses in 100% of patients with mismatch repair-deficient (dMMR) tumors and in 27% of patients with MMR-proficient (pMMR) tumors. Myriam Chalabi, MD, of the Netherlands Cancer Institute in Amsterdam, and colleagues reported these results in Nature Medicine.

The open-label, exploratory trial included 40 patients with resectable, early-stage colon adenocarcinoma, 21 of whom had dMMR tumors and 20 of whom had pMMR tumors (1 patient had both tumor types). The patients underwent surgery within 6 weeks of study enrollment.

Prior to surgery, patients received ipilimumab (1 mg/kg) on day 1 plus nivolumab (3 mg/kg) on days 1 and 15. Those with pMMR tumors also received celecoxib (200 mg) from day 1 until the day leading up to surgery. The primary endpoints were safety and feasibility. Efficacy was evaluated using histopathological response.Grade 3-4 treatment‐related adverse events (AEs) were reported in 5 patients (13%). These AEs included rash, colitis, and asymptomatic rises in laboratory parameters. Grade 3 surgery-related AEs occurred in 8 patients (20%).

“This treatment is both safe and feasible, with few treatment-related AEs and without compromising surgery,” the authors wrote.

There were 35 patients evaluable for response. Among patients with dMMR tumors, pathological responses occurred in 100% (n = 20), major pathological responses (<10% residual vital tumor) occurred in 95% (n = 19), and complete responses occurred in 60% (n = 12).

Among patients with pMMR tumors, 27% (n = 4) had a pathological response, 20% (n = 3) had a major pathological response, and 7% (n = 1) had a partial response.

The researchers acknowledged that the small sample size and short duration of postoperative follow-up were key limitations of this study, but they said this combination should be studied further.

“Neoadjuvant immunotherapy in early-stage colon cancers warrants further research and, when validated in larger studies with longer follow­-up, may become a new standard of care in dMMR and possibly a subgroup of pMMR colon cancers,” the authors concluded.

This study was sponsored by the Netherlands Cancer Institute in collaboration with Bristol-Myers Squibb. Authors reported financial relationships with Bristol-Myers Squibb and many other companies.

SOURCE: Chalabi M et al. Nat Med. 2020 Apr 6. doi: 10.1038/s41591-020-0805-8.

Preoperative nivolumab plus ipilimumab appears safe and feasible for patients with early-stage colon cancer, according to researchers.

The combination produced few grade 3/4 toxicities in a phase 2 trial. It also produced pathological responses in 100% of patients with mismatch repair-deficient (dMMR) tumors and in 27% of patients with MMR-proficient (pMMR) tumors. Myriam Chalabi, MD, of the Netherlands Cancer Institute in Amsterdam, and colleagues reported these results in Nature Medicine.

The open-label, exploratory trial included 40 patients with resectable, early-stage colon adenocarcinoma, 21 of whom had dMMR tumors and 20 of whom had pMMR tumors (1 patient had both tumor types). The patients underwent surgery within 6 weeks of study enrollment.

Prior to surgery, patients received ipilimumab (1 mg/kg) on day 1 plus nivolumab (3 mg/kg) on days 1 and 15. Those with pMMR tumors also received celecoxib (200 mg) from day 1 until the day leading up to surgery. The primary endpoints were safety and feasibility. Efficacy was evaluated using histopathological response.Grade 3-4 treatment‐related adverse events (AEs) were reported in 5 patients (13%). These AEs included rash, colitis, and asymptomatic rises in laboratory parameters. Grade 3 surgery-related AEs occurred in 8 patients (20%).

“This treatment is both safe and feasible, with few treatment-related AEs and without compromising surgery,” the authors wrote.

There were 35 patients evaluable for response. Among patients with dMMR tumors, pathological responses occurred in 100% (n = 20), major pathological responses (<10% residual vital tumor) occurred in 95% (n = 19), and complete responses occurred in 60% (n = 12).

Among patients with pMMR tumors, 27% (n = 4) had a pathological response, 20% (n = 3) had a major pathological response, and 7% (n = 1) had a partial response.

The researchers acknowledged that the small sample size and short duration of postoperative follow-up were key limitations of this study, but they said this combination should be studied further.

“Neoadjuvant immunotherapy in early-stage colon cancers warrants further research and, when validated in larger studies with longer follow­-up, may become a new standard of care in dMMR and possibly a subgroup of pMMR colon cancers,” the authors concluded.

This study was sponsored by the Netherlands Cancer Institute in collaboration with Bristol-Myers Squibb. Authors reported financial relationships with Bristol-Myers Squibb and many other companies.

SOURCE: Chalabi M et al. Nat Med. 2020 Apr 6. doi: 10.1038/s41591-020-0805-8.

Preoperative nivolumab plus ipilimumab appears safe and feasible for patients with early-stage colon cancer, according to researchers.

The combination produced few grade 3/4 toxicities in a phase 2 trial. It also produced pathological responses in 100% of patients with mismatch repair-deficient (dMMR) tumors and in 27% of patients with MMR-proficient (pMMR) tumors. Myriam Chalabi, MD, of the Netherlands Cancer Institute in Amsterdam, and colleagues reported these results in Nature Medicine.

The open-label, exploratory trial included 40 patients with resectable, early-stage colon adenocarcinoma, 21 of whom had dMMR tumors and 20 of whom had pMMR tumors (1 patient had both tumor types). The patients underwent surgery within 6 weeks of study enrollment.

Prior to surgery, patients received ipilimumab (1 mg/kg) on day 1 plus nivolumab (3 mg/kg) on days 1 and 15. Those with pMMR tumors also received celecoxib (200 mg) from day 1 until the day leading up to surgery. The primary endpoints were safety and feasibility. Efficacy was evaluated using histopathological response.Grade 3-4 treatment‐related adverse events (AEs) were reported in 5 patients (13%). These AEs included rash, colitis, and asymptomatic rises in laboratory parameters. Grade 3 surgery-related AEs occurred in 8 patients (20%).

“This treatment is both safe and feasible, with few treatment-related AEs and without compromising surgery,” the authors wrote.

There were 35 patients evaluable for response. Among patients with dMMR tumors, pathological responses occurred in 100% (n = 20), major pathological responses (<10% residual vital tumor) occurred in 95% (n = 19), and complete responses occurred in 60% (n = 12).

Among patients with pMMR tumors, 27% (n = 4) had a pathological response, 20% (n = 3) had a major pathological response, and 7% (n = 1) had a partial response.

The researchers acknowledged that the small sample size and short duration of postoperative follow-up were key limitations of this study, but they said this combination should be studied further.

“Neoadjuvant immunotherapy in early-stage colon cancers warrants further research and, when validated in larger studies with longer follow­-up, may become a new standard of care in dMMR and possibly a subgroup of pMMR colon cancers,” the authors concluded.

This study was sponsored by the Netherlands Cancer Institute in collaboration with Bristol-Myers Squibb. Authors reported financial relationships with Bristol-Myers Squibb and many other companies.

SOURCE: Chalabi M et al. Nat Med. 2020 Apr 6. doi: 10.1038/s41591-020-0805-8.

Consider nucleoside reverse transcriptase inhibitors (NRTIs) prescribed for HIV infection as a possible cause of neutrophilic eccrine hidradenitis (NEH) arising in an affected patient, Jessica Kalen, MD, advised during a virtual meeting held by the George Washington University department of dermatology.

The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic.

In a presentation entitled, “When HAART [highly active antiretroviral therapy] Hurts,” Dr. Kalen, a dermatology resident at the university, presented a case report involving a 65-year-old man who presented with juicy red edematous papules and plaques on his scalp and ears. He was on the three-drug combination of rilpivirine (a non-nucleoside reverse transcriptase inhibitor), and the NRTIs tenofovir, and emtricitabine (Odefsey) for treatment of HIV infection, which was well controlled, with no detectable viral load.

The patient was also on insulin detemir for diabetes; pravastatin, amlodipine, and lisinopril for hypertension; and episodic acyclovir for recurrent herpes simplex outbreaks. However, none of those drugs has been associated with NEH. In contrast, Dr. Kalen found three published case reports describing a link between NRTIs and NEH.

Lesional biopsy of her patient showed the classic features of NEH: a dermal neutrophilic infiltrate surrounding the eccrine secretory coils and ducts, with vacuolar degeneration that spared the acrosyringium.

The most common causes of NEH, a rare dermatologic disorder first described in 1982, are hematologic malignancies and some of the chemotherapeutic agents used in treating them. Particularly prominent are acute myelogenous leukemia and cytarabine, which are often prescribed for that cancer. Carbamazepine, granulocyte-colony stimulating factor, and BRAF inhibitors have also been associated with NEH.

The pathogenesis of NEH is not fully worked out; however, NRTIs are secreted via eccrine structures, and that close contact could potentially promote an environment favoring inflammation and destruction of the eccrine coils. Also, NRTIs inhibit DNA polymerase, as does cytarabine, Dr. Kalen noted.

Her patient’s NEH was treated with triamcinolone. His skin condition resolved completely while he remained on NRTI therapy, with no relapses to date.

Dr. Kalen reported having no financial conflicts regarding her presentation.
 

bjancin@mdedge.com

Consider nucleoside reverse transcriptase inhibitors (NRTIs) prescribed for HIV infection as a possible cause of neutrophilic eccrine hidradenitis (NEH) arising in an affected patient, Jessica Kalen, MD, advised during a virtual meeting held by the George Washington University department of dermatology.

The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic.

In a presentation entitled, “When HAART [highly active antiretroviral therapy] Hurts,” Dr. Kalen, a dermatology resident at the university, presented a case report involving a 65-year-old man who presented with juicy red edematous papules and plaques on his scalp and ears. He was on the three-drug combination of rilpivirine (a non-nucleoside reverse transcriptase inhibitor), and the NRTIs tenofovir, and emtricitabine (Odefsey) for treatment of HIV infection, which was well controlled, with no detectable viral load.

The patient was also on insulin detemir for diabetes; pravastatin, amlodipine, and lisinopril for hypertension; and episodic acyclovir for recurrent herpes simplex outbreaks. However, none of those drugs has been associated with NEH. In contrast, Dr. Kalen found three published case reports describing a link between NRTIs and NEH.

Lesional biopsy of her patient showed the classic features of NEH: a dermal neutrophilic infiltrate surrounding the eccrine secretory coils and ducts, with vacuolar degeneration that spared the acrosyringium.

The most common causes of NEH, a rare dermatologic disorder first described in 1982, are hematologic malignancies and some of the chemotherapeutic agents used in treating them. Particularly prominent are acute myelogenous leukemia and cytarabine, which are often prescribed for that cancer. Carbamazepine, granulocyte-colony stimulating factor, and BRAF inhibitors have also been associated with NEH.

The pathogenesis of NEH is not fully worked out; however, NRTIs are secreted via eccrine structures, and that close contact could potentially promote an environment favoring inflammation and destruction of the eccrine coils. Also, NRTIs inhibit DNA polymerase, as does cytarabine, Dr. Kalen noted.

Her patient’s NEH was treated with triamcinolone. His skin condition resolved completely while he remained on NRTI therapy, with no relapses to date.

Dr. Kalen reported having no financial conflicts regarding her presentation.
 

bjancin@mdedge.com

Consider nucleoside reverse transcriptase inhibitors (NRTIs) prescribed for HIV infection as a possible cause of neutrophilic eccrine hidradenitis (NEH) arising in an affected patient, Jessica Kalen, MD, advised during a virtual meeting held by the George Washington University department of dermatology.

The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic.

In a presentation entitled, “When HAART [highly active antiretroviral therapy] Hurts,” Dr. Kalen, a dermatology resident at the university, presented a case report involving a 65-year-old man who presented with juicy red edematous papules and plaques on his scalp and ears. He was on the three-drug combination of rilpivirine (a non-nucleoside reverse transcriptase inhibitor), and the NRTIs tenofovir, and emtricitabine (Odefsey) for treatment of HIV infection, which was well controlled, with no detectable viral load.

The patient was also on insulin detemir for diabetes; pravastatin, amlodipine, and lisinopril for hypertension; and episodic acyclovir for recurrent herpes simplex outbreaks. However, none of those drugs has been associated with NEH. In contrast, Dr. Kalen found three published case reports describing a link between NRTIs and NEH.

Lesional biopsy of her patient showed the classic features of NEH: a dermal neutrophilic infiltrate surrounding the eccrine secretory coils and ducts, with vacuolar degeneration that spared the acrosyringium.

The most common causes of NEH, a rare dermatologic disorder first described in 1982, are hematologic malignancies and some of the chemotherapeutic agents used in treating them. Particularly prominent are acute myelogenous leukemia and cytarabine, which are often prescribed for that cancer. Carbamazepine, granulocyte-colony stimulating factor, and BRAF inhibitors have also been associated with NEH.

The pathogenesis of NEH is not fully worked out; however, NRTIs are secreted via eccrine structures, and that close contact could potentially promote an environment favoring inflammation and destruction of the eccrine coils. Also, NRTIs inhibit DNA polymerase, as does cytarabine, Dr. Kalen noted.

Her patient’s NEH was treated with triamcinolone. His skin condition resolved completely while he remained on NRTI therapy, with no relapses to date.

Dr. Kalen reported having no financial conflicts regarding her presentation.
 

bjancin@mdedge.com

In the clinical opinion of Kaiane A. Habeshian, MD, dermatologists shouldn’t think twice about using systemic agents in pediatric patients with severe dermatologic diseases.

“By the time patients come to us pediatric dermatologists, they have been treated by multiple other doctors, and are frustrated,” Dr. Habeshian said during a virtual meeting held by the George Washington University department of dermatology. “Childhood eczema affects not only patients, but the whole family. For instance, if the child is not sleeping due to itch, their parents are probably not sleeping, either. Parental well-being and workplace productivity are affected, and finances are affected.”

Only a limited number of medications are Food and Drug Administration approved in pediatric patients for common dermatologic indications. These include dupilumab for atopic dermatitis (AD), etanercept and ustekinumab for psoriasis, adalimumab for hidradenitis suppurativa, and omalizumab for chronic idiopathic urticaria. “The approvals are mainly for the adolescent age group, except for etanercept, which is approved at the age of 4 years and above,” said Dr. Habeshian of the department of dermatology at Children’s National Hospital, Washington.

In clinical practice, off-label, nontargeted systemic agents are used mostly commonly in pediatric skin disease, particularly methotrexate and cyclosporine for both AD and psoriasis. “These agents are approved for other indications in infants and have many years of data to describe their use in these other conditions, although comprehensive randomized, controlled studies in pediatric patients for dermatologic conditions are lacking,” she said. “What’s in clinical trials for pediatric skin disease? There are multiple ongoing clinical studies of biologic agents in pediatric dermatology, mainly for psoriasis and also for dupilumab in younger patients, as well as a JAK [Janus kinase] inhibitor for alopecia areata.”

Dr. Habeshian noted that while some clinicians may have a knee-jerk reaction to go straight to dupilumab, which was approved in March of 2019 for adolescents with moderate to severe AD, that agent is not currently approved for the most sizable pediatric population with this condition – those under 12 years of age. “FDA approval is important in part because it helps establish safety and optimal dosing, which is often different and weight based in children,” she said. “In addition, FDA approval significantly impacts access to these newer, more expensive medications.”

Speaking from her experience treating patients in the DC/Maryland/Virginia area, Medicaid has consistently denied dupilumab coverage in children under age 12, “even in severe eczema that is suboptimally controlled with both methotrexate and cyclosporine, despite multiple levels of appeal, including letters of medical necessity and peer-to-peer evaluation,” she said. “This can vary across the country among states. However, dupilumab has been completely unattainable in those under 12 in our practice.”

When dupilumab is approved, most insurers first require step therapy with off-label agents for at least 3 months, as well as documented failure of topical corticosteroids, calcineurin inhibitors, crisaborole ointment, and phototherapy (if done). “It’s important to document an objective measure of severity at the very first visit with the SCORAD [scoring atopic dermatitis] or IGA [investigator global assessment],” she said. “Often, that is required if there is any hope for coverage. A familiarity with these requirements is often acquired through trial and error, and may change over time. This can lead to many delays in getting patients these treatments.” Additional information to consider documenting include the disease impact on quality of life, sleep, and school attendance, any hospitalizations for AD flares or secondary infections, and comorbid disease such as asthma.

