Phd

Background

IDH1 mutations are detected in 3-4% of MDS, nearly always with one or more co-mutations. Treatment with IDH1 inhibitor ivosidenib typically resulted in regression of the abnormal clone in 15 reported responders. However, in a few cases differentiation was restored from the abnormal clone. Here we report a durable MDS remission despite sustained proliferation of a clone with IDH1 and ZRSR2 mutations.

Case Presentation

A 49-year-old man developed severe neutropenia and macrocytic anemia in January 2019. Mild marrow dysplasia developed by March 2020 with IDH1 (31.1%) and splicing gene ZRSR2 (55.7%) mutations. In October 2022 biopsy showed MDS with 4% blasts, megakaryocytic/granulocytic hypoplasia, normal cytogenetics and 43% IDH1/89% ZRSR2. After azacytidine failure, ivosidenib was started in November 2023 following FDA approval. Within weeks ANCs increased from 170 to 1580 and hemoglobin from 7.9 to 11.6 with MCV 115, reticulocytes 1.72%. At 3 months a CBC was normal except for MCV 111. IDH1 and ZRSR2 were 36.4% and 71%. After 6 months, ANC was 2380, hemoglobin 14.7, MCV 108.6, reticulo-cytes 1.77%. IDH1 PCR showed a 33.1% allele frequency consistent with a clonal remission.

Discussion

IDH1 mutations in MDS/AML frequently co-occur with mutations in RNA splicing genes SRSF2 or ZRSR2. For ZRSR2, we previously reported that isolated mutations of this gene cause refractory macrocytic anemias without dysplasia, thus presenting as clonal cytopenias of undetermined significance (Fleischman et al., Leuk Res, 2017). In this MDS case, after ivosidenib treatment the ZRSR2 splicing defect sustained clonal dominance over polyclonal hematopoiesis while accounting for macrocytosis. Longitudinal data for two ivosidenib-treated IDH1/SRSF2 MDS cases are incomplete, but one case of IDH2/SRSF2 MDS treated with the inhibitor enasidenib similarly achieved complete remission without regression of the mutated clone for 12 months.

Conclusions

Following the FDA approval of ivosidenib, all cases of MDS should have DNA sequencing performed at diagnosis to identify IDH1 mutations. Treatment induces high rates of remission even when polyclonal hematopoiesis does not recover. Moreover, the restoration of hematopoietic differentiation by the abnormal clone provides unique insights into the clinical phenotype and fitness advantage conferred by the co-existing driver mutations.

Background

IDH1 mutations are detected in 3-4% of MDS, nearly always with one or more co-mutations. Treatment with IDH1 inhibitor ivosidenib typically resulted in regression of the abnormal clone in 15 reported responders. However, in a few cases differentiation was restored from the abnormal clone. Here we report a durable MDS remission despite sustained proliferation of a clone with IDH1 and ZRSR2 mutations.

Case Presentation

A 49-year-old man developed severe neutropenia and macrocytic anemia in January 2019. Mild marrow dysplasia developed by March 2020 with IDH1 (31.1%) and splicing gene ZRSR2 (55.7%) mutations. In October 2022 biopsy showed MDS with 4% blasts, megakaryocytic/granulocytic hypoplasia, normal cytogenetics and 43% IDH1/89% ZRSR2. After azacytidine failure, ivosidenib was started in November 2023 following FDA approval. Within weeks ANCs increased from 170 to 1580 and hemoglobin from 7.9 to 11.6 with MCV 115, reticulocytes 1.72%. At 3 months a CBC was normal except for MCV 111. IDH1 and ZRSR2 were 36.4% and 71%. After 6 months, ANC was 2380, hemoglobin 14.7, MCV 108.6, reticulo-cytes 1.77%. IDH1 PCR showed a 33.1% allele frequency consistent with a clonal remission.

Discussion

IDH1 mutations in MDS/AML frequently co-occur with mutations in RNA splicing genes SRSF2 or ZRSR2. For ZRSR2, we previously reported that isolated mutations of this gene cause refractory macrocytic anemias without dysplasia, thus presenting as clonal cytopenias of undetermined significance (Fleischman et al., Leuk Res, 2017). In this MDS case, after ivosidenib treatment the ZRSR2 splicing defect sustained clonal dominance over polyclonal hematopoiesis while accounting for macrocytosis. Longitudinal data for two ivosidenib-treated IDH1/SRSF2 MDS cases are incomplete, but one case of IDH2/SRSF2 MDS treated with the inhibitor enasidenib similarly achieved complete remission without regression of the mutated clone for 12 months.

Conclusions

Following the FDA approval of ivosidenib, all cases of MDS should have DNA sequencing performed at diagnosis to identify IDH1 mutations. Treatment induces high rates of remission even when polyclonal hematopoiesis does not recover. Moreover, the restoration of hematopoietic differentiation by the abnormal clone provides unique insights into the clinical phenotype and fitness advantage conferred by the co-existing driver mutations.

Background

IDH1 mutations are detected in 3-4% of MDS, nearly always with one or more co-mutations. Treatment with IDH1 inhibitor ivosidenib typically resulted in regression of the abnormal clone in 15 reported responders. However, in a few cases differentiation was restored from the abnormal clone. Here we report a durable MDS remission despite sustained proliferation of a clone with IDH1 and ZRSR2 mutations.

Case Presentation

A 49-year-old man developed severe neutropenia and macrocytic anemia in January 2019. Mild marrow dysplasia developed by March 2020 with IDH1 (31.1%) and splicing gene ZRSR2 (55.7%) mutations. In October 2022 biopsy showed MDS with 4% blasts, megakaryocytic/granulocytic hypoplasia, normal cytogenetics and 43% IDH1/89% ZRSR2. After azacytidine failure, ivosidenib was started in November 2023 following FDA approval. Within weeks ANCs increased from 170 to 1580 and hemoglobin from 7.9 to 11.6 with MCV 115, reticulocytes 1.72%. At 3 months a CBC was normal except for MCV 111. IDH1 and ZRSR2 were 36.4% and 71%. After 6 months, ANC was 2380, hemoglobin 14.7, MCV 108.6, reticulo-cytes 1.77%. IDH1 PCR showed a 33.1% allele frequency consistent with a clonal remission.

Discussion

IDH1 mutations in MDS/AML frequently co-occur with mutations in RNA splicing genes SRSF2 or ZRSR2. For ZRSR2, we previously reported that isolated mutations of this gene cause refractory macrocytic anemias without dysplasia, thus presenting as clonal cytopenias of undetermined significance (Fleischman et al., Leuk Res, 2017). In this MDS case, after ivosidenib treatment the ZRSR2 splicing defect sustained clonal dominance over polyclonal hematopoiesis while accounting for macrocytosis. Longitudinal data for two ivosidenib-treated IDH1/SRSF2 MDS cases are incomplete, but one case of IDH2/SRSF2 MDS treated with the inhibitor enasidenib similarly achieved complete remission without regression of the mutated clone for 12 months.

Conclusions

Following the FDA approval of ivosidenib, all cases of MDS should have DNA sequencing performed at diagnosis to identify IDH1 mutations. Treatment induces high rates of remission even when polyclonal hematopoiesis does not recover. Moreover, the restoration of hematopoietic differentiation by the abnormal clone provides unique insights into the clinical phenotype and fitness advantage conferred by the co-existing driver mutations.

When skin diseases affect the palm or sole, they can have a disproportionately large negative effect on patients' lives. Hand and foot dermatitis can be disabling. Simpson and colleagues find that dupilumab is an effective treatment for AD of the hands and feet. Having safe and effective treatment for hand and foot dermatitis will be life-changing for many of our patients.

Patients often do very well with biologic treatment. When they do, they often wonder, Do I need to continue taking the medication? Lasheras-Pérez and colleagues found that the great majority of patients doing well taking dupilumab for AD could stretch out their dosing interval. I suspect a lot of our patients are doing this already. I used to worry that stretching out the dosing interval might lead to antidrug antibodies and loss of activity. Such loss of activity doesn't appear common. Because we also have multiple alternative treatments for severe AD, I think it may be quite reasonable for patients to try spreading out their doses after their disease has been well controlled for a good long time.

