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Immunotherapy could fill unmet need in leptomeningeal metastases
Results from the trial were reported at the Society for Immunotherapy of Cancer’s 35th Anniversary Annual Meeting.
“Unfortunately, when patients present with leptomeningeal disease, they usually have a poor prognosis. Their median survival is measured at 6-24 weeks,” commented lead study author Jarushka Naidoo, MBBCh, an adjunct assistant professor of oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, and a consultant medical oncologist at Beaumont Hospital in Dublin.
“While there may be some standard approaches for how we treat leptomeningeal disease, there are no universal standard therapies that are efficacious across solid tumor types,” Dr. Naidoo added.
With this in mind, Dr. Naidoo and colleagues tested systemic pembrolizumab in a trial of patients with leptomeningeal metastases from solid tumors.
The trial closed early because of poor accrual, after enrolling 13 patients: 5 with breast carcinoma, 3 with high-grade glioma, 3 with non–small cell lung cancer, 1 with squamous cell carcinoma of the skin, and 1 with head and neck squamous carcinoma. Nine patients (69%) had received at least two prior lines of systemic therapy.
Response, safety, and biomarkers
Overall, five patients (38%) had a central nervous system response, as ascertained from radiologic response on MRI, cytologic response in cerebrospinal fluid (CSF), and/or clinical response in neurologic symptoms, Dr. Naidoo reported.
Two patients had a complete CNS response: a patient with squamous cell carcinoma of the skin, who was still alive at 3 years, and a patient with non–small cell lung cancer, who survived 9 months but succumbed to metastases elsewhere.
For the entire cohort, median CNS progression-free survival was 2.9 months, and median overall survival was 4.9 months.
“This is consistent with published prospective studies of systemic agents for leptomeningeal disease,” Dr. Naidoo pointed out. “Notably, even though numbers are small, we do see the tail-on-the-curve phenomenon in both of these survival curves, which is consistent with immune checkpoint blockade prospective studies.”
The rate of grade 3 or higher treatment-related adverse events was 15.4%, and there were no grade 3 or higher immune-related adverse events.
The number of patients was too small for formal correlational testing, but both patients who achieved a complete response developed immune-related adverse events.
The trial’s biomarker analyses showed that an aneuploidy assay using CSF tumor-derived DNA performed well at detecting leptomeningeal metastases, with sensitivity of 84.6%, compared with just 53.8% for CSF cytopathology (the current preferred method).
A multiplex assay of CSF cytokines identified similar baseline profiles for patients who went on to have responses and showed similar changes in profile (notably a reduction in proinflammatory cytokines) for the two patients who had complete responses.
Given the trial’s 38% CNS response rate, pembrolizumab “needs to be studied in larger populations of patients to confirm this result, but it could be used as a potential treatment option for patients with leptomeningeal disease from solid tumors,” Dr. Naidoo concluded. “Reassuringly, pembrolizumab was well tolerated, and this is extremely important in a patient population that is traditionally quite frail and in which other standard therapies that are used, such as high-dose methotrexate or intrathecal chemotherapy, are associated with far higher rates of toxicity.”
An unmet need
“Leptomeningeal metastasis is a strong unmet need, although its occurrence is fortunately quite rare,” commented Kim Margolin, MD, a clinical professor and medical oncologist at City of Hope National Medical Center in Duarte, Calif., who was not involved in this study.
The trial is noteworthy for showing activity of programmed death–1 (PD-1) blockade given only systemically and not with additional intrathecal therapy (as has been done in a concurrent study at MD Anderson Cancer Center) and for providing insight into various biomarkers, Dr. Margolin said in an interview.
“I cannot take a stand on author conclusions other than to agree it warrants further evaluation in carefully selected patients, and it would be great to compare something like peripheral PD-1 blockade alone versus in combination with intrathecal therapy versus a combination such as CTLA4 blockade plus PD-1 blockade such as our group and others have shown to have increased activity in CNS metastases over PD-1 block alone,” Dr. Margolin said.
“The drugs in this class are already approved, so there is no reason not to try them,” she noted.
However, patients with leptomeningeal metastases of melanoma, for example, are likely to have already received anti-PD-1 immunotherapy.
“So the settings in which off-the-shelf PD-1 blockade would be useful are extremely limited,” she concluded.
The current trial was funded by Merck, the National Institutes of Health, the Lung Cancer Foundation of America, the International Association for the Study of Lung Cancer, and Johns Hopkins University Seed Grants. Dr. Naidoo disclosed relationships with AstraZeneca, Merck, Bristol Myers Squibb, and Roche/Genentech. Dr. Margolin disclosed no relevant conflicts of interest.
SOURCE: Naidoo J et al. SITC 2020, Abstract 788.
Results from the trial were reported at the Society for Immunotherapy of Cancer’s 35th Anniversary Annual Meeting.
“Unfortunately, when patients present with leptomeningeal disease, they usually have a poor prognosis. Their median survival is measured at 6-24 weeks,” commented lead study author Jarushka Naidoo, MBBCh, an adjunct assistant professor of oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, and a consultant medical oncologist at Beaumont Hospital in Dublin.
“While there may be some standard approaches for how we treat leptomeningeal disease, there are no universal standard therapies that are efficacious across solid tumor types,” Dr. Naidoo added.
With this in mind, Dr. Naidoo and colleagues tested systemic pembrolizumab in a trial of patients with leptomeningeal metastases from solid tumors.
The trial closed early because of poor accrual, after enrolling 13 patients: 5 with breast carcinoma, 3 with high-grade glioma, 3 with non–small cell lung cancer, 1 with squamous cell carcinoma of the skin, and 1 with head and neck squamous carcinoma. Nine patients (69%) had received at least two prior lines of systemic therapy.
Response, safety, and biomarkers
Overall, five patients (38%) had a central nervous system response, as ascertained from radiologic response on MRI, cytologic response in cerebrospinal fluid (CSF), and/or clinical response in neurologic symptoms, Dr. Naidoo reported.
Two patients had a complete CNS response: a patient with squamous cell carcinoma of the skin, who was still alive at 3 years, and a patient with non–small cell lung cancer, who survived 9 months but succumbed to metastases elsewhere.
For the entire cohort, median CNS progression-free survival was 2.9 months, and median overall survival was 4.9 months.
“This is consistent with published prospective studies of systemic agents for leptomeningeal disease,” Dr. Naidoo pointed out. “Notably, even though numbers are small, we do see the tail-on-the-curve phenomenon in both of these survival curves, which is consistent with immune checkpoint blockade prospective studies.”
The rate of grade 3 or higher treatment-related adverse events was 15.4%, and there were no grade 3 or higher immune-related adverse events.
The number of patients was too small for formal correlational testing, but both patients who achieved a complete response developed immune-related adverse events.
The trial’s biomarker analyses showed that an aneuploidy assay using CSF tumor-derived DNA performed well at detecting leptomeningeal metastases, with sensitivity of 84.6%, compared with just 53.8% for CSF cytopathology (the current preferred method).
A multiplex assay of CSF cytokines identified similar baseline profiles for patients who went on to have responses and showed similar changes in profile (notably a reduction in proinflammatory cytokines) for the two patients who had complete responses.
Given the trial’s 38% CNS response rate, pembrolizumab “needs to be studied in larger populations of patients to confirm this result, but it could be used as a potential treatment option for patients with leptomeningeal disease from solid tumors,” Dr. Naidoo concluded. “Reassuringly, pembrolizumab was well tolerated, and this is extremely important in a patient population that is traditionally quite frail and in which other standard therapies that are used, such as high-dose methotrexate or intrathecal chemotherapy, are associated with far higher rates of toxicity.”
An unmet need
“Leptomeningeal metastasis is a strong unmet need, although its occurrence is fortunately quite rare,” commented Kim Margolin, MD, a clinical professor and medical oncologist at City of Hope National Medical Center in Duarte, Calif., who was not involved in this study.
The trial is noteworthy for showing activity of programmed death–1 (PD-1) blockade given only systemically and not with additional intrathecal therapy (as has been done in a concurrent study at MD Anderson Cancer Center) and for providing insight into various biomarkers, Dr. Margolin said in an interview.
“I cannot take a stand on author conclusions other than to agree it warrants further evaluation in carefully selected patients, and it would be great to compare something like peripheral PD-1 blockade alone versus in combination with intrathecal therapy versus a combination such as CTLA4 blockade plus PD-1 blockade such as our group and others have shown to have increased activity in CNS metastases over PD-1 block alone,” Dr. Margolin said.
“The drugs in this class are already approved, so there is no reason not to try them,” she noted.
However, patients with leptomeningeal metastases of melanoma, for example, are likely to have already received anti-PD-1 immunotherapy.
“So the settings in which off-the-shelf PD-1 blockade would be useful are extremely limited,” she concluded.
The current trial was funded by Merck, the National Institutes of Health, the Lung Cancer Foundation of America, the International Association for the Study of Lung Cancer, and Johns Hopkins University Seed Grants. Dr. Naidoo disclosed relationships with AstraZeneca, Merck, Bristol Myers Squibb, and Roche/Genentech. Dr. Margolin disclosed no relevant conflicts of interest.
SOURCE: Naidoo J et al. SITC 2020, Abstract 788.
Results from the trial were reported at the Society for Immunotherapy of Cancer’s 35th Anniversary Annual Meeting.
“Unfortunately, when patients present with leptomeningeal disease, they usually have a poor prognosis. Their median survival is measured at 6-24 weeks,” commented lead study author Jarushka Naidoo, MBBCh, an adjunct assistant professor of oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, and a consultant medical oncologist at Beaumont Hospital in Dublin.
“While there may be some standard approaches for how we treat leptomeningeal disease, there are no universal standard therapies that are efficacious across solid tumor types,” Dr. Naidoo added.
With this in mind, Dr. Naidoo and colleagues tested systemic pembrolizumab in a trial of patients with leptomeningeal metastases from solid tumors.
The trial closed early because of poor accrual, after enrolling 13 patients: 5 with breast carcinoma, 3 with high-grade glioma, 3 with non–small cell lung cancer, 1 with squamous cell carcinoma of the skin, and 1 with head and neck squamous carcinoma. Nine patients (69%) had received at least two prior lines of systemic therapy.
Response, safety, and biomarkers
Overall, five patients (38%) had a central nervous system response, as ascertained from radiologic response on MRI, cytologic response in cerebrospinal fluid (CSF), and/or clinical response in neurologic symptoms, Dr. Naidoo reported.
Two patients had a complete CNS response: a patient with squamous cell carcinoma of the skin, who was still alive at 3 years, and a patient with non–small cell lung cancer, who survived 9 months but succumbed to metastases elsewhere.
For the entire cohort, median CNS progression-free survival was 2.9 months, and median overall survival was 4.9 months.
“This is consistent with published prospective studies of systemic agents for leptomeningeal disease,” Dr. Naidoo pointed out. “Notably, even though numbers are small, we do see the tail-on-the-curve phenomenon in both of these survival curves, which is consistent with immune checkpoint blockade prospective studies.”
The rate of grade 3 or higher treatment-related adverse events was 15.4%, and there were no grade 3 or higher immune-related adverse events.
The number of patients was too small for formal correlational testing, but both patients who achieved a complete response developed immune-related adverse events.
The trial’s biomarker analyses showed that an aneuploidy assay using CSF tumor-derived DNA performed well at detecting leptomeningeal metastases, with sensitivity of 84.6%, compared with just 53.8% for CSF cytopathology (the current preferred method).
A multiplex assay of CSF cytokines identified similar baseline profiles for patients who went on to have responses and showed similar changes in profile (notably a reduction in proinflammatory cytokines) for the two patients who had complete responses.
Given the trial’s 38% CNS response rate, pembrolizumab “needs to be studied in larger populations of patients to confirm this result, but it could be used as a potential treatment option for patients with leptomeningeal disease from solid tumors,” Dr. Naidoo concluded. “Reassuringly, pembrolizumab was well tolerated, and this is extremely important in a patient population that is traditionally quite frail and in which other standard therapies that are used, such as high-dose methotrexate or intrathecal chemotherapy, are associated with far higher rates of toxicity.”
An unmet need
“Leptomeningeal metastasis is a strong unmet need, although its occurrence is fortunately quite rare,” commented Kim Margolin, MD, a clinical professor and medical oncologist at City of Hope National Medical Center in Duarte, Calif., who was not involved in this study.
The trial is noteworthy for showing activity of programmed death–1 (PD-1) blockade given only systemically and not with additional intrathecal therapy (as has been done in a concurrent study at MD Anderson Cancer Center) and for providing insight into various biomarkers, Dr. Margolin said in an interview.
“I cannot take a stand on author conclusions other than to agree it warrants further evaluation in carefully selected patients, and it would be great to compare something like peripheral PD-1 blockade alone versus in combination with intrathecal therapy versus a combination such as CTLA4 blockade plus PD-1 blockade such as our group and others have shown to have increased activity in CNS metastases over PD-1 block alone,” Dr. Margolin said.
“The drugs in this class are already approved, so there is no reason not to try them,” she noted.
However, patients with leptomeningeal metastases of melanoma, for example, are likely to have already received anti-PD-1 immunotherapy.
“So the settings in which off-the-shelf PD-1 blockade would be useful are extremely limited,” she concluded.
The current trial was funded by Merck, the National Institutes of Health, the Lung Cancer Foundation of America, the International Association for the Study of Lung Cancer, and Johns Hopkins University Seed Grants. Dr. Naidoo disclosed relationships with AstraZeneca, Merck, Bristol Myers Squibb, and Roche/Genentech. Dr. Margolin disclosed no relevant conflicts of interest.
SOURCE: Naidoo J et al. SITC 2020, Abstract 788.
FROM SITC 2020
Expert shares key facts about keloid therapy
although few understand what this process entails, according to Hilary E. Baldwin, MD, of Rutgers Robert Wood Johnson Medical School, New Brunswick, N.J.
A key point to keep in mind about keloids is that, while they result from trauma, however slight, trauma alone does not cause them, Dr. Baldwin said in a presentation at the virtual MedscapeLive’s annual Las Vegas Dermatology Seminar.
In general, people with darker skin form keloids more easily and consistently than those with lighter skin, but keloids in people with darker skin are often easier to treat, Dr. Baldwin added. Also worth noting is the fact that earlobe keloids recur less frequently, she said.
Most patients with keloids are not surgical candidates, and they need convincing to pursue alternative options, Dr. Baldwin said.
However, successful management of keloids starts with sorting out what the patient wants. Some want “eradication with normal skin,” which is not realistic, versus simply flattening, lightening, or eradication of the keloid and leaving a scar, she noted. “That skin is never going to look normal,” she said. “Very often, they don’t need the whole thing gone, they just want to be better, and not itch or cause them to think about it all the time.”
Quality clinical research on the management of keloids is limited, Dr. Baldwin continued. “If you are holding out for a good randomized, placebo-controlled, double-blind study with a healthy ‘N,’ adequate follow-up rational conclusions, don’t hold your breath,” she said. The few literature reviews on keloids in recent decades concluded that modalities used to treat keloids are based on anecdotal evidence rather than rigorous research, she noted.
Size (and shape) matters
The decision to cut a keloid depends on several factors, including lesion size, shape, age, and location, but especially patient commitment to follow up and postsurgery care, said Dr. Baldwin.
She noted that larger keloids are no more difficult to remove than smaller ones, and patients tend to be more satisfied with the outcome with larger keloids. In terms of shape, pedunculated lesions are most amenable to surgery because of their small footprint. “Often the base does not contain keloidal tissue, and the patient gets the maximum benefit for the least risk,” she said. In addition, the residue from the removal of large keloids is often more acceptable.
Options for adjunctive therapy when excising keloids include corticosteroids, radiation, interferon, pressure dressings, dextran hydrogel scaffolding, and possibly botulinum toxin A, Dr. Baldwin said.
Adjunctive treatment alternatives
Intralesional corticosteroids can prevent the recurrence of keloids, and Dr. Baldwin recommends a 40 mg/cc injection into the base and walls of the excision site immediately postop, with repeat injections every 2 weeks for 2 months regardless of the patient’s clinical appearance. However, appearance determines the dose and concentration during 6 months of monthly follow-up, she said.