Meanwhile, dupilumab is under priority review for children aged 6-11 years with moderate to severe AD, with a target action date of May 26, 2020. “It’s unclear how recent events [with the COVID-19 pandemic] will impact that, but there is something to look forward to, and give us hope for our patients,” she said.

Typically, Dr. Habeshian starts her pediatric patients with moderate to severe AD on methotrexate, which she characterized as “a time-tested, affordable, and very accessible option. It requires a little bit less monitoring upon initiation than cyclosporine, and it can be used for longer periods of time before weaning is required.”

In cases when disease is severe or intolerable, she often starts methotrexate and cyclosporine together. “I will usually start right at the 0.5 mg/kg per week rather than titrating up, because this maximizes the response and reduces the amount of blood work needed, unless they have an underlying risk factor for GI distress, or obese patients who are at increased risk for LFT [liver function test] elevation,” she noted. “Patients will note some improvement as early as 2 weeks on methotrexate, but I counsel them to expect 4-6 weeks for maximum improvement. We do not do a test dose of methotrexate at our institution. If there is a slight LFT elevation upon checking labs, ensure that the labs were done at least 4-6 days after the dose, because transient LFT dose elevations are common in 3-4 days.”

GI distress is by far the most common clinical side effect of methotrexate. “We do not do much intramuscular injection of methotrexate, so we rely a lot on folic acid, which reduces the risk of GI distress and elevated LFTs without reducing efficacy,” she said. “We recommend daily folic acid for simplicity, or folic acid 6 days per week.”

Dr. Habeshian said that many pediatric patients can swallow the 2.5 mg tablets of methotrexate “because they’re quite small, and most patients don’t have a problem taking the methotrexate when it’s crushed and mixed with food such as apple sauce or pudding. However, it is critical to discuss proper handling to avoid lung toxicity.” This includes placing the pills in a plastic bag prior to crushing, avoiding inhalation, and avoiding handling near pregnant women and pets, she noted. In addition, she said, “in adolescents, we need to consider the teratogenicity of methotrexate, as well as the possibility of alcohol consumption worsening liver complications. If I prescribe methotrexate in patients of childbearing age, I will counsel them extensively regarding the risk of fetal death and birth defects. If needed, I will start combined oral contraceptives. Ultimately, I’m willing to use these medicines safely, with significant counseling.”

When addressing the risk of methotrexate overdose, she reminds parents to store the medication in a safe place, out of the reach of children. “Patients are at the highest risk of overdose complications if they are given the medication multiple days in a row rather than a one-time, single high dose,” she said. “The literature suggests that one-time overdoses of methotrexate – deliberate or accidental – are unlikely to cause acute bone marrow suppression or hepatitis. This is probably because GI absorption of methotrexate reaches a saturation point, and the kidneys passively and actively excrete the medication at quite a rapid pace so that the methotrexate is often undetectable in the blood at 24 hours post ingestion. I do prescribe a limited supply to help prevent accidental overdoses. In part, this is because if the patient is receiving the medication daily, they’ll run out very quickly, and it will come the family’s attention and to your attention that it’s not being administered correctly.”

Another treatment option to consider for cases of moderate to severe AD is cyclosporine, “which works extremely quickly,” Dr. Habeshian said. “It is very good to rapidly control severe disease while methotrexate or other modes of treatment kick in. It’s best used as a bridge, given the risks of renal damage with long-term use. I like to limit its use to 6 months.”

Cyclosporine comes in two formulations: a modified oral formulation and a nonmodified oral formulation. The modified formulation is absorbed much better than the unmodified formulation. “We start at 5 mg/kg divided b.i.d., which is higher than the recommended dosing for dermatologic conditions in adults,” she said. “This is because children may not absorb the medication as well and may have improved renal clearance. Higher doses may be needed to achieve the desirable effect. In contrast to methotrexate, cyclosporine is available in a capsule, so it cannot be crushed.”

The choice of medication for psoriasis is generally guided by insurance step therapy requirements and is limited in the pediatric population (new guidelines on the care of pediatric psoriasis patients can be found at J Am Acad Dermatol 2020; 82[1]:161-201). In Dr. Habeshian’s experience, methotrexate is the go-to for most patients. “It treats concomitant psoriatic arthritis and can be used as monotherapy or combined with biologics,” she said. “Cyclosporine is useful for erythrodermic, pustular, and severe plaque psoriasis as a bridge. Other options include etanercept weekly in patients age 4-17 years and ustekinumab weekly dosing in patients age 12-17 years.”

Acitretin can be a useful adjunct for younger patients who are unable to obtain biologic agents. “It is most useful in widespread guttate and pustular psoriasis, but can be used be used in plaque psoriasis as well,” Dr. Habeshian said. “It is usually dosed as 0.1-1 mg/kg per day. Improvement in plaque disease is generally seen in 2-3 months of therapy, so it has a slow onset, whereas improvement in pustular psoriasis is seen within 3 weeks.” The most common side effects are dry skin and mucous membranes, while an important consideration is the potential for inducing premature bone toxicity. “It is thought that the risk is relatively low if the daily and total doses are kept low,” she said. “There is no consensus for monitoring bone health. Some clinicians will consider radiography periodically.”

Dr. Habeshian concluded her talk by noting that clinicians should give vaccinations/boosters before starting systemic therapy in young children. “The safety and efficacy of live immunization administered to children on biologics is not known,” she said. “Therefore, if live vaccination is needed, it’s generally recommended to postpone initiating biologic treatment.” The MMR and varicella vaccines are given at 12-15 months of life, with a booster at 4-6 years. The varicella vaccine should be given at least 6 weeks before starting immunosuppressive therapy, and the MMR vaccine at least 4 weeks before starting therapy.

The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic. Dr. Habeshian reported having no disclosures.

dbrunk@mdedge.com

In the clinical opinion of Kaiane A. Habeshian, MD, dermatologists shouldn’t think twice about using systemic agents in pediatric patients with severe dermatologic diseases.

“By the time patients come to us pediatric dermatologists, they have been treated by multiple other doctors, and are frustrated,” Dr. Habeshian said during a virtual meeting held by the George Washington University department of dermatology. “Childhood eczema affects not only patients, but the whole family. For instance, if the child is not sleeping due to itch, their parents are probably not sleeping, either. Parental well-being and workplace productivity are affected, and finances are affected.”

Only a limited number of medications are Food and Drug Administration approved in pediatric patients for common dermatologic indications. These include dupilumab for atopic dermatitis (AD), etanercept and ustekinumab for psoriasis, adalimumab for hidradenitis suppurativa, and omalizumab for chronic idiopathic urticaria. “The approvals are mainly for the adolescent age group, except for etanercept, which is approved at the age of 4 years and above,” said Dr. Habeshian of the department of dermatology at Children’s National Hospital, Washington.

In clinical practice, off-label, nontargeted systemic agents are used mostly commonly in pediatric skin disease, particularly methotrexate and cyclosporine for both AD and psoriasis. “These agents are approved for other indications in infants and have many years of data to describe their use in these other conditions, although comprehensive randomized, controlled studies in pediatric patients for dermatologic conditions are lacking,” she said. “What’s in clinical trials for pediatric skin disease? There are multiple ongoing clinical studies of biologic agents in pediatric dermatology, mainly for psoriasis and also for dupilumab in younger patients, as well as a JAK [Janus kinase] inhibitor for alopecia areata.”

Dr. Habeshian noted that while some clinicians may have a knee-jerk reaction to go straight to dupilumab, which was approved in March of 2019 for adolescents with moderate to severe AD, that agent is not currently approved for the most sizable pediatric population with this condition – those under 12 years of age. “FDA approval is important in part because it helps establish safety and optimal dosing, which is often different and weight based in children,” she said. “In addition, FDA approval significantly impacts access to these newer, more expensive medications.”

Speaking from her experience treating patients in the DC/Maryland/Virginia area, Medicaid has consistently denied dupilumab coverage in children under age 12, “even in severe eczema that is suboptimally controlled with both methotrexate and cyclosporine, despite multiple levels of appeal, including letters of medical necessity and peer-to-peer evaluation,” she said. “This can vary across the country among states. However, dupilumab has been completely unattainable in those under 12 in our practice.”

When dupilumab is approved, most insurers first require step therapy with off-label agents for at least 3 months, as well as documented failure of topical corticosteroids, calcineurin inhibitors, crisaborole ointment, and phototherapy (if done). “It’s important to document an objective measure of severity at the very first visit with the SCORAD [scoring atopic dermatitis] or IGA [investigator global assessment],” she said. “Often, that is required if there is any hope for coverage. A familiarity with these requirements is often acquired through trial and error, and may change over time. This can lead to many delays in getting patients these treatments.” Additional information to consider documenting include the disease impact on quality of life, sleep, and school attendance, any hospitalizations for AD flares or secondary infections, and comorbid disease such as asthma.

Meanwhile, dupilumab is under priority review for children aged 6-11 years with moderate to severe AD, with a target action date of May 26, 2020. “It’s unclear how recent events [with the COVID-19 pandemic] will impact that, but there is something to look forward to, and give us hope for our patients,” she said.

Typically, Dr. Habeshian starts her pediatric patients with moderate to severe AD on methotrexate, which she characterized as “a time-tested, affordable, and very accessible option. It requires a little bit less monitoring upon initiation than cyclosporine, and it can be used for longer periods of time before weaning is required.”

In cases when disease is severe or intolerable, she often starts methotrexate and cyclosporine together. “I will usually start right at the 0.5 mg/kg per week rather than titrating up, because this maximizes the response and reduces the amount of blood work needed, unless they have an underlying risk factor for GI distress, or obese patients who are at increased risk for LFT [liver function test] elevation,” she noted. “Patients will note some improvement as early as 2 weeks on methotrexate, but I counsel them to expect 4-6 weeks for maximum improvement. We do not do a test dose of methotrexate at our institution. If there is a slight LFT elevation upon checking labs, ensure that the labs were done at least 4-6 days after the dose, because transient LFT dose elevations are common in 3-4 days.”

GI distress is by far the most common clinical side effect of methotrexate. “We do not do much intramuscular injection of methotrexate, so we rely a lot on folic acid, which reduces the risk of GI distress and elevated LFTs without reducing efficacy,” she said. “We recommend daily folic acid for simplicity, or folic acid 6 days per week.”

Dr. Habeshian said that many pediatric patients can swallow the 2.5 mg tablets of methotrexate “because they’re quite small, and most patients don’t have a problem taking the methotrexate when it’s crushed and mixed with food such as apple sauce or pudding. However, it is critical to discuss proper handling to avoid lung toxicity.” This includes placing the pills in a plastic bag prior to crushing, avoiding inhalation, and avoiding handling near pregnant women and pets, she noted. In addition, she said, “in adolescents, we need to consider the teratogenicity of methotrexate, as well as the possibility of alcohol consumption worsening liver complications. If I prescribe methotrexate in patients of childbearing age, I will counsel them extensively regarding the risk of fetal death and birth defects. If needed, I will start combined oral contraceptives. Ultimately, I’m willing to use these medicines safely, with significant counseling.”

When addressing the risk of methotrexate overdose, she reminds parents to store the medication in a safe place, out of the reach of children. “Patients are at the highest risk of overdose complications if they are given the medication multiple days in a row rather than a one-time, single high dose,” she said. “The literature suggests that one-time overdoses of methotrexate – deliberate or accidental – are unlikely to cause acute bone marrow suppression or hepatitis. This is probably because GI absorption of methotrexate reaches a saturation point, and the kidneys passively and actively excrete the medication at quite a rapid pace so that the methotrexate is often undetectable in the blood at 24 hours post ingestion. I do prescribe a limited supply to help prevent accidental overdoses. In part, this is because if the patient is receiving the medication daily, they’ll run out very quickly, and it will come the family’s attention and to your attention that it’s not being administered correctly.”

Another treatment option to consider for cases of moderate to severe AD is cyclosporine, “which works extremely quickly,” Dr. Habeshian said. “It is very good to rapidly control severe disease while methotrexate or other modes of treatment kick in. It’s best used as a bridge, given the risks of renal damage with long-term use. I like to limit its use to 6 months.”

Cyclosporine comes in two formulations: a modified oral formulation and a nonmodified oral formulation. The modified formulation is absorbed much better than the unmodified formulation. “We start at 5 mg/kg divided b.i.d., which is higher than the recommended dosing for dermatologic conditions in adults,” she said. “This is because children may not absorb the medication as well and may have improved renal clearance. Higher doses may be needed to achieve the desirable effect. In contrast to methotrexate, cyclosporine is available in a capsule, so it cannot be crushed.”

The choice of medication for psoriasis is generally guided by insurance step therapy requirements and is limited in the pediatric population (new guidelines on the care of pediatric psoriasis patients can be found at J Am Acad Dermatol 2020; 82[1]:161-201). In Dr. Habeshian’s experience, methotrexate is the go-to for most patients. “It treats concomitant psoriatic arthritis and can be used as monotherapy or combined with biologics,” she said. “Cyclosporine is useful for erythrodermic, pustular, and severe plaque psoriasis as a bridge. Other options include etanercept weekly in patients age 4-17 years and ustekinumab weekly dosing in patients age 12-17 years.”

Acitretin can be a useful adjunct for younger patients who are unable to obtain biologic agents. “It is most useful in widespread guttate and pustular psoriasis, but can be used be used in plaque psoriasis as well,” Dr. Habeshian said. “It is usually dosed as 0.1-1 mg/kg per day. Improvement in plaque disease is generally seen in 2-3 months of therapy, so it has a slow onset, whereas improvement in pustular psoriasis is seen within 3 weeks.” The most common side effects are dry skin and mucous membranes, while an important consideration is the potential for inducing premature bone toxicity. “It is thought that the risk is relatively low if the daily and total doses are kept low,” she said. “There is no consensus for monitoring bone health. Some clinicians will consider radiography periodically.”

Dr. Habeshian concluded her talk by noting that clinicians should give vaccinations/boosters before starting systemic therapy in young children. “The safety and efficacy of live immunization administered to children on biologics is not known,” she said. “Therefore, if live vaccination is needed, it’s generally recommended to postpone initiating biologic treatment.” The MMR and varicella vaccines are given at 12-15 months of life, with a booster at 4-6 years. The varicella vaccine should be given at least 6 weeks before starting immunosuppressive therapy, and the MMR vaccine at least 4 weeks before starting therapy.

The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic. Dr. Habeshian reported having no disclosures.

dbrunk@mdedge.com

In the clinical opinion of Kaiane A. Habeshian, MD, dermatologists shouldn’t think twice about using systemic agents in pediatric patients with severe dermatologic diseases.

“By the time patients come to us pediatric dermatologists, they have been treated by multiple other doctors, and are frustrated,” Dr. Habeshian said during a virtual meeting held by the George Washington University department of dermatology. “Childhood eczema affects not only patients, but the whole family. For instance, if the child is not sleeping due to itch, their parents are probably not sleeping, either. Parental well-being and workplace productivity are affected, and finances are affected.”

Only a limited number of medications are Food and Drug Administration approved in pediatric patients for common dermatologic indications. These include dupilumab for atopic dermatitis (AD), etanercept and ustekinumab for psoriasis, adalimumab for hidradenitis suppurativa, and omalizumab for chronic idiopathic urticaria. “The approvals are mainly for the adolescent age group, except for etanercept, which is approved at the age of 4 years and above,” said Dr. Habeshian of the department of dermatology at Children’s National Hospital, Washington.

In clinical practice, off-label, nontargeted systemic agents are used mostly commonly in pediatric skin disease, particularly methotrexate and cyclosporine for both AD and psoriasis. “These agents are approved for other indications in infants and have many years of data to describe their use in these other conditions, although comprehensive randomized, controlled studies in pediatric patients for dermatologic conditions are lacking,” she said. “What’s in clinical trials for pediatric skin disease? There are multiple ongoing clinical studies of biologic agents in pediatric dermatology, mainly for psoriasis and also for dupilumab in younger patients, as well as a JAK [Janus kinase] inhibitor for alopecia areata.”