Superficial skin infections aren't rare in children, particularly children with AD. Paller and colleagues' study is informative about the safety of dupilumab in children. The drug, which blocks a pathway of the immune system, was associated with fewer infections. This is good news. The reduction in infections could be through restoring "immune balance" (whatever that means) or by improving skin barrier function. Perhaps the low rate of infection explains why dupilumab is not considered immunosuppressive.

I love studies of drug survival because I think that knowing the percentage of patients who stay with drug treatment is a good measure of overall safety and efficacy. Pezzolo and colleagues found — perhaps not surprisingly given the extraordinary efficacy of upadacitinib for AD — that almost no one discontinued the drug over 1.5 years due to lack of efficacy. There were patients who discontinued due to adverse events (and additional patients lost to follow-up who perhaps also discontinued the drug), but 80% of patients were still in the study at the end of 1.5 years. Three patients who weren't vaccinated for shingles developed shingles; encouraging patients to get the shingles vaccine may be a prudent measure when starting patients taking upadacitinib. 
 

When skin diseases affect the palm or sole, they can have a disproportionately large negative effect on patients' lives. Hand and foot dermatitis can be disabling. Simpson and colleagues find that dupilumab is an effective treatment for AD of the hands and feet. Having safe and effective treatment for hand and foot dermatitis will be life-changing for many of our patients.

Patients often do very well with biologic treatment. When they do, they often wonder, Do I need to continue taking the medication? Lasheras-Pérez and colleagues found that the great majority of patients doing well taking dupilumab for AD could stretch out their dosing interval. I suspect a lot of our patients are doing this already. I used to worry that stretching out the dosing interval might lead to antidrug antibodies and loss of activity. Such loss of activity doesn't appear common. Because we also have multiple alternative treatments for severe AD, I think it may be quite reasonable for patients to try spreading out their doses after their disease has been well controlled for a good long time.

Superficial skin infections aren't rare in children, particularly children with AD. Paller and colleagues' study is informative about the safety of dupilumab in children. The drug, which blocks a pathway of the immune system, was associated with fewer infections. This is good news. The reduction in infections could be through restoring "immune balance" (whatever that means) or by improving skin barrier function. Perhaps the low rate of infection explains why dupilumab is not considered immunosuppressive.

I love studies of drug survival because I think that knowing the percentage of patients who stay with drug treatment is a good measure of overall safety and efficacy. Pezzolo and colleagues found — perhaps not surprisingly given the extraordinary efficacy of upadacitinib for AD — that almost no one discontinued the drug over 1.5 years due to lack of efficacy. There were patients who discontinued due to adverse events (and additional patients lost to follow-up who perhaps also discontinued the drug), but 80% of patients were still in the study at the end of 1.5 years. Three patients who weren't vaccinated for shingles developed shingles; encouraging patients to get the shingles vaccine may be a prudent measure when starting patients taking upadacitinib. 
 

When skin diseases affect the palm or sole, they can have a disproportionately large negative effect on patients' lives. Hand and foot dermatitis can be disabling. Simpson and colleagues find that dupilumab is an effective treatment for AD of the hands and feet. Having safe and effective treatment for hand and foot dermatitis will be life-changing for many of our patients.

Patients often do very well with biologic treatment. When they do, they often wonder, Do I need to continue taking the medication? Lasheras-Pérez and colleagues found that the great majority of patients doing well taking dupilumab for AD could stretch out their dosing interval. I suspect a lot of our patients are doing this already. I used to worry that stretching out the dosing interval might lead to antidrug antibodies and loss of activity. Such loss of activity doesn't appear common. Because we also have multiple alternative treatments for severe AD, I think it may be quite reasonable for patients to try spreading out their doses after their disease has been well controlled for a good long time.

Superficial skin infections aren't rare in children, particularly children with AD. Paller and colleagues' study is informative about the safety of dupilumab in children. The drug, which blocks a pathway of the immune system, was associated with fewer infections. This is good news. The reduction in infections could be through restoring "immune balance" (whatever that means) or by improving skin barrier function. Perhaps the low rate of infection explains why dupilumab is not considered immunosuppressive.

I love studies of drug survival because I think that knowing the percentage of patients who stay with drug treatment is a good measure of overall safety and efficacy. Pezzolo and colleagues found — perhaps not surprisingly given the extraordinary efficacy of upadacitinib for AD — that almost no one discontinued the drug over 1.5 years due to lack of efficacy. There were patients who discontinued due to adverse events (and additional patients lost to follow-up who perhaps also discontinued the drug), but 80% of patients were still in the study at the end of 1.5 years. Three patients who weren't vaccinated for shingles developed shingles; encouraging patients to get the shingles vaccine may be a prudent measure when starting patients taking upadacitinib. 
 

To the Editor:

Biologic medications are increasingly utilized in adults with moderate to severe atopic dermatitis (AD) that is inadequately controlled with topical medication. By targeting the IL-4 receptor alpha subunit, dupilumab inhibits the biologic effects of IL-4 and IL-13, resulting in remarkable improvement in disease and quality of life for many patients with refractory AD.¹

In 2017, the US Food and Drug Administration approved dupilumab for use in AD, asthma, and chronic rhinosinusitis. However, there is evidence of the drug’s off-label efficacy in conditions such as eosinophilic annular erythema.² We present a patient with dyshidrotic eczema treated with dupilumab who experienced contemporaneous secondary improvement in chronic eosinophilic pneumonia (CEP) and interstitial lung disease (ILD).

A 45-year-old man was referred to our dermatology clinic for chronic hand dermatitis refractory to increasing strengths of topical corticosteroids. He had a history of progressive shortness of breath of unknown cause, which began 2 years prior, and he was being followed at our institution’s ILD clinic. Earlier pulmonary function testing revealed a restrictive pattern with interstitial infiltrates seen on chest computed tomography. A lung biopsy demonstrated features of fibrotic nonspecific interstitial pneumonitis with superimposed eosinophilic pneumonia. His pulmonary symptoms had progressively worsened; over a period of several months, the supplemental oxygen requirement had increased to 6 L at rest and 12 L upon exertion. Prednisone therapy was initiated, which alleviated respiratory symptoms; however, the patient was unable to tolerate a gradual wean of the medication, which rendered him steroid dependent at 30 mg/d.

Along with respiratory symptoms, the patient reported symptoms consistent with an autoimmune process, including dry eyes. Muscle weakness and tenderness also were noted. Ultimately, a diagnosis of anti–PL-7 (anti-threonyl-transfer RNA synthetase) antisynthetase syndrome was rendered by identification of anti–PL-7 antibodies and an elevated level of creatinine kinase.

Physical examination at our clinic revealed subtle palmar scaling on the hands and multiple small clear vesicles on the lateral aspects of the digits (Figure, A), consistent with dyshidrotic eczema. He initially was treated with clobetasol propionate ointment 0.05%. Despite adherence to this high-potency topical corticosteroid, he experienced only minimal improvement over a period of 3 months. Dupilumab was started at standard dosing—600 mg at initiation, followed by 300 mg every 2 weeks. The patient reported rapid improvement in dyshidrotic eczema over several months with near-complete resolution (Figure, B).

Concurrent with initiation and continued use of dupilumab, without other changes in his medication regimen, the patient noted gradual improvement in respiratory symptoms. At 6-month follow-up he reported notable improvement in respiratory function and quality of life. He then tolerated a gradual wean of prednisone to 10 mg/d, with a similar reduction in supplemental oxygen.