Radiation therapy, while not an effective monotherapy for keloids, can be used as an adjunct. A short radiation treatment plan may improve compliance, and no local malignancies linked to radiation therapy for keloids have been reported, she said. Dr. Baldwin also shared details of using an in-office superficial radiation therapy with the SRT-100 device, which she said has shown some ability to reduce recurrence of keloids.
Interferon, which can reduce production of collagen and increase collagenase can be used in an amount of 1.5 million units per linear cm around the base and walls of a keloid excision (maximum is 5 million units a day). Be aware that patients can develop flulike symptoms within a day or so, and warn patients to take it easy and monitor for symptoms, she said.
Studies of imiquimod for keloid recurrence have yielded mixed results, and a 2020 literature review concluded that it is not recommended as a treatment option for keloids, said Dr. Baldwin. Pressure dressings also have not shown effectiveness on existing lesions.
Botulinum toxin A has been studied as a way to prevent hypertrophic scars and keloids and potentially for preventing recurrence by injecting at the wound edges, she said. A meta-analysis showed that botulinum toxin was superior to corticosteroids for treating keloids, but “there were a lot of problems with the studies,” she said.
One other option for postexcision keloid treatment is dextran hydrogel scaffolding, which involves a triple-stranded collagen denatured by heat, with the addition of dextran to form a scaffold for fibroblasts, Dr. Baldwin said. This product, when injected prior to the final closure of surgical excision of keloids, may improve outcomes in certain areas, such as the earlobe, she said.
Dr. Baldwin concluded with comments about preventing other keloids from getting out of hand, which is extraordinarily challenging. However, treatment with dupilumab might provide an answer, although data are limited and more research is needed. She cited a case study of a male patient who had severe atopic dermatitis, with two keloids that improved after 7 months on dupilumab. The Th2 cytokines interleukin (IL)–4 and IL-13 have been implicated as key mediators in the pathogenesis of fibroproliferative disorders, which may respond to dupilumab, which targets Th2, she noted.
Dr. Baldwin had no relevant financial conflicts to disclose.
MedscapeLive and this news organization are owned by the same parent company.
although few understand what this process entails, according to Hilary E. Baldwin, MD, of Rutgers Robert Wood Johnson Medical School, New Brunswick, N.J.
A key point to keep in mind about keloids is that, while they result from trauma, however slight, trauma alone does not cause them, Dr. Baldwin said in a presentation at the virtual MedscapeLive’s annual Las Vegas Dermatology Seminar.
In general, people with darker skin form keloids more easily and consistently than those with lighter skin, but keloids in people with darker skin are often easier to treat, Dr. Baldwin added. Also worth noting is the fact that earlobe keloids recur less frequently, she said.
Most patients with keloids are not surgical candidates, and they need convincing to pursue alternative options, Dr. Baldwin said.
However, successful management of keloids starts with sorting out what the patient wants. Some want “eradication with normal skin,” which is not realistic, versus simply flattening, lightening, or eradication of the keloid and leaving a scar, she noted. “That skin is never going to look normal,” she said. “Very often, they don’t need the whole thing gone, they just want to be better, and not itch or cause them to think about it all the time.”
Quality clinical research on the management of keloids is limited, Dr. Baldwin continued. “If you are holding out for a good randomized, placebo-controlled, double-blind study with a healthy ‘N,’ adequate follow-up rational conclusions, don’t hold your breath,” she said. The few literature reviews on keloids in recent decades concluded that modalities used to treat keloids are based on anecdotal evidence rather than rigorous research, she noted.
Size (and shape) matters
The decision to cut a keloid depends on several factors, including lesion size, shape, age, and location, but especially patient commitment to follow up and postsurgery care, said Dr. Baldwin.
She noted that larger keloids are no more difficult to remove than smaller ones, and patients tend to be more satisfied with the outcome with larger keloids. In terms of shape, pedunculated lesions are most amenable to surgery because of their small footprint. “Often the base does not contain keloidal tissue, and the patient gets the maximum benefit for the least risk,” she said. In addition, the residue from the removal of large keloids is often more acceptable.
Options for adjunctive therapy when excising keloids include corticosteroids, radiation, interferon, pressure dressings, dextran hydrogel scaffolding, and possibly botulinum toxin A, Dr. Baldwin said.
Adjunctive treatment alternatives
Intralesional corticosteroids can prevent the recurrence of keloids, and Dr. Baldwin recommends a 40 mg/cc injection into the base and walls of the excision site immediately postop, with repeat injections every 2 weeks for 2 months regardless of the patient’s clinical appearance. However, appearance determines the dose and concentration during 6 months of monthly follow-up, she said.
Radiation therapy, while not an effective monotherapy for keloids, can be used as an adjunct. A short radiation treatment plan may improve compliance, and no local malignancies linked to radiation therapy for keloids have been reported, she said. Dr. Baldwin also shared details of using an in-office superficial radiation therapy with the SRT-100 device, which she said has shown some ability to reduce recurrence of keloids.
Interferon, which can reduce production of collagen and increase collagenase can be used in an amount of 1.5 million units per linear cm around the base and walls of a keloid excision (maximum is 5 million units a day). Be aware that patients can develop flulike symptoms within a day or so, and warn patients to take it easy and monitor for symptoms, she said.
Studies of imiquimod for keloid recurrence have yielded mixed results, and a 2020 literature review concluded that it is not recommended as a treatment option for keloids, said Dr. Baldwin. Pressure dressings also have not shown effectiveness on existing lesions.
Botulinum toxin A has been studied as a way to prevent hypertrophic scars and keloids and potentially for preventing recurrence by injecting at the wound edges, she said. A meta-analysis showed that botulinum toxin was superior to corticosteroids for treating keloids, but “there were a lot of problems with the studies,” she said.
One other option for postexcision keloid treatment is dextran hydrogel scaffolding, which involves a triple-stranded collagen denatured by heat, with the addition of dextran to form a scaffold for fibroblasts, Dr. Baldwin said. This product, when injected prior to the final closure of surgical excision of keloids, may improve outcomes in certain areas, such as the earlobe, she said.
Dr. Baldwin concluded with comments about preventing other keloids from getting out of hand, which is extraordinarily challenging. However, treatment with dupilumab might provide an answer, although data are limited and more research is needed. She cited a case study of a male patient who had severe atopic dermatitis, with two keloids that improved after 7 months on dupilumab. The Th2 cytokines interleukin (IL)–4 and IL-13 have been implicated as key mediators in the pathogenesis of fibroproliferative disorders, which may respond to dupilumab, which targets Th2, she noted.
Dr. Baldwin had no relevant financial conflicts to disclose.
MedscapeLive and this news organization are owned by the same parent company.
although few understand what this process entails, according to Hilary E. Baldwin, MD, of Rutgers Robert Wood Johnson Medical School, New Brunswick, N.J.
A key point to keep in mind about keloids is that, while they result from trauma, however slight, trauma alone does not cause them, Dr. Baldwin said in a presentation at the virtual MedscapeLive’s annual Las Vegas Dermatology Seminar.
In general, people with darker skin form keloids more easily and consistently than those with lighter skin, but keloids in people with darker skin are often easier to treat, Dr. Baldwin added. Also worth noting is the fact that earlobe keloids recur less frequently, she said.
Most patients with keloids are not surgical candidates, and they need convincing to pursue alternative options, Dr. Baldwin said.
However, successful management of keloids starts with sorting out what the patient wants. Some want “eradication with normal skin,” which is not realistic, versus simply flattening, lightening, or eradication of the keloid and leaving a scar, she noted. “That skin is never going to look normal,” she said. “Very often, they don’t need the whole thing gone, they just want to be better, and not itch or cause them to think about it all the time.”
Quality clinical research on the management of keloids is limited, Dr. Baldwin continued. “If you are holding out for a good randomized, placebo-controlled, double-blind study with a healthy ‘N,’ adequate follow-up rational conclusions, don’t hold your breath,” she said. The few literature reviews on keloids in recent decades concluded that modalities used to treat keloids are based on anecdotal evidence rather than rigorous research, she noted.
Size (and shape) matters
The decision to cut a keloid depends on several factors, including lesion size, shape, age, and location, but especially patient commitment to follow up and postsurgery care, said Dr. Baldwin.
She noted that larger keloids are no more difficult to remove than smaller ones, and patients tend to be more satisfied with the outcome with larger keloids. In terms of shape, pedunculated lesions are most amenable to surgery because of their small footprint. “Often the base does not contain keloidal tissue, and the patient gets the maximum benefit for the least risk,” she said. In addition, the residue from the removal of large keloids is often more acceptable.
Options for adjunctive therapy when excising keloids include corticosteroids, radiation, interferon, pressure dressings, dextran hydrogel scaffolding, and possibly botulinum toxin A, Dr. Baldwin said.
Adjunctive treatment alternatives
Intralesional corticosteroids can prevent the recurrence of keloids, and Dr. Baldwin recommends a 40 mg/cc injection into the base and walls of the excision site immediately postop, with repeat injections every 2 weeks for 2 months regardless of the patient’s clinical appearance. However, appearance determines the dose and concentration during 6 months of monthly follow-up, she said.
Radiation therapy, while not an effective monotherapy for keloids, can be used as an adjunct. A short radiation treatment plan may improve compliance, and no local malignancies linked to radiation therapy for keloids have been reported, she said. Dr. Baldwin also shared details of using an in-office superficial radiation therapy with the SRT-100 device, which she said has shown some ability to reduce recurrence of keloids.
Interferon, which can reduce production of collagen and increase collagenase can be used in an amount of 1.5 million units per linear cm around the base and walls of a keloid excision (maximum is 5 million units a day). Be aware that patients can develop flulike symptoms within a day or so, and warn patients to take it easy and monitor for symptoms, she said.
Studies of imiquimod for keloid recurrence have yielded mixed results, and a 2020 literature review concluded that it is not recommended as a treatment option for keloids, said Dr. Baldwin. Pressure dressings also have not shown effectiveness on existing lesions.
Botulinum toxin A has been studied as a way to prevent hypertrophic scars and keloids and potentially for preventing recurrence by injecting at the wound edges, she said. A meta-analysis showed that botulinum toxin was superior to corticosteroids for treating keloids, but “there were a lot of problems with the studies,” she said.
One other option for postexcision keloid treatment is dextran hydrogel scaffolding, which involves a triple-stranded collagen denatured by heat, with the addition of dextran to form a scaffold for fibroblasts, Dr. Baldwin said. This product, when injected prior to the final closure of surgical excision of keloids, may improve outcomes in certain areas, such as the earlobe, she said.
Dr. Baldwin concluded with comments about preventing other keloids from getting out of hand, which is extraordinarily challenging. However, treatment with dupilumab might provide an answer, although data are limited and more research is needed. She cited a case study of a male patient who had severe atopic dermatitis, with two keloids that improved after 7 months on dupilumab. The Th2 cytokines interleukin (IL)–4 and IL-13 have been implicated as key mediators in the pathogenesis of fibroproliferative disorders, which may respond to dupilumab, which targets Th2, she noted.
Dr. Baldwin had no relevant financial conflicts to disclose.
MedscapeLive and this news organization are owned by the same parent company.
FROM MEDSCAPELIVE LAS VEGAS DERMATOLOGY SEMINAR
Food preservative for early psychosis: Final word?
Adjunctive use of sodium benzoate (BZ), a common food preservative that has previously shown promise in the treatment of chronic refractory psychosis, appears to be ineffective in the early stages of the disorder, new research suggests.
Results of a randomized controlled trial show the agent was no more effective than placebo in reducing early psychosis symptoms, although it was safe and well tolerated.
“Both groups of patients improved over the 12 weeks of the study, [suggesting] that most people with early psychosis will get well with antipsychotic medication and psychosocial interventions and adding sodium benzoate to their treatment does not add any additional benefits,” the study’s lead author, James Scott, MBBS, PhD, head of mental health research, QIMR Berghofer Medical Research Institute, Herston, Australia, told Medscape Medical News.
The paper was published online November 10 in JAMA Network Open.
Positive outcomes in chronic disease
Despite treatment with antipsychotics, many patients with psychosis experience persistent impairment, the investigators note.
Most antipsychotics are dopaminergic in action, but it is now recognized that the pathophysiology underlying psychosis extends beyond dopaminergic dysregulation with hypofunction of the N-methyl-D-aspartate (NMDA) receptors also implicated but not addressed by standard antipsychotics, they add.
NMDA receptors consist of two main subunits – the glutamate and glycine-binding sites. D-amino acids (DAAs) are agonists of the glycine subunit and have shown promise as adjunctive therapies for the treatment of schizophrenia, the investigators note.
DAAs are subject to oxidation by the flavoenzyme D-amino acid oxidase (DAAO). The oxidation limits their bioavailability and can cause nephrotoxic side effects. The food preservative BZ, which is not related to the benzodiazepine class of medications, inhibits DAAO and therefore may make DAAs safer and more effective.
Scott noted that two previous trials of BZ – a 2013 study and a 2017 investigation – in chronic, treatment-refractory schizophrenia have “reported excellent outcomes with significant improvement in clinical symptoms.”
“We saw that sodium benzoate was a safe and well-tolerated agent, and we thought it was important to conduct a trial of this medication in people in the early stages of psychotic illness,” he said.
To investigate, the researchers randomly assigned 100 individuals who were experiencing early psychosis, which was defined as illness onset within the last 2 years, to receive either 500 mg of BZ twice daily or placebo for 12 weeks.
Participants (mean [SD] age 21.4 [4.1] years, 73% male) were required to be taking antipsychotic medications for at least 1 continuous month during the previous 2 years and to be free of comorbid physical illnesses requiring additional treatment or hospitalization.
Most participants (84%) had schizophrenia and the remainder had affective psychoses. Most participants (88%) lived independently.
The BZ and the placebo groups were similar with respect to baseline characteristics, except that the mean waist circumference was higher in the placebo group than in the BZ group.
The majority of patients were being treated with antipsychotics alone (83%), followed by antipsychotics in combination with mood stabilizers (13%) and a small number were taking mood stabilizers alone (4%). The most commonly used antipsychotics were olanzapine and aripiprazole.
Not recommended
Psychosis was confirmed using the Positive and Negative Syndrome Scale (PANSS), and the inclusion criteria was a baseline score of ≥ 55. Secondary outcomes were scores on the Hamilton Depression Rating Scale, the clinician-rated Global Assessment of Function, and the Assessment of Quality of Life Scale.
The researchers also measured concentrations of the amino acids oxidized by DAAO (D-alanine and L-alanine, D-serine and L-serine).
Although both groups experienced a reduction in total PANSS scores during the study, there were no significant differences in PANSS total score between the BZ and the placebo groups at 12 weeks (endpoint least-square mean difference [SE] −1.2 [2.4] t = −0.49, P = .63).
There were also no significant differences between the groups on all PANSS subscales as well as any of the secondary clinical measures (P < .007).
A total of 122 adverse events (AEs) overall were reported by 66 participants, but rates of AEs were comparable between the BZ and placebo groups at 55% vs. 46% respectively. There were 11 serious AEs reported by 10 participants. Only one of these was related to the study drug.
There were no statistically significant changes in amino acid concentrations between the two groups.
The authors note several limitations of the study, including the possibility that protective agents may need longer times than 12 weeks – possibly as long as 6 to 12 months – to show efficacy. Moreover, the dose of BZ needed to produce a response remains “uncertain.”
“ and should further investigate whether benzoate acts by altering amino acid levels or by reducing oxidative stress in people with schizophrenia,” the authors suggest.
Scott added that further research in patients with treatment-refractory schizophrenia is needed to determine whether BZ “has a role in this patient population.”
The authors conclude that at present, “the routine use of this agent as an adjunctive treatment for early psychosis is not recommended.”
No surprise?
Commenting on the study for Medscape Medical News, Kenji Hashimoto, PhD, Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan, said that, although previous studies of BZ showed benefit in stable patients with chronic schizophrenia, “it is unlikely that [sodium] benzoate may have beneficial effects in the acute phase of psychosis.”
Hashimoto, who was not involved with the study, noted that BZ is a “weak DAAO inhibitor and that DAAO expression in the frontal cortex of human beings is very low.”