Dr. Habeshian noted that while some clinicians may have a knee-jerk reaction to go straight to dupilumab, which was approved in March of 2019 for adolescents with moderate to severe AD, that agent is not currently approved for the most sizable pediatric population with this condition – those under 12 years of age. “FDA approval is important in part because it helps establish safety and optimal dosing, which is often different and weight based in children,” she said. “In addition, FDA approval significantly impacts access to these newer, more expensive medications.”

Speaking from her experience treating patients in the DC/Maryland/Virginia area, Medicaid has consistently denied dupilumab coverage in children under age 12, “even in severe eczema that is suboptimally controlled with both methotrexate and cyclosporine, despite multiple levels of appeal, including letters of medical necessity and peer-to-peer evaluation,” she said. “This can vary across the country among states. However, dupilumab has been completely unattainable in those under 12 in our practice.”

When dupilumab is approved, most insurers first require step therapy with off-label agents for at least 3 months, as well as documented failure of topical corticosteroids, calcineurin inhibitors, crisaborole ointment, and phototherapy (if done). “It’s important to document an objective measure of severity at the very first visit with the SCORAD [scoring atopic dermatitis] or IGA [investigator global assessment],” she said. “Often, that is required if there is any hope for coverage. A familiarity with these requirements is often acquired through trial and error, and may change over time. This can lead to many delays in getting patients these treatments.” Additional information to consider documenting include the disease impact on quality of life, sleep, and school attendance, any hospitalizations for AD flares or secondary infections, and comorbid disease such as asthma.

Meanwhile, dupilumab is under priority review for children aged 6-11 years with moderate to severe AD, with a target action date of May 26, 2020. “It’s unclear how recent events [with the COVID-19 pandemic] will impact that, but there is something to look forward to, and give us hope for our patients,” she said.

Typically, Dr. Habeshian starts her pediatric patients with moderate to severe AD on methotrexate, which she characterized as “a time-tested, affordable, and very accessible option. It requires a little bit less monitoring upon initiation than cyclosporine, and it can be used for longer periods of time before weaning is required.”

In cases when disease is severe or intolerable, she often starts methotrexate and cyclosporine together. “I will usually start right at the 0.5 mg/kg per week rather than titrating up, because this maximizes the response and reduces the amount of blood work needed, unless they have an underlying risk factor for GI distress, or obese patients who are at increased risk for LFT [liver function test] elevation,” she noted. “Patients will note some improvement as early as 2 weeks on methotrexate, but I counsel them to expect 4-6 weeks for maximum improvement. We do not do a test dose of methotrexate at our institution. If there is a slight LFT elevation upon checking labs, ensure that the labs were done at least 4-6 days after the dose, because transient LFT dose elevations are common in 3-4 days.”

GI distress is by far the most common clinical side effect of methotrexate. “We do not do much intramuscular injection of methotrexate, so we rely a lot on folic acid, which reduces the risk of GI distress and elevated LFTs without reducing efficacy,” she said. “We recommend daily folic acid for simplicity, or folic acid 6 days per week.”

Dr. Habeshian said that many pediatric patients can swallow the 2.5 mg tablets of methotrexate “because they’re quite small, and most patients don’t have a problem taking the methotrexate when it’s crushed and mixed with food such as apple sauce or pudding. However, it is critical to discuss proper handling to avoid lung toxicity.” This includes placing the pills in a plastic bag prior to crushing, avoiding inhalation, and avoiding handling near pregnant women and pets, she noted. In addition, she said, “in adolescents, we need to consider the teratogenicity of methotrexate, as well as the possibility of alcohol consumption worsening liver complications. If I prescribe methotrexate in patients of childbearing age, I will counsel them extensively regarding the risk of fetal death and birth defects. If needed, I will start combined oral contraceptives. Ultimately, I’m willing to use these medicines safely, with significant counseling.”

When addressing the risk of methotrexate overdose, she reminds parents to store the medication in a safe place, out of the reach of children. “Patients are at the highest risk of overdose complications if they are given the medication multiple days in a row rather than a one-time, single high dose,” she said. “The literature suggests that one-time overdoses of methotrexate – deliberate or accidental – are unlikely to cause acute bone marrow suppression or hepatitis. This is probably because GI absorption of methotrexate reaches a saturation point, and the kidneys passively and actively excrete the medication at quite a rapid pace so that the methotrexate is often undetectable in the blood at 24 hours post ingestion. I do prescribe a limited supply to help prevent accidental overdoses. In part, this is because if the patient is receiving the medication daily, they’ll run out very quickly, and it will come the family’s attention and to your attention that it’s not being administered correctly.”

Another treatment option to consider for cases of moderate to severe AD is cyclosporine, “which works extremely quickly,” Dr. Habeshian said. “It is very good to rapidly control severe disease while methotrexate or other modes of treatment kick in. It’s best used as a bridge, given the risks of renal damage with long-term use. I like to limit its use to 6 months.”

Cyclosporine comes in two formulations: a modified oral formulation and a nonmodified oral formulation. The modified formulation is absorbed much better than the unmodified formulation. “We start at 5 mg/kg divided b.i.d., which is higher than the recommended dosing for dermatologic conditions in adults,” she said. “This is because children may not absorb the medication as well and may have improved renal clearance. Higher doses may be needed to achieve the desirable effect. In contrast to methotrexate, cyclosporine is available in a capsule, so it cannot be crushed.”

The choice of medication for psoriasis is generally guided by insurance step therapy requirements and is limited in the pediatric population (new guidelines on the care of pediatric psoriasis patients can be found at J Am Acad Dermatol 2020; 82[1]:161-201). In Dr. Habeshian’s experience, methotrexate is the go-to for most patients. “It treats concomitant psoriatic arthritis and can be used as monotherapy or combined with biologics,” she said. “Cyclosporine is useful for erythrodermic, pustular, and severe plaque psoriasis as a bridge. Other options include etanercept weekly in patients age 4-17 years and ustekinumab weekly dosing in patients age 12-17 years.”

Acitretin can be a useful adjunct for younger patients who are unable to obtain biologic agents. “It is most useful in widespread guttate and pustular psoriasis, but can be used be used in plaque psoriasis as well,” Dr. Habeshian said. “It is usually dosed as 0.1-1 mg/kg per day. Improvement in plaque disease is generally seen in 2-3 months of therapy, so it has a slow onset, whereas improvement in pustular psoriasis is seen within 3 weeks.” The most common side effects are dry skin and mucous membranes, while an important consideration is the potential for inducing premature bone toxicity. “It is thought that the risk is relatively low if the daily and total doses are kept low,” she said. “There is no consensus for monitoring bone health. Some clinicians will consider radiography periodically.”

Dr. Habeshian concluded her talk by noting that clinicians should give vaccinations/boosters before starting systemic therapy in young children. “The safety and efficacy of live immunization administered to children on biologics is not known,” she said. “Therefore, if live vaccination is needed, it’s generally recommended to postpone initiating biologic treatment.” The MMR and varicella vaccines are given at 12-15 months of life, with a booster at 4-6 years. The varicella vaccine should be given at least 6 weeks before starting immunosuppressive therapy, and the MMR vaccine at least 4 weeks before starting therapy.

The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled because of the COVID-19 pandemic. Dr. Habeshian reported having no disclosures.

dbrunk@mdedge.com

In their advocacy column, “OTC hormonal contraception: An important goal in the fight for reproductive justice” (January 2020), Abby L. Schultz, MD, and Megan L. Evans, MD, MPH, discussed a recent committee opinion from the American College of Obstetricians and Gynecologists (ACOG) focused on improving contraception access by offering oral contraceptive pills, progesterone-only pills, the patch, vaginal rings, and depot medroxyprogesterone acetate over the counter (OTC). The authors agreed with ACOG’s stance and offered several reasons why.

OBG Management polled readers to see their thoughts on the question of whether or not hormonal contraception should be offered OTC.

In their advocacy column, “OTC hormonal contraception: An important goal in the fight for reproductive justice” (January 2020), Abby L. Schultz, MD, and Megan L. Evans, MD, MPH, discussed a recent committee opinion from the American College of Obstetricians and Gynecologists (ACOG) focused on improving contraception access by offering oral contraceptive pills, progesterone-only pills, the patch, vaginal rings, and depot medroxyprogesterone acetate over the counter (OTC). The authors agreed with ACOG’s stance and offered several reasons why.

OBG Management polled readers to see their thoughts on the question of whether or not hormonal contraception should be offered OTC.

In their advocacy column, “OTC hormonal contraception: An important goal in the fight for reproductive justice” (January 2020), Abby L. Schultz, MD, and Megan L. Evans, MD, MPH, discussed a recent committee opinion from the American College of Obstetricians and Gynecologists (ACOG) focused on improving contraception access by offering oral contraceptive pills, progesterone-only pills, the patch, vaginal rings, and depot medroxyprogesterone acetate over the counter (OTC). The authors agreed with ACOG’s stance and offered several reasons why.

OBG Management polled readers to see their thoughts on the question of whether or not hormonal contraception should be offered OTC.

A natural language processing algorithm, designed to scour emergency department records for fracture cases, has the potential to improve treatment of osteoporosis and prevent future, more severe fractures.

The approach led to a notable increase in referrals to the osteoporosis refracture prevention service at the Prince of Wales Hospital in Sydney, where the work was done.

The strongest predictor of a future fracture is a recent previous fracture, said Christopher White, MBBS, the hospital’s director of research, who presented results of an analysis at a virtual news conference held by the Endocrine Society. The study was slated for presentation during ENDO 2020, the society’s annual meeting, which was canceled because of the COVID-19 pandemic.

“We have really effective therapies that can reduce the risk of [future] fractures by 50%, and yet 80% of osteoporotic patients leave the hospital untreated after fracture,” said Dr. White.

That, he explained, is because of a fundamental disconnect in fracture care – emergency department physicians tackle the immediate aftermath of a broken bone, but they are not tasked with treating the underlying condition. As a result, many patients who would be candidates for follow-up care are not referred.

The current work grew out of Dr. White’s frustration with not being able to recruit patients for osteoporosis clinical trials. In fact, he got so annoyed trying to recruit and not getting patients referred to him – even though he’d find they were actually in the hospital – that he decided “to start an AI [artificial intelligence] program that would read the radiology report and bypass the referrer,” he said.

To that end, with the help of an industry partner, he developed a software program called XRAIT (X-Ray Artificial Intelligence Tool), which analyzed the reports and, with Dr. White’s iterated guidance, learned to identify fractures.

The system performed a little too well. “You have to be careful what you wish for, because suddenly I went from 70 referrals to 339,” he said.

That influx is a potential downside, however, according to Angela Cheung, MD, PhD, director of the Centre of Excellence in Skeletal Health Assessment and Osteoporosis Program at the University of Toronto’s University Health Network. Natural language processing can help identify patients that a human reviewer would miss, because reviewers tend to focus on cases in which the fracture was the reason for the hospital visit, rather than on incidental findings. But not all incidental findings are clinically important. “A pneumonia patient might have had the fracture 30 years ago, falling off a tree as a college student. It may not pick up the highest-risk group in terms of fractures, because we know that recency of fractures matters,” Dr. Cheung, who was not associated with the research, said in an interview.

“It means the fracture liaison coordinator would need to review [more] numbers in trying to figure out whether the patient should get attention and whether they should be treated as well,” said Dr. Cheung, adding that more studies would need to be done to determine if the approach would be cost effective.

The researchers performed a technical evaluation of 2,445 nonfracture and 433 fracture reports, in which the tool performed with more than 99% sensitivity and specificity.

In a clinical validation, a fracture clinician and XRAIT reviewed 5,089 x-ray and computed tomography reports from ED patients who were older than 50 years. The ED referred 70 cases, leading to identification of 65 fractures. The combination of ED referral and a fracture clinician’s review of 224 cases revealed 98 fracture cases. By contrast, XRAIT nearly instantaneously analyzed 5,089 reports from 3,217 patients, and identified fractures in 349 patients – a nearly fivefold higher number than the manual case finding of 70. Of those 349 patients, results for 10 were false positives, leading to a total find of 339 patients.

In all, 57 cases were found both by XRAIT and the ED referral/fracture clinician, resulting in 282 unique cases identified by XRAIT alone. That translated to a 3.5-fold increase in cases that were identifiable using XRAIT.

In an external validation, the researchers tested the system on 327 reports from a subset of the Dubbo Osteoporosis Epidemiology Study, based in the city of Dubbo in New South Wales, Australia. In that cohort, XRAIT identified 97 positive cases, of which 87 were true fractures (10 false positives). Of 230 cases that it considered not to be fractures, there were 38 false negatives. Those numbers translated to a sensitivity of 69.6% and a specificity of 95.0%.

All of those hits have the potential to overwhelm osteoporosis services. “I now have to adjust to that, and further development will be to link the AI with clinical risk factors and treatment data to assist my fracture coordinators to target the right patients. We’ll increase the number of patients with osteoporosis on treatment, improve productivity and safety, and reduce the burden of care,” said Dr. White.

The study was funded by The Sydney Partnership for Health, Education, Research and Enterprise and the Musculoskeletal Consumer Advisory Group. The researchers reported no financial conflicts of interest, as did Dr. Cheung.

The research will be published in a special supplemental issue of the Journal of the Endocrine Society. In addition to a series of news conferences on March 30-31, the society will host ENDO Online 2020 during June 8-22, which will present programming for clinicians and researchers.
 

A natural language processing algorithm, designed to scour emergency department records for fracture cases, has the potential to improve treatment of osteoporosis and prevent future, more severe fractures.

The approach led to a notable increase in referrals to the osteoporosis refracture prevention service at the Prince of Wales Hospital in Sydney, where the work was done.

The strongest predictor of a future fracture is a recent previous fracture, said Christopher White, MBBS, the hospital’s director of research, who presented results of an analysis at a virtual news conference held by the Endocrine Society. The study was slated for presentation during ENDO 2020, the society’s annual meeting, which was canceled because of the COVID-19 pandemic.

“We have really effective therapies that can reduce the risk of [future] fractures by 50%, and yet 80% of osteoporotic patients leave the hospital untreated after fracture,” said Dr. White.

That, he explained, is because of a fundamental disconnect in fracture care – emergency department physicians tackle the immediate aftermath of a broken bone, but they are not tasked with treating the underlying condition. As a result, many patients who would be candidates for follow-up care are not referred.

The current work grew out of Dr. White’s frustration with not being able to recruit patients for osteoporosis clinical trials. In fact, he got so annoyed trying to recruit and not getting patients referred to him – even though he’d find they were actually in the hospital – that he decided “to start an AI [artificial intelligence] program that would read the radiology report and bypass the referrer,” he said.

To that end, with the help of an industry partner, he developed a software program called XRAIT (X-Ray Artificial Intelligence Tool), which analyzed the reports and, with Dr. White’s iterated guidance, learned to identify fractures.

The system performed a little too well. “You have to be careful what you wish for, because suddenly I went from 70 referrals to 339,” he said.

That influx is a potential downside, however, according to Angela Cheung, MD, PhD, director of the Centre of Excellence in Skeletal Health Assessment and Osteoporosis Program at the University of Toronto’s University Health Network. Natural language processing can help identify patients that a human reviewer would miss, because reviewers tend to focus on cases in which the fracture was the reason for the hospital visit, rather than on incidental findings. But not all incidental findings are clinically important. “A pneumonia patient might have had the fracture 30 years ago, falling off a tree as a college student. It may not pick up the highest-risk group in terms of fractures, because we know that recency of fractures matters,” Dr. Cheung, who was not associated with the research, said in an interview.

“It means the fracture liaison coordinator would need to review [more] numbers in trying to figure out whether the patient should get attention and whether they should be treated as well,” said Dr. Cheung, adding that more studies would need to be done to determine if the approach would be cost effective.

The researchers performed a technical evaluation of 2,445 nonfracture and 433 fracture reports, in which the tool performed with more than 99% sensitivity and specificity.

In a clinical validation, a fracture clinician and XRAIT reviewed 5,089 x-ray and computed tomography reports from ED patients who were older than 50 years. The ED referred 70 cases, leading to identification of 65 fractures. The combination of ED referral and a fracture clinician’s review of 224 cases revealed 98 fracture cases. By contrast, XRAIT nearly instantaneously analyzed 5,089 reports from 3,217 patients, and identified fractures in 349 patients – a nearly fivefold higher number than the manual case finding of 70. Of those 349 patients, results for 10 were false positives, leading to a total find of 339 patients.