Off-label use of dupilumab for various eosinophilic conditions has shown promising efficacy. Our patient experienced improvement in CEP shortly after initiation of dupilumab, enabling weaning of prednisone, which has a well established adverse effect profile associated with long term use.^3,4 In comparison, dupilumab generally is well tolerated, with rare ophthalmologic complications and injection-site reactions.⁵

One case report suggested that CEP may represent a potential rare adverse effect of dupilumab initiation.⁶ However, prior to initiation of dupilumab, that patient had poorly controlled asthma requiring frequent oral corticosteroid therapy. It is possible that CEP was subclinical prior to initiation of dupilumab and became more noticeable once the patient was weaned from corticosteroids, which had served as an indirect treatment.⁶ Nonetheless, more research is needed to definitively establish the efficacy of dupilumab in CEP prior to more widespread use.

Irrespective of the potential efficacy of dupilumab for the treatment of CEP, our case highlights the growing body of evidence that dupilumab should be considered in the treatment of dyshidrotic eczema, particularly in cases refractory to topical treatment.⁷ When a systemic medication is preferred, dupilumab likely represents an option with a relatively well-tolerated adverse effect profile compared to traditional systemic treatments for dyshidrotic eczema.

To the Editor:

Biologic medications are increasingly utilized in adults with moderate to severe atopic dermatitis (AD) that is inadequately controlled with topical medication. By targeting the IL-4 receptor alpha subunit, dupilumab inhibits the biologic effects of IL-4 and IL-13, resulting in remarkable improvement in disease and quality of life for many patients with refractory AD.¹

In 2017, the US Food and Drug Administration approved dupilumab for use in AD, asthma, and chronic rhinosinusitis. However, there is evidence of the drug’s off-label efficacy in conditions such as eosinophilic annular erythema.² We present a patient with dyshidrotic eczema treated with dupilumab who experienced contemporaneous secondary improvement in chronic eosinophilic pneumonia (CEP) and interstitial lung disease (ILD).

A 45-year-old man was referred to our dermatology clinic for chronic hand dermatitis refractory to increasing strengths of topical corticosteroids. He had a history of progressive shortness of breath of unknown cause, which began 2 years prior, and he was being followed at our institution’s ILD clinic. Earlier pulmonary function testing revealed a restrictive pattern with interstitial infiltrates seen on chest computed tomography. A lung biopsy demonstrated features of fibrotic nonspecific interstitial pneumonitis with superimposed eosinophilic pneumonia. His pulmonary symptoms had progressively worsened; over a period of several months, the supplemental oxygen requirement had increased to 6 L at rest and 12 L upon exertion. Prednisone therapy was initiated, which alleviated respiratory symptoms; however, the patient was unable to tolerate a gradual wean of the medication, which rendered him steroid dependent at 30 mg/d.

Along with respiratory symptoms, the patient reported symptoms consistent with an autoimmune process, including dry eyes. Muscle weakness and tenderness also were noted. Ultimately, a diagnosis of anti–PL-7 (anti-threonyl-transfer RNA synthetase) antisynthetase syndrome was rendered by identification of anti–PL-7 antibodies and an elevated level of creatinine kinase.

Physical examination at our clinic revealed subtle palmar scaling on the hands and multiple small clear vesicles on the lateral aspects of the digits (Figure, A), consistent with dyshidrotic eczema. He initially was treated with clobetasol propionate ointment 0.05%. Despite adherence to this high-potency topical corticosteroid, he experienced only minimal improvement over a period of 3 months. Dupilumab was started at standard dosing—600 mg at initiation, followed by 300 mg every 2 weeks. The patient reported rapid improvement in dyshidrotic eczema over several months with near-complete resolution (Figure, B).

Concurrent with initiation and continued use of dupilumab, without other changes in his medication regimen, the patient noted gradual improvement in respiratory symptoms. At 6-month follow-up he reported notable improvement in respiratory function and quality of life. He then tolerated a gradual wean of prednisone to 10 mg/d, with a similar reduction in supplemental oxygen.

Off-label use of dupilumab for various eosinophilic conditions has shown promising efficacy. Our patient experienced improvement in CEP shortly after initiation of dupilumab, enabling weaning of prednisone, which has a well established adverse effect profile associated with long term use.^3,4 In comparison, dupilumab generally is well tolerated, with rare ophthalmologic complications and injection-site reactions.⁵

One case report suggested that CEP may represent a potential rare adverse effect of dupilumab initiation.⁶ However, prior to initiation of dupilumab, that patient had poorly controlled asthma requiring frequent oral corticosteroid therapy. It is possible that CEP was subclinical prior to initiation of dupilumab and became more noticeable once the patient was weaned from corticosteroids, which had served as an indirect treatment.⁶ Nonetheless, more research is needed to definitively establish the efficacy of dupilumab in CEP prior to more widespread use.

Irrespective of the potential efficacy of dupilumab for the treatment of CEP, our case highlights the growing body of evidence that dupilumab should be considered in the treatment of dyshidrotic eczema, particularly in cases refractory to topical treatment.⁷ When a systemic medication is preferred, dupilumab likely represents an option with a relatively well-tolerated adverse effect profile compared to traditional systemic treatments for dyshidrotic eczema.

To the Editor:

Biologic medications are increasingly utilized in adults with moderate to severe atopic dermatitis (AD) that is inadequately controlled with topical medication. By targeting the IL-4 receptor alpha subunit, dupilumab inhibits the biologic effects of IL-4 and IL-13, resulting in remarkable improvement in disease and quality of life for many patients with refractory AD.¹

In 2017, the US Food and Drug Administration approved dupilumab for use in AD, asthma, and chronic rhinosinusitis. However, there is evidence of the drug’s off-label efficacy in conditions such as eosinophilic annular erythema.² We present a patient with dyshidrotic eczema treated with dupilumab who experienced contemporaneous secondary improvement in chronic eosinophilic pneumonia (CEP) and interstitial lung disease (ILD).

A 45-year-old man was referred to our dermatology clinic for chronic hand dermatitis refractory to increasing strengths of topical corticosteroids. He had a history of progressive shortness of breath of unknown cause, which began 2 years prior, and he was being followed at our institution’s ILD clinic. Earlier pulmonary function testing revealed a restrictive pattern with interstitial infiltrates seen on chest computed tomography. A lung biopsy demonstrated features of fibrotic nonspecific interstitial pneumonitis with superimposed eosinophilic pneumonia. His pulmonary symptoms had progressively worsened; over a period of several months, the supplemental oxygen requirement had increased to 6 L at rest and 12 L upon exertion. Prednisone therapy was initiated, which alleviated respiratory symptoms; however, the patient was unable to tolerate a gradual wean of the medication, which rendered him steroid dependent at 30 mg/d.

Along with respiratory symptoms, the patient reported symptoms consistent with an autoimmune process, including dry eyes. Muscle weakness and tenderness also were noted. Ultimately, a diagnosis of anti–PL-7 (anti-threonyl-transfer RNA synthetase) antisynthetase syndrome was rendered by identification of anti–PL-7 antibodies and an elevated level of creatinine kinase.

Physical examination at our clinic revealed subtle palmar scaling on the hands and multiple small clear vesicles on the lateral aspects of the digits (Figure, A), consistent with dyshidrotic eczema. He initially was treated with clobetasol propionate ointment 0.05%. Despite adherence to this high-potency topical corticosteroid, he experienced only minimal improvement over a period of 3 months. Dupilumab was started at standard dosing—600 mg at initiation, followed by 300 mg every 2 weeks. The patient reported rapid improvement in dyshidrotic eczema over several months with near-complete resolution (Figure, B).

Concurrent with initiation and continued use of dupilumab, without other changes in his medication regimen, the patient noted gradual improvement in respiratory symptoms. At 6-month follow-up he reported notable improvement in respiratory function and quality of life. He then tolerated a gradual wean of prednisone to 10 mg/d, with a similar reduction in supplemental oxygen.