This project was supported by a John Cade Fellowship from the National Health and Medical Research Council and support from the Queensland Centre for Mental Health Research, which receives funding from the Queensland Health Department. Scott is supported by an NHMRC Practitioner Fellowship. The other authors’ disclosures are listed on the original article. Hashimoto has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Adjunctive use of sodium benzoate (BZ), a common food preservative that has previously shown promise in the treatment of chronic refractory psychosis, appears to be ineffective in the early stages of the disorder, new research suggests.
Results of a randomized controlled trial show the agent was no more effective than placebo in reducing early psychosis symptoms, although it was safe and well tolerated.
“Both groups of patients improved over the 12 weeks of the study, [suggesting] that most people with early psychosis will get well with antipsychotic medication and psychosocial interventions and adding sodium benzoate to their treatment does not add any additional benefits,” the study’s lead author, James Scott, MBBS, PhD, head of mental health research, QIMR Berghofer Medical Research Institute, Herston, Australia, told Medscape Medical News.
The paper was published online November 10 in JAMA Network Open.
Positive outcomes in chronic disease
Despite treatment with antipsychotics, many patients with psychosis experience persistent impairment, the investigators note.
Most antipsychotics are dopaminergic in action, but it is now recognized that the pathophysiology underlying psychosis extends beyond dopaminergic dysregulation with hypofunction of the N-methyl-D-aspartate (NMDA) receptors also implicated but not addressed by standard antipsychotics, they add.
NMDA receptors consist of two main subunits – the glutamate and glycine-binding sites. D-amino acids (DAAs) are agonists of the glycine subunit and have shown promise as adjunctive therapies for the treatment of schizophrenia, the investigators note.
DAAs are subject to oxidation by the flavoenzyme D-amino acid oxidase (DAAO). The oxidation limits their bioavailability and can cause nephrotoxic side effects. The food preservative BZ, which is not related to the benzodiazepine class of medications, inhibits DAAO and therefore may make DAAs safer and more effective.
Scott noted that two previous trials of BZ – a 2013 study and a 2017 investigation – in chronic, treatment-refractory schizophrenia have “reported excellent outcomes with significant improvement in clinical symptoms.”
“We saw that sodium benzoate was a safe and well-tolerated agent, and we thought it was important to conduct a trial of this medication in people in the early stages of psychotic illness,” he said.
To investigate, the researchers randomly assigned 100 individuals who were experiencing early psychosis, which was defined as illness onset within the last 2 years, to receive either 500 mg of BZ twice daily or placebo for 12 weeks.
Participants (mean [SD] age 21.4 [4.1] years, 73% male) were required to be taking antipsychotic medications for at least 1 continuous month during the previous 2 years and to be free of comorbid physical illnesses requiring additional treatment or hospitalization.
Most participants (84%) had schizophrenia and the remainder had affective psychoses. Most participants (88%) lived independently.
The BZ and the placebo groups were similar with respect to baseline characteristics, except that the mean waist circumference was higher in the placebo group than in the BZ group.
The majority of patients were being treated with antipsychotics alone (83%), followed by antipsychotics in combination with mood stabilizers (13%) and a small number were taking mood stabilizers alone (4%). The most commonly used antipsychotics were olanzapine and aripiprazole.
Not recommended
Psychosis was confirmed using the Positive and Negative Syndrome Scale (PANSS), and the inclusion criteria was a baseline score of ≥ 55. Secondary outcomes were scores on the Hamilton Depression Rating Scale, the clinician-rated Global Assessment of Function, and the Assessment of Quality of Life Scale.
The researchers also measured concentrations of the amino acids oxidized by DAAO (D-alanine and L-alanine, D-serine and L-serine).
Although both groups experienced a reduction in total PANSS scores during the study, there were no significant differences in PANSS total score between the BZ and the placebo groups at 12 weeks (endpoint least-square mean difference [SE] −1.2 [2.4] t = −0.49, P = .63).
There were also no significant differences between the groups on all PANSS subscales as well as any of the secondary clinical measures (P < .007).
A total of 122 adverse events (AEs) overall were reported by 66 participants, but rates of AEs were comparable between the BZ and placebo groups at 55% vs. 46% respectively. There were 11 serious AEs reported by 10 participants. Only one of these was related to the study drug.
There were no statistically significant changes in amino acid concentrations between the two groups.
The authors note several limitations of the study, including the possibility that protective agents may need longer times than 12 weeks – possibly as long as 6 to 12 months – to show efficacy. Moreover, the dose of BZ needed to produce a response remains “uncertain.”
“ and should further investigate whether benzoate acts by altering amino acid levels or by reducing oxidative stress in people with schizophrenia,” the authors suggest.
Scott added that further research in patients with treatment-refractory schizophrenia is needed to determine whether BZ “has a role in this patient population.”
The authors conclude that at present, “the routine use of this agent as an adjunctive treatment for early psychosis is not recommended.”
No surprise?
Commenting on the study for Medscape Medical News, Kenji Hashimoto, PhD, Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan, said that, although previous studies of BZ showed benefit in stable patients with chronic schizophrenia, “it is unlikely that [sodium] benzoate may have beneficial effects in the acute phase of psychosis.”
Hashimoto, who was not involved with the study, noted that BZ is a “weak DAAO inhibitor and that DAAO expression in the frontal cortex of human beings is very low.”
This project was supported by a John Cade Fellowship from the National Health and Medical Research Council and support from the Queensland Centre for Mental Health Research, which receives funding from the Queensland Health Department. Scott is supported by an NHMRC Practitioner Fellowship. The other authors’ disclosures are listed on the original article. Hashimoto has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Adjunctive use of sodium benzoate (BZ), a common food preservative that has previously shown promise in the treatment of chronic refractory psychosis, appears to be ineffective in the early stages of the disorder, new research suggests.
Results of a randomized controlled trial show the agent was no more effective than placebo in reducing early psychosis symptoms, although it was safe and well tolerated.
“Both groups of patients improved over the 12 weeks of the study, [suggesting] that most people with early psychosis will get well with antipsychotic medication and psychosocial interventions and adding sodium benzoate to their treatment does not add any additional benefits,” the study’s lead author, James Scott, MBBS, PhD, head of mental health research, QIMR Berghofer Medical Research Institute, Herston, Australia, told Medscape Medical News.
The paper was published online November 10 in JAMA Network Open.
Positive outcomes in chronic disease
Despite treatment with antipsychotics, many patients with psychosis experience persistent impairment, the investigators note.
Most antipsychotics are dopaminergic in action, but it is now recognized that the pathophysiology underlying psychosis extends beyond dopaminergic dysregulation with hypofunction of the N-methyl-D-aspartate (NMDA) receptors also implicated but not addressed by standard antipsychotics, they add.
NMDA receptors consist of two main subunits – the glutamate and glycine-binding sites. D-amino acids (DAAs) are agonists of the glycine subunit and have shown promise as adjunctive therapies for the treatment of schizophrenia, the investigators note.
DAAs are subject to oxidation by the flavoenzyme D-amino acid oxidase (DAAO). The oxidation limits their bioavailability and can cause nephrotoxic side effects. The food preservative BZ, which is not related to the benzodiazepine class of medications, inhibits DAAO and therefore may make DAAs safer and more effective.
Scott noted that two previous trials of BZ – a 2013 study and a 2017 investigation – in chronic, treatment-refractory schizophrenia have “reported excellent outcomes with significant improvement in clinical symptoms.”
“We saw that sodium benzoate was a safe and well-tolerated agent, and we thought it was important to conduct a trial of this medication in people in the early stages of psychotic illness,” he said.
To investigate, the researchers randomly assigned 100 individuals who were experiencing early psychosis, which was defined as illness onset within the last 2 years, to receive either 500 mg of BZ twice daily or placebo for 12 weeks.
Participants (mean [SD] age 21.4 [4.1] years, 73% male) were required to be taking antipsychotic medications for at least 1 continuous month during the previous 2 years and to be free of comorbid physical illnesses requiring additional treatment or hospitalization.
Most participants (84%) had schizophrenia and the remainder had affective psychoses. Most participants (88%) lived independently.
The BZ and the placebo groups were similar with respect to baseline characteristics, except that the mean waist circumference was higher in the placebo group than in the BZ group.
The majority of patients were being treated with antipsychotics alone (83%), followed by antipsychotics in combination with mood stabilizers (13%) and a small number were taking mood stabilizers alone (4%). The most commonly used antipsychotics were olanzapine and aripiprazole.
Not recommended
Psychosis was confirmed using the Positive and Negative Syndrome Scale (PANSS), and the inclusion criteria was a baseline score of ≥ 55. Secondary outcomes were scores on the Hamilton Depression Rating Scale, the clinician-rated Global Assessment of Function, and the Assessment of Quality of Life Scale.
The researchers also measured concentrations of the amino acids oxidized by DAAO (D-alanine and L-alanine, D-serine and L-serine).
Although both groups experienced a reduction in total PANSS scores during the study, there were no significant differences in PANSS total score between the BZ and the placebo groups at 12 weeks (endpoint least-square mean difference [SE] −1.2 [2.4] t = −0.49, P = .63).
There were also no significant differences between the groups on all PANSS subscales as well as any of the secondary clinical measures (P < .007).
A total of 122 adverse events (AEs) overall were reported by 66 participants, but rates of AEs were comparable between the BZ and placebo groups at 55% vs. 46% respectively. There were 11 serious AEs reported by 10 participants. Only one of these was related to the study drug.
There were no statistically significant changes in amino acid concentrations between the two groups.
The authors note several limitations of the study, including the possibility that protective agents may need longer times than 12 weeks – possibly as long as 6 to 12 months – to show efficacy. Moreover, the dose of BZ needed to produce a response remains “uncertain.”
“ and should further investigate whether benzoate acts by altering amino acid levels or by reducing oxidative stress in people with schizophrenia,” the authors suggest.
Scott added that further research in patients with treatment-refractory schizophrenia is needed to determine whether BZ “has a role in this patient population.”
The authors conclude that at present, “the routine use of this agent as an adjunctive treatment for early psychosis is not recommended.”
No surprise?
Commenting on the study for Medscape Medical News, Kenji Hashimoto, PhD, Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan, said that, although previous studies of BZ showed benefit in stable patients with chronic schizophrenia, “it is unlikely that [sodium] benzoate may have beneficial effects in the acute phase of psychosis.”
Hashimoto, who was not involved with the study, noted that BZ is a “weak DAAO inhibitor and that DAAO expression in the frontal cortex of human beings is very low.”
This project was supported by a John Cade Fellowship from the National Health and Medical Research Council and support from the Queensland Centre for Mental Health Research, which receives funding from the Queensland Health Department. Scott is supported by an NHMRC Practitioner Fellowship. The other authors’ disclosures are listed on the original article. Hashimoto has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Pfizer files for FDA emergency use authorization of COVID vaccine
Pfizer and its German partner BioNTech have filed an application with the US Food and Drug Administration (FDA) for an emergency use authorization of its vaccine against COVID-19, the disease caused by SARS-CoV-2, according to a company news release.
It is the latest step in what has been an extraordinarily fast-paced development and testing process, with the companies having reported interim results of phase 3 trials on November 9 and final results this past Wednesday, as reported by Medscape Medical News. The vaccine, BNT162b2, which uses a messenger RNA-based platform, was ultimately found to have 95% efficacy and more than 94% efficacy in individuals over age 65.
“The process of the speed did not compromise at all safety, nor did it compromise scientific integrity,” said Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases at a White House press briefing yesterday.
“We need to put to rest any concept that this was rushed in an inappropriate way,” he said. “This is really solid.”
Pfizer and BioNTech said they believe they have met the FDA’s safety data requirements for emergency use authorization (EUA). The agency in October outlined its expectations for safety and efficacy to secure an EUA.
“Filing in the US represents a critical milestone in our journey to deliver a COVID-19 vaccine to the world, and we now have a more complete picture of both the efficacy and safety profile of our vaccine, giving us confidence in its potential,” said Albert Bourla, MD, Pfizer’s chairman and CEO, in its release.
The FDA is expected to hold a meeting of its Vaccines and Related Biological Products Advisory Committee sometime in December to review the safety and efficacy data in the companies’ application. The committee will review:
- Efficacy data from a total 170 confirmed cases of COVID-19 in the phase 3 study.
- Safety data from a randomly assigned subset of 8000 participants 18 years and older.
- Data on 19,000 enrollees who have been followed for a median of 2 months after the second and final dose.
- Data on the manufacturing processes.
According to Pfizer, the companies plan to submit the efficacy and safety data to a peer-reviewed journal once they have completed their analysis.
Vaccine logistics
The companies — which funded their own trials — signed an agreement with the US government’s Operation Warp Speed program in July to provide 100 million doses of its vaccine following FDA authorization or approval in exchange for $1.95 billion. The US government has the option to acquire up to 500 million more doses.
Pfizer and BioNTech said they will be able to supply 50 million doses globally in 2020 and up to 1.3 billion doses by the end of 2021. The vaccine must be given in two doses, spaced 21 days apart. Pfizer expects to be ready to distribute the vaccine within hours after FDA authorization.
The US government is still on track to deliver the Pfizer vaccine within 24 hours of an FDA authorization, said Operation Warp Speed’s Chief Operating Officer Gen. Gustave F. Perna at yesterday’s White House briefing.
Vice President Mike Pence emphasized that point at the briefing: “The moment that the FDA concludes that that vaccine is safe and effective, we have a system in place to begin within 24 hours shipping that vaccine to hospitals, healthcare facilities and, 24 hours after that, literally injecting that vaccine into Americans,” he said.
The vaccine will be pushed out through 64 jurisdictions already part of the Centers for Disease Control and Prevention’s vaccines for children distribution program, and will likely be divided up according to population, said Perna.
Pfizer’s vaccine must be shipped and stored at –70°C (–94°F), which has presented logistical and storage issues. The company is testing out delivery methods, including a pilot delivery program in New Mexico, Rhode Island, Tennessee, and Texas that will be active after an FDA authorization. States, hospitals, and pharmacy chains are also buying special freezers.
The National Academies of Sciences, Engineering, and Medicine issued recommendations in October that healthcare workers, first responders, older Americans living in congregate settings (eg, nursing homes), and people with underlying health conditions be the first to receive a coronavirus vaccine. The CDC’s Advisory Committee on Immunization Practices will also be issuing recommendations as soon as the FDA authorizes a vaccine.
Pfizer and BioNTech are also seeking approval for the vaccine with several regulatory agencies around the world, including the European Medicines Agency and the Medicines & Healthcare Products Regulatory Agency (MHRA) in the United Kingdom.
This article first appeared on Medscape.com.
Pfizer and its German partner BioNTech have filed an application with the US Food and Drug Administration (FDA) for an emergency use authorization of its vaccine against COVID-19, the disease caused by SARS-CoV-2, according to a company news release.
It is the latest step in what has been an extraordinarily fast-paced development and testing process, with the companies having reported interim results of phase 3 trials on November 9 and final results this past Wednesday, as reported by Medscape Medical News. The vaccine, BNT162b2, which uses a messenger RNA-based platform, was ultimately found to have 95% efficacy and more than 94% efficacy in individuals over age 65.
“The process of the speed did not compromise at all safety, nor did it compromise scientific integrity,” said Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases at a White House press briefing yesterday.
“We need to put to rest any concept that this was rushed in an inappropriate way,” he said. “This is really solid.”
Pfizer and BioNTech said they believe they have met the FDA’s safety data requirements for emergency use authorization (EUA). The agency in October outlined its expectations for safety and efficacy to secure an EUA.
“Filing in the US represents a critical milestone in our journey to deliver a COVID-19 vaccine to the world, and we now have a more complete picture of both the efficacy and safety profile of our vaccine, giving us confidence in its potential,” said Albert Bourla, MD, Pfizer’s chairman and CEO, in its release.
The FDA is expected to hold a meeting of its Vaccines and Related Biological Products Advisory Committee sometime in December to review the safety and efficacy data in the companies’ application. The committee will review:
- Efficacy data from a total 170 confirmed cases of COVID-19 in the phase 3 study.
- Safety data from a randomly assigned subset of 8000 participants 18 years and older.