In all, 57 cases were found both by XRAIT and the ED referral/fracture clinician, resulting in 282 unique cases identified by XRAIT alone. That translated to a 3.5-fold increase in cases that were identifiable using XRAIT.

In an external validation, the researchers tested the system on 327 reports from a subset of the Dubbo Osteoporosis Epidemiology Study, based in the city of Dubbo in New South Wales, Australia. In that cohort, XRAIT identified 97 positive cases, of which 87 were true fractures (10 false positives). Of 230 cases that it considered not to be fractures, there were 38 false negatives. Those numbers translated to a sensitivity of 69.6% and a specificity of 95.0%.

All of those hits have the potential to overwhelm osteoporosis services. “I now have to adjust to that, and further development will be to link the AI with clinical risk factors and treatment data to assist my fracture coordinators to target the right patients. We’ll increase the number of patients with osteoporosis on treatment, improve productivity and safety, and reduce the burden of care,” said Dr. White.

The study was funded by The Sydney Partnership for Health, Education, Research and Enterprise and the Musculoskeletal Consumer Advisory Group. The researchers reported no financial conflicts of interest, as did Dr. Cheung.

The research will be published in a special supplemental issue of the Journal of the Endocrine Society. In addition to a series of news conferences on March 30-31, the society will host ENDO Online 2020 during June 8-22, which will present programming for clinicians and researchers.
 

A natural language processing algorithm, designed to scour emergency department records for fracture cases, has the potential to improve treatment of osteoporosis and prevent future, more severe fractures.

The approach led to a notable increase in referrals to the osteoporosis refracture prevention service at the Prince of Wales Hospital in Sydney, where the work was done.

The strongest predictor of a future fracture is a recent previous fracture, said Christopher White, MBBS, the hospital’s director of research, who presented results of an analysis at a virtual news conference held by the Endocrine Society. The study was slated for presentation during ENDO 2020, the society’s annual meeting, which was canceled because of the COVID-19 pandemic.

“We have really effective therapies that can reduce the risk of [future] fractures by 50%, and yet 80% of osteoporotic patients leave the hospital untreated after fracture,” said Dr. White.

That, he explained, is because of a fundamental disconnect in fracture care – emergency department physicians tackle the immediate aftermath of a broken bone, but they are not tasked with treating the underlying condition. As a result, many patients who would be candidates for follow-up care are not referred.

The current work grew out of Dr. White’s frustration with not being able to recruit patients for osteoporosis clinical trials. In fact, he got so annoyed trying to recruit and not getting patients referred to him – even though he’d find they were actually in the hospital – that he decided “to start an AI [artificial intelligence] program that would read the radiology report and bypass the referrer,” he said.

To that end, with the help of an industry partner, he developed a software program called XRAIT (X-Ray Artificial Intelligence Tool), which analyzed the reports and, with Dr. White’s iterated guidance, learned to identify fractures.

The system performed a little too well. “You have to be careful what you wish for, because suddenly I went from 70 referrals to 339,” he said.

That influx is a potential downside, however, according to Angela Cheung, MD, PhD, director of the Centre of Excellence in Skeletal Health Assessment and Osteoporosis Program at the University of Toronto’s University Health Network. Natural language processing can help identify patients that a human reviewer would miss, because reviewers tend to focus on cases in which the fracture was the reason for the hospital visit, rather than on incidental findings. But not all incidental findings are clinically important. “A pneumonia patient might have had the fracture 30 years ago, falling off a tree as a college student. It may not pick up the highest-risk group in terms of fractures, because we know that recency of fractures matters,” Dr. Cheung, who was not associated with the research, said in an interview.

“It means the fracture liaison coordinator would need to review [more] numbers in trying to figure out whether the patient should get attention and whether they should be treated as well,” said Dr. Cheung, adding that more studies would need to be done to determine if the approach would be cost effective.

The researchers performed a technical evaluation of 2,445 nonfracture and 433 fracture reports, in which the tool performed with more than 99% sensitivity and specificity.

In a clinical validation, a fracture clinician and XRAIT reviewed 5,089 x-ray and computed tomography reports from ED patients who were older than 50 years. The ED referred 70 cases, leading to identification of 65 fractures. The combination of ED referral and a fracture clinician’s review of 224 cases revealed 98 fracture cases. By contrast, XRAIT nearly instantaneously analyzed 5,089 reports from 3,217 patients, and identified fractures in 349 patients – a nearly fivefold higher number than the manual case finding of 70. Of those 349 patients, results for 10 were false positives, leading to a total find of 339 patients.

In all, 57 cases were found both by XRAIT and the ED referral/fracture clinician, resulting in 282 unique cases identified by XRAIT alone. That translated to a 3.5-fold increase in cases that were identifiable using XRAIT.

In an external validation, the researchers tested the system on 327 reports from a subset of the Dubbo Osteoporosis Epidemiology Study, based in the city of Dubbo in New South Wales, Australia. In that cohort, XRAIT identified 97 positive cases, of which 87 were true fractures (10 false positives). Of 230 cases that it considered not to be fractures, there were 38 false negatives. Those numbers translated to a sensitivity of 69.6% and a specificity of 95.0%.

All of those hits have the potential to overwhelm osteoporosis services. “I now have to adjust to that, and further development will be to link the AI with clinical risk factors and treatment data to assist my fracture coordinators to target the right patients. We’ll increase the number of patients with osteoporosis on treatment, improve productivity and safety, and reduce the burden of care,” said Dr. White.

The study was funded by The Sydney Partnership for Health, Education, Research and Enterprise and the Musculoskeletal Consumer Advisory Group. The researchers reported no financial conflicts of interest, as did Dr. Cheung.

The research will be published in a special supplemental issue of the Journal of the Endocrine Society. In addition to a series of news conferences on March 30-31, the society will host ENDO Online 2020 during June 8-22, which will present programming for clinicians and researchers.
 

The American Society of Clinical Oncology (ASCO) has launched a registry to collect data on cancer patients with COVID-19 and is asking oncology practices across the United States to share information about their patients with the infection for educational purposes.

The new registry joins at least two other cancer and COVID-19 patient registries already underway in the U.S.

In a statement, ASCO President Howard “Skip” Burris III, MD said there is a need to know “how the virus is impacting our patients, their cancer treatment, and outcomes to inform current cancer care” and future care.

The web-based registry, known as the American Society of Clinical Oncology (ASCO) Survey on COVID-19 in Oncology Registry, is open to all U.S. oncology practices. Participating practices will receive an unspecified “nominal” payment for their data entry efforts.

The registry patient information will be stored on ASCO’s “Big Data” platform, known as CancerLinQ, but is being held apart from that pool of data. The registry information will not be available for commercial purposes, ASCO spokesperson Rachel Martin recently told Medscape Medical News.

Separately, CancerLinQ, which is a wholly owned subsidiary of ASCO, will continue to collect data from its participant oncology practices (as usual), including COVID-19 information.

CancerLinQ has been criticized by ethicists for allowing partner companies to sell access to its data (after stripping off patient identifiers), but without asking for patients’ permission, as reported last year by Medscape Medical News.

Eleven practices, including academic enterprises, have so far expressed interested in participating in the ASCO COVID-19 Registry.

Participating practices are requested to send in details about cancer patients with a confirmed COVID-19 diagnosis. As well as a baseline data capture form, they will need to provide details of subsequent status, treatment, and outcomes. Some patient-identifying data, including zip code, date of birth, gender, race, ethnicity, type of cancer, and comorbidities, will be collected for the purposes of analysis.

ASCO hopes to learn about characteristics of patients with cancer most impacted by COVID-19; estimates of disease severity; treatment modifications or delays; implementation of telemedicine in the cancer treatment setting; and clinical outcomes related to both COVID-19 and cancer.

ASCO says it will deliver periodic reports to the cancer community and the broader public on these and other “key learnings.” It also says that the registry is designed to capture point-in-time data as well as longitudinal data on how the virus will impact care and outcomes into 2021.

ASCO is not alone in its data collection efforts.

The COVID-19 and Cancer Consortium is already collecting information from more than 50 cancer centers and organizations on COVID-19 in patients with cancer. The American Society of Hematology (ASH) Research Collaborative COVID-19 Registry for Hematologic Malignancy is doing the same but with a focus on hematologic malignancies.

This article first appeared on Medscape.com.

The American Society of Clinical Oncology (ASCO) has launched a registry to collect data on cancer patients with COVID-19 and is asking oncology practices across the United States to share information about their patients with the infection for educational purposes.

The new registry joins at least two other cancer and COVID-19 patient registries already underway in the U.S.

In a statement, ASCO President Howard “Skip” Burris III, MD said there is a need to know “how the virus is impacting our patients, their cancer treatment, and outcomes to inform current cancer care” and future care.

The web-based registry, known as the American Society of Clinical Oncology (ASCO) Survey on COVID-19 in Oncology Registry, is open to all U.S. oncology practices. Participating practices will receive an unspecified “nominal” payment for their data entry efforts.

The registry patient information will be stored on ASCO’s “Big Data” platform, known as CancerLinQ, but is being held apart from that pool of data. The registry information will not be available for commercial purposes, ASCO spokesperson Rachel Martin recently told Medscape Medical News.

Separately, CancerLinQ, which is a wholly owned subsidiary of ASCO, will continue to collect data from its participant oncology practices (as usual), including COVID-19 information.

CancerLinQ has been criticized by ethicists for allowing partner companies to sell access to its data (after stripping off patient identifiers), but without asking for patients’ permission, as reported last year by Medscape Medical News.

Eleven practices, including academic enterprises, have so far expressed interested in participating in the ASCO COVID-19 Registry.

Participating practices are requested to send in details about cancer patients with a confirmed COVID-19 diagnosis. As well as a baseline data capture form, they will need to provide details of subsequent status, treatment, and outcomes. Some patient-identifying data, including zip code, date of birth, gender, race, ethnicity, type of cancer, and comorbidities, will be collected for the purposes of analysis.

ASCO hopes to learn about characteristics of patients with cancer most impacted by COVID-19; estimates of disease severity; treatment modifications or delays; implementation of telemedicine in the cancer treatment setting; and clinical outcomes related to both COVID-19 and cancer.

ASCO says it will deliver periodic reports to the cancer community and the broader public on these and other “key learnings.” It also says that the registry is designed to capture point-in-time data as well as longitudinal data on how the virus will impact care and outcomes into 2021.

ASCO is not alone in its data collection efforts.

The COVID-19 and Cancer Consortium is already collecting information from more than 50 cancer centers and organizations on COVID-19 in patients with cancer. The American Society of Hematology (ASH) Research Collaborative COVID-19 Registry for Hematologic Malignancy is doing the same but with a focus on hematologic malignancies.

This article first appeared on Medscape.com.

The American Society of Clinical Oncology (ASCO) has launched a registry to collect data on cancer patients with COVID-19 and is asking oncology practices across the United States to share information about their patients with the infection for educational purposes.

The new registry joins at least two other cancer and COVID-19 patient registries already underway in the U.S.

In a statement, ASCO President Howard “Skip” Burris III, MD said there is a need to know “how the virus is impacting our patients, their cancer treatment, and outcomes to inform current cancer care” and future care.

The web-based registry, known as the American Society of Clinical Oncology (ASCO) Survey on COVID-19 in Oncology Registry, is open to all U.S. oncology practices. Participating practices will receive an unspecified “nominal” payment for their data entry efforts.

The registry patient information will be stored on ASCO’s “Big Data” platform, known as CancerLinQ, but is being held apart from that pool of data. The registry information will not be available for commercial purposes, ASCO spokesperson Rachel Martin recently told Medscape Medical News.

Separately, CancerLinQ, which is a wholly owned subsidiary of ASCO, will continue to collect data from its participant oncology practices (as usual), including COVID-19 information.

CancerLinQ has been criticized by ethicists for allowing partner companies to sell access to its data (after stripping off patient identifiers), but without asking for patients’ permission, as reported last year by Medscape Medical News.

Eleven practices, including academic enterprises, have so far expressed interested in participating in the ASCO COVID-19 Registry.

Participating practices are requested to send in details about cancer patients with a confirmed COVID-19 diagnosis. As well as a baseline data capture form, they will need to provide details of subsequent status, treatment, and outcomes. Some patient-identifying data, including zip code, date of birth, gender, race, ethnicity, type of cancer, and comorbidities, will be collected for the purposes of analysis.

ASCO hopes to learn about characteristics of patients with cancer most impacted by COVID-19; estimates of disease severity; treatment modifications or delays; implementation of telemedicine in the cancer treatment setting; and clinical outcomes related to both COVID-19 and cancer.

ASCO says it will deliver periodic reports to the cancer community and the broader public on these and other “key learnings.” It also says that the registry is designed to capture point-in-time data as well as longitudinal data on how the virus will impact care and outcomes into 2021.

ASCO is not alone in its data collection efforts.

The COVID-19 and Cancer Consortium is already collecting information from more than 50 cancer centers and organizations on COVID-19 in patients with cancer. The American Society of Hematology (ASH) Research Collaborative COVID-19 Registry for Hematologic Malignancy is doing the same but with a focus on hematologic malignancies.

This article first appeared on Medscape.com.

Patients who underwent complex PCI for acute coronary syndrome followed by 3 months of dual-antiplatelet therapy (DAPT) with ticagrelor plus aspirin fared significantly better by dropping aspirin at that point in favor of long-term ticagrelor monotherapy than with continued dual-antiplatelet therapy in the TWILIGHT-COMPLEX study.

The rate of clinically relevant bleeding was significantly lower at 12 months of follow-up in the ticagrelor monotherapy group than it was in patients randomized to continued DAPT. Moreover, this major benefit came at no cost in terms of ischemic events, which were actually numerically less frequent in the ticagrelor plus placebo group, George D. Dangas, MD, reported at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.

“We found that the aspirin just doesn’t add that much, even in complex patients – just bleeding complications, for the most part,” explained Dr. Dangas, professor of medicine and of surgery at the Icahn School of Medicine at Mount Sinai, New York.

The TWILIGHT-COMPLEX study was a secondary post hoc analysis of outcomes in 2,342 participants in the previously reported larger parent TWILIGHT randomized trial who underwent complex PCI. The main TWILIGHT trial included 7,119 patients in 11 countries who underwent PCI for acute coronary syndrome, successfully completed 3 months of DAPT with ticagrelor plus aspirin without incident, and were then randomized double blind to 12 months of ticagrelor plus placebo or to another 12 months of ticagrelor and aspirin.

In the overall TWILIGHT trial, ticagrelor alone resulted in a significantly lower clinically relevant bleeding rate than did long-term ticagrelor plus aspirin, with no increase in the risk of death, MI, or stroke (N Engl J Med 2019; 381:2032-42). But the results left many interventional cardiologists wondering if a ticagrelor monotherapy strategy was really applicable to their more challenging patients undergoing complex PCI given that the risk of ischemic events is known to climb with PCI complexity. The TWILIGHT-COMPLEX study was specifically designed to address that concern.

To be eligible for TWILIGHT-COMPLEX, patients had to meet one or more prespecified angiographic or procedural criteria for complex PCI, such as a total stent length in excess of 60 mm, three or more treated lesions, use of an atherectomy device, or PCI of a left main lesion, a chronic total occlusion, or a bifurcation lesion with two stents. These complex PCI patients accounted for one-third of the total study population in TWILIGHT; 36% of them met more than one criteria for complex PCI.
 

TWILIGHT-COMPLEX findings

In the 12 months after randomization, patients who received ticagrelor plus placebo had a 4.2% incidence of clinically significant Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding, which was significantly lower than the 7.7% rate in the group on long-term DAPT and represented a 46% relative risk reduction. Severe or fatal bleeding – that is, BARC type 3 or 5 – occurred in 1.1% of those on ticagrelor monotherapy and 2.6% of the DAPT group, for a significant 59% relative risk reduction.