Off-label use of dupilumab for various eosinophilic conditions has shown promising efficacy. Our patient experienced improvement in CEP shortly after initiation of dupilumab, enabling weaning of prednisone, which has a well established adverse effect profile associated with long term use.^3,4 In comparison, dupilumab generally is well tolerated, with rare ophthalmologic complications and injection-site reactions.⁵

One case report suggested that CEP may represent a potential rare adverse effect of dupilumab initiation.⁶ However, prior to initiation of dupilumab, that patient had poorly controlled asthma requiring frequent oral corticosteroid therapy. It is possible that CEP was subclinical prior to initiation of dupilumab and became more noticeable once the patient was weaned from corticosteroids, which had served as an indirect treatment.⁶ Nonetheless, more research is needed to definitively establish the efficacy of dupilumab in CEP prior to more widespread use.

Irrespective of the potential efficacy of dupilumab for the treatment of CEP, our case highlights the growing body of evidence that dupilumab should be considered in the treatment of dyshidrotic eczema, particularly in cases refractory to topical treatment.⁷ When a systemic medication is preferred, dupilumab likely represents an option with a relatively well-tolerated adverse effect profile compared to traditional systemic treatments for dyshidrotic eczema.

The Veterans Health Administration (VHA)—along with systems across the world—has spent the past 2 years continuously adapting to meet the emerging needs of persons infected with COVID-19. With the development of effective vaccines and global efforts to mitigate transmission, attention has now shifted to long COVID care as the need for further outpatient health care becomes increasingly apparent.^1,2

Background

Multiple terms describe the lingering, multisystem sequelae of COVID-19 that last longer than 4 weeks: long COVID, postacute COVID-19 syndrome, post-COVID condition, postacute sequalae of COVID-19, and COVID long hauler.^1,3 Common symptoms include fatigue, shortness of breath, cough, sleep disorders, brain fog or cognitive dysfunction, depression, anxiety, pain, and changes in taste or smell that impact a person’s functioning.^4,5 The multisystem nature of the postacute course of COVID-19 necessitates an interdisciplinary approach to devise comprehensive and individualized care plans.^6-9 Research is needed to better understand this postacute state (eg, prevalence, underlying effects, characteristics of those who experience long COVID) to establish and evaluate cost-effective treatment approaches.

Many patients who are experiencing symptoms beyond the acute course of COVID-19 have been referred to general outpatient clinics or home health, which may lack the capacity and knowledge of this novel disease to effectively manage complex long COVID cases.^2,3 To address this growing need, clinicians and leadership across a variety of disciplines and settings in the VHA created a community of practice (CoP) to create a mechanism for cross-facility communication, identify gaps in long COVID care and research, and cocreate knowledge on best practices for care delivery.

In this spirit, we are embracing a learning health system (LHS) approach that uses rapid-cycle methods to integrate data and real-world experience to iteratively evaluate and adapt models of long COVID care.¹⁰ Our clinically identified and data-driven objective is to provide high value health care to patients with long COVID sequalae by creating a framework to learn about this novel condition and develop innovative care models. This article provides an overview of our emerging LHS approach to the study of long COVID care that is fostering innovation and adaptability within the VHA. We describe 3 aspects of our engagement approach central to LHS: the ongoing development of a long COVID CoP dedicated to iteratively informing the bidirectional cycle of data from practice to research, results of a broad environmental scan of VHA long COVID care, and results of a survey administered to CoP members to inform ongoing needs of the community and identify early successful outcomes from participation.

Learning Health System Approach

The VHA is one of the largest integrated health care systems in the United States serving more than 9 million veterans.¹¹ Since 2017, the VHA has articulated a vision to become an LHS that informs and improves patient-centered care through practice-based and data-driven research (eAppendix).¹² During the early COVID-19 pandemic, an LHS approach in the VHA was critical to rapidly establishing a data infrastructure for disease surveillance, coordinating data-driven solutions, leveraging use of technology, collaborating across the globe to identify best practices, and implementing systematic responses (eg, policies, workforce adjustments).

Our long COVID CoP was developed as clinical observations and ongoing conversations with stakeholders (eg, veterans, health care practitioners [HCPs], leadership) identified a need to effectively identify and treat the growing number of veterans with long COVID. This clinical issue is compounded by the limited but emerging evidence on the clinical presentation of prolonged COVID-19 symptoms, treatment, and subsequent care pathways. The VHA’s efforts and lessons learned within the lens of an LHS are applicable to other systems confronting the complex identification and management of patients with persistent and encumbering long COVID symptoms. The VHA is building upon the LHS approach to proactively prepare for and address future clinical or public health challenges that require cross-system and sector collaborations, expediency, inclusivity, and patient/family centeredness.¹¹

Community of Practice

As of January 25, 2022, our workgroup consisted of 128 VHA employees representing 29 VHA medical centers. Members of the multidisciplinary workgroup have diverse backgrounds with HCPs from primary care (eg, physicians, nurse practitioners), rehabilitation (eg, physical therapists), specialty care (eg, pulmonologists, physiatrists), mental health (eg, psychologists), and complementary and integrated health/Whole Health services (eg, practitoners of services such as yoga, tai chi, mindfulness, acupuncture). Members also include clinical, operations, and research leadership at local, regional, and national VHA levels. Our first objective as a large, diverse group was to establish shared goals, which included: (1) determining efficient communication pathways; (2) identifying gaps in care or research; and (3) cocreating knowledge to provide solutions to identified gaps.

Communication Mechanisms

Our first goal was to create an efficient mechanism for cross-facility communication. The initial CoP was formed in April 2021 and the first virtual meeting focused on reaching a consensus regarding the best way to communicate and proceed. We agreed to convene weekly at a consistent time, created a standard agenda template, and elected a lead facilitator of meeting proceedings. In addition, a member of the CoP recorded and took extensive meeting notes, which were later distributed to the entire CoP to accommodate varying schedules and ability to attend live meetings. Approximately 20 to 30 participants attend the meetings in real-time.

To consolidate working documents, information, and resources in one location, we created a platform to communicate via a Microsoft Teams channel. All CoP members are given access to the folders and allowed to add to the growing library of resources. Resources include clinical assessment and note templates for electronic documentation of care, site-specific process maps, relevant literature on screening and interventions identified by practice members, and meeting notes along with the recordings. A chat feature alerts CoP members to questions posed by other members. Any resources or information shared on the chat discussion are curated by CoP leaders to disseminate to all members. Importantly, this platform allowed us to communicate efficiently within the VHA organization by creating a centralized space for documents and the ability to correspond with all or select members of the CoP. Additional VHA employees can easily be referred and request access.

To increase awareness of the CoP, expand reach, and diversify perspectives, every participant was encouraged to invite colleagues and stakeholders with interest or experience in long COVID care to join. While patients are not included in this CoP, we are working closely with the VHA user experience workgroup (many members overlap) that is gathering patient and caregiver perspectives on their COVID-19 experience and long COVID care. Concurrently, CoP members and leadership facilitate communication and set up formal collaborations with other non-VHA health care systems to create an intersystem network of collaboration for long COVID care. This approach further enhances the speed at which we can work together to share lessons learned and stay up-to-date on emerging evidence surrounding long COVID care.

Identifying Gaps in Care and Research

Our second goal was to identify gaps in care or knowledge to inform future research and quality improvement initiatives, while also creating a foundation to cocreate knowledge about safe, effective care management of the novel long COVID sequelae. To translate knowledge, we must first identify and understand the gaps between the current, best available evidence and current care practices or policies impacting that delivery.¹³ As such, the structured meeting agenda and facilitated meeting discussions focused on understanding current clinical decision making and the evidence base. We shared VHA evidence synthesis reports and living rapid reviews on complications following COVID-19 illness (ie, major organ damage and posthospitalization health care use) that provided an objective evidence base on common long COVID complications.^14,15

Since long COVID is a novel condition, we drew from literature in similar patient populations and translated that information in the context of our current knowledge of this unique syndrome. For example, we discussed the predominant and persistent symptom of fatigue post-COVID.⁵ In particular, the CoP discussed challenges in identifying and treating post-COVID fatigue, which is often a vague symptom with multiple or interacting etiologies that require a comprehensive, interdisciplinary approach. As such, we reviewed, adapted, and translated identification and treatment strategies from the literature on chronic fatigue syndrome to patients with post-COVID syndrome.^16,17 We continue to work collaboratively and engage the appropriate stakeholders to provide input on the gaps to prioritize targeting.