- Data on 19,000 enrollees who have been followed for a median of 2 months after the second and final dose.
- Data on the manufacturing processes.
According to Pfizer, the companies plan to submit the efficacy and safety data to a peer-reviewed journal once they have completed their analysis.
Vaccine logistics
The companies — which funded their own trials — signed an agreement with the US government’s Operation Warp Speed program in July to provide 100 million doses of its vaccine following FDA authorization or approval in exchange for $1.95 billion. The US government has the option to acquire up to 500 million more doses.
Pfizer and BioNTech said they will be able to supply 50 million doses globally in 2020 and up to 1.3 billion doses by the end of 2021. The vaccine must be given in two doses, spaced 21 days apart. Pfizer expects to be ready to distribute the vaccine within hours after FDA authorization.
The US government is still on track to deliver the Pfizer vaccine within 24 hours of an FDA authorization, said Operation Warp Speed’s Chief Operating Officer Gen. Gustave F. Perna at yesterday’s White House briefing.
Vice President Mike Pence emphasized that point at the briefing: “The moment that the FDA concludes that that vaccine is safe and effective, we have a system in place to begin within 24 hours shipping that vaccine to hospitals, healthcare facilities and, 24 hours after that, literally injecting that vaccine into Americans,” he said.
The vaccine will be pushed out through 64 jurisdictions already part of the Centers for Disease Control and Prevention’s vaccines for children distribution program, and will likely be divided up according to population, said Perna.
Pfizer’s vaccine must be shipped and stored at –70°C (–94°F), which has presented logistical and storage issues. The company is testing out delivery methods, including a pilot delivery program in New Mexico, Rhode Island, Tennessee, and Texas that will be active after an FDA authorization. States, hospitals, and pharmacy chains are also buying special freezers.
The National Academies of Sciences, Engineering, and Medicine issued recommendations in October that healthcare workers, first responders, older Americans living in congregate settings (eg, nursing homes), and people with underlying health conditions be the first to receive a coronavirus vaccine. The CDC’s Advisory Committee on Immunization Practices will also be issuing recommendations as soon as the FDA authorizes a vaccine.
Pfizer and BioNTech are also seeking approval for the vaccine with several regulatory agencies around the world, including the European Medicines Agency and the Medicines & Healthcare Products Regulatory Agency (MHRA) in the United Kingdom.
This article first appeared on Medscape.com.
Pfizer and its German partner BioNTech have filed an application with the US Food and Drug Administration (FDA) for an emergency use authorization of its vaccine against COVID-19, the disease caused by SARS-CoV-2, according to a company news release.
It is the latest step in what has been an extraordinarily fast-paced development and testing process, with the companies having reported interim results of phase 3 trials on November 9 and final results this past Wednesday, as reported by Medscape Medical News. The vaccine, BNT162b2, which uses a messenger RNA-based platform, was ultimately found to have 95% efficacy and more than 94% efficacy in individuals over age 65.
“The process of the speed did not compromise at all safety, nor did it compromise scientific integrity,” said Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases at a White House press briefing yesterday.
“We need to put to rest any concept that this was rushed in an inappropriate way,” he said. “This is really solid.”
Pfizer and BioNTech said they believe they have met the FDA’s safety data requirements for emergency use authorization (EUA). The agency in October outlined its expectations for safety and efficacy to secure an EUA.
“Filing in the US represents a critical milestone in our journey to deliver a COVID-19 vaccine to the world, and we now have a more complete picture of both the efficacy and safety profile of our vaccine, giving us confidence in its potential,” said Albert Bourla, MD, Pfizer’s chairman and CEO, in its release.
The FDA is expected to hold a meeting of its Vaccines and Related Biological Products Advisory Committee sometime in December to review the safety and efficacy data in the companies’ application. The committee will review:
- Efficacy data from a total 170 confirmed cases of COVID-19 in the phase 3 study.
- Safety data from a randomly assigned subset of 8000 participants 18 years and older.
- Data on 19,000 enrollees who have been followed for a median of 2 months after the second and final dose.
- Data on the manufacturing processes.
According to Pfizer, the companies plan to submit the efficacy and safety data to a peer-reviewed journal once they have completed their analysis.
Vaccine logistics
The companies — which funded their own trials — signed an agreement with the US government’s Operation Warp Speed program in July to provide 100 million doses of its vaccine following FDA authorization or approval in exchange for $1.95 billion. The US government has the option to acquire up to 500 million more doses.
Pfizer and BioNTech said they will be able to supply 50 million doses globally in 2020 and up to 1.3 billion doses by the end of 2021. The vaccine must be given in two doses, spaced 21 days apart. Pfizer expects to be ready to distribute the vaccine within hours after FDA authorization.
The US government is still on track to deliver the Pfizer vaccine within 24 hours of an FDA authorization, said Operation Warp Speed’s Chief Operating Officer Gen. Gustave F. Perna at yesterday’s White House briefing.
Vice President Mike Pence emphasized that point at the briefing: “The moment that the FDA concludes that that vaccine is safe and effective, we have a system in place to begin within 24 hours shipping that vaccine to hospitals, healthcare facilities and, 24 hours after that, literally injecting that vaccine into Americans,” he said.
The vaccine will be pushed out through 64 jurisdictions already part of the Centers for Disease Control and Prevention’s vaccines for children distribution program, and will likely be divided up according to population, said Perna.
Pfizer’s vaccine must be shipped and stored at –70°C (–94°F), which has presented logistical and storage issues. The company is testing out delivery methods, including a pilot delivery program in New Mexico, Rhode Island, Tennessee, and Texas that will be active after an FDA authorization. States, hospitals, and pharmacy chains are also buying special freezers.
The National Academies of Sciences, Engineering, and Medicine issued recommendations in October that healthcare workers, first responders, older Americans living in congregate settings (eg, nursing homes), and people with underlying health conditions be the first to receive a coronavirus vaccine. The CDC’s Advisory Committee on Immunization Practices will also be issuing recommendations as soon as the FDA authorizes a vaccine.
Pfizer and BioNTech are also seeking approval for the vaccine with several regulatory agencies around the world, including the European Medicines Agency and the Medicines & Healthcare Products Regulatory Agency (MHRA) in the United Kingdom.
This article first appeared on Medscape.com.
Aspirin and statins in chronic hepatitis B: It’s complicated
For patients with chronic hepatitis B, the protective effects of aspirin against hepatocellular carcinoma (HCC) can vary with cirrhosis status and statin treatment, a pair of new studies finds.
One study showed that, although aspirin is linked to a reduction in risk for HCC in these patients, comedication with statins could explain some of that effect. The other showed that cirrhosis dampens the risk-reduction benefit of aspirin.
Currently, there is a link between a reduction in HCC risk and aspirin or statins in patients with chronic hepatitis B, said investigator Won-Mook Choi, MD, PhD, from the University of Ulsan College of Medicine, in Seoul, Republic of Korea.
In one of their analyses, Choi and his colleagues teased out the contribution of each drug and found that the decrease in HCC risk conferred by statins is similar whether or not patients also take aspirin.
“Only statins showed consistent and significant dose-dependent reductions in the risk of HCC, regardless of study design,” said Choi, who presented the findings at The Liver Meeting 2020.
The second study, which looked at the association between aspirin and the risk for HCC in patients with and without cirrhosis, was presented by Heejoon Jang, MD, from the Seoul National University College of Medicine.
Aspirin was shown to be associated with a reduced risk for HCC, but cirrhosis “had a substantial effect on this association,” erasing the benefit of aspirin, Jang reported.
Statins and aspirin
Statins and aspirin are more likely to be prescribed together for patients with chronic hepatitis B but no cirrhosis, said Choi. For that reason, he and his colleagues analyzed data from the Korean National Health Insurance Service database from 2005 to 2015.
In their nested case-control analysis, 17,150 patients with HCC were matched for sex, age, and other factors to 817,675 patients without HCC. All participants had chronic hepatitis B without cirrhosis and had never received antiviral treatment.
The team also analyzed the incidence of HCC in two historic cohorts of patients with chronic hepatitis B but no cirrhosis, one consisting of 673,107 people who took aspirin and the other with 588,045 who took statins.
The nested case-control analysis showed an 11% risk reduction with aspirin use (adjusted odds ratio [OR], 0.89; 95% CI, 0.85 - 0.94) and a 61% risk reduction with statin use (adjusted OR, 0.39; 95% CI, 0.36 - 0.40). There was a dose-response effect with statins, but not with aspirin.
The historic cohort analysis showed a 33% reduction in the risk for HCC with aspirin (adjusted hazard ratio [HR], 0.67; 95% CI, 0.63 - 0.72) and a 67% reduction with statins (adjusted HR, 0.33; 95% CI, 0.30 - 0.37). However, stratified analyses by drug showed a statin benefit with or without aspirin (P < .001 for both), but no aspirin benefit without statins.
Cirrhosis and aspirin
To assess the interaction between cirrhosis and aspirin, Jang and his colleagues identified 329,635 patients with chronic hepatitis B in the Korean National Health Insurance Service database.
A total of 20,200 had taken aspirin for at least 90 consecutive days, and the rest had never received antiplatelet therapy. Treated and untreated patients were matched for several factors, and HCC incidence was assessed after a median follow-up of 6.7 years.
Among the 2,697 patients who developed HCC during follow-up, the cumulative incidence of HCC was significantly lower for those who took aspirin than for those who did not (P < .001). There was a 15% reduction in the risk for HCC in the aspirin group (adjusted HR, 0.85; 95% CI, 0.78 - 0.92).
However, in patients with cirrhosis, the benefit of aspirin disappeared. Patients without cirrhosis still had a 13% reduction in risk for HCC (adjusted HR, 0.87: 95% CI, 0.79 - 0.95). This group also had a slightly elevated risk for major bleeding (adjusted HR, 1.1; 95% CI, 1.03 - 1.28).
The findings from these two studies add to a growing body of literature that shows the promise of statins and aspirin, which are both readily available and relatively safe, said Amit Singal, MD, from the UT Southwestern Medical Center in Dallas, who was not involved with either study.
“The studies are relatively simple but really do tackle an area of immense need in the field,” he said. Short of having higher-quality data, however, statins and aspirin aren’t quite ready to become bespoke chemotherapies in the clinic, he added, although the results show promise for future randomized trials.
The subgroup analyses that looked at cirrhosis and the interplay of aspirin and statins can help with the planning of such trials, which “is really important for trial design,” Singal noted.
He also pointed to studies that, unlike these results, have found a benefit of aspirin in patients with cirrhosis, underscoring the need for randomized trials. However, “each study does provide a data point that can help to inform those trials,” he said.
Choi and Jang have disclosed no relevant financial relationships. Singal is a consultant for Genentech, Bayer, Eisai, Exelixis, Bristol-Myers Squibb, Roche, Glycotest, FujiFilm, GRAIL, and Exact Sciences, primarily in relation to HCC treatment and screening, not chemoprevention.
This article first appeared on Medscape.com.
For patients with chronic hepatitis B, the protective effects of aspirin against hepatocellular carcinoma (HCC) can vary with cirrhosis status and statin treatment, a pair of new studies finds.
One study showed that, although aspirin is linked to a reduction in risk for HCC in these patients, comedication with statins could explain some of that effect. The other showed that cirrhosis dampens the risk-reduction benefit of aspirin.
Currently, there is a link between a reduction in HCC risk and aspirin or statins in patients with chronic hepatitis B, said investigator Won-Mook Choi, MD, PhD, from the University of Ulsan College of Medicine, in Seoul, Republic of Korea.
In one of their analyses, Choi and his colleagues teased out the contribution of each drug and found that the decrease in HCC risk conferred by statins is similar whether or not patients also take aspirin.
“Only statins showed consistent and significant dose-dependent reductions in the risk of HCC, regardless of study design,” said Choi, who presented the findings at The Liver Meeting 2020.
The second study, which looked at the association between aspirin and the risk for HCC in patients with and without cirrhosis, was presented by Heejoon Jang, MD, from the Seoul National University College of Medicine.
Aspirin was shown to be associated with a reduced risk for HCC, but cirrhosis “had a substantial effect on this association,” erasing the benefit of aspirin, Jang reported.
Statins and aspirin
Statins and aspirin are more likely to be prescribed together for patients with chronic hepatitis B but no cirrhosis, said Choi. For that reason, he and his colleagues analyzed data from the Korean National Health Insurance Service database from 2005 to 2015.
In their nested case-control analysis, 17,150 patients with HCC were matched for sex, age, and other factors to 817,675 patients without HCC. All participants had chronic hepatitis B without cirrhosis and had never received antiviral treatment.
The team also analyzed the incidence of HCC in two historic cohorts of patients with chronic hepatitis B but no cirrhosis, one consisting of 673,107 people who took aspirin and the other with 588,045 who took statins.
The nested case-control analysis showed an 11% risk reduction with aspirin use (adjusted odds ratio [OR], 0.89; 95% CI, 0.85 - 0.94) and a 61% risk reduction with statin use (adjusted OR, 0.39; 95% CI, 0.36 - 0.40). There was a dose-response effect with statins, but not with aspirin.
The historic cohort analysis showed a 33% reduction in the risk for HCC with aspirin (adjusted hazard ratio [HR], 0.67; 95% CI, 0.63 - 0.72) and a 67% reduction with statins (adjusted HR, 0.33; 95% CI, 0.30 - 0.37). However, stratified analyses by drug showed a statin benefit with or without aspirin (P < .001 for both), but no aspirin benefit without statins.
Cirrhosis and aspirin
To assess the interaction between cirrhosis and aspirin, Jang and his colleagues identified 329,635 patients with chronic hepatitis B in the Korean National Health Insurance Service database.
A total of 20,200 had taken aspirin for at least 90 consecutive days, and the rest had never received antiplatelet therapy. Treated and untreated patients were matched for several factors, and HCC incidence was assessed after a median follow-up of 6.7 years.
Among the 2,697 patients who developed HCC during follow-up, the cumulative incidence of HCC was significantly lower for those who took aspirin than for those who did not (P < .001). There was a 15% reduction in the risk for HCC in the aspirin group (adjusted HR, 0.85; 95% CI, 0.78 - 0.92).
However, in patients with cirrhosis, the benefit of aspirin disappeared. Patients without cirrhosis still had a 13% reduction in risk for HCC (adjusted HR, 0.87: 95% CI, 0.79 - 0.95). This group also had a slightly elevated risk for major bleeding (adjusted HR, 1.1; 95% CI, 1.03 - 1.28).
The findings from these two studies add to a growing body of literature that shows the promise of statins and aspirin, which are both readily available and relatively safe, said Amit Singal, MD, from the UT Southwestern Medical Center in Dallas, who was not involved with either study.
“The studies are relatively simple but really do tackle an area of immense need in the field,” he said. Short of having higher-quality data, however, statins and aspirin aren’t quite ready to become bespoke chemotherapies in the clinic, he added, although the results show promise for future randomized trials.
The subgroup analyses that looked at cirrhosis and the interplay of aspirin and statins can help with the planning of such trials, which “is really important for trial design,” Singal noted.
He also pointed to studies that, unlike these results, have found a benefit of aspirin in patients with cirrhosis, underscoring the need for randomized trials. However, “each study does provide a data point that can help to inform those trials,” he said.
Choi and Jang have disclosed no relevant financial relationships. Singal is a consultant for Genentech, Bayer, Eisai, Exelixis, Bristol-Myers Squibb, Roche, Glycotest, FujiFilm, GRAIL, and Exact Sciences, primarily in relation to HCC treatment and screening, not chemoprevention.
This article first appeared on Medscape.com.
For patients with chronic hepatitis B, the protective effects of aspirin against hepatocellular carcinoma (HCC) can vary with cirrhosis status and statin treatment, a pair of new studies finds.
One study showed that, although aspirin is linked to a reduction in risk for HCC in these patients, comedication with statins could explain some of that effect. The other showed that cirrhosis dampens the risk-reduction benefit of aspirin.
Currently, there is a link between a reduction in HCC risk and aspirin or statins in patients with chronic hepatitis B, said investigator Won-Mook Choi, MD, PhD, from the University of Ulsan College of Medicine, in Seoul, Republic of Korea.