The composite ischemic endpoint comprising cardiovascular death, MI, or ischemic stroke occurred in 3.6% of the ticagrelor monotherapy group and 4.8% of patients on long-term DAPT, a trend that didn’t achieve statistical significance. The all-cause mortality rate was 0.9% in the ticagrelor monotherapy group and 1.5% with extended DAPT, again a nonsignificant difference. Similarly, the rate of definite or probable stent thrombosis was numerically lower with ticagrelor monotherapy, by a margin of 0.4% versus 0.8%, a nonsignificant difference.

The results were consistent regardless of which specific criteria for complex PCI a patient had or how many of them.
 

Results are ‘reassuring’

At a press conference where Dr. Dangas presented the TWILIGHT-COMPLEX results, discussant Claire S. Duvernoy, MD, said she was “very impressed” with just how complex the PCIs were in the study participants.

“Really, these are the patients that in my own practice we’ve always been the most cautious about, the most worried about thrombotic risk, and the ones where we get down on our house staff when they drop an antiplatelet agent. So this study is very reassuring,” said Dr. Duvernoy, professor of medicine at the University of Michigan, Ann Arbor.

She identified two key differences between TWILIGHT-COMPLEX and earlier studies that showed a benefit for extended DAPT in higher-risk patients. In the earlier studies, it was the P2Y12 inhibitor that was dropped; TWILIGHT was the first major randomized trial to discontinue the aspirin instead. And patients in the TWILIGHT study received second-generation drug-eluting stents.

“That makes a huge difference,” Dr. Duvernoy said. “We have stents now that are much safer than the old ones were, and that’s what allows us to gain this incredible benefit of reduced bleeding.”

Dr. Dangas cautioned that since this was a secondary post hoc analysis, the TWILIGHT-COMPLEX study must be viewed as hypothesis-generating.

The TWILIGHT trial was funded by AstraZeneca. Dr. Dangas reported receiving institutional research grants from that company as well as Bayer and Daichi-Sankyo. He also served as a paid consultant to Abbott Vascular, Boston Scientific, and Biosensors.

Simultaneous with his presentation at ACC 2020, the TWILIGHT-COMPLEX results were published online (J Am Coll Cardiol. 2020 Mar 13. doi: 10.1016/j.jacc.2020.03.011).

SOURCE: Dangas GD. ACC 20, Abstract 410-09.

Patients who underwent complex PCI for acute coronary syndrome followed by 3 months of dual-antiplatelet therapy (DAPT) with ticagrelor plus aspirin fared significantly better by dropping aspirin at that point in favor of long-term ticagrelor monotherapy than with continued dual-antiplatelet therapy in the TWILIGHT-COMPLEX study.

The rate of clinically relevant bleeding was significantly lower at 12 months of follow-up in the ticagrelor monotherapy group than it was in patients randomized to continued DAPT. Moreover, this major benefit came at no cost in terms of ischemic events, which were actually numerically less frequent in the ticagrelor plus placebo group, George D. Dangas, MD, reported at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.

“We found that the aspirin just doesn’t add that much, even in complex patients – just bleeding complications, for the most part,” explained Dr. Dangas, professor of medicine and of surgery at the Icahn School of Medicine at Mount Sinai, New York.

The TWILIGHT-COMPLEX study was a secondary post hoc analysis of outcomes in 2,342 participants in the previously reported larger parent TWILIGHT randomized trial who underwent complex PCI. The main TWILIGHT trial included 7,119 patients in 11 countries who underwent PCI for acute coronary syndrome, successfully completed 3 months of DAPT with ticagrelor plus aspirin without incident, and were then randomized double blind to 12 months of ticagrelor plus placebo or to another 12 months of ticagrelor and aspirin.

In the overall TWILIGHT trial, ticagrelor alone resulted in a significantly lower clinically relevant bleeding rate than did long-term ticagrelor plus aspirin, with no increase in the risk of death, MI, or stroke (N Engl J Med 2019; 381:2032-42). But the results left many interventional cardiologists wondering if a ticagrelor monotherapy strategy was really applicable to their more challenging patients undergoing complex PCI given that the risk of ischemic events is known to climb with PCI complexity. The TWILIGHT-COMPLEX study was specifically designed to address that concern.

To be eligible for TWILIGHT-COMPLEX, patients had to meet one or more prespecified angiographic or procedural criteria for complex PCI, such as a total stent length in excess of 60 mm, three or more treated lesions, use of an atherectomy device, or PCI of a left main lesion, a chronic total occlusion, or a bifurcation lesion with two stents. These complex PCI patients accounted for one-third of the total study population in TWILIGHT; 36% of them met more than one criteria for complex PCI.
 

TWILIGHT-COMPLEX findings

In the 12 months after randomization, patients who received ticagrelor plus placebo had a 4.2% incidence of clinically significant Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding, which was significantly lower than the 7.7% rate in the group on long-term DAPT and represented a 46% relative risk reduction. Severe or fatal bleeding – that is, BARC type 3 or 5 – occurred in 1.1% of those on ticagrelor monotherapy and 2.6% of the DAPT group, for a significant 59% relative risk reduction.

The composite ischemic endpoint comprising cardiovascular death, MI, or ischemic stroke occurred in 3.6% of the ticagrelor monotherapy group and 4.8% of patients on long-term DAPT, a trend that didn’t achieve statistical significance. The all-cause mortality rate was 0.9% in the ticagrelor monotherapy group and 1.5% with extended DAPT, again a nonsignificant difference. Similarly, the rate of definite or probable stent thrombosis was numerically lower with ticagrelor monotherapy, by a margin of 0.4% versus 0.8%, a nonsignificant difference.

The results were consistent regardless of which specific criteria for complex PCI a patient had or how many of them.
 

Results are ‘reassuring’

At a press conference where Dr. Dangas presented the TWILIGHT-COMPLEX results, discussant Claire S. Duvernoy, MD, said she was “very impressed” with just how complex the PCIs were in the study participants.

“Really, these are the patients that in my own practice we’ve always been the most cautious about, the most worried about thrombotic risk, and the ones where we get down on our house staff when they drop an antiplatelet agent. So this study is very reassuring,” said Dr. Duvernoy, professor of medicine at the University of Michigan, Ann Arbor.

She identified two key differences between TWILIGHT-COMPLEX and earlier studies that showed a benefit for extended DAPT in higher-risk patients. In the earlier studies, it was the P2Y12 inhibitor that was dropped; TWILIGHT was the first major randomized trial to discontinue the aspirin instead. And patients in the TWILIGHT study received second-generation drug-eluting stents.

“That makes a huge difference,” Dr. Duvernoy said. “We have stents now that are much safer than the old ones were, and that’s what allows us to gain this incredible benefit of reduced bleeding.”

Dr. Dangas cautioned that since this was a secondary post hoc analysis, the TWILIGHT-COMPLEX study must be viewed as hypothesis-generating.

The TWILIGHT trial was funded by AstraZeneca. Dr. Dangas reported receiving institutional research grants from that company as well as Bayer and Daichi-Sankyo. He also served as a paid consultant to Abbott Vascular, Boston Scientific, and Biosensors.

Simultaneous with his presentation at ACC 2020, the TWILIGHT-COMPLEX results were published online (J Am Coll Cardiol. 2020 Mar 13. doi: 10.1016/j.jacc.2020.03.011).

SOURCE: Dangas GD. ACC 20, Abstract 410-09.

Patients who underwent complex PCI for acute coronary syndrome followed by 3 months of dual-antiplatelet therapy (DAPT) with ticagrelor plus aspirin fared significantly better by dropping aspirin at that point in favor of long-term ticagrelor monotherapy than with continued dual-antiplatelet therapy in the TWILIGHT-COMPLEX study.

The rate of clinically relevant bleeding was significantly lower at 12 months of follow-up in the ticagrelor monotherapy group than it was in patients randomized to continued DAPT. Moreover, this major benefit came at no cost in terms of ischemic events, which were actually numerically less frequent in the ticagrelor plus placebo group, George D. Dangas, MD, reported at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.

“We found that the aspirin just doesn’t add that much, even in complex patients – just bleeding complications, for the most part,” explained Dr. Dangas, professor of medicine and of surgery at the Icahn School of Medicine at Mount Sinai, New York.

The TWILIGHT-COMPLEX study was a secondary post hoc analysis of outcomes in 2,342 participants in the previously reported larger parent TWILIGHT randomized trial who underwent complex PCI. The main TWILIGHT trial included 7,119 patients in 11 countries who underwent PCI for acute coronary syndrome, successfully completed 3 months of DAPT with ticagrelor plus aspirin without incident, and were then randomized double blind to 12 months of ticagrelor plus placebo or to another 12 months of ticagrelor and aspirin.

In the overall TWILIGHT trial, ticagrelor alone resulted in a significantly lower clinically relevant bleeding rate than did long-term ticagrelor plus aspirin, with no increase in the risk of death, MI, or stroke (N Engl J Med 2019; 381:2032-42). But the results left many interventional cardiologists wondering if a ticagrelor monotherapy strategy was really applicable to their more challenging patients undergoing complex PCI given that the risk of ischemic events is known to climb with PCI complexity. The TWILIGHT-COMPLEX study was specifically designed to address that concern.

To be eligible for TWILIGHT-COMPLEX, patients had to meet one or more prespecified angiographic or procedural criteria for complex PCI, such as a total stent length in excess of 60 mm, three or more treated lesions, use of an atherectomy device, or PCI of a left main lesion, a chronic total occlusion, or a bifurcation lesion with two stents. These complex PCI patients accounted for one-third of the total study population in TWILIGHT; 36% of them met more than one criteria for complex PCI.
 

TWILIGHT-COMPLEX findings

In the 12 months after randomization, patients who received ticagrelor plus placebo had a 4.2% incidence of clinically significant Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding, which was significantly lower than the 7.7% rate in the group on long-term DAPT and represented a 46% relative risk reduction. Severe or fatal bleeding – that is, BARC type 3 or 5 – occurred in 1.1% of those on ticagrelor monotherapy and 2.6% of the DAPT group, for a significant 59% relative risk reduction.

The composite ischemic endpoint comprising cardiovascular death, MI, or ischemic stroke occurred in 3.6% of the ticagrelor monotherapy group and 4.8% of patients on long-term DAPT, a trend that didn’t achieve statistical significance. The all-cause mortality rate was 0.9% in the ticagrelor monotherapy group and 1.5% with extended DAPT, again a nonsignificant difference. Similarly, the rate of definite or probable stent thrombosis was numerically lower with ticagrelor monotherapy, by a margin of 0.4% versus 0.8%, a nonsignificant difference.

The results were consistent regardless of which specific criteria for complex PCI a patient had or how many of them.
 

Results are ‘reassuring’

At a press conference where Dr. Dangas presented the TWILIGHT-COMPLEX results, discussant Claire S. Duvernoy, MD, said she was “very impressed” with just how complex the PCIs were in the study participants.

“Really, these are the patients that in my own practice we’ve always been the most cautious about, the most worried about thrombotic risk, and the ones where we get down on our house staff when they drop an antiplatelet agent. So this study is very reassuring,” said Dr. Duvernoy, professor of medicine at the University of Michigan, Ann Arbor.

She identified two key differences between TWILIGHT-COMPLEX and earlier studies that showed a benefit for extended DAPT in higher-risk patients. In the earlier studies, it was the P2Y12 inhibitor that was dropped; TWILIGHT was the first major randomized trial to discontinue the aspirin instead. And patients in the TWILIGHT study received second-generation drug-eluting stents.

“That makes a huge difference,” Dr. Duvernoy said. “We have stents now that are much safer than the old ones were, and that’s what allows us to gain this incredible benefit of reduced bleeding.”

Dr. Dangas cautioned that since this was a secondary post hoc analysis, the TWILIGHT-COMPLEX study must be viewed as hypothesis-generating.

The TWILIGHT trial was funded by AstraZeneca. Dr. Dangas reported receiving institutional research grants from that company as well as Bayer and Daichi-Sankyo. He also served as a paid consultant to Abbott Vascular, Boston Scientific, and Biosensors.

Simultaneous with his presentation at ACC 2020, the TWILIGHT-COMPLEX results were published online (J Am Coll Cardiol. 2020 Mar 13. doi: 10.1016/j.jacc.2020.03.011).

SOURCE: Dangas GD. ACC 20, Abstract 410-09.

Health systems around the world have been called upon to expand acute care capacity to manage the current and projected surge of adults with COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).¹ There has been mixed guidance on how pediatric facilities should consolidate and coordinate pediatric care in a way that optimizes the capacity of hospital beds, staff, and supplies, such as ventilators and medications, for both adults and children in a community.² Furthermore, if and how these pediatric facilities should expand capacity to care for adult patients safely is uncertain.

For the last 5 years, both Boston Children’s Hospital and Cincinnati Children’s Hospital Medical Center have been caring for specific adult populations in free-standing pediatric hospitals because of the increasing prevalence of young adults with rare, complex, and historically fatal conditions (eg, chromosomal abnormalities). In the past, low life expectancies for children with such conditions contributed to the evolution of specialized care in pediatric health systems that often does not exist in adult health systems. Our teams in Boston and Cincinnati have gained insight into the multifaceted infrastructure and teams necessary to provide safe care for adults hospitalized in a pediatric setting.

In this perspective piece, we will highlight important principles that pediatric facilities and providers should prioritize if they anticipate caring for hospitalized adults during this pandemic. Designing and implementing an adult care model requires iteratively addressing the following key areas: development of a multistakeholder team, system readiness for intensive care unit (ICU) care of adults, institutional situation awareness, scope of practice, staffing considerations, patient safety, and patient populations and special considerations (eg, adults with chronic conditions of childhood onset). With these areas in mind, pediatric facilities should then consider whether they have the capacity to manage hospitalized adults.

Providing care for any hospitalized patient requires engagement with many health system stakeholders. By involving key stakeholders early in the planning process for our adult care model, we were able to anticipate potential obstacles when caring for a unique subset of patients and gain support of multidisciplinary partners. For instance, inclusion of bedside and support staff highlighted specific needs, such as nurses with adult training and a revised formulary to include common adult medications (eg, clopidogrel for adults with a drug-eluting stent).

Responding to the surge of hospitalized adult patients will require increasing hospital capacity.³ In pediatric settings, this will require consideration of innovative care models. These care models may include pediatric systems flexing to care for adult patients. We recommend hospital leaders from both pediatric and adult facilities have formal discussions on the best ways for pediatric facilities to respond to serve their local population. Inclusion of other key stakeholders will ensure factors imperative to the safe care of adults will not be missed.

There were three levels of consideration for the use of our local pediatric ICU for these patients. First, our institutional policies allow care for adults throughout the system, which we describe in more detail later, in the “Scope of Practice” section. Second, our free-standing pediatric hospital ICUs have accreditation for the care of adults. Third, we developed clear guidelines for subspecialists regarding when adults can safely be admitted or transferred to the pediatric ICU.

Responding to a crisis still necessitates establishing a clear care-escalation plan. An initial barrier may be that some systems do not have a pediatric ICU accredited for care of patients above a certain age. During a crisis, however, as hospital volumes and mortalities rise, states may pursue executive orders, as New York State did, that ease these age restrictions.⁴ Otherwise, we recommend a clear transfer plan to an adult ICU or emergency credentialing and privileging of adult intensivists. Both of these options may pose challenges during a pandemic because adult ICUs will likely be full.

Institutional situation awareness for the identification and mitigation of risks inherent in adult care in a pediatric setting is essential for patient safety. Tracking of admitted adult patients via our electronic health record (EHR) occurs daily by an adult care–team member. Our adult care teams partner with physician safety officers and attend daily institutional multidisciplinary safety huddles to create a shared mental model for the care of adult patients. Daily huddle reports include discussion regarding the number of admitted adults, review of illness acuity, consultative advice on management, and contingency planning for potential decompensation.^5,6 This integration into institutional huddles has been instrumental in proactively identifying hospitalized adults who are at risk for clinical decompensation and mitigating those risks.

Should a pediatric system admit adults to new sites or units, we recommend leveraging preexisting patient safety infrastructure similarly to identify and mitigate risks. If possible, any institutional communication about adult patients should involve adult-trained staff. Mechanisms for tracking patients will depend on local EHRs but are important to guide regular check-ins with providers caring for those patients.