Cocreate Knowledge

Our third goal was to cocreate knowledge regarding the care of patients with long COVID. To accomplish this, our structured meetings and communication pathways invited members to share experiences on the who (delivers and receives care), what (type of care or HCPs), when (identification of post-COVID and access), and how (eg, telehealth) of care to patients post-COVID. As part of the workgroup, we identified and shared resources on standardized, facility-level practices to reduce variability across the VHA system. These resources included intake/assessment forms, care processes, and batteries of tests/measures used for screening and assessment. The knowledge obtained from outside the CoP and cocreated within is being used to inform data-driven tools to support and evaluate care for patients with long COVID. As such, members of the workgroup are in the formative stages of participating in quality improvement innovation pilots to test technologies and processes designed to improve and validate long COVID care pathways. These technologies include screening tools, clinical decision support tools, and population health management technologies. In addition, we are developing a formal collaboration with the VHA Office of Research and Development to create standardized intake forms across VHA long COVID clinics to facilitate both clinical monitoring and research.

Surveys

The US Department of Veterans Affairs Central Office collaborated with our workgroup to draft an initial set of survey questions designed to understand how each VHA facility defines, identifies, and provides care to veterans experiencing post-COVID sequalae. The 41-question survey was distributed through regional directors and chief medical officers at 139 VHA facilities in August 2021. One hundred nineteen responses (86%) were received. Sixteen facilities indicated they had established programs and 26 facilities were considering a program. Our CoP had representation from the 16 facilities with established programs indicating the deep and well-connected nature of our grassroots efforts to bring together stakeholders to learn as part of a CoP.

A separate, follow-up survey generated responses from 18 facilities and identified the need to capture evolving innovations and to develop smaller workstreams (eg, best practices, electronic documentation templates, pathway for referrals, veteran engagement, outcome measures). The survey not only exposed ongoing challenges to providing long COVID care, but importantly, outlined the ways in which CoP members were leveraging community knowledge and resources to inform innovations and processes of care changes at their specific sites. Fourteen of 18 facilities with long COVID programs in place explicitly identified the CoP as a resource they have found most beneficial when employing such innovations. Specific innovations reported included changes in care delivery, engagement in active outreach with veterans and local facility, and infrastructure development to sustain local long COVID clinics (Table).

Future Directions

Our CoP strives to contribute to an evidence base for long COVID care. At the system level, the CoP has the potential to impact access and continuity of care by identifying appropriate processes and ensuring that VHA patients receive outreach and an opportunity for post-COVID care. Comprehensive care requires input from HCP, clinical leadership, and operations levels. In this sense, our CoP provides an opportunity for diverse stakeholders to come together, discuss barriers to screening and delivering post-COVID care, and create an action plan to remove or lessen such barriers.¹⁸ Part of the process to remove barriers is to identify and support efficient resource allocation. Our CoP has worked to address issues in resource allocation (eg, space, personnel) for post-COVID care. For example, one facility is currently implementing interdisciplinary virtual post-COVID care. Another facility identified and restructured working assignments for psychologists who served in different capacities throughout the system to fill the need within the long COVID team.

At the HCP level, the CoP is currently developing workshops, media campaigns, written clinical resources, skills training, publications, and webinars/seminars with continuing medical education credits.¹⁹ The CoP may also provide learning and growth opportunities, such as clinical or VHA operational fellowships and research grants.

We are still in the formative stages of post-COVID care and future efforts will explore patient-centered outcomes. We are drawing on the Centers for Disease Control and Prevention’s guidance for evaluating patients with long COVID symptoms and examining the feasibility within VHA, as well as patient perspectives on post-COVID sequalae, to ensure we are selecting assessments that measure patient-centered constructs.¹⁸

Conclusions

A VHA-wide LHS approach is identifying issues related to the identification, delivery, and evaluation of long COVID care. This long COVID CoP has developed an infrastructure for communication, identified gaps in care, and cocreated knowledge related to best current practices for post-COVID care. This work is contributing to systemwide LHS efforts dedicated to creating a culture of quality care and innovation and is a process that is transferrable to other areas of care in the VHA, as well as other health care systems. The LHS approach continues to be highly relevant as we persist through the COVID-19 pandemic and reimagine a postpandemic world.

Acknowledgments

We thank all the members of the Veterans Health Administration long COVID Community of Practice who participate in the meetings and contribute to the sharing and spread of knowledge.

The Veterans Health Administration (VHA)—along with systems across the world—has spent the past 2 years continuously adapting to meet the emerging needs of persons infected with COVID-19. With the development of effective vaccines and global efforts to mitigate transmission, attention has now shifted to long COVID care as the need for further outpatient health care becomes increasingly apparent.^1,2

Background

Multiple terms describe the lingering, multisystem sequelae of COVID-19 that last longer than 4 weeks: long COVID, postacute COVID-19 syndrome, post-COVID condition, postacute sequalae of COVID-19, and COVID long hauler.^1,3 Common symptoms include fatigue, shortness of breath, cough, sleep disorders, brain fog or cognitive dysfunction, depression, anxiety, pain, and changes in taste or smell that impact a person’s functioning.^4,5 The multisystem nature of the postacute course of COVID-19 necessitates an interdisciplinary approach to devise comprehensive and individualized care plans.^6-9 Research is needed to better understand this postacute state (eg, prevalence, underlying effects, characteristics of those who experience long COVID) to establish and evaluate cost-effective treatment approaches.

Many patients who are experiencing symptoms beyond the acute course of COVID-19 have been referred to general outpatient clinics or home health, which may lack the capacity and knowledge of this novel disease to effectively manage complex long COVID cases.^2,3 To address this growing need, clinicians and leadership across a variety of disciplines and settings in the VHA created a community of practice (CoP) to create a mechanism for cross-facility communication, identify gaps in long COVID care and research, and cocreate knowledge on best practices for care delivery.

In this spirit, we are embracing a learning health system (LHS) approach that uses rapid-cycle methods to integrate data and real-world experience to iteratively evaluate and adapt models of long COVID care.¹⁰ Our clinically identified and data-driven objective is to provide high value health care to patients with long COVID sequalae by creating a framework to learn about this novel condition and develop innovative care models. This article provides an overview of our emerging LHS approach to the study of long COVID care that is fostering innovation and adaptability within the VHA. We describe 3 aspects of our engagement approach central to LHS: the ongoing development of a long COVID CoP dedicated to iteratively informing the bidirectional cycle of data from practice to research, results of a broad environmental scan of VHA long COVID care, and results of a survey administered to CoP members to inform ongoing needs of the community and identify early successful outcomes from participation.

Learning Health System Approach

The VHA is one of the largest integrated health care systems in the United States serving more than 9 million veterans.¹¹ Since 2017, the VHA has articulated a vision to become an LHS that informs and improves patient-centered care through practice-based and data-driven research (eAppendix).¹² During the early COVID-19 pandemic, an LHS approach in the VHA was critical to rapidly establishing a data infrastructure for disease surveillance, coordinating data-driven solutions, leveraging use of technology, collaborating across the globe to identify best practices, and implementing systematic responses (eg, policies, workforce adjustments).