In one of their analyses, Choi and his colleagues teased out the contribution of each drug and found that the decrease in HCC risk conferred by statins is similar whether or not patients also take aspirin.
“Only statins showed consistent and significant dose-dependent reductions in the risk of HCC, regardless of study design,” said Choi, who presented the findings at The Liver Meeting 2020.
The second study, which looked at the association between aspirin and the risk for HCC in patients with and without cirrhosis, was presented by Heejoon Jang, MD, from the Seoul National University College of Medicine.
Aspirin was shown to be associated with a reduced risk for HCC, but cirrhosis “had a substantial effect on this association,” erasing the benefit of aspirin, Jang reported.
Statins and aspirin
Statins and aspirin are more likely to be prescribed together for patients with chronic hepatitis B but no cirrhosis, said Choi. For that reason, he and his colleagues analyzed data from the Korean National Health Insurance Service database from 2005 to 2015.
In their nested case-control analysis, 17,150 patients with HCC were matched for sex, age, and other factors to 817,675 patients without HCC. All participants had chronic hepatitis B without cirrhosis and had never received antiviral treatment.
The team also analyzed the incidence of HCC in two historic cohorts of patients with chronic hepatitis B but no cirrhosis, one consisting of 673,107 people who took aspirin and the other with 588,045 who took statins.
The nested case-control analysis showed an 11% risk reduction with aspirin use (adjusted odds ratio [OR], 0.89; 95% CI, 0.85 - 0.94) and a 61% risk reduction with statin use (adjusted OR, 0.39; 95% CI, 0.36 - 0.40). There was a dose-response effect with statins, but not with aspirin.
The historic cohort analysis showed a 33% reduction in the risk for HCC with aspirin (adjusted hazard ratio [HR], 0.67; 95% CI, 0.63 - 0.72) and a 67% reduction with statins (adjusted HR, 0.33; 95% CI, 0.30 - 0.37). However, stratified analyses by drug showed a statin benefit with or without aspirin (P < .001 for both), but no aspirin benefit without statins.
Cirrhosis and aspirin
To assess the interaction between cirrhosis and aspirin, Jang and his colleagues identified 329,635 patients with chronic hepatitis B in the Korean National Health Insurance Service database.
A total of 20,200 had taken aspirin for at least 90 consecutive days, and the rest had never received antiplatelet therapy. Treated and untreated patients were matched for several factors, and HCC incidence was assessed after a median follow-up of 6.7 years.
Among the 2,697 patients who developed HCC during follow-up, the cumulative incidence of HCC was significantly lower for those who took aspirin than for those who did not (P < .001). There was a 15% reduction in the risk for HCC in the aspirin group (adjusted HR, 0.85; 95% CI, 0.78 - 0.92).
However, in patients with cirrhosis, the benefit of aspirin disappeared. Patients without cirrhosis still had a 13% reduction in risk for HCC (adjusted HR, 0.87: 95% CI, 0.79 - 0.95). This group also had a slightly elevated risk for major bleeding (adjusted HR, 1.1; 95% CI, 1.03 - 1.28).
The findings from these two studies add to a growing body of literature that shows the promise of statins and aspirin, which are both readily available and relatively safe, said Amit Singal, MD, from the UT Southwestern Medical Center in Dallas, who was not involved with either study.
“The studies are relatively simple but really do tackle an area of immense need in the field,” he said. Short of having higher-quality data, however, statins and aspirin aren’t quite ready to become bespoke chemotherapies in the clinic, he added, although the results show promise for future randomized trials.
The subgroup analyses that looked at cirrhosis and the interplay of aspirin and statins can help with the planning of such trials, which “is really important for trial design,” Singal noted.
He also pointed to studies that, unlike these results, have found a benefit of aspirin in patients with cirrhosis, underscoring the need for randomized trials. However, “each study does provide a data point that can help to inform those trials,” he said.
Choi and Jang have disclosed no relevant financial relationships. Singal is a consultant for Genentech, Bayer, Eisai, Exelixis, Bristol-Myers Squibb, Roche, Glycotest, FujiFilm, GRAIL, and Exact Sciences, primarily in relation to HCC treatment and screening, not chemoprevention.
This article first appeared on Medscape.com.
Tips for physicians, patients to make the most of the holidays amid COVID
“We must accept finite disappointment, but never lose infinite hope,” Martin Luther King, Jr.
This holiday season will be like no other. We will remember it for the rest of our lives, and we will look back to see how we faced the holidays during a pandemic.
Like the rest of 2020, the holidays will need to be reimagined. Years and even decades of tradition will be broken as we place health above merriment.
Here are a few tips to help all of us and our patients make the most of this holiday season.
- Reprioritize: This holiday season will be about depth not breadth, quality not quantity, and less not more. Trips are canceled and gatherings have shrunk. We are not running from store to store or party to party. Instead, you will find yourself surrounded by fewer friends and family. Some will be alone to optimally protect their health and the health of others. Do your best to focus on the half-full portion.
- Embrace change: Don’t compare or try to make this year like previous years. Be creative and try to find ways to make a new format fun. Meeting during the day and limiting alcohol intake can assist in making sure everyone stays safe. It has been interesting to see how many of my patients have decreased their alcohol use during quarantine. I hope this pattern will continue over the next weeks and months.
- Practice self-care: As health care professionals, we must remember the old adage “physician, heal thyself.” This year has been so difficult for almost all of us. It was filled with unprecedented levels of personal and professional stress. Holidays are often about what we can do for others, but this year we may need to place self-care first. Do what brings you happiness.
Even though you aren’t traveling, you can still disconnect from work. Set up a schedule and stick to it making sure you take plenty of time to rest and enjoy. Many of us have been working extremely long hours and a break is so needed. Take it if you possibly can. Detox from your screen! Limit the news. Creativity and productivity will be enhanced in 2021 if we can come in recharged.
For those remaining on the front lines, be patient; the end is nearing. Take care of yourself when you are not working. We are all so grateful to those in our field who have sacrificed so much to care for others. Eat, drink, and rest well to keep your immune system strong.
- Acknowledge your negative emotions: As we all know, if you try to deny negative emotions, they continue to pop up. If we give them time and space to be felt, we will find they diminish in intensity. Long work hours may have prevented us from feeling our emotions, so don’t be surprised if they surface when we take a break.
Let yourself feel the sadness for what you have experienced this year. Be open about missing those who can’t be with you because of travel or other restrictions. Let yourself feel the disappointment about your holiday travel plans that you can’t embark upon.
You may elect to share these emotions with someone close to you or with a professional. To paraphrase Carl Jung, “what we resist, persists,” so don’t try to hide from your negative emotions. Most of us had lots of them in 2020, so don’t be shy about admitting it.
- Focus on growth: What have we learned from 2020 and how can we be better equipped in 2021 and beyond?
Trauma can bring growth not just disorder. This year has returned well-deserved prestige to our fields. We are being lauded as heroes as we have scarified our health and the health of our loved ones to serve others. Can we choose to celebrate our accomplishments?
We have become more resilient and learned to continue on in the face of great hardship. Many of us have gained confidence as we confronted this historic challenge. As we have been reminded of death daily, we learn to appreciate life more fully and not take any day for granted.
I am proud to be a physician during this pandemic, and I hope you are, too!
- Find joy: Often times, we find real happiness in smaller moments and experiences. For many, this time of year is filled with so much stress that it can be hard to carve out moments of joy. As we may be less busy socially this holiday season, might we find even more joy?
Joy can only be experienced in the present moment. Tap into all your senses. Eat slowly making sure to smell and taste every bite. Cherish those who can still gather at your table. If you find yourself alone, embrace that experience. Safety must continue to come first, and we can’t let down our guard now.
- Reflect: New Year’s Eve is always a time for reflection and hope for the future. Most of us will be glad to see 2020 in the rearview mirror. With multiple and very promising vaccines on the horizon, we can anticipate a brighter future. We must continue to work hard; remain patient; and be creative, resilient, and optimistic. Let’s try to fill our days with hope and purpose and work together to achieve a brighter future for all.
“Learn from yesterday, live for today, hope for tomorrow,” Albert Einstein
Wishing you health and happiness in this holiday season and beyond.
Dr. Ritvo, a psychiatrist with more than 25 years’ experience, practices in Miami Beach. She is the author of “Bekindr – The Transformative Power of Kindness” (Hellertown, Pa.: Momosa Publishing, 2018). She also is founder of the Bekindr Global Initiative, a movement aimed at cultivating kindness in the world.
“We must accept finite disappointment, but never lose infinite hope,” Martin Luther King, Jr.
This holiday season will be like no other. We will remember it for the rest of our lives, and we will look back to see how we faced the holidays during a pandemic.
Like the rest of 2020, the holidays will need to be reimagined. Years and even decades of tradition will be broken as we place health above merriment.
Here are a few tips to help all of us and our patients make the most of this holiday season.
- Reprioritize: This holiday season will be about depth not breadth, quality not quantity, and less not more. Trips are canceled and gatherings have shrunk. We are not running from store to store or party to party. Instead, you will find yourself surrounded by fewer friends and family. Some will be alone to optimally protect their health and the health of others. Do your best to focus on the half-full portion.
- Embrace change: Don’t compare or try to make this year like previous years. Be creative and try to find ways to make a new format fun. Meeting during the day and limiting alcohol intake can assist in making sure everyone stays safe. It has been interesting to see how many of my patients have decreased their alcohol use during quarantine. I hope this pattern will continue over the next weeks and months.
- Practice self-care: As health care professionals, we must remember the old adage “physician, heal thyself.” This year has been so difficult for almost all of us. It was filled with unprecedented levels of personal and professional stress. Holidays are often about what we can do for others, but this year we may need to place self-care first. Do what brings you happiness.
Even though you aren’t traveling, you can still disconnect from work. Set up a schedule and stick to it making sure you take plenty of time to rest and enjoy. Many of us have been working extremely long hours and a break is so needed. Take it if you possibly can. Detox from your screen! Limit the news. Creativity and productivity will be enhanced in 2021 if we can come in recharged.
For those remaining on the front lines, be patient; the end is nearing. Take care of yourself when you are not working. We are all so grateful to those in our field who have sacrificed so much to care for others. Eat, drink, and rest well to keep your immune system strong.
- Acknowledge your negative emotions: As we all know, if you try to deny negative emotions, they continue to pop up. If we give them time and space to be felt, we will find they diminish in intensity. Long work hours may have prevented us from feeling our emotions, so don’t be surprised if they surface when we take a break.
Let yourself feel the sadness for what you have experienced this year. Be open about missing those who can’t be with you because of travel or other restrictions. Let yourself feel the disappointment about your holiday travel plans that you can’t embark upon.
You may elect to share these emotions with someone close to you or with a professional. To paraphrase Carl Jung, “what we resist, persists,” so don’t try to hide from your negative emotions. Most of us had lots of them in 2020, so don’t be shy about admitting it.
- Focus on growth: What have we learned from 2020 and how can we be better equipped in 2021 and beyond?
Trauma can bring growth not just disorder. This year has returned well-deserved prestige to our fields. We are being lauded as heroes as we have scarified our health and the health of our loved ones to serve others. Can we choose to celebrate our accomplishments?
We have become more resilient and learned to continue on in the face of great hardship. Many of us have gained confidence as we confronted this historic challenge. As we have been reminded of death daily, we learn to appreciate life more fully and not take any day for granted.
I am proud to be a physician during this pandemic, and I hope you are, too!
- Find joy: Often times, we find real happiness in smaller moments and experiences. For many, this time of year is filled with so much stress that it can be hard to carve out moments of joy. As we may be less busy socially this holiday season, might we find even more joy?
Joy can only be experienced in the present moment. Tap into all your senses. Eat slowly making sure to smell and taste every bite. Cherish those who can still gather at your table. If you find yourself alone, embrace that experience. Safety must continue to come first, and we can’t let down our guard now.
- Reflect: New Year’s Eve is always a time for reflection and hope for the future. Most of us will be glad to see 2020 in the rearview mirror. With multiple and very promising vaccines on the horizon, we can anticipate a brighter future. We must continue to work hard; remain patient; and be creative, resilient, and optimistic. Let’s try to fill our days with hope and purpose and work together to achieve a brighter future for all.
“Learn from yesterday, live for today, hope for tomorrow,” Albert Einstein
Wishing you health and happiness in this holiday season and beyond.
Dr. Ritvo, a psychiatrist with more than 25 years’ experience, practices in Miami Beach. She is the author of “Bekindr – The Transformative Power of Kindness” (Hellertown, Pa.: Momosa Publishing, 2018). She also is founder of the Bekindr Global Initiative, a movement aimed at cultivating kindness in the world.
“We must accept finite disappointment, but never lose infinite hope,” Martin Luther King, Jr.
This holiday season will be like no other. We will remember it for the rest of our lives, and we will look back to see how we faced the holidays during a pandemic.
Like the rest of 2020, the holidays will need to be reimagined. Years and even decades of tradition will be broken as we place health above merriment.
Here are a few tips to help all of us and our patients make the most of this holiday season.
- Reprioritize: This holiday season will be about depth not breadth, quality not quantity, and less not more. Trips are canceled and gatherings have shrunk. We are not running from store to store or party to party. Instead, you will find yourself surrounded by fewer friends and family. Some will be alone to optimally protect their health and the health of others. Do your best to focus on the half-full portion.
- Embrace change: Don’t compare or try to make this year like previous years. Be creative and try to find ways to make a new format fun. Meeting during the day and limiting alcohol intake can assist in making sure everyone stays safe. It has been interesting to see how many of my patients have decreased their alcohol use during quarantine. I hope this pattern will continue over the next weeks and months.
- Practice self-care: As health care professionals, we must remember the old adage “physician, heal thyself.” This year has been so difficult for almost all of us. It was filled with unprecedented levels of personal and professional stress. Holidays are often about what we can do for others, but this year we may need to place self-care first. Do what brings you happiness.
Even though you aren’t traveling, you can still disconnect from work. Set up a schedule and stick to it making sure you take plenty of time to rest and enjoy. Many of us have been working extremely long hours and a break is so needed. Take it if you possibly can. Detox from your screen! Limit the news. Creativity and productivity will be enhanced in 2021 if we can come in recharged.
For those remaining on the front lines, be patient; the end is nearing. Take care of yourself when you are not working. We are all so grateful to those in our field who have sacrificed so much to care for others. Eat, drink, and rest well to keep your immune system strong.
- Acknowledge your negative emotions: As we all know, if you try to deny negative emotions, they continue to pop up. If we give them time and space to be felt, we will find they diminish in intensity. Long work hours may have prevented us from feeling our emotions, so don’t be surprised if they surface when we take a break.
Let yourself feel the sadness for what you have experienced this year. Be open about missing those who can’t be with you because of travel or other restrictions. Let yourself feel the disappointment about your holiday travel plans that you can’t embark upon.
You may elect to share these emotions with someone close to you or with a professional. To paraphrase Carl Jung, “what we resist, persists,” so don’t try to hide from your negative emotions. Most of us had lots of them in 2020, so don’t be shy about admitting it.
- Focus on growth: What have we learned from 2020 and how can we be better equipped in 2021 and beyond?
Trauma can bring growth not just disorder. This year has returned well-deserved prestige to our fields. We are being lauded as heroes as we have scarified our health and the health of our loved ones to serve others. Can we choose to celebrate our accomplishments?
We have become more resilient and learned to continue on in the face of great hardship. Many of us have gained confidence as we confronted this historic challenge. As we have been reminded of death daily, we learn to appreciate life more fully and not take any day for granted.
I am proud to be a physician during this pandemic, and I hope you are, too!
- Find joy: Often times, we find real happiness in smaller moments and experiences. For many, this time of year is filled with so much stress that it can be hard to carve out moments of joy. As we may be less busy socially this holiday season, might we find even more joy?
Joy can only be experienced in the present moment. Tap into all your senses. Eat slowly making sure to smell and taste every bite. Cherish those who can still gather at your table. If you find yourself alone, embrace that experience. Safety must continue to come first, and we can’t let down our guard now.