Multiple levels of regulation affect a provider’s scope of practice. The most general of these regulations are state guidelines, followed by local institutional policy. Our institutions require consults for older adults—age varies at our specific institutions—by our adult-care team for assessment of risk and comanagement of adult-specific comorbidities. Additionally, we have agreements with our affiliated adult health facilities that allow in-person adult subspecialty consultation.

While state and institutional policies lay the foundation for pediatric systems considering new adult-care models, provider-level considerations are also needed. Often the patient’s age is a primary consideration, but comorbid conditions also affect the provider’s comfort and ability to care for these patients. We urge practitioners to exercise the full range of their capacities, but also to think critically about the ethical scope of one’s practice. As healthcare providers, it is our duty to hold each other accountable, voice concerns, and advocate to increase health system capacity equitably.⁷ It’s paramount that channels of communication, in-person or virtual, be arranged for supportive adult subspecialist consultation.

Med-Peds physicians and advanced practice providers are the foundation of the clinical care provided to adults at our institutions. Our Med-Peds providers practice in both the free-standing pediatric hospital and an affiliated adult health system. They offer expertise in adult clinical care and navigate between pediatric and adult systems when the need arises (eg, adult requiring urgent intervention for an acute myocardial infarction). Adult competencies of other staff must be addressed. For example, our cardiac ICUs include nurses with adult clinical care experience because critically ill adults with congenital heart disease are admitted. Advanced Care Life Support (ACLS) training is also required for staff caring for adults throughout the hospital.

There are many ways, even during a crisis, to develop an adult care model in a pediatric setting. Depending on workforce availability, internal medicine, Med-Peds, family medicine, critical care, and emergency medicine physicians could serve on either a primary service or as a consultant to support pediatrics-trained providers in caring for adults should the patient volume and acuity require staffing restructuring. Adult subspecialty access must be addressed. Telehealth may play a significant role in extending clinicians in all of these clinical roles both during the current crisis but also in underresourced settings.⁸ A clear process and indication for emergency or temporary credentialing and privileging necessitates understanding and addressing such challenges early. Training in adult care, or lack thereof, for other staff, such as nurses and respiratory therapists, is also crucial to consider.

Adults are more likely than children to have comorbidities and clinical deterioration while hospitalized. At our institutions, when a rapid response team is called for an adult patient, an adult care–team provider responds to aid in clinical management and determines the appropriate care setting. Additionally, given that the incidence of coronary artery disease increases starting at age 35 years,⁹ our systems have developed procedures for managing time-sensitive conditions seen more commonly in adults, such as acute myocardial infarction, stroke, and pulmonary embolism. Despite simulation training for pediatric providers and staff, it is clear that implementing these procedures is highly dependent on involvement of the adult care team.

With the urgency of implementation, pediatric systems should consider increasing the number of providers and staff with ACLS training, especially for rapid response and code teams. Many pediatric systems may need to evaluate how their code carts are stocked and ensure they are equipped with appropriate medication dosages and sizes of supplies. Emergent and accessible adult care will be needed, especially for issues with time-to-intervention criteria like acute myocardial infarction and stroke. Hospitalized adults with COVID-19 may also have a higher incidence of arrhythmia, cardiac ischemia, and stroke.¹⁰ Consider proactively simulating common COVID-19–related scenarios to build interdisciplinary teamwork in emergency scenarios. Interhospital agreements and pathways exist for sharing medications. Outreach to pharmacies may be indicated to ensure accessibility for medications not commonly found in pediatric systems.

Our children’s hospitals care for certain adult populations with chronic conditions of childhood origin because of the availability of subspecialty clinical expertise. Our adult care team aids in contingency planning to help determine place of admission (adult vs pediatric hospital) depending on patient clinical needs and system expertise. For instance, an adult with congenital heart disease may have two cardiologists—one for congenital heart disease and one for coronary artery disease. Patients with an acute issue such as new-onset arrhythmia may be admitted to our pediatric hospital; however, for a stroke they would be admitted to the adult hospital.

While important and tempting to address this issue first, creating criteria to determine which patient population to admit should be a last consideration during a pandemic. Consider if the decision to admit should be determined based on COVID-19 infection status. From there, types of conditions thought to be within the purview of pediatric practice can be considered. These include basic infectious diseases pathology (eg, skin/soft-tissue infections and pyelonephritis) and chronic conditions of childhood origin (eg, cystic fibrosis, diabetes, and inflammatory bowel disease), which have specialty providers who could work across an extended age range. Conditions potentially more challenging to safely care for in pediatric facilities include acute cardiac conditions (eg, angina, acute coronary syndrome, and arrhythmias), alcohol withdrawal, end-stage liver or kidney disease, and gastrointestinal bleeds. Considerations need to be made for research protocols and novel therapies only available at adult institutions. Through this whole process, it is especially crucial to note care equity and ensure that all patients have access to the highest attainable care possible.

Policymakers at pediatric facilities should think critically about their institution’s capacity to manage adults. In some circumstances, the decision might be to not admit adult patients based on the factors discussed in this paper or other contextual factors of the local healthcare systems. Our role in providing care for adults in pediatric hospitals involves not only ensuring age-appropriate care, but also in supporting patients and other healthcare providers to navigate a fragmented health system. Our adult-care models required building relationships between pediatric and adult health systems. Building these relationships in the setting of crisis can strengthen health systems and healthcare communities beyond the era of COVID-19. Because it’s promoted enhanced collaboration between pediatric and adult facilities, COVID-19 can be a platform to build a better system to support our already vulnerable young adults with chronic conditions of childhood origin for years to come.

Health systems around the world have been called upon to expand acute care capacity to manage the current and projected surge of adults with COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).¹ There has been mixed guidance on how pediatric facilities should consolidate and coordinate pediatric care in a way that optimizes the capacity of hospital beds, staff, and supplies, such as ventilators and medications, for both adults and children in a community.² Furthermore, if and how these pediatric facilities should expand capacity to care for adult patients safely is uncertain.

For the last 5 years, both Boston Children’s Hospital and Cincinnati Children’s Hospital Medical Center have been caring for specific adult populations in free-standing pediatric hospitals because of the increasing prevalence of young adults with rare, complex, and historically fatal conditions (eg, chromosomal abnormalities). In the past, low life expectancies for children with such conditions contributed to the evolution of specialized care in pediatric health systems that often does not exist in adult health systems. Our teams in Boston and Cincinnati have gained insight into the multifaceted infrastructure and teams necessary to provide safe care for adults hospitalized in a pediatric setting.

In this perspective piece, we will highlight important principles that pediatric facilities and providers should prioritize if they anticipate caring for hospitalized adults during this pandemic. Designing and implementing an adult care model requires iteratively addressing the following key areas: development of a multistakeholder team, system readiness for intensive care unit (ICU) care of adults, institutional situation awareness, scope of practice, staffing considerations, patient safety, and patient populations and special considerations (eg, adults with chronic conditions of childhood onset). With these areas in mind, pediatric facilities should then consider whether they have the capacity to manage hospitalized adults.

Providing care for any hospitalized patient requires engagement with many health system stakeholders. By involving key stakeholders early in the planning process for our adult care model, we were able to anticipate potential obstacles when caring for a unique subset of patients and gain support of multidisciplinary partners. For instance, inclusion of bedside and support staff highlighted specific needs, such as nurses with adult training and a revised formulary to include common adult medications (eg, clopidogrel for adults with a drug-eluting stent).

Responding to the surge of hospitalized adult patients will require increasing hospital capacity.³ In pediatric settings, this will require consideration of innovative care models. These care models may include pediatric systems flexing to care for adult patients. We recommend hospital leaders from both pediatric and adult facilities have formal discussions on the best ways for pediatric facilities to respond to serve their local population. Inclusion of other key stakeholders will ensure factors imperative to the safe care of adults will not be missed.

There were three levels of consideration for the use of our local pediatric ICU for these patients. First, our institutional policies allow care for adults throughout the system, which we describe in more detail later, in the “Scope of Practice” section. Second, our free-standing pediatric hospital ICUs have accreditation for the care of adults. Third, we developed clear guidelines for subspecialists regarding when adults can safely be admitted or transferred to the pediatric ICU.

Responding to a crisis still necessitates establishing a clear care-escalation plan. An initial barrier may be that some systems do not have a pediatric ICU accredited for care of patients above a certain age. During a crisis, however, as hospital volumes and mortalities rise, states may pursue executive orders, as New York State did, that ease these age restrictions.⁴ Otherwise, we recommend a clear transfer plan to an adult ICU or emergency credentialing and privileging of adult intensivists. Both of these options may pose challenges during a pandemic because adult ICUs will likely be full.

Institutional situation awareness for the identification and mitigation of risks inherent in adult care in a pediatric setting is essential for patient safety. Tracking of admitted adult patients via our electronic health record (EHR) occurs daily by an adult care–team member. Our adult care teams partner with physician safety officers and attend daily institutional multidisciplinary safety huddles to create a shared mental model for the care of adult patients. Daily huddle reports include discussion regarding the number of admitted adults, review of illness acuity, consultative advice on management, and contingency planning for potential decompensation.^5,6 This integration into institutional huddles has been instrumental in proactively identifying hospitalized adults who are at risk for clinical decompensation and mitigating those risks.

Should a pediatric system admit adults to new sites or units, we recommend leveraging preexisting patient safety infrastructure similarly to identify and mitigate risks. If possible, any institutional communication about adult patients should involve adult-trained staff. Mechanisms for tracking patients will depend on local EHRs but are important to guide regular check-ins with providers caring for those patients.

Multiple levels of regulation affect a provider’s scope of practice. The most general of these regulations are state guidelines, followed by local institutional policy. Our institutions require consults for older adults—age varies at our specific institutions—by our adult-care team for assessment of risk and comanagement of adult-specific comorbidities. Additionally, we have agreements with our affiliated adult health facilities that allow in-person adult subspecialty consultation.

While state and institutional policies lay the foundation for pediatric systems considering new adult-care models, provider-level considerations are also needed. Often the patient’s age is a primary consideration, but comorbid conditions also affect the provider’s comfort and ability to care for these patients. We urge practitioners to exercise the full range of their capacities, but also to think critically about the ethical scope of one’s practice. As healthcare providers, it is our duty to hold each other accountable, voice concerns, and advocate to increase health system capacity equitably.⁷ It’s paramount that channels of communication, in-person or virtual, be arranged for supportive adult subspecialist consultation.

Med-Peds physicians and advanced practice providers are the foundation of the clinical care provided to adults at our institutions. Our Med-Peds providers practice in both the free-standing pediatric hospital and an affiliated adult health system. They offer expertise in adult clinical care and navigate between pediatric and adult systems when the need arises (eg, adult requiring urgent intervention for an acute myocardial infarction). Adult competencies of other staff must be addressed. For example, our cardiac ICUs include nurses with adult clinical care experience because critically ill adults with congenital heart disease are admitted. Advanced Care Life Support (ACLS) training is also required for staff caring for adults throughout the hospital.

There are many ways, even during a crisis, to develop an adult care model in a pediatric setting. Depending on workforce availability, internal medicine, Med-Peds, family medicine, critical care, and emergency medicine physicians could serve on either a primary service or as a consultant to support pediatrics-trained providers in caring for adults should the patient volume and acuity require staffing restructuring. Adult subspecialty access must be addressed. Telehealth may play a significant role in extending clinicians in all of these clinical roles both during the current crisis but also in underresourced settings.⁸ A clear process and indication for emergency or temporary credentialing and privileging necessitates understanding and addressing such challenges early. Training in adult care, or lack thereof, for other staff, such as nurses and respiratory therapists, is also crucial to consider.

Adults are more likely than children to have comorbidities and clinical deterioration while hospitalized. At our institutions, when a rapid response team is called for an adult patient, an adult care–team provider responds to aid in clinical management and determines the appropriate care setting. Additionally, given that the incidence of coronary artery disease increases starting at age 35 years,⁹ our systems have developed procedures for managing time-sensitive conditions seen more commonly in adults, such as acute myocardial infarction, stroke, and pulmonary embolism. Despite simulation training for pediatric providers and staff, it is clear that implementing these procedures is highly dependent on involvement of the adult care team.

With the urgency of implementation, pediatric systems should consider increasing the number of providers and staff with ACLS training, especially for rapid response and code teams. Many pediatric systems may need to evaluate how their code carts are stocked and ensure they are equipped with appropriate medication dosages and sizes of supplies. Emergent and accessible adult care will be needed, especially for issues with time-to-intervention criteria like acute myocardial infarction and stroke. Hospitalized adults with COVID-19 may also have a higher incidence of arrhythmia, cardiac ischemia, and stroke.¹⁰ Consider proactively simulating common COVID-19–related scenarios to build interdisciplinary teamwork in emergency scenarios. Interhospital agreements and pathways exist for sharing medications. Outreach to pharmacies may be indicated to ensure accessibility for medications not commonly found in pediatric systems.

Our children’s hospitals care for certain adult populations with chronic conditions of childhood origin because of the availability of subspecialty clinical expertise. Our adult care team aids in contingency planning to help determine place of admission (adult vs pediatric hospital) depending on patient clinical needs and system expertise. For instance, an adult with congenital heart disease may have two cardiologists—one for congenital heart disease and one for coronary artery disease. Patients with an acute issue such as new-onset arrhythmia may be admitted to our pediatric hospital; however, for a stroke they would be admitted to the adult hospital.

While important and tempting to address this issue first, creating criteria to determine which patient population to admit should be a last consideration during a pandemic. Consider if the decision to admit should be determined based on COVID-19 infection status. From there, types of conditions thought to be within the purview of pediatric practice can be considered. These include basic infectious diseases pathology (eg, skin/soft-tissue infections and pyelonephritis) and chronic conditions of childhood origin (eg, cystic fibrosis, diabetes, and inflammatory bowel disease), which have specialty providers who could work across an extended age range. Conditions potentially more challenging to safely care for in pediatric facilities include acute cardiac conditions (eg, angina, acute coronary syndrome, and arrhythmias), alcohol withdrawal, end-stage liver or kidney disease, and gastrointestinal bleeds. Considerations need to be made for research protocols and novel therapies only available at adult institutions. Through this whole process, it is especially crucial to note care equity and ensure that all patients have access to the highest attainable care possible.

Policymakers at pediatric facilities should think critically about their institution’s capacity to manage adults. In some circumstances, the decision might be to not admit adult patients based on the factors discussed in this paper or other contextual factors of the local healthcare systems. Our role in providing care for adults in pediatric hospitals involves not only ensuring age-appropriate care, but also in supporting patients and other healthcare providers to navigate a fragmented health system. Our adult-care models required building relationships between pediatric and adult health systems. Building these relationships in the setting of crisis can strengthen health systems and healthcare communities beyond the era of COVID-19. Because it’s promoted enhanced collaboration between pediatric and adult facilities, COVID-19 can be a platform to build a better system to support our already vulnerable young adults with chronic conditions of childhood origin for years to come.

Health systems around the world have been called upon to expand acute care capacity to manage the current and projected surge of adults with COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).¹ There has been mixed guidance on how pediatric facilities should consolidate and coordinate pediatric care in a way that optimizes the capacity of hospital beds, staff, and supplies, such as ventilators and medications, for both adults and children in a community.² Furthermore, if and how these pediatric facilities should expand capacity to care for adult patients safely is uncertain.

For the last 5 years, both Boston Children’s Hospital and Cincinnati Children’s Hospital Medical Center have been caring for specific adult populations in free-standing pediatric hospitals because of the increasing prevalence of young adults with rare, complex, and historically fatal conditions (eg, chromosomal abnormalities). In the past, low life expectancies for children with such conditions contributed to the evolution of specialized care in pediatric health systems that often does not exist in adult health systems. Our teams in Boston and Cincinnati have gained insight into the multifaceted infrastructure and teams necessary to provide safe care for adults hospitalized in a pediatric setting.

In this perspective piece, we will highlight important principles that pediatric facilities and providers should prioritize if they anticipate caring for hospitalized adults during this pandemic. Designing and implementing an adult care model requires iteratively addressing the following key areas: development of a multistakeholder team, system readiness for intensive care unit (ICU) care of adults, institutional situation awareness, scope of practice, staffing considerations, patient safety, and patient populations and special considerations (eg, adults with chronic conditions of childhood onset). With these areas in mind, pediatric facilities should then consider whether they have the capacity to manage hospitalized adults.