Our long COVID CoP was developed as clinical observations and ongoing conversations with stakeholders (eg, veterans, health care practitioners [HCPs], leadership) identified a need to effectively identify and treat the growing number of veterans with long COVID. This clinical issue is compounded by the limited but emerging evidence on the clinical presentation of prolonged COVID-19 symptoms, treatment, and subsequent care pathways. The VHA’s efforts and lessons learned within the lens of an LHS are applicable to other systems confronting the complex identification and management of patients with persistent and encumbering long COVID symptoms. The VHA is building upon the LHS approach to proactively prepare for and address future clinical or public health challenges that require cross-system and sector collaborations, expediency, inclusivity, and patient/family centeredness.¹¹

Community of Practice

As of January 25, 2022, our workgroup consisted of 128 VHA employees representing 29 VHA medical centers. Members of the multidisciplinary workgroup have diverse backgrounds with HCPs from primary care (eg, physicians, nurse practitioners), rehabilitation (eg, physical therapists), specialty care (eg, pulmonologists, physiatrists), mental health (eg, psychologists), and complementary and integrated health/Whole Health services (eg, practitoners of services such as yoga, tai chi, mindfulness, acupuncture). Members also include clinical, operations, and research leadership at local, regional, and national VHA levels. Our first objective as a large, diverse group was to establish shared goals, which included: (1) determining efficient communication pathways; (2) identifying gaps in care or research; and (3) cocreating knowledge to provide solutions to identified gaps.

Communication Mechanisms

Our first goal was to create an efficient mechanism for cross-facility communication. The initial CoP was formed in April 2021 and the first virtual meeting focused on reaching a consensus regarding the best way to communicate and proceed. We agreed to convene weekly at a consistent time, created a standard agenda template, and elected a lead facilitator of meeting proceedings. In addition, a member of the CoP recorded and took extensive meeting notes, which were later distributed to the entire CoP to accommodate varying schedules and ability to attend live meetings. Approximately 20 to 30 participants attend the meetings in real-time.

To consolidate working documents, information, and resources in one location, we created a platform to communicate via a Microsoft Teams channel. All CoP members are given access to the folders and allowed to add to the growing library of resources. Resources include clinical assessment and note templates for electronic documentation of care, site-specific process maps, relevant literature on screening and interventions identified by practice members, and meeting notes along with the recordings. A chat feature alerts CoP members to questions posed by other members. Any resources or information shared on the chat discussion are curated by CoP leaders to disseminate to all members. Importantly, this platform allowed us to communicate efficiently within the VHA organization by creating a centralized space for documents and the ability to correspond with all or select members of the CoP. Additional VHA employees can easily be referred and request access.

To increase awareness of the CoP, expand reach, and diversify perspectives, every participant was encouraged to invite colleagues and stakeholders with interest or experience in long COVID care to join. While patients are not included in this CoP, we are working closely with the VHA user experience workgroup (many members overlap) that is gathering patient and caregiver perspectives on their COVID-19 experience and long COVID care. Concurrently, CoP members and leadership facilitate communication and set up formal collaborations with other non-VHA health care systems to create an intersystem network of collaboration for long COVID care. This approach further enhances the speed at which we can work together to share lessons learned and stay up-to-date on emerging evidence surrounding long COVID care.

Identifying Gaps in Care and Research

Our second goal was to identify gaps in care or knowledge to inform future research and quality improvement initiatives, while also creating a foundation to cocreate knowledge about safe, effective care management of the novel long COVID sequelae. To translate knowledge, we must first identify and understand the gaps between the current, best available evidence and current care practices or policies impacting that delivery.¹³ As such, the structured meeting agenda and facilitated meeting discussions focused on understanding current clinical decision making and the evidence base. We shared VHA evidence synthesis reports and living rapid reviews on complications following COVID-19 illness (ie, major organ damage and posthospitalization health care use) that provided an objective evidence base on common long COVID complications.^14,15

Since long COVID is a novel condition, we drew from literature in similar patient populations and translated that information in the context of our current knowledge of this unique syndrome. For example, we discussed the predominant and persistent symptom of fatigue post-COVID.⁵ In particular, the CoP discussed challenges in identifying and treating post-COVID fatigue, which is often a vague symptom with multiple or interacting etiologies that require a comprehensive, interdisciplinary approach. As such, we reviewed, adapted, and translated identification and treatment strategies from the literature on chronic fatigue syndrome to patients with post-COVID syndrome.^16,17 We continue to work collaboratively and engage the appropriate stakeholders to provide input on the gaps to prioritize targeting.

Cocreate Knowledge

Our third goal was to cocreate knowledge regarding the care of patients with long COVID. To accomplish this, our structured meetings and communication pathways invited members to share experiences on the who (delivers and receives care), what (type of care or HCPs), when (identification of post-COVID and access), and how (eg, telehealth) of care to patients post-COVID. As part of the workgroup, we identified and shared resources on standardized, facility-level practices to reduce variability across the VHA system. These resources included intake/assessment forms, care processes, and batteries of tests/measures used for screening and assessment. The knowledge obtained from outside the CoP and cocreated within is being used to inform data-driven tools to support and evaluate care for patients with long COVID. As such, members of the workgroup are in the formative stages of participating in quality improvement innovation pilots to test technologies and processes designed to improve and validate long COVID care pathways. These technologies include screening tools, clinical decision support tools, and population health management technologies. In addition, we are developing a formal collaboration with the VHA Office of Research and Development to create standardized intake forms across VHA long COVID clinics to facilitate both clinical monitoring and research.

Surveys

The US Department of Veterans Affairs Central Office collaborated with our workgroup to draft an initial set of survey questions designed to understand how each VHA facility defines, identifies, and provides care to veterans experiencing post-COVID sequalae. The 41-question survey was distributed through regional directors and chief medical officers at 139 VHA facilities in August 2021. One hundred nineteen responses (86%) were received. Sixteen facilities indicated they had established programs and 26 facilities were considering a program. Our CoP had representation from the 16 facilities with established programs indicating the deep and well-connected nature of our grassroots efforts to bring together stakeholders to learn as part of a CoP.

A separate, follow-up survey generated responses from 18 facilities and identified the need to capture evolving innovations and to develop smaller workstreams (eg, best practices, electronic documentation templates, pathway for referrals, veteran engagement, outcome measures). The survey not only exposed ongoing challenges to providing long COVID care, but importantly, outlined the ways in which CoP members were leveraging community knowledge and resources to inform innovations and processes of care changes at their specific sites. Fourteen of 18 facilities with long COVID programs in place explicitly identified the CoP as a resource they have found most beneficial when employing such innovations. Specific innovations reported included changes in care delivery, engagement in active outreach with veterans and local facility, and infrastructure development to sustain local long COVID clinics (Table).

Future Directions

Our CoP strives to contribute to an evidence base for long COVID care. At the system level, the CoP has the potential to impact access and continuity of care by identifying appropriate processes and ensuring that VHA patients receive outreach and an opportunity for post-COVID care. Comprehensive care requires input from HCP, clinical leadership, and operations levels. In this sense, our CoP provides an opportunity for diverse stakeholders to come together, discuss barriers to screening and delivering post-COVID care, and create an action plan to remove or lessen such barriers.¹⁸ Part of the process to remove barriers is to identify and support efficient resource allocation. Our CoP has worked to address issues in resource allocation (eg, space, personnel) for post-COVID care. For example, one facility is currently implementing interdisciplinary virtual post-COVID care. Another facility identified and restructured working assignments for psychologists who served in different capacities throughout the system to fill the need within the long COVID team.

At the HCP level, the CoP is currently developing workshops, media campaigns, written clinical resources, skills training, publications, and webinars/seminars with continuing medical education credits.¹⁹ The CoP may also provide learning and growth opportunities, such as clinical or VHA operational fellowships and research grants.

We are still in the formative stages of post-COVID care and future efforts will explore patient-centered outcomes. We are drawing on the Centers for Disease Control and Prevention’s guidance for evaluating patients with long COVID symptoms and examining the feasibility within VHA, as well as patient perspectives on post-COVID sequalae, to ensure we are selecting assessments that measure patient-centered constructs.¹⁸

Conclusions

A VHA-wide LHS approach is identifying issues related to the identification, delivery, and evaluation of long COVID care. This long COVID CoP has developed an infrastructure for communication, identified gaps in care, and cocreated knowledge related to best current practices for post-COVID care. This work is contributing to systemwide LHS efforts dedicated to creating a culture of quality care and innovation and is a process that is transferrable to other areas of care in the VHA, as well as other health care systems. The LHS approach continues to be highly relevant as we persist through the COVID-19 pandemic and reimagine a postpandemic world.