- Reflect: New Year’s Eve is always a time for reflection and hope for the future. Most of us will be glad to see 2020 in the rearview mirror. With multiple and very promising vaccines on the horizon, we can anticipate a brighter future. We must continue to work hard; remain patient; and be creative, resilient, and optimistic. Let’s try to fill our days with hope and purpose and work together to achieve a brighter future for all.
“Learn from yesterday, live for today, hope for tomorrow,” Albert Einstein
Wishing you health and happiness in this holiday season and beyond.
Dr. Ritvo, a psychiatrist with more than 25 years’ experience, practices in Miami Beach. She is the author of “Bekindr – The Transformative Power of Kindness” (Hellertown, Pa.: Momosa Publishing, 2018). She also is founder of the Bekindr Global Initiative, a movement aimed at cultivating kindness in the world.
COVID exposure risk outside of work increasing for clinicians
One-third of COVID-19 exposures among health care providers (HCPs) in Minnesota are caused by family or community exposure, not patient care, according to a study conducted by the Minnesota Department of Health and published online Oct. 30 in Morbidity and Mortality Weekly Report. And nonwork exposures were more likely to lead to COVID-19 infections.
Between March 6 and July 11, 2020, researchers with the Minnesota Department of Health evaluated 21,406 incidences of HCP exposure to confirmed COVID-19 cases. Of those, 5,374 (25%) were classified as higher-risk exposures, meaning the provider had close contact for 15 minutes or more, or during an aerosol-generating procedure.
Two-thirds (66%) of the higher-risk exposures occurred during direct patient care and 34% were related to nonpatient care interactions (e.g., coworkers and social and household contacts). Overall, 6.9% (373) of the HCPs with a higher-risk exposure received a positive SARS-CoV-2 test result within 14 days of the exposure. Notably, HCPs with household or social exposure had the highest positivity rate across all exposure types at 13%.
“Since the time period covered in this report, we’ve seen a significant increase in the proportion of HCPs who have had higher-risk exposures outside of work due to household or social contacts,” said lead author Ashley Fell, MPH, from the Minnesota Department of Health.
“HCPs with household or social exposures are also more likely to test positive than HCPs with higher risk exposures within the healthcare setting, which is an important message for both HCPs and the community at large that more COVID-19 spreading in our communities poses a greater risk to our HCPs and health care system,” Ms. Fell said in an interview.
When evaluating personal protective equipment use among exposed HCPs, researchers found that 90% of providers in acute or ambulatory care were wearing a respirator or medical-grade face mask at time of exposure, compared with just 68% of HCPs working in congregate living or long-term care facilities.
Further, investigators found that an HCP with a positive SARS-CoV-2 test working in a congregate living or long-term care facility resulted in exposure of a median of three additional HCPs (interquartile range, 1-6), compared with a median of one additional HCP exposure in acute or ambulatory care (IQR, 1-3).
The researchers also found that, compared with HCPs in acute or ambulatory settings, HCPs working in long-term care or congregate living settings were more likely to return to work following a high-risk exposure (57% vs. 37%) and work while symptomatic (4.8% vs. 1.3%).
When asked whether these findings apply to HCPs in other states, Andrew T. Chan, MD, from Massachusetts General Hospital, Boston, noted: “These data are not surprising and confirm what many of us have been seeing in our own areas.
“Clearly, the risk of contracting COVID-19 is particularly high for frontline health care workers in long-term care facilities and nursing homes,” Dr. Chan said.
“Furthermore, the infection control practices in these care settings are often not as rigorous, and together these factors are probably contributing to higher risks of infection,” he said.
The authors acknowledged potential study limitations including misclassification of HCP risk for exposure or misclassification of community exposure as workplace exposure.
“We also recognize that HCPs, like the rest of the community, are experiencing COVID fatigue and that facilities have to constantly be innovative and vigilant to help HCPs maintain rigorous safety precautions with their patients and around their colleagues,” Ms. Fell concluded.
The authors and Dr. Chan disclosed no relevant financial relationships.
For the latest clinical guidance, education, research and physician resources about coronavirus, visit the AGA COVID-19 Resource Center at www.gastro.org/COVID.
This article first appeared on Medscape.com.
One-third of COVID-19 exposures among health care providers (HCPs) in Minnesota are caused by family or community exposure, not patient care, according to a study conducted by the Minnesota Department of Health and published online Oct. 30 in Morbidity and Mortality Weekly Report. And nonwork exposures were more likely to lead to COVID-19 infections.
Between March 6 and July 11, 2020, researchers with the Minnesota Department of Health evaluated 21,406 incidences of HCP exposure to confirmed COVID-19 cases. Of those, 5,374 (25%) were classified as higher-risk exposures, meaning the provider had close contact for 15 minutes or more, or during an aerosol-generating procedure.
Two-thirds (66%) of the higher-risk exposures occurred during direct patient care and 34% were related to nonpatient care interactions (e.g., coworkers and social and household contacts). Overall, 6.9% (373) of the HCPs with a higher-risk exposure received a positive SARS-CoV-2 test result within 14 days of the exposure. Notably, HCPs with household or social exposure had the highest positivity rate across all exposure types at 13%.
“Since the time period covered in this report, we’ve seen a significant increase in the proportion of HCPs who have had higher-risk exposures outside of work due to household or social contacts,” said lead author Ashley Fell, MPH, from the Minnesota Department of Health.
“HCPs with household or social exposures are also more likely to test positive than HCPs with higher risk exposures within the healthcare setting, which is an important message for both HCPs and the community at large that more COVID-19 spreading in our communities poses a greater risk to our HCPs and health care system,” Ms. Fell said in an interview.
When evaluating personal protective equipment use among exposed HCPs, researchers found that 90% of providers in acute or ambulatory care were wearing a respirator or medical-grade face mask at time of exposure, compared with just 68% of HCPs working in congregate living or long-term care facilities.
Further, investigators found that an HCP with a positive SARS-CoV-2 test working in a congregate living or long-term care facility resulted in exposure of a median of three additional HCPs (interquartile range, 1-6), compared with a median of one additional HCP exposure in acute or ambulatory care (IQR, 1-3).
The researchers also found that, compared with HCPs in acute or ambulatory settings, HCPs working in long-term care or congregate living settings were more likely to return to work following a high-risk exposure (57% vs. 37%) and work while symptomatic (4.8% vs. 1.3%).
When asked whether these findings apply to HCPs in other states, Andrew T. Chan, MD, from Massachusetts General Hospital, Boston, noted: “These data are not surprising and confirm what many of us have been seeing in our own areas.
“Clearly, the risk of contracting COVID-19 is particularly high for frontline health care workers in long-term care facilities and nursing homes,” Dr. Chan said.
“Furthermore, the infection control practices in these care settings are often not as rigorous, and together these factors are probably contributing to higher risks of infection,” he said.
The authors acknowledged potential study limitations including misclassification of HCP risk for exposure or misclassification of community exposure as workplace exposure.
“We also recognize that HCPs, like the rest of the community, are experiencing COVID fatigue and that facilities have to constantly be innovative and vigilant to help HCPs maintain rigorous safety precautions with their patients and around their colleagues,” Ms. Fell concluded.
The authors and Dr. Chan disclosed no relevant financial relationships.
For the latest clinical guidance, education, research and physician resources about coronavirus, visit the AGA COVID-19 Resource Center at www.gastro.org/COVID.
This article first appeared on Medscape.com.
One-third of COVID-19 exposures among health care providers (HCPs) in Minnesota are caused by family or community exposure, not patient care, according to a study conducted by the Minnesota Department of Health and published online Oct. 30 in Morbidity and Mortality Weekly Report. And nonwork exposures were more likely to lead to COVID-19 infections.
Between March 6 and July 11, 2020, researchers with the Minnesota Department of Health evaluated 21,406 incidences of HCP exposure to confirmed COVID-19 cases. Of those, 5,374 (25%) were classified as higher-risk exposures, meaning the provider had close contact for 15 minutes or more, or during an aerosol-generating procedure.
Two-thirds (66%) of the higher-risk exposures occurred during direct patient care and 34% were related to nonpatient care interactions (e.g., coworkers and social and household contacts). Overall, 6.9% (373) of the HCPs with a higher-risk exposure received a positive SARS-CoV-2 test result within 14 days of the exposure. Notably, HCPs with household or social exposure had the highest positivity rate across all exposure types at 13%.
“Since the time period covered in this report, we’ve seen a significant increase in the proportion of HCPs who have had higher-risk exposures outside of work due to household or social contacts,” said lead author Ashley Fell, MPH, from the Minnesota Department of Health.
“HCPs with household or social exposures are also more likely to test positive than HCPs with higher risk exposures within the healthcare setting, which is an important message for both HCPs and the community at large that more COVID-19 spreading in our communities poses a greater risk to our HCPs and health care system,” Ms. Fell said in an interview.
When evaluating personal protective equipment use among exposed HCPs, researchers found that 90% of providers in acute or ambulatory care were wearing a respirator or medical-grade face mask at time of exposure, compared with just 68% of HCPs working in congregate living or long-term care facilities.
Further, investigators found that an HCP with a positive SARS-CoV-2 test working in a congregate living or long-term care facility resulted in exposure of a median of three additional HCPs (interquartile range, 1-6), compared with a median of one additional HCP exposure in acute or ambulatory care (IQR, 1-3).
The researchers also found that, compared with HCPs in acute or ambulatory settings, HCPs working in long-term care or congregate living settings were more likely to return to work following a high-risk exposure (57% vs. 37%) and work while symptomatic (4.8% vs. 1.3%).
When asked whether these findings apply to HCPs in other states, Andrew T. Chan, MD, from Massachusetts General Hospital, Boston, noted: “These data are not surprising and confirm what many of us have been seeing in our own areas.
“Clearly, the risk of contracting COVID-19 is particularly high for frontline health care workers in long-term care facilities and nursing homes,” Dr. Chan said.
“Furthermore, the infection control practices in these care settings are often not as rigorous, and together these factors are probably contributing to higher risks of infection,” he said.
The authors acknowledged potential study limitations including misclassification of HCP risk for exposure or misclassification of community exposure as workplace exposure.
“We also recognize that HCPs, like the rest of the community, are experiencing COVID fatigue and that facilities have to constantly be innovative and vigilant to help HCPs maintain rigorous safety precautions with their patients and around their colleagues,” Ms. Fell concluded.
The authors and Dr. Chan disclosed no relevant financial relationships.
For the latest clinical guidance, education, research and physician resources about coronavirus, visit the AGA COVID-19 Resource Center at www.gastro.org/COVID.
This article first appeared on Medscape.com.
FDA authorizes baricitinib combo for COVID-19
The US Food and Drug Administration (FDA) Nov. 19 issued an emergency use authorization (EUA) for the Janus kinase inhibitor baricitinib (Olumiant, Eli Lilly) in combination with remdesivir (Veklury, Gilead) for treating hospitalized adults and children at least 2 years old with suspected or confirmed COVID-19.
The combination treatment is meant for patients who need supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).
Baricitinib/remdesivir was shown in a clinical trial to reduce time to recovery within 29 days of starting the treatment compared with a control group who received placebo/remdesivir, according to the FDA press release.
The median time to recovery from COVID-19 was 7 days for the combination group vs. 8 days for those in the placebo/remdesivir group. Recovery was defined as either discharge from the hospital or “being hospitalized but not requiring supplemental oxygen and no longer requiring ongoing medical care,” the agency explained in the press release.
The odds of a patient dying or being ventilated at day 29 was lower in the combination group compared with those taking placebo/remdesivir, the press release said without providing specific data. “For all of these endpoints, the effects were statistically significant,” the agency stated.
The safety and efficacy continues to be evaluated. Baricitinib alone is not approved as a treatment for COVID-19.
“The FDA’s emergency authorization of this combination therapy represents an incremental step forward in the treatment of COVID-19 in hospitalized patients, and FDA’s first authorization of a drug that acts on the inflammation pathway,” said Patrizia Cavazzoni, MD, acting director of the FDA’s Center for Drug Evaluation and Research.
“Despite advances in the management of COVID-19 infection since the onset of the pandemic, we need more therapies to accelerate recovery and additional clinical research will be essential to identifying therapies that slow disease progression and lower mortality in the sicker patients,” she said.
As a JAK inhibitor, baricitinib interferes with a pathway that leads to inflammation. Baricitinib is already prescribed as an oral medication and is FDA-approved for treating moderate to severe rheumatoid arthritis.
The data supporting the EUA for the combination treatment are based on a randomized, double-blind, placebo-controlled clinical trial (ACTT-2), conducted by the National Institute of Allergy and Infectious Diseases (NIAID).
The trial followed patients for 29 days and included 1,033 patients with moderate to severe COVID-19; 515 patients received baricitinib/remdesivir, and 518 patients received placebo/remdesivir.
The FDA emphasizes that an EUA is not a full FDA approval.
In reviewing the combination, the FDA “determined that it is reasonable to believe that baricitinib, in combination with remdesivir, may be effective in treating COVID-19 for the authorized population” and the known benefits outweigh the known and potential risks. Additionally, there are no adequate, approved, and available alternatives for the treatment population.
“Today’s action demonstrates the FDA’s steadfast efforts to make potential COVID-19 treatments available in a timely manner, where appropriate, while continuing to support research to further evaluate whether they are safe and effective,” said FDA Commissioner Stephen M. Hahn, MD. “As part of our Coronavirus Treatment Acceleration Program, the FDA continues to use every possible avenue to facilitate new treatments for patients as quickly as possible to combat COVID-19.”
This article first appeared on Medscape.com.
The US Food and Drug Administration (FDA) Nov. 19 issued an emergency use authorization (EUA) for the Janus kinase inhibitor baricitinib (Olumiant, Eli Lilly) in combination with remdesivir (Veklury, Gilead) for treating hospitalized adults and children at least 2 years old with suspected or confirmed COVID-19.
The combination treatment is meant for patients who need supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).
Baricitinib/remdesivir was shown in a clinical trial to reduce time to recovery within 29 days of starting the treatment compared with a control group who received placebo/remdesivir, according to the FDA press release.
The median time to recovery from COVID-19 was 7 days for the combination group vs. 8 days for those in the placebo/remdesivir group. Recovery was defined as either discharge from the hospital or “being hospitalized but not requiring supplemental oxygen and no longer requiring ongoing medical care,” the agency explained in the press release.
The odds of a patient dying or being ventilated at day 29 was lower in the combination group compared with those taking placebo/remdesivir, the press release said without providing specific data. “For all of these endpoints, the effects were statistically significant,” the agency stated.
The safety and efficacy continues to be evaluated. Baricitinib alone is not approved as a treatment for COVID-19.
“The FDA’s emergency authorization of this combination therapy represents an incremental step forward in the treatment of COVID-19 in hospitalized patients, and FDA’s first authorization of a drug that acts on the inflammation pathway,” said Patrizia Cavazzoni, MD, acting director of the FDA’s Center for Drug Evaluation and Research.
“Despite advances in the management of COVID-19 infection since the onset of the pandemic, we need more therapies to accelerate recovery and additional clinical research will be essential to identifying therapies that slow disease progression and lower mortality in the sicker patients,” she said.
As a JAK inhibitor, baricitinib interferes with a pathway that leads to inflammation. Baricitinib is already prescribed as an oral medication and is FDA-approved for treating moderate to severe rheumatoid arthritis.
The data supporting the EUA for the combination treatment are based on a randomized, double-blind, placebo-controlled clinical trial (ACTT-2), conducted by the National Institute of Allergy and Infectious Diseases (NIAID).
The trial followed patients for 29 days and included 1,033 patients with moderate to severe COVID-19; 515 patients received baricitinib/remdesivir, and 518 patients received placebo/remdesivir.
The FDA emphasizes that an EUA is not a full FDA approval.
In reviewing the combination, the FDA “determined that it is reasonable to believe that baricitinib, in combination with remdesivir, may be effective in treating COVID-19 for the authorized population” and the known benefits outweigh the known and potential risks. Additionally, there are no adequate, approved, and available alternatives for the treatment population.