Providing care for any hospitalized patient requires engagement with many health system stakeholders. By involving key stakeholders early in the planning process for our adult care model, we were able to anticipate potential obstacles when caring for a unique subset of patients and gain support of multidisciplinary partners. For instance, inclusion of bedside and support staff highlighted specific needs, such as nurses with adult training and a revised formulary to include common adult medications (eg, clopidogrel for adults with a drug-eluting stent).

Responding to the surge of hospitalized adult patients will require increasing hospital capacity.³ In pediatric settings, this will require consideration of innovative care models. These care models may include pediatric systems flexing to care for adult patients. We recommend hospital leaders from both pediatric and adult facilities have formal discussions on the best ways for pediatric facilities to respond to serve their local population. Inclusion of other key stakeholders will ensure factors imperative to the safe care of adults will not be missed.

There were three levels of consideration for the use of our local pediatric ICU for these patients. First, our institutional policies allow care for adults throughout the system, which we describe in more detail later, in the “Scope of Practice” section. Second, our free-standing pediatric hospital ICUs have accreditation for the care of adults. Third, we developed clear guidelines for subspecialists regarding when adults can safely be admitted or transferred to the pediatric ICU.

Responding to a crisis still necessitates establishing a clear care-escalation plan. An initial barrier may be that some systems do not have a pediatric ICU accredited for care of patients above a certain age. During a crisis, however, as hospital volumes and mortalities rise, states may pursue executive orders, as New York State did, that ease these age restrictions.⁴ Otherwise, we recommend a clear transfer plan to an adult ICU or emergency credentialing and privileging of adult intensivists. Both of these options may pose challenges during a pandemic because adult ICUs will likely be full.

Institutional situation awareness for the identification and mitigation of risks inherent in adult care in a pediatric setting is essential for patient safety. Tracking of admitted adult patients via our electronic health record (EHR) occurs daily by an adult care–team member. Our adult care teams partner with physician safety officers and attend daily institutional multidisciplinary safety huddles to create a shared mental model for the care of adult patients. Daily huddle reports include discussion regarding the number of admitted adults, review of illness acuity, consultative advice on management, and contingency planning for potential decompensation.^5,6 This integration into institutional huddles has been instrumental in proactively identifying hospitalized adults who are at risk for clinical decompensation and mitigating those risks.

Should a pediatric system admit adults to new sites or units, we recommend leveraging preexisting patient safety infrastructure similarly to identify and mitigate risks. If possible, any institutional communication about adult patients should involve adult-trained staff. Mechanisms for tracking patients will depend on local EHRs but are important to guide regular check-ins with providers caring for those patients.

Multiple levels of regulation affect a provider’s scope of practice. The most general of these regulations are state guidelines, followed by local institutional policy. Our institutions require consults for older adults—age varies at our specific institutions—by our adult-care team for assessment of risk and comanagement of adult-specific comorbidities. Additionally, we have agreements with our affiliated adult health facilities that allow in-person adult subspecialty consultation.

While state and institutional policies lay the foundation for pediatric systems considering new adult-care models, provider-level considerations are also needed. Often the patient’s age is a primary consideration, but comorbid conditions also affect the provider’s comfort and ability to care for these patients. We urge practitioners to exercise the full range of their capacities, but also to think critically about the ethical scope of one’s practice. As healthcare providers, it is our duty to hold each other accountable, voice concerns, and advocate to increase health system capacity equitably.⁷ It’s paramount that channels of communication, in-person or virtual, be arranged for supportive adult subspecialist consultation.

Med-Peds physicians and advanced practice providers are the foundation of the clinical care provided to adults at our institutions. Our Med-Peds providers practice in both the free-standing pediatric hospital and an affiliated adult health system. They offer expertise in adult clinical care and navigate between pediatric and adult systems when the need arises (eg, adult requiring urgent intervention for an acute myocardial infarction). Adult competencies of other staff must be addressed. For example, our cardiac ICUs include nurses with adult clinical care experience because critically ill adults with congenital heart disease are admitted. Advanced Care Life Support (ACLS) training is also required for staff caring for adults throughout the hospital.

There are many ways, even during a crisis, to develop an adult care model in a pediatric setting. Depending on workforce availability, internal medicine, Med-Peds, family medicine, critical care, and emergency medicine physicians could serve on either a primary service or as a consultant to support pediatrics-trained providers in caring for adults should the patient volume and acuity require staffing restructuring. Adult subspecialty access must be addressed. Telehealth may play a significant role in extending clinicians in all of these clinical roles both during the current crisis but also in underresourced settings.⁸ A clear process and indication for emergency or temporary credentialing and privileging necessitates understanding and addressing such challenges early. Training in adult care, or lack thereof, for other staff, such as nurses and respiratory therapists, is also crucial to consider.

Adults are more likely than children to have comorbidities and clinical deterioration while hospitalized. At our institutions, when a rapid response team is called for an adult patient, an adult care–team provider responds to aid in clinical management and determines the appropriate care setting. Additionally, given that the incidence of coronary artery disease increases starting at age 35 years,⁹ our systems have developed procedures for managing time-sensitive conditions seen more commonly in adults, such as acute myocardial infarction, stroke, and pulmonary embolism. Despite simulation training for pediatric providers and staff, it is clear that implementing these procedures is highly dependent on involvement of the adult care team.

With the urgency of implementation, pediatric systems should consider increasing the number of providers and staff with ACLS training, especially for rapid response and code teams. Many pediatric systems may need to evaluate how their code carts are stocked and ensure they are equipped with appropriate medication dosages and sizes of supplies. Emergent and accessible adult care will be needed, especially for issues with time-to-intervention criteria like acute myocardial infarction and stroke. Hospitalized adults with COVID-19 may also have a higher incidence of arrhythmia, cardiac ischemia, and stroke.¹⁰ Consider proactively simulating common COVID-19–related scenarios to build interdisciplinary teamwork in emergency scenarios. Interhospital agreements and pathways exist for sharing medications. Outreach to pharmacies may be indicated to ensure accessibility for medications not commonly found in pediatric systems.

Our children’s hospitals care for certain adult populations with chronic conditions of childhood origin because of the availability of subspecialty clinical expertise. Our adult care team aids in contingency planning to help determine place of admission (adult vs pediatric hospital) depending on patient clinical needs and system expertise. For instance, an adult with congenital heart disease may have two cardiologists—one for congenital heart disease and one for coronary artery disease. Patients with an acute issue such as new-onset arrhythmia may be admitted to our pediatric hospital; however, for a stroke they would be admitted to the adult hospital.

While important and tempting to address this issue first, creating criteria to determine which patient population to admit should be a last consideration during a pandemic. Consider if the decision to admit should be determined based on COVID-19 infection status. From there, types of conditions thought to be within the purview of pediatric practice can be considered. These include basic infectious diseases pathology (eg, skin/soft-tissue infections and pyelonephritis) and chronic conditions of childhood origin (eg, cystic fibrosis, diabetes, and inflammatory bowel disease), which have specialty providers who could work across an extended age range. Conditions potentially more challenging to safely care for in pediatric facilities include acute cardiac conditions (eg, angina, acute coronary syndrome, and arrhythmias), alcohol withdrawal, end-stage liver or kidney disease, and gastrointestinal bleeds. Considerations need to be made for research protocols and novel therapies only available at adult institutions. Through this whole process, it is especially crucial to note care equity and ensure that all patients have access to the highest attainable care possible.

Policymakers at pediatric facilities should think critically about their institution’s capacity to manage adults. In some circumstances, the decision might be to not admit adult patients based on the factors discussed in this paper or other contextual factors of the local healthcare systems. Our role in providing care for adults in pediatric hospitals involves not only ensuring age-appropriate care, but also in supporting patients and other healthcare providers to navigate a fragmented health system. Our adult-care models required building relationships between pediatric and adult health systems. Building these relationships in the setting of crisis can strengthen health systems and healthcare communities beyond the era of COVID-19. Because it’s promoted enhanced collaboration between pediatric and adult facilities, COVID-19 can be a platform to build a better system to support our already vulnerable young adults with chronic conditions of childhood origin for years to come.

“There are decades where nothing happens,” wrote Vladimir Lenin, “and there are weeks where decades happen.” Barely a dozen weeks ago, no one knew that the SARS-CoV-2 virus existed. Now, it has spread to almost every country on Earth, infecting over 1.8 million people whom we know about, and many more whom we do not. In so doing, it has crashed economies and health care systems, filled hospitals, emptied public spaces, and separated people from their workplaces and their friends on a scale that few of us have ever witnessed.

It has also triggered an avalanche of questions as to why our initial response was so thoroughly lethargic, rudderless, and uncoordinated; while there is plenty of blame to go around, that is for another time. The glaring question for many – including physicians trying to keep our private practices viable – is: What now?

The answer depends, of course, on how the pandemic plays out. No one yet knows exactly what will happen, but much depends on two properties of the virus, both of which are currently unknown. First: seasonality. Coronaviruses tend to thrive in winter and wane in the summer. That may also be true for SARS-CoV-2, but seasonal variations might not sufficiently slow the virus when it has so many immunologically naive hosts to infect. As I write this in mid-April, we wait anxiously to see what – if anything – summer temperatures do to its transmission in the Northern Hemisphere.

The second wild card is duration of immunity. Determining that will involve developing accurate serologic tests and administering them widely. Immune citizens, once identified, can return to work, care for the vulnerable, and anchor the economy during future outbreaks.

Even if we do get a summer hiatus, seasonal viruses typically return as winter approaches. We could conceivably still be mopping up from this outbreak when the virus – if it is seasonal – comes roaring back in October or November. Will we be ready? Or will it catch us with our pants amidships yet again?

I can envision two possibilities: Assuming we luck into a seasonal reprieve in the next few weeks, infection rates should drop, which could allow our private practices to return toward some semblance of normal – if health workers and patients alike can be convinced that our offices and clinics are safe. This might be accomplished as part of our overall preparation for a potential winter recurrence, by checking every patient’s temperature at the waiting room door. Similarly, all students should get a daily temperature check at school, as should all commuters, airline passengers, and individuals at any sizable gathering. Every fever should trigger a COVID-19 test, and every positive test should launch aggressive contact tracing and quarantines. Meanwhile, treatments and vaccines should get fast-tracked.

That’s what should happen. If it doesn’t, and COVID-19 recurs next winter, worse than before, it is anybody’s guess whether most private medical practices will be able to weather a second onslaught. Further government funding is not assured. We won’t have a vaccine by November. Chloroquine, hydroxychloroquine, and azithromycin might turn out to be helpful, but we can’t count on them.

Even if we do get lucky with seasonality, the question remains of how long it will take to restore public confidence and reboot the economy. Economies generally do not function like light switches that can be turned off for a while then simply turned back on, but act more like campfires. If you pour a bucket of water on one, it takes some time to get it cranked up again. After the “Great Recession” of 2008, it took nearly 10 years.

So now, with great reluctance, I must trot out a hoary old cliché: Hope for the best, but plan for the worst. Everyone’s situation will be different, of course, but I can make a few general suggestions. Perform a difficult mental exercise: What will you do if SARS-CoV-2 outlasts emergency funds from the Paycheck Protection and Economic Injury Disaster programs? Do the math – how long can you keep your practice afloat without floating further loans or dipping into personal savings? If you don’t know how many patients you need to see per day to break even, figure it out – now. On what day will you run out of money? When will you start putting your future at risk?

None of us thought we would ever have to face questions like these, of course – and how ironic is it that a medical emergency has forced them upon us? I sincerely hope that none of us will need to actually confront this Hobson’s choice in the coming months, but far better to address the hypothetical now than the reality later. As always, consult with your own attorney, accountant, and other business advisors before making any life-altering decisions.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at dermnews@mdedge.com. He has no disclosures.

“There are decades where nothing happens,” wrote Vladimir Lenin, “and there are weeks where decades happen.” Barely a dozen weeks ago, no one knew that the SARS-CoV-2 virus existed. Now, it has spread to almost every country on Earth, infecting over 1.8 million people whom we know about, and many more whom we do not. In so doing, it has crashed economies and health care systems, filled hospitals, emptied public spaces, and separated people from their workplaces and their friends on a scale that few of us have ever witnessed.

It has also triggered an avalanche of questions as to why our initial response was so thoroughly lethargic, rudderless, and uncoordinated; while there is plenty of blame to go around, that is for another time. The glaring question for many – including physicians trying to keep our private practices viable – is: What now?

The answer depends, of course, on how the pandemic plays out. No one yet knows exactly what will happen, but much depends on two properties of the virus, both of which are currently unknown. First: seasonality. Coronaviruses tend to thrive in winter and wane in the summer. That may also be true for SARS-CoV-2, but seasonal variations might not sufficiently slow the virus when it has so many immunologically naive hosts to infect. As I write this in mid-April, we wait anxiously to see what – if anything – summer temperatures do to its transmission in the Northern Hemisphere.

The second wild card is duration of immunity. Determining that will involve developing accurate serologic tests and administering them widely. Immune citizens, once identified, can return to work, care for the vulnerable, and anchor the economy during future outbreaks.

Even if we do get a summer hiatus, seasonal viruses typically return as winter approaches. We could conceivably still be mopping up from this outbreak when the virus – if it is seasonal – comes roaring back in October or November. Will we be ready? Or will it catch us with our pants amidships yet again?

I can envision two possibilities: Assuming we luck into a seasonal reprieve in the next few weeks, infection rates should drop, which could allow our private practices to return toward some semblance of normal – if health workers and patients alike can be convinced that our offices and clinics are safe. This might be accomplished as part of our overall preparation for a potential winter recurrence, by checking every patient’s temperature at the waiting room door. Similarly, all students should get a daily temperature check at school, as should all commuters, airline passengers, and individuals at any sizable gathering. Every fever should trigger a COVID-19 test, and every positive test should launch aggressive contact tracing and quarantines. Meanwhile, treatments and vaccines should get fast-tracked.

That’s what should happen. If it doesn’t, and COVID-19 recurs next winter, worse than before, it is anybody’s guess whether most private medical practices will be able to weather a second onslaught. Further government funding is not assured. We won’t have a vaccine by November. Chloroquine, hydroxychloroquine, and azithromycin might turn out to be helpful, but we can’t count on them.

Even if we do get lucky with seasonality, the question remains of how long it will take to restore public confidence and reboot the economy. Economies generally do not function like light switches that can be turned off for a while then simply turned back on, but act more like campfires. If you pour a bucket of water on one, it takes some time to get it cranked up again. After the “Great Recession” of 2008, it took nearly 10 years.

So now, with great reluctance, I must trot out a hoary old cliché: Hope for the best, but plan for the worst. Everyone’s situation will be different, of course, but I can make a few general suggestions. Perform a difficult mental exercise: What will you do if SARS-CoV-2 outlasts emergency funds from the Paycheck Protection and Economic Injury Disaster programs? Do the math – how long can you keep your practice afloat without floating further loans or dipping into personal savings? If you don’t know how many patients you need to see per day to break even, figure it out – now. On what day will you run out of money? When will you start putting your future at risk?

None of us thought we would ever have to face questions like these, of course – and how ironic is it that a medical emergency has forced them upon us? I sincerely hope that none of us will need to actually confront this Hobson’s choice in the coming months, but far better to address the hypothetical now than the reality later. As always, consult with your own attorney, accountant, and other business advisors before making any life-altering decisions.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at dermnews@mdedge.com. He has no disclosures.

“There are decades where nothing happens,” wrote Vladimir Lenin, “and there are weeks where decades happen.” Barely a dozen weeks ago, no one knew that the SARS-CoV-2 virus existed. Now, it has spread to almost every country on Earth, infecting over 1.8 million people whom we know about, and many more whom we do not. In so doing, it has crashed economies and health care systems, filled hospitals, emptied public spaces, and separated people from their workplaces and their friends on a scale that few of us have ever witnessed.