Acknowledgments

We thank all the members of the Veterans Health Administration long COVID Community of Practice who participate in the meetings and contribute to the sharing and spread of knowledge.

The Veterans Health Administration (VHA)—along with systems across the world—has spent the past 2 years continuously adapting to meet the emerging needs of persons infected with COVID-19. With the development of effective vaccines and global efforts to mitigate transmission, attention has now shifted to long COVID care as the need for further outpatient health care becomes increasingly apparent.^1,2

Background

Multiple terms describe the lingering, multisystem sequelae of COVID-19 that last longer than 4 weeks: long COVID, postacute COVID-19 syndrome, post-COVID condition, postacute sequalae of COVID-19, and COVID long hauler.^1,3 Common symptoms include fatigue, shortness of breath, cough, sleep disorders, brain fog or cognitive dysfunction, depression, anxiety, pain, and changes in taste or smell that impact a person’s functioning.^4,5 The multisystem nature of the postacute course of COVID-19 necessitates an interdisciplinary approach to devise comprehensive and individualized care plans.^6-9 Research is needed to better understand this postacute state (eg, prevalence, underlying effects, characteristics of those who experience long COVID) to establish and evaluate cost-effective treatment approaches.

Many patients who are experiencing symptoms beyond the acute course of COVID-19 have been referred to general outpatient clinics or home health, which may lack the capacity and knowledge of this novel disease to effectively manage complex long COVID cases.^2,3 To address this growing need, clinicians and leadership across a variety of disciplines and settings in the VHA created a community of practice (CoP) to create a mechanism for cross-facility communication, identify gaps in long COVID care and research, and cocreate knowledge on best practices for care delivery.

In this spirit, we are embracing a learning health system (LHS) approach that uses rapid-cycle methods to integrate data and real-world experience to iteratively evaluate and adapt models of long COVID care.¹⁰ Our clinically identified and data-driven objective is to provide high value health care to patients with long COVID sequalae by creating a framework to learn about this novel condition and develop innovative care models. This article provides an overview of our emerging LHS approach to the study of long COVID care that is fostering innovation and adaptability within the VHA. We describe 3 aspects of our engagement approach central to LHS: the ongoing development of a long COVID CoP dedicated to iteratively informing the bidirectional cycle of data from practice to research, results of a broad environmental scan of VHA long COVID care, and results of a survey administered to CoP members to inform ongoing needs of the community and identify early successful outcomes from participation.

Learning Health System Approach

The VHA is one of the largest integrated health care systems in the United States serving more than 9 million veterans.¹¹ Since 2017, the VHA has articulated a vision to become an LHS that informs and improves patient-centered care through practice-based and data-driven research (eAppendix).¹² During the early COVID-19 pandemic, an LHS approach in the VHA was critical to rapidly establishing a data infrastructure for disease surveillance, coordinating data-driven solutions, leveraging use of technology, collaborating across the globe to identify best practices, and implementing systematic responses (eg, policies, workforce adjustments).

Our long COVID CoP was developed as clinical observations and ongoing conversations with stakeholders (eg, veterans, health care practitioners [HCPs], leadership) identified a need to effectively identify and treat the growing number of veterans with long COVID. This clinical issue is compounded by the limited but emerging evidence on the clinical presentation of prolonged COVID-19 symptoms, treatment, and subsequent care pathways. The VHA’s efforts and lessons learned within the lens of an LHS are applicable to other systems confronting the complex identification and management of patients with persistent and encumbering long COVID symptoms. The VHA is building upon the LHS approach to proactively prepare for and address future clinical or public health challenges that require cross-system and sector collaborations, expediency, inclusivity, and patient/family centeredness.¹¹

Community of Practice

As of January 25, 2022, our workgroup consisted of 128 VHA employees representing 29 VHA medical centers. Members of the multidisciplinary workgroup have diverse backgrounds with HCPs from primary care (eg, physicians, nurse practitioners), rehabilitation (eg, physical therapists), specialty care (eg, pulmonologists, physiatrists), mental health (eg, psychologists), and complementary and integrated health/Whole Health services (eg, practitoners of services such as yoga, tai chi, mindfulness, acupuncture). Members also include clinical, operations, and research leadership at local, regional, and national VHA levels. Our first objective as a large, diverse group was to establish shared goals, which included: (1) determining efficient communication pathways; (2) identifying gaps in care or research; and (3) cocreating knowledge to provide solutions to identified gaps.

Communication Mechanisms

Our first goal was to create an efficient mechanism for cross-facility communication. The initial CoP was formed in April 2021 and the first virtual meeting focused on reaching a consensus regarding the best way to communicate and proceed. We agreed to convene weekly at a consistent time, created a standard agenda template, and elected a lead facilitator of meeting proceedings. In addition, a member of the CoP recorded and took extensive meeting notes, which were later distributed to the entire CoP to accommodate varying schedules and ability to attend live meetings. Approximately 20 to 30 participants attend the meetings in real-time.

To consolidate working documents, information, and resources in one location, we created a platform to communicate via a Microsoft Teams channel. All CoP members are given access to the folders and allowed to add to the growing library of resources. Resources include clinical assessment and note templates for electronic documentation of care, site-specific process maps, relevant literature on screening and interventions identified by practice members, and meeting notes along with the recordings. A chat feature alerts CoP members to questions posed by other members. Any resources or information shared on the chat discussion are curated by CoP leaders to disseminate to all members. Importantly, this platform allowed us to communicate efficiently within the VHA organization by creating a centralized space for documents and the ability to correspond with all or select members of the CoP. Additional VHA employees can easily be referred and request access.

To increase awareness of the CoP, expand reach, and diversify perspectives, every participant was encouraged to invite colleagues and stakeholders with interest or experience in long COVID care to join. While patients are not included in this CoP, we are working closely with the VHA user experience workgroup (many members overlap) that is gathering patient and caregiver perspectives on their COVID-19 experience and long COVID care. Concurrently, CoP members and leadership facilitate communication and set up formal collaborations with other non-VHA health care systems to create an intersystem network of collaboration for long COVID care. This approach further enhances the speed at which we can work together to share lessons learned and stay up-to-date on emerging evidence surrounding long COVID care.

Identifying Gaps in Care and Research

Our second goal was to identify gaps in care or knowledge to inform future research and quality improvement initiatives, while also creating a foundation to cocreate knowledge about safe, effective care management of the novel long COVID sequelae. To translate knowledge, we must first identify and understand the gaps between the current, best available evidence and current care practices or policies impacting that delivery.¹³ As such, the structured meeting agenda and facilitated meeting discussions focused on understanding current clinical decision making and the evidence base. We shared VHA evidence synthesis reports and living rapid reviews on complications following COVID-19 illness (ie, major organ damage and posthospitalization health care use) that provided an objective evidence base on common long COVID complications.^14,15

Since long COVID is a novel condition, we drew from literature in similar patient populations and translated that information in the context of our current knowledge of this unique syndrome. For example, we discussed the predominant and persistent symptom of fatigue post-COVID.⁵ In particular, the CoP discussed challenges in identifying and treating post-COVID fatigue, which is often a vague symptom with multiple or interacting etiologies that require a comprehensive, interdisciplinary approach. As such, we reviewed, adapted, and translated identification and treatment strategies from the literature on chronic fatigue syndrome to patients with post-COVID syndrome.^16,17 We continue to work collaboratively and engage the appropriate stakeholders to provide input on the gaps to prioritize targeting.