“Today’s action demonstrates the FDA’s steadfast efforts to make potential COVID-19 treatments available in a timely manner, where appropriate, while continuing to support research to further evaluate whether they are safe and effective,” said FDA Commissioner Stephen M. Hahn, MD. “As part of our Coronavirus Treatment Acceleration Program, the FDA continues to use every possible avenue to facilitate new treatments for patients as quickly as possible to combat COVID-19.”
This article first appeared on Medscape.com.
The US Food and Drug Administration (FDA) Nov. 19 issued an emergency use authorization (EUA) for the Janus kinase inhibitor baricitinib (Olumiant, Eli Lilly) in combination with remdesivir (Veklury, Gilead) for treating hospitalized adults and children at least 2 years old with suspected or confirmed COVID-19.
The combination treatment is meant for patients who need supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).
Baricitinib/remdesivir was shown in a clinical trial to reduce time to recovery within 29 days of starting the treatment compared with a control group who received placebo/remdesivir, according to the FDA press release.
The median time to recovery from COVID-19 was 7 days for the combination group vs. 8 days for those in the placebo/remdesivir group. Recovery was defined as either discharge from the hospital or “being hospitalized but not requiring supplemental oxygen and no longer requiring ongoing medical care,” the agency explained in the press release.
The odds of a patient dying or being ventilated at day 29 was lower in the combination group compared with those taking placebo/remdesivir, the press release said without providing specific data. “For all of these endpoints, the effects were statistically significant,” the agency stated.
The safety and efficacy continues to be evaluated. Baricitinib alone is not approved as a treatment for COVID-19.
“The FDA’s emergency authorization of this combination therapy represents an incremental step forward in the treatment of COVID-19 in hospitalized patients, and FDA’s first authorization of a drug that acts on the inflammation pathway,” said Patrizia Cavazzoni, MD, acting director of the FDA’s Center for Drug Evaluation and Research.
“Despite advances in the management of COVID-19 infection since the onset of the pandemic, we need more therapies to accelerate recovery and additional clinical research will be essential to identifying therapies that slow disease progression and lower mortality in the sicker patients,” she said.
As a JAK inhibitor, baricitinib interferes with a pathway that leads to inflammation. Baricitinib is already prescribed as an oral medication and is FDA-approved for treating moderate to severe rheumatoid arthritis.
The data supporting the EUA for the combination treatment are based on a randomized, double-blind, placebo-controlled clinical trial (ACTT-2), conducted by the National Institute of Allergy and Infectious Diseases (NIAID).
The trial followed patients for 29 days and included 1,033 patients with moderate to severe COVID-19; 515 patients received baricitinib/remdesivir, and 518 patients received placebo/remdesivir.
The FDA emphasizes that an EUA is not a full FDA approval.
In reviewing the combination, the FDA “determined that it is reasonable to believe that baricitinib, in combination with remdesivir, may be effective in treating COVID-19 for the authorized population” and the known benefits outweigh the known and potential risks. Additionally, there are no adequate, approved, and available alternatives for the treatment population.
“Today’s action demonstrates the FDA’s steadfast efforts to make potential COVID-19 treatments available in a timely manner, where appropriate, while continuing to support research to further evaluate whether they are safe and effective,” said FDA Commissioner Stephen M. Hahn, MD. “As part of our Coronavirus Treatment Acceleration Program, the FDA continues to use every possible avenue to facilitate new treatments for patients as quickly as possible to combat COVID-19.”
This article first appeared on Medscape.com.
Vaccine regimen boosts immune response in malignant melanoma
“[This] study supports the potential of combining [the] CDX-1401 vaccine and CDX-301 with checkpoint inhibitors, which are standard-of-care therapy,” study author Nina Bhardwaj, MD, PhD, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues wrote.
The team described their study in Nature Cancer.
The multicenter, open-label, randomized study included 60 patients with resected stage IIb-IV melanoma, all of whom had not received any prior treatment, including radiotherapy, biologics, and chemotherapy.
Patients randomized to the combination arm (cohort 1; n = 30) received the anti–DEC-205-NY-ESO-1 vaccine CDX-1401 and were pretreated with CDX-301, while those in the comparator arm (cohort 2; n = 30) received CDX-1401 alone.
Serial blood samples were collected to evaluate response to the vaccine antigen (NY-ESO-1) before each cycle, as well as 4 weeks and 12 weeks after the last vaccination. The primary endpoint was immune response prior to the third vaccination.
T-cell responses were detected in 76% of patients who received CDX-301 and 33% of patients who did not (P < .0011). In addition, the magnitude of response was significantly higher with the combination than with CDX-1401 alone (mean of 41 and 17 corrected spots per well, respectively; P = .032).
“All 30 (100%) cohort 1 participants had NY-ESO-1–specific T-cell responses for at least one time point, whereas 8 (27%) cohort 2 participants had no responses at any time point,” the researchers wrote.
Responses were maintained up to 12 weeks after the final vaccination, but there was no statistically significant difference between cohorts 1 and 2 at 12 weeks (54% and 38%, respectively; P = .2).
The researchers acknowledged that a key limitation of this trial was that it was not sized to evaluate relapse or overall survival.
“Given that ipilimumab, pembrolizumab, and nivolumab are approved as adjuvant therapy for high-risk stage III melanoma, vaccines incorporating CDX-301 and suitable antigen-containing platforms merit clinical investigation in the adjuvant setting in combination with immune checkpoint blockade,” the authors wrote.
“I am hopeful that highly immunogenic cancer vaccines can be added to currently approved immunotherapies, thus boosting an individual’s anticancer immune response even further,” Dr. Bhardwaj said in an interview.
This study was supported by grant funding from the National Cancer Institute. Some authors reported financial affiliations with Celldex Therapeutics, NanoString Technologies, and Oncovir. Dr. Bhardwaj disclosed relationships with Celldex and Oncovir.
SOURCE: Bhardwaj N et al. Nat Cancer. 2020 Nov 16. doi: 10.1038/s43018-020-00143-y.
“[This] study supports the potential of combining [the] CDX-1401 vaccine and CDX-301 with checkpoint inhibitors, which are standard-of-care therapy,” study author Nina Bhardwaj, MD, PhD, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues wrote.
The team described their study in Nature Cancer.
The multicenter, open-label, randomized study included 60 patients with resected stage IIb-IV melanoma, all of whom had not received any prior treatment, including radiotherapy, biologics, and chemotherapy.
Patients randomized to the combination arm (cohort 1; n = 30) received the anti–DEC-205-NY-ESO-1 vaccine CDX-1401 and were pretreated with CDX-301, while those in the comparator arm (cohort 2; n = 30) received CDX-1401 alone.
Serial blood samples were collected to evaluate response to the vaccine antigen (NY-ESO-1) before each cycle, as well as 4 weeks and 12 weeks after the last vaccination. The primary endpoint was immune response prior to the third vaccination.
T-cell responses were detected in 76% of patients who received CDX-301 and 33% of patients who did not (P < .0011). In addition, the magnitude of response was significantly higher with the combination than with CDX-1401 alone (mean of 41 and 17 corrected spots per well, respectively; P = .032).
“All 30 (100%) cohort 1 participants had NY-ESO-1–specific T-cell responses for at least one time point, whereas 8 (27%) cohort 2 participants had no responses at any time point,” the researchers wrote.
Responses were maintained up to 12 weeks after the final vaccination, but there was no statistically significant difference between cohorts 1 and 2 at 12 weeks (54% and 38%, respectively; P = .2).
The researchers acknowledged that a key limitation of this trial was that it was not sized to evaluate relapse or overall survival.
“Given that ipilimumab, pembrolizumab, and nivolumab are approved as adjuvant therapy for high-risk stage III melanoma, vaccines incorporating CDX-301 and suitable antigen-containing platforms merit clinical investigation in the adjuvant setting in combination with immune checkpoint blockade,” the authors wrote.
“I am hopeful that highly immunogenic cancer vaccines can be added to currently approved immunotherapies, thus boosting an individual’s anticancer immune response even further,” Dr. Bhardwaj said in an interview.
This study was supported by grant funding from the National Cancer Institute. Some authors reported financial affiliations with Celldex Therapeutics, NanoString Technologies, and Oncovir. Dr. Bhardwaj disclosed relationships with Celldex and Oncovir.
SOURCE: Bhardwaj N et al. Nat Cancer. 2020 Nov 16. doi: 10.1038/s43018-020-00143-y.
“[This] study supports the potential of combining [the] CDX-1401 vaccine and CDX-301 with checkpoint inhibitors, which are standard-of-care therapy,” study author Nina Bhardwaj, MD, PhD, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues wrote.
The team described their study in Nature Cancer.
The multicenter, open-label, randomized study included 60 patients with resected stage IIb-IV melanoma, all of whom had not received any prior treatment, including radiotherapy, biologics, and chemotherapy.
Patients randomized to the combination arm (cohort 1; n = 30) received the anti–DEC-205-NY-ESO-1 vaccine CDX-1401 and were pretreated with CDX-301, while those in the comparator arm (cohort 2; n = 30) received CDX-1401 alone.
Serial blood samples were collected to evaluate response to the vaccine antigen (NY-ESO-1) before each cycle, as well as 4 weeks and 12 weeks after the last vaccination. The primary endpoint was immune response prior to the third vaccination.
T-cell responses were detected in 76% of patients who received CDX-301 and 33% of patients who did not (P < .0011). In addition, the magnitude of response was significantly higher with the combination than with CDX-1401 alone (mean of 41 and 17 corrected spots per well, respectively; P = .032).
“All 30 (100%) cohort 1 participants had NY-ESO-1–specific T-cell responses for at least one time point, whereas 8 (27%) cohort 2 participants had no responses at any time point,” the researchers wrote.
Responses were maintained up to 12 weeks after the final vaccination, but there was no statistically significant difference between cohorts 1 and 2 at 12 weeks (54% and 38%, respectively; P = .2).
The researchers acknowledged that a key limitation of this trial was that it was not sized to evaluate relapse or overall survival.
“Given that ipilimumab, pembrolizumab, and nivolumab are approved as adjuvant therapy for high-risk stage III melanoma, vaccines incorporating CDX-301 and suitable antigen-containing platforms merit clinical investigation in the adjuvant setting in combination with immune checkpoint blockade,” the authors wrote.
“I am hopeful that highly immunogenic cancer vaccines can be added to currently approved immunotherapies, thus boosting an individual’s anticancer immune response even further,” Dr. Bhardwaj said in an interview.
This study was supported by grant funding from the National Cancer Institute. Some authors reported financial affiliations with Celldex Therapeutics, NanoString Technologies, and Oncovir. Dr. Bhardwaj disclosed relationships with Celldex and Oncovir.
SOURCE: Bhardwaj N et al. Nat Cancer. 2020 Nov 16. doi: 10.1038/s43018-020-00143-y.
FROM NATURE CANCER
New HCM guidelines make shared decision-making top priority
Greater involvement of the patient and family in decision-making, clarity on the role of genetic testing and parameters for team-oriented care, and use of high-volume specialty centers are cornerstones of the first update in almost a decade of the American Heart Association/American College of Cardiology guideline for patients with hypertrophic cardiomyopathy (HCM).
The update lists 133 recommendations for HCM care in six categories: shared decision-making; role of high-volume HCM centers; diagnosis, initial evaluation, and follow-up; risk assessment and prevention of sudden cardiac death (SCD); management of HCM; and lifestyle considerations for patients.
“The guideline puts the patient front and center in the shared decision-making process and emphasizes the importance of incorporating patient’s lifestyle choices and preferences when making complex, life-altering decisions,” writing committee vice chair Seema Mital, MD, of the University of Toronto and the Hospital for Sick Children, also in Toronto, said in an interview.
The fully updated guideline, authored by a joint committee of the AHA and ACC with input from other specialty societies, has been published online in the Journal of the American College of Cardiology. It replaces the 2011 guideline.
Another key component of the update is the strong recommendation to utilize multidisciplinary care, said Matthew W. Martinez, MD, a writing committee member and sports cardiologists at Morristown (N.J.) Medical Center. “This is not only as a part of shared decision-making, but really in care for the patients,” he said, “that there’s a level of expertise that is provided by centers of excellence who handle HCM, and we did lay out some recommendations with regards to surgery, imaging, interventionists, and management with electrophysiology, and the care of athletes with potential for HCM and pregnant women.”
The update ranks recommendations by class of recommendation (COR), ranging from strong benefit much greater than risk to harm with risk exceeding benefit, and level of evidence (LOE). The recommendation for shared decision making, for example, carries at COR of 1, the highest rating, and a mid-level LOE of B-NR, meaning from nonrandomized studies. Patients who need septal reduction therapy (SRT) should be referred to a comprehensive or primary HCM center – a recommendation with a COR of 1 but an LOE of C-LD, meaning there are limited data.
From diagnosis to follow-up
The most extensive list of recommendations falls under the category covering diagnosis, initial evaluation and follow-up. They include a three-generation family history as part of the initial diagnostic assessment (COR, 1; LOE, B-NR), high-level recommendations for use of transthoracic echocardiogram in the initial work-up, every 1 or 2 years or when the patient’s status changes in confirmed cases, as well as parameters for using other imaging and diagnostic tests. Cardiovascular MRI, for example, is indicated when echocardiography is inconclusive (COR, 1; LOE, B-NR) and in other scenarios. When echocardiography is inconclusive but cardiac MRI isn’t available, cardiac CT is an option, albeit at a lower level of evidence (COR, 2b; LOE, C-LD).
Heart rhythm assessment has a high level of recommendation in multiple scenarios, even in first-degree relatives of HCM patients. Invasive hemodynamic assessment is in order for candidates of SRT whose left ventricular (LV) outflow tract obstruction status is unknown. This category also sets parameters for angiography, and exercise stress testing.
The most extensive recommendations for diagnosis and follow-up cover genetic testing; it consists of nine high-level recommendations.
“The guideline highlights not only the importance of genetic testing of an affected patient and genetic screening of family members, but also emphasizes ongoing reassessment of variant classification as this may evolve with time and change how we recommend ongoing family screening,” Dr. Mital noted.
“The guideline proposes initiating screening of family members at the earliest regardless of age given HCM can manifest at any age in affected families,” she added.
The guideline notes that the usefulness of genetic testing to evaluate the risk of sudden cardiac death (SCD) is uncertain. There’s even guidance for implementing those test results. Further testing is recommended for patients who are genotype positive and phenotype negative for HCM (COR, 1; LOE, B-NR). Those same patients may participate in competitive sports (COR, 2a; LOE, C-LD), but a pacemaker isn’t recommended as a primary prevention (COR, 3 [no benefit]; LOE, B-NR).
Risk evaluation and prevention
For SCD risk evaluation and prevention, the guideline spells out five components for the initial and follow-up evaluations (COR, 1; LOE, B-NR). That includes maximal LV wall thickness, ejection fraction, and LV apical aneurysm. The section include multiple recommendations for patient selection for placement of an implantable cardioverter-defibrillator (ICD). For example, it’s recommended for patient’s who’ve had a heart attack or sustained ventricular tachycardia (COR, 1; LOE, B-NR), but not so much for patients without risk factors or for participating in sports (COR, 3 [harm]; LOE, B-NR). The guideline even provides recommendations for selecting an ICD.
Management recommendations address when medical therapy is indicated, including which therapies are indicated for specific scenarios, as well as higher level interventions such as SRT for severely symptomatic patients with obstructive HCM (COR, 2b; LOE, C-LD) and surgical myectomy with ablation in patients with HCM and atrial fibrillation (COR, 2a; LOE, B-NR). This section also provides recommendations for managing patients with HCM and ventricular arrhythmias or advanced heart failure.
The guideline also includes a host of lifestyle considerations. Mild to moderate exercise is beneficial (COR, 1; LOE, B-NR), but athletes with HCM should consult with an “expert provider” (COR, 1; LOE, C, meaning based on expert opinion). Truck drivers, pilots and people who do strenuous physical labor with HCM should meet specific standards.
These recommendations again emphasize the role of shared decision-making, said Dr. Martinez. “It’s not a cookie-cutter discussion. It is taking all of the information, incorporating what the patient’s needs are, and then making sure you appropriately tell them what are the risks of exercising and not exercising. I have as many discussions through the day about what the risks of exercise are as I do the risks of not exercising.”