It has also triggered an avalanche of questions as to why our initial response was so thoroughly lethargic, rudderless, and uncoordinated; while there is plenty of blame to go around, that is for another time. The glaring question for many – including physicians trying to keep our private practices viable – is: What now?

The answer depends, of course, on how the pandemic plays out. No one yet knows exactly what will happen, but much depends on two properties of the virus, both of which are currently unknown. First: seasonality. Coronaviruses tend to thrive in winter and wane in the summer. That may also be true for SARS-CoV-2, but seasonal variations might not sufficiently slow the virus when it has so many immunologically naive hosts to infect. As I write this in mid-April, we wait anxiously to see what – if anything – summer temperatures do to its transmission in the Northern Hemisphere.

The second wild card is duration of immunity. Determining that will involve developing accurate serologic tests and administering them widely. Immune citizens, once identified, can return to work, care for the vulnerable, and anchor the economy during future outbreaks.

Even if we do get a summer hiatus, seasonal viruses typically return as winter approaches. We could conceivably still be mopping up from this outbreak when the virus – if it is seasonal – comes roaring back in October or November. Will we be ready? Or will it catch us with our pants amidships yet again?

I can envision two possibilities: Assuming we luck into a seasonal reprieve in the next few weeks, infection rates should drop, which could allow our private practices to return toward some semblance of normal – if health workers and patients alike can be convinced that our offices and clinics are safe. This might be accomplished as part of our overall preparation for a potential winter recurrence, by checking every patient’s temperature at the waiting room door. Similarly, all students should get a daily temperature check at school, as should all commuters, airline passengers, and individuals at any sizable gathering. Every fever should trigger a COVID-19 test, and every positive test should launch aggressive contact tracing and quarantines. Meanwhile, treatments and vaccines should get fast-tracked.

That’s what should happen. If it doesn’t, and COVID-19 recurs next winter, worse than before, it is anybody’s guess whether most private medical practices will be able to weather a second onslaught. Further government funding is not assured. We won’t have a vaccine by November. Chloroquine, hydroxychloroquine, and azithromycin might turn out to be helpful, but we can’t count on them.

Even if we do get lucky with seasonality, the question remains of how long it will take to restore public confidence and reboot the economy. Economies generally do not function like light switches that can be turned off for a while then simply turned back on, but act more like campfires. If you pour a bucket of water on one, it takes some time to get it cranked up again. After the “Great Recession” of 2008, it took nearly 10 years.

So now, with great reluctance, I must trot out a hoary old cliché: Hope for the best, but plan for the worst. Everyone’s situation will be different, of course, but I can make a few general suggestions. Perform a difficult mental exercise: What will you do if SARS-CoV-2 outlasts emergency funds from the Paycheck Protection and Economic Injury Disaster programs? Do the math – how long can you keep your practice afloat without floating further loans or dipping into personal savings? If you don’t know how many patients you need to see per day to break even, figure it out – now. On what day will you run out of money? When will you start putting your future at risk?

None of us thought we would ever have to face questions like these, of course – and how ironic is it that a medical emergency has forced them upon us? I sincerely hope that none of us will need to actually confront this Hobson’s choice in the coming months, but far better to address the hypothetical now than the reality later. As always, consult with your own attorney, accountant, and other business advisors before making any life-altering decisions.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at dermnews@mdedge.com. He has no disclosures.

As the COVID-19 pandemic continues, minimizing risks of infection to patients with cancer while maintaining good outcomes remains a priority. An international panel of experts has now issued recommendations for treating patients with rectal cancer, which includes using a short pre-operative course of radiotherapy (SCRT) and then delaying surgery.

Using SCRT translates to fewer hospital appointments, which will keep patients safer and allow them to maintain social distancing. The panel also found that surgery can be safely delayed by up to 12 weeks, and thus will allow procedures to be rescheduled after the pandemic peaks.

“The COVID-19 pandemic is a global emergency and we needed to work very quickly to identify changes that would benefit patients,” said David Sebag-Montefiore, MD, a professor of clinical oncology at the University of Leeds and honorary clinical oncologist with the Leeds Teaching Hospitals NHS Trust, who led the 15 member panel. “Our recommendations were published 20 days after our first meeting.”

“This process normally takes many months, if not years,” he said in a statement.

The recommendations were published online April 2 in Radiotherapy and Oncology.

The panel used the European Society for Medical Oncology (ESMO) rectal cancer guidelines as a framework to describe these new recommendations.

Recommendations by Stage

The recommendations were categorized into four subgroups based on cancer stage.

Early stage

• The ESMO guidelines recommend total mesorectal excision (TME) surgery without pre-operative radiotherapy for most cases.
• Panel recommendation also strongly supports the use of TME without pre-operative radiotherapy.

Intermediate stage

• The ESMO guidelines recommend TME alone or combined with SCRT or conventional radiotherapy (CRT) if there is uncertainty that a good quality mesorectal excision can be achieved.
• The panel strongly recommends TME alone in regions where high quality surgery is performed. The use of radiotherapy in this subgroup requires careful discussion, as the benefits of preoperative radiotherapy are likely to be small. If radiotherapy is used, then the preferred option should be SCRT.

Locally advanced

• The ESMO guideline recommends either pre-operative SCRT or CRT.
• The panel strongly recommends the use of SCRT and notes two phase 3 trials have compared SCRT and CRT and showed comparable outcomes for local recurrence, disease-free survival, overall survival, and late toxicity. In the COVID-19 setting, the panel points out that SCRT has many advantages over CRT, namely that there is less acute toxicity, fewer treatments which translate to less travel and contact with other patients and staff, and a significantly reduced risk of COVID-19 infection during treatment.

Timing of surgery after SCRT

• The ESMO guideline does not have any recommendations as they were issued before the Stockholm III trial (Lancet Oncol. 2017;18:336-46).
• The panel notes that the use of SCRT and delaying surgery has advantages that can be beneficial in both routine clinical practice and the COVID-19 setting. Several clinical trials have recommended that surgery should be performed within 3-7 days of completing radiotherapy, but the Stockholm III trial reported no difference in outcomes when surgery was delayed. It compared surgery performed within 1 week versus 4-8 weeks following SCRT and there was no difference in any survival endpoints. In addition, a longer delay to surgery was associated with a reduction in post-operative and surgical morbidity although no differences in severe complications or re-operations.

Advanced subgroup

• The ESMO guidelines recommend the use of pre-operative CRT or SCRT followed by neoadjuvant chemotherapy. CRT should be given as a fluoropyrimidine (usually capecitabine) combined with radiotherapy of 45-50.4 Gy over 5-5.5 weeks. Adjuvant chemotherapy should be considered but there is wide international variation in its use.
• The panel recommends that two options be considered based on the current evidence. The first is pre-op CRT, which is the most established standard of care, with the duration of concurrent capecitabine chemotherapy limited to 5-5.5 weeks. The second option is SCRT with or without neoadjuvant chemotherapy. In this case, the duration of radiotherapy is substantially less and has advantages versus CRT. “We consider both options to be acceptable but note the advantages of using SCRT in the COVID-19 setting,” the authors write. “The decision to use neoadjuvant chemotherapy in option 2 will reflect the attitudes to neoadjuvant and adjuvant chemotherapy in each country, the assessment of the risk-benefit ratio, considering the risk factors for COVID-19 increased mortality, and the capacity and prioritization of chemotherapy delivery.”

Organ Preservation

Organ preservation is being increasingly considered when a complete clinical response is achieved after CRT or SCRT, the panel points out. “An organ preservation approach may be considered during the COVID-19 period providing that resources for an adequate surveillance including imaging and endoscopy are available to detect local failures that require salvage surgery,” they write.

This article first appeared on Medscape.com.

As the COVID-19 pandemic continues, minimizing risks of infection to patients with cancer while maintaining good outcomes remains a priority. An international panel of experts has now issued recommendations for treating patients with rectal cancer, which includes using a short pre-operative course of radiotherapy (SCRT) and then delaying surgery.

Using SCRT translates to fewer hospital appointments, which will keep patients safer and allow them to maintain social distancing. The panel also found that surgery can be safely delayed by up to 12 weeks, and thus will allow procedures to be rescheduled after the pandemic peaks.

“The COVID-19 pandemic is a global emergency and we needed to work very quickly to identify changes that would benefit patients,” said David Sebag-Montefiore, MD, a professor of clinical oncology at the University of Leeds and honorary clinical oncologist with the Leeds Teaching Hospitals NHS Trust, who led the 15 member panel. “Our recommendations were published 20 days after our first meeting.”

“This process normally takes many months, if not years,” he said in a statement.

The recommendations were published online April 2 in Radiotherapy and Oncology.

The panel used the European Society for Medical Oncology (ESMO) rectal cancer guidelines as a framework to describe these new recommendations.

Recommendations by Stage

The recommendations were categorized into four subgroups based on cancer stage.

Early stage

• The ESMO guidelines recommend total mesorectal excision (TME) surgery without pre-operative radiotherapy for most cases.
• Panel recommendation also strongly supports the use of TME without pre-operative radiotherapy.

Intermediate stage

• The ESMO guidelines recommend TME alone or combined with SCRT or conventional radiotherapy (CRT) if there is uncertainty that a good quality mesorectal excision can be achieved.
• The panel strongly recommends TME alone in regions where high quality surgery is performed. The use of radiotherapy in this subgroup requires careful discussion, as the benefits of preoperative radiotherapy are likely to be small. If radiotherapy is used, then the preferred option should be SCRT.

Locally advanced

• The ESMO guideline recommends either pre-operative SCRT or CRT.
• The panel strongly recommends the use of SCRT and notes two phase 3 trials have compared SCRT and CRT and showed comparable outcomes for local recurrence, disease-free survival, overall survival, and late toxicity. In the COVID-19 setting, the panel points out that SCRT has many advantages over CRT, namely that there is less acute toxicity, fewer treatments which translate to less travel and contact with other patients and staff, and a significantly reduced risk of COVID-19 infection during treatment.

Timing of surgery after SCRT

• The ESMO guideline does not have any recommendations as they were issued before the Stockholm III trial (Lancet Oncol. 2017;18:336-46).
• The panel notes that the use of SCRT and delaying surgery has advantages that can be beneficial in both routine clinical practice and the COVID-19 setting. Several clinical trials have recommended that surgery should be performed within 3-7 days of completing radiotherapy, but the Stockholm III trial reported no difference in outcomes when surgery was delayed. It compared surgery performed within 1 week versus 4-8 weeks following SCRT and there was no difference in any survival endpoints. In addition, a longer delay to surgery was associated with a reduction in post-operative and surgical morbidity although no differences in severe complications or re-operations.

Advanced subgroup

• The ESMO guidelines recommend the use of pre-operative CRT or SCRT followed by neoadjuvant chemotherapy. CRT should be given as a fluoropyrimidine (usually capecitabine) combined with radiotherapy of 45-50.4 Gy over 5-5.5 weeks. Adjuvant chemotherapy should be considered but there is wide international variation in its use.
• The panel recommends that two options be considered based on the current evidence. The first is pre-op CRT, which is the most established standard of care, with the duration of concurrent capecitabine chemotherapy limited to 5-5.5 weeks. The second option is SCRT with or without neoadjuvant chemotherapy. In this case, the duration of radiotherapy is substantially less and has advantages versus CRT. “We consider both options to be acceptable but note the advantages of using SCRT in the COVID-19 setting,” the authors write. “The decision to use neoadjuvant chemotherapy in option 2 will reflect the attitudes to neoadjuvant and adjuvant chemotherapy in each country, the assessment of the risk-benefit ratio, considering the risk factors for COVID-19 increased mortality, and the capacity and prioritization of chemotherapy delivery.”

Organ Preservation

Organ preservation is being increasingly considered when a complete clinical response is achieved after CRT or SCRT, the panel points out. “An organ preservation approach may be considered during the COVID-19 period providing that resources for an adequate surveillance including imaging and endoscopy are available to detect local failures that require salvage surgery,” they write.

This article first appeared on Medscape.com.

As the COVID-19 pandemic continues, minimizing risks of infection to patients with cancer while maintaining good outcomes remains a priority. An international panel of experts has now issued recommendations for treating patients with rectal cancer, which includes using a short pre-operative course of radiotherapy (SCRT) and then delaying surgery.

Using SCRT translates to fewer hospital appointments, which will keep patients safer and allow them to maintain social distancing. The panel also found that surgery can be safely delayed by up to 12 weeks, and thus will allow procedures to be rescheduled after the pandemic peaks.

“The COVID-19 pandemic is a global emergency and we needed to work very quickly to identify changes that would benefit patients,” said David Sebag-Montefiore, MD, a professor of clinical oncology at the University of Leeds and honorary clinical oncologist with the Leeds Teaching Hospitals NHS Trust, who led the 15 member panel. “Our recommendations were published 20 days after our first meeting.”

“This process normally takes many months, if not years,” he said in a statement.

The recommendations were published online April 2 in Radiotherapy and Oncology.

The panel used the European Society for Medical Oncology (ESMO) rectal cancer guidelines as a framework to describe these new recommendations.

Recommendations by Stage

The recommendations were categorized into four subgroups based on cancer stage.

Early stage

• The ESMO guidelines recommend total mesorectal excision (TME) surgery without pre-operative radiotherapy for most cases.
• Panel recommendation also strongly supports the use of TME without pre-operative radiotherapy.

Intermediate stage

• The ESMO guidelines recommend TME alone or combined with SCRT or conventional radiotherapy (CRT) if there is uncertainty that a good quality mesorectal excision can be achieved.
• The panel strongly recommends TME alone in regions where high quality surgery is performed. The use of radiotherapy in this subgroup requires careful discussion, as the benefits of preoperative radiotherapy are likely to be small. If radiotherapy is used, then the preferred option should be SCRT.

Locally advanced

• The ESMO guideline recommends either pre-operative SCRT or CRT.
• The panel strongly recommends the use of SCRT and notes two phase 3 trials have compared SCRT and CRT and showed comparable outcomes for local recurrence, disease-free survival, overall survival, and late toxicity. In the COVID-19 setting, the panel points out that SCRT has many advantages over CRT, namely that there is less acute toxicity, fewer treatments which translate to less travel and contact with other patients and staff, and a significantly reduced risk of COVID-19 infection during treatment.

Timing of surgery after SCRT

• The ESMO guideline does not have any recommendations as they were issued before the Stockholm III trial (Lancet Oncol. 2017;18:336-46).
• The panel notes that the use of SCRT and delaying surgery has advantages that can be beneficial in both routine clinical practice and the COVID-19 setting. Several clinical trials have recommended that surgery should be performed within 3-7 days of completing radiotherapy, but the Stockholm III trial reported no difference in outcomes when surgery was delayed. It compared surgery performed within 1 week versus 4-8 weeks following SCRT and there was no difference in any survival endpoints. In addition, a longer delay to surgery was associated with a reduction in post-operative and surgical morbidity although no differences in severe complications or re-operations.

Advanced subgroup

• The ESMO guidelines recommend the use of pre-operative CRT or SCRT followed by neoadjuvant chemotherapy. CRT should be given as a fluoropyrimidine (usually capecitabine) combined with radiotherapy of 45-50.4 Gy over 5-5.5 weeks. Adjuvant chemotherapy should be considered but there is wide international variation in its use.
• The panel recommends that two options be considered based on the current evidence. The first is pre-op CRT, which is the most established standard of care, with the duration of concurrent capecitabine chemotherapy limited to 5-5.5 weeks. The second option is SCRT with or without neoadjuvant chemotherapy. In this case, the duration of radiotherapy is substantially less and has advantages versus CRT. “We consider both options to be acceptable but note the advantages of using SCRT in the COVID-19 setting,” the authors write. “The decision to use neoadjuvant chemotherapy in option 2 will reflect the attitudes to neoadjuvant and adjuvant chemotherapy in each country, the assessment of the risk-benefit ratio, considering the risk factors for COVID-19 increased mortality, and the capacity and prioritization of chemotherapy delivery.”

Organ Preservation

Organ preservation is being increasingly considered when a complete clinical response is achieved after CRT or SCRT, the panel points out. “An organ preservation approach may be considered during the COVID-19 period providing that resources for an adequate surveillance including imaging and endoscopy are available to detect local failures that require salvage surgery,” they write.

This article first appeared on Medscape.com.