Cocreate Knowledge

Our third goal was to cocreate knowledge regarding the care of patients with long COVID. To accomplish this, our structured meetings and communication pathways invited members to share experiences on the who (delivers and receives care), what (type of care or HCPs), when (identification of post-COVID and access), and how (eg, telehealth) of care to patients post-COVID. As part of the workgroup, we identified and shared resources on standardized, facility-level practices to reduce variability across the VHA system. These resources included intake/assessment forms, care processes, and batteries of tests/measures used for screening and assessment. The knowledge obtained from outside the CoP and cocreated within is being used to inform data-driven tools to support and evaluate care for patients with long COVID. As such, members of the workgroup are in the formative stages of participating in quality improvement innovation pilots to test technologies and processes designed to improve and validate long COVID care pathways. These technologies include screening tools, clinical decision support tools, and population health management technologies. In addition, we are developing a formal collaboration with the VHA Office of Research and Development to create standardized intake forms across VHA long COVID clinics to facilitate both clinical monitoring and research.

Surveys

The US Department of Veterans Affairs Central Office collaborated with our workgroup to draft an initial set of survey questions designed to understand how each VHA facility defines, identifies, and provides care to veterans experiencing post-COVID sequalae. The 41-question survey was distributed through regional directors and chief medical officers at 139 VHA facilities in August 2021. One hundred nineteen responses (86%) were received. Sixteen facilities indicated they had established programs and 26 facilities were considering a program. Our CoP had representation from the 16 facilities with established programs indicating the deep and well-connected nature of our grassroots efforts to bring together stakeholders to learn as part of a CoP.

A separate, follow-up survey generated responses from 18 facilities and identified the need to capture evolving innovations and to develop smaller workstreams (eg, best practices, electronic documentation templates, pathway for referrals, veteran engagement, outcome measures). The survey not only exposed ongoing challenges to providing long COVID care, but importantly, outlined the ways in which CoP members were leveraging community knowledge and resources to inform innovations and processes of care changes at their specific sites. Fourteen of 18 facilities with long COVID programs in place explicitly identified the CoP as a resource they have found most beneficial when employing such innovations. Specific innovations reported included changes in care delivery, engagement in active outreach with veterans and local facility, and infrastructure development to sustain local long COVID clinics (Table).

Future Directions

Our CoP strives to contribute to an evidence base for long COVID care. At the system level, the CoP has the potential to impact access and continuity of care by identifying appropriate processes and ensuring that VHA patients receive outreach and an opportunity for post-COVID care. Comprehensive care requires input from HCP, clinical leadership, and operations levels. In this sense, our CoP provides an opportunity for diverse stakeholders to come together, discuss barriers to screening and delivering post-COVID care, and create an action plan to remove or lessen such barriers.¹⁸ Part of the process to remove barriers is to identify and support efficient resource allocation. Our CoP has worked to address issues in resource allocation (eg, space, personnel) for post-COVID care. For example, one facility is currently implementing interdisciplinary virtual post-COVID care. Another facility identified and restructured working assignments for psychologists who served in different capacities throughout the system to fill the need within the long COVID team.

At the HCP level, the CoP is currently developing workshops, media campaigns, written clinical resources, skills training, publications, and webinars/seminars with continuing medical education credits.¹⁹ The CoP may also provide learning and growth opportunities, such as clinical or VHA operational fellowships and research grants.

We are still in the formative stages of post-COVID care and future efforts will explore patient-centered outcomes. We are drawing on the Centers for Disease Control and Prevention’s guidance for evaluating patients with long COVID symptoms and examining the feasibility within VHA, as well as patient perspectives on post-COVID sequalae, to ensure we are selecting assessments that measure patient-centered constructs.¹⁸

Conclusions

A VHA-wide LHS approach is identifying issues related to the identification, delivery, and evaluation of long COVID care. This long COVID CoP has developed an infrastructure for communication, identified gaps in care, and cocreated knowledge related to best current practices for post-COVID care. This work is contributing to systemwide LHS efforts dedicated to creating a culture of quality care and innovation and is a process that is transferrable to other areas of care in the VHA, as well as other health care systems. The LHS approach continues to be highly relevant as we persist through the COVID-19 pandemic and reimagine a postpandemic world.

Acknowledgments

We thank all the members of the Veterans Health Administration long COVID Community of Practice who participate in the meetings and contribute to the sharing and spread of knowledge.

Edoardo Caronna, MD and Patricia Pozo-Rosich, MD, PhD,  Neurology Department, Hospital Universitari Vall d’Hebron, Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain; and Headache and Neurological Pain Research Group, Vall d’Hebron Research Institute, Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain. Dr. Pozo-Rosich also serves on the boards of the International Headache Society and Council of the European Headache Federation and is an editor for various peer-reviewed journals, including Cephalalgia and Headache.

Headache is a symptom of the coronavirus disease 2019 (Covid-19), caused by the novel, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the pandemic began, researchers have tried to describe, understand, and help clinicians manage headache in the setting of Covid-19.

The reason is simple: Headache is common, often debilitating, and difficult to treat.¹

Moreover, headache could manifest both in the acute phase of the infection and, once the infection has resolved, in the post-acute phase.¹ Therefore, it is critical for clinicians to know more about headache, as headache can be a common reason that patients seek help, both in the specialized and non-specialized medical care setting.

Definitions and manifestations

While the first step in such a communication would be to define headache attributed to Covid-19, no specific definition exists, as this is a new disease. Therefore, headache attributed to Covid-19 should be defined under the diagnostic criteria, as contained in the International Classification of Headache Disorders-3, as headache attributed to a systemic viral infection.² As this is a secondary headache appearing with an infection, the treating physician needs to rule out possible underlying meningitis and/or encephalitis in the diagnosis. Moreover, other secondary headaches (eg, cerebral venous thrombosis) may appear, so clinicians need to carefully evaluate patients with headache during Covid-19 to detect signs or symptoms that point to other etiologies.

It is also advisable to know the clinical manifestations of headache attributed to Covid-19. Studies published so far have observed two main phenotypes of headache in the acute phase of the infection: one resembles migraine, the other, a tension-type headache.^1,3 Although patients with history of migraine who contract Covid-19 report headache that is more similar to primary headache disorder,⁴ two relevant aspects should be considered. Namely, migraine-like features can be observed in patients without personal migraine history; and Covid-19 patients with such history may perceive that headache they experience in the infection’s acute phase differs from their usual experience, especially regarding increased severity or duration.^5,6 Of note, headache can be a prodromal symptom of the SARS-CoV-2 infection.¹

Evolution of a headache

 Because headache appearing after the acute phase of the infection can persist, often manifesting migraine-like features, it is inordinately helpful for clinicians to know its evolution.¹ This persistent headache, sometimes referred to as post-covid headache, is not aptly named because the post-covid headache is not just one type of headache, but instead can manifest as different headache types.

 A recently published case series in Headache discussed three Covid patients who all experienced persistent headache during the infection’s post-acute phase.⁷ These patients experienced a migraine-like phenotype as have others with mild Covid-19, but their personal history of migraine, as well as their experience with Covid-19 related headache, were substantially different. Some patients had personal migraine history while others did not; some patients experienced no headache in the acute phase but did so in the post-acute phase; and the concomitant symptoms of the post-acute phase, such as insomnia, memory loss, dizziness, fatigue, and brain fog, were differentially expressed by patients.⁷ 

 This case series introduces the concept that patients with no prior history of migraine or any other primary headache disorder can develop a de novo headache because of their SARS-CoV-2 infection. Moreover, it could manifest as a new daily persistent headache. And patients with personal history of migraine may experience sudden chronification in their headache’s characteristics, rather than develop a new type of headache.⁷

 In another study, soon to be published in Cephalalgia, researchers observed that the median duration of headache in the acute phase is 2 weeks. This multicenter Spanish study, in which data on headache duration were available for 874 patients, found that 16% of these particular patients had persistent headache after 9 months. According to this study, headache that does not resolve within the first 3 months is less likely to do so later on.

Treatment

For clinicians, the significance of these findings is straightforward: Patients with headache experienced in the infection’s acute phase that does not seem to resolve post-infection requires continued medical attention. Patients should be monitored, carefully managed, and treated to