Refining nomenclature, pathophysiology
The writing committee addressed the nomenclature for HCM. The use of HCM to describe increased LV wall thickness linked to systemic diseases or secondary to LV hypertrophy “can lead to confusion,” the committee stated, so other cardiac or systemic causes of LV hypertrophy shouldn’t be labeled HCM. Other etiologies can cause secondary LV hypertrophy that can overlap with HCM; clinical markers and testing can help differentiate these mimickers from HCM. When echocardiography is inconclusive, cardiovascular MRI is indicated (COR, 1; LOE, B-NR).
The guideline update also provides clarity on the pathophysiology of HCM: It consists of dynamic LV outflow tract obstruction, mitral regurgitation, diastolic dysfunction, myocardial ischemia, arrhythmias, or autonomic dysfunction. “For a given patient with HCM, the clinical outcome may be dominated by one of these components or may be the result of a complex interplay,” the guideline states. The clinical evaluation should consider all these conditions.
This update also provides “clear separation” between care of HCM with and without obstruction, Dr. Martinez said. “The role of advanced therapies and referrals with advanced treatment options such as heart transplantation or CRT therapy in this group is different than before, recognizing that people with obstruction have symptoms that may be similar to those without obstruction, and the individual should be [thoroughly] investigated to make sure that you can discern between those two groups to make appropriate recommendations.”
The guideline was developed in collaboration with and endorsed by the American Association for Thoracic Surgery, American Society of Echocardiography, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society for Cardiovascular Magnetic Resonance. It’s also been endorsed by the Pediatric & Congenital Electrophysiology Society.
Dr. Mital and Dr. Martinez have no relevant financial relationships to disclose.
SOURCE: Mital S et al. J Am Coll Cardiol. 2020 Nov 20. doi: 10.1016/j.jacc.2020.08.044.
Greater involvement of the patient and family in decision-making, clarity on the role of genetic testing and parameters for team-oriented care, and use of high-volume specialty centers are cornerstones of the first update in almost a decade of the American Heart Association/American College of Cardiology guideline for patients with hypertrophic cardiomyopathy (HCM).
The update lists 133 recommendations for HCM care in six categories: shared decision-making; role of high-volume HCM centers; diagnosis, initial evaluation, and follow-up; risk assessment and prevention of sudden cardiac death (SCD); management of HCM; and lifestyle considerations for patients.
“The guideline puts the patient front and center in the shared decision-making process and emphasizes the importance of incorporating patient’s lifestyle choices and preferences when making complex, life-altering decisions,” writing committee vice chair Seema Mital, MD, of the University of Toronto and the Hospital for Sick Children, also in Toronto, said in an interview.
The fully updated guideline, authored by a joint committee of the AHA and ACC with input from other specialty societies, has been published online in the Journal of the American College of Cardiology. It replaces the 2011 guideline.
Another key component of the update is the strong recommendation to utilize multidisciplinary care, said Matthew W. Martinez, MD, a writing committee member and sports cardiologists at Morristown (N.J.) Medical Center. “This is not only as a part of shared decision-making, but really in care for the patients,” he said, “that there’s a level of expertise that is provided by centers of excellence who handle HCM, and we did lay out some recommendations with regards to surgery, imaging, interventionists, and management with electrophysiology, and the care of athletes with potential for HCM and pregnant women.”
The update ranks recommendations by class of recommendation (COR), ranging from strong benefit much greater than risk to harm with risk exceeding benefit, and level of evidence (LOE). The recommendation for shared decision making, for example, carries at COR of 1, the highest rating, and a mid-level LOE of B-NR, meaning from nonrandomized studies. Patients who need septal reduction therapy (SRT) should be referred to a comprehensive or primary HCM center – a recommendation with a COR of 1 but an LOE of C-LD, meaning there are limited data.
From diagnosis to follow-up
The most extensive list of recommendations falls under the category covering diagnosis, initial evaluation and follow-up. They include a three-generation family history as part of the initial diagnostic assessment (COR, 1; LOE, B-NR), high-level recommendations for use of transthoracic echocardiogram in the initial work-up, every 1 or 2 years or when the patient’s status changes in confirmed cases, as well as parameters for using other imaging and diagnostic tests. Cardiovascular MRI, for example, is indicated when echocardiography is inconclusive (COR, 1; LOE, B-NR) and in other scenarios. When echocardiography is inconclusive but cardiac MRI isn’t available, cardiac CT is an option, albeit at a lower level of evidence (COR, 2b; LOE, C-LD).
Heart rhythm assessment has a high level of recommendation in multiple scenarios, even in first-degree relatives of HCM patients. Invasive hemodynamic assessment is in order for candidates of SRT whose left ventricular (LV) outflow tract obstruction status is unknown. This category also sets parameters for angiography, and exercise stress testing.
The most extensive recommendations for diagnosis and follow-up cover genetic testing; it consists of nine high-level recommendations.
“The guideline highlights not only the importance of genetic testing of an affected patient and genetic screening of family members, but also emphasizes ongoing reassessment of variant classification as this may evolve with time and change how we recommend ongoing family screening,” Dr. Mital noted.
“The guideline proposes initiating screening of family members at the earliest regardless of age given HCM can manifest at any age in affected families,” she added.
The guideline notes that the usefulness of genetic testing to evaluate the risk of sudden cardiac death (SCD) is uncertain. There’s even guidance for implementing those test results. Further testing is recommended for patients who are genotype positive and phenotype negative for HCM (COR, 1; LOE, B-NR). Those same patients may participate in competitive sports (COR, 2a; LOE, C-LD), but a pacemaker isn’t recommended as a primary prevention (COR, 3 [no benefit]; LOE, B-NR).
Risk evaluation and prevention
For SCD risk evaluation and prevention, the guideline spells out five components for the initial and follow-up evaluations (COR, 1; LOE, B-NR). That includes maximal LV wall thickness, ejection fraction, and LV apical aneurysm. The section include multiple recommendations for patient selection for placement of an implantable cardioverter-defibrillator (ICD). For example, it’s recommended for patient’s who’ve had a heart attack or sustained ventricular tachycardia (COR, 1; LOE, B-NR), but not so much for patients without risk factors or for participating in sports (COR, 3 [harm]; LOE, B-NR). The guideline even provides recommendations for selecting an ICD.
Management recommendations address when medical therapy is indicated, including which therapies are indicated for specific scenarios, as well as higher level interventions such as SRT for severely symptomatic patients with obstructive HCM (COR, 2b; LOE, C-LD) and surgical myectomy with ablation in patients with HCM and atrial fibrillation (COR, 2a; LOE, B-NR). This section also provides recommendations for managing patients with HCM and ventricular arrhythmias or advanced heart failure.
The guideline also includes a host of lifestyle considerations. Mild to moderate exercise is beneficial (COR, 1; LOE, B-NR), but athletes with HCM should consult with an “expert provider” (COR, 1; LOE, C, meaning based on expert opinion). Truck drivers, pilots and people who do strenuous physical labor with HCM should meet specific standards.
These recommendations again emphasize the role of shared decision-making, said Dr. Martinez. “It’s not a cookie-cutter discussion. It is taking all of the information, incorporating what the patient’s needs are, and then making sure you appropriately tell them what are the risks of exercising and not exercising. I have as many discussions through the day about what the risks of exercise are as I do the risks of not exercising.”
Refining nomenclature, pathophysiology
The writing committee addressed the nomenclature for HCM. The use of HCM to describe increased LV wall thickness linked to systemic diseases or secondary to LV hypertrophy “can lead to confusion,” the committee stated, so other cardiac or systemic causes of LV hypertrophy shouldn’t be labeled HCM. Other etiologies can cause secondary LV hypertrophy that can overlap with HCM; clinical markers and testing can help differentiate these mimickers from HCM. When echocardiography is inconclusive, cardiovascular MRI is indicated (COR, 1; LOE, B-NR).
The guideline update also provides clarity on the pathophysiology of HCM: It consists of dynamic LV outflow tract obstruction, mitral regurgitation, diastolic dysfunction, myocardial ischemia, arrhythmias, or autonomic dysfunction. “For a given patient with HCM, the clinical outcome may be dominated by one of these components or may be the result of a complex interplay,” the guideline states. The clinical evaluation should consider all these conditions.
This update also provides “clear separation” between care of HCM with and without obstruction, Dr. Martinez said. “The role of advanced therapies and referrals with advanced treatment options such as heart transplantation or CRT therapy in this group is different than before, recognizing that people with obstruction have symptoms that may be similar to those without obstruction, and the individual should be [thoroughly] investigated to make sure that you can discern between those two groups to make appropriate recommendations.”
The guideline was developed in collaboration with and endorsed by the American Association for Thoracic Surgery, American Society of Echocardiography, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society for Cardiovascular Magnetic Resonance. It’s also been endorsed by the Pediatric & Congenital Electrophysiology Society.
Dr. Mital and Dr. Martinez have no relevant financial relationships to disclose.
SOURCE: Mital S et al. J Am Coll Cardiol. 2020 Nov 20. doi: 10.1016/j.jacc.2020.08.044.
Greater involvement of the patient and family in decision-making, clarity on the role of genetic testing and parameters for team-oriented care, and use of high-volume specialty centers are cornerstones of the first update in almost a decade of the American Heart Association/American College of Cardiology guideline for patients with hypertrophic cardiomyopathy (HCM).
The update lists 133 recommendations for HCM care in six categories: shared decision-making; role of high-volume HCM centers; diagnosis, initial evaluation, and follow-up; risk assessment and prevention of sudden cardiac death (SCD); management of HCM; and lifestyle considerations for patients.
“The guideline puts the patient front and center in the shared decision-making process and emphasizes the importance of incorporating patient’s lifestyle choices and preferences when making complex, life-altering decisions,” writing committee vice chair Seema Mital, MD, of the University of Toronto and the Hospital for Sick Children, also in Toronto, said in an interview.
The fully updated guideline, authored by a joint committee of the AHA and ACC with input from other specialty societies, has been published online in the Journal of the American College of Cardiology. It replaces the 2011 guideline.
Another key component of the update is the strong recommendation to utilize multidisciplinary care, said Matthew W. Martinez, MD, a writing committee member and sports cardiologists at Morristown (N.J.) Medical Center. “This is not only as a part of shared decision-making, but really in care for the patients,” he said, “that there’s a level of expertise that is provided by centers of excellence who handle HCM, and we did lay out some recommendations with regards to surgery, imaging, interventionists, and management with electrophysiology, and the care of athletes with potential for HCM and pregnant women.”
The update ranks recommendations by class of recommendation (COR), ranging from strong benefit much greater than risk to harm with risk exceeding benefit, and level of evidence (LOE). The recommendation for shared decision making, for example, carries at COR of 1, the highest rating, and a mid-level LOE of B-NR, meaning from nonrandomized studies. Patients who need septal reduction therapy (SRT) should be referred to a comprehensive or primary HCM center – a recommendation with a COR of 1 but an LOE of C-LD, meaning there are limited data.
From diagnosis to follow-up
The most extensive list of recommendations falls under the category covering diagnosis, initial evaluation and follow-up. They include a three-generation family history as part of the initial diagnostic assessment (COR, 1; LOE, B-NR), high-level recommendations for use of transthoracic echocardiogram in the initial work-up, every 1 or 2 years or when the patient’s status changes in confirmed cases, as well as parameters for using other imaging and diagnostic tests. Cardiovascular MRI, for example, is indicated when echocardiography is inconclusive (COR, 1; LOE, B-NR) and in other scenarios. When echocardiography is inconclusive but cardiac MRI isn’t available, cardiac CT is an option, albeit at a lower level of evidence (COR, 2b; LOE, C-LD).
Heart rhythm assessment has a high level of recommendation in multiple scenarios, even in first-degree relatives of HCM patients. Invasive hemodynamic assessment is in order for candidates of SRT whose left ventricular (LV) outflow tract obstruction status is unknown. This category also sets parameters for angiography, and exercise stress testing.
The most extensive recommendations for diagnosis and follow-up cover genetic testing; it consists of nine high-level recommendations.
“The guideline highlights not only the importance of genetic testing of an affected patient and genetic screening of family members, but also emphasizes ongoing reassessment of variant classification as this may evolve with time and change how we recommend ongoing family screening,” Dr. Mital noted.
“The guideline proposes initiating screening of family members at the earliest regardless of age given HCM can manifest at any age in affected families,” she added.
The guideline notes that the usefulness of genetic testing to evaluate the risk of sudden cardiac death (SCD) is uncertain. There’s even guidance for implementing those test results. Further testing is recommended for patients who are genotype positive and phenotype negative for HCM (COR, 1; LOE, B-NR). Those same patients may participate in competitive sports (COR, 2a; LOE, C-LD), but a pacemaker isn’t recommended as a primary prevention (COR, 3 [no benefit]; LOE, B-NR).
Risk evaluation and prevention
For SCD risk evaluation and prevention, the guideline spells out five components for the initial and follow-up evaluations (COR, 1; LOE, B-NR). That includes maximal LV wall thickness, ejection fraction, and LV apical aneurysm. The section include multiple recommendations for patient selection for placement of an implantable cardioverter-defibrillator (ICD). For example, it’s recommended for patient’s who’ve had a heart attack or sustained ventricular tachycardia (COR, 1; LOE, B-NR), but not so much for patients without risk factors or for participating in sports (COR, 3 [harm]; LOE, B-NR). The guideline even provides recommendations for selecting an ICD.
Management recommendations address when medical therapy is indicated, including which therapies are indicated for specific scenarios, as well as higher level interventions such as SRT for severely symptomatic patients with obstructive HCM (COR, 2b; LOE, C-LD) and surgical myectomy with ablation in patients with HCM and atrial fibrillation (COR, 2a; LOE, B-NR). This section also provides recommendations for managing patients with HCM and ventricular arrhythmias or advanced heart failure.
The guideline also includes a host of lifestyle considerations. Mild to moderate exercise is beneficial (COR, 1; LOE, B-NR), but athletes with HCM should consult with an “expert provider” (COR, 1; LOE, C, meaning based on expert opinion). Truck drivers, pilots and people who do strenuous physical labor with HCM should meet specific standards.
These recommendations again emphasize the role of shared decision-making, said Dr. Martinez. “It’s not a cookie-cutter discussion. It is taking all of the information, incorporating what the patient’s needs are, and then making sure you appropriately tell them what are the risks of exercising and not exercising. I have as many discussions through the day about what the risks of exercise are as I do the risks of not exercising.”
Refining nomenclature, pathophysiology
The writing committee addressed the nomenclature for HCM. The use of HCM to describe increased LV wall thickness linked to systemic diseases or secondary to LV hypertrophy “can lead to confusion,” the committee stated, so other cardiac or systemic causes of LV hypertrophy shouldn’t be labeled HCM. Other etiologies can cause secondary LV hypertrophy that can overlap with HCM; clinical markers and testing can help differentiate these mimickers from HCM. When echocardiography is inconclusive, cardiovascular MRI is indicated (COR, 1; LOE, B-NR).
The guideline update also provides clarity on the pathophysiology of HCM: It consists of dynamic LV outflow tract obstruction, mitral regurgitation, diastolic dysfunction, myocardial ischemia, arrhythmias, or autonomic dysfunction. “For a given patient with HCM, the clinical outcome may be dominated by one of these components or may be the result of a complex interplay,” the guideline states. The clinical evaluation should consider all these conditions.
This update also provides “clear separation” between care of HCM with and without obstruction, Dr. Martinez said. “The role of advanced therapies and referrals with advanced treatment options such as heart transplantation or CRT therapy in this group is different than before, recognizing that people with obstruction have symptoms that may be similar to those without obstruction, and the individual should be [thoroughly] investigated to make sure that you can discern between those two groups to make appropriate recommendations.”
The guideline was developed in collaboration with and endorsed by the American Association for Thoracic Surgery, American Society of Echocardiography, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society for Cardiovascular Magnetic Resonance. It’s also been endorsed by the Pediatric & Congenital Electrophysiology Society.
Dr. Mital and Dr. Martinez have no relevant financial relationships to disclose.
SOURCE: Mital S et al. J Am Coll Cardiol. 2020 Nov 20. doi: 10.1016/j.jacc.2020.08.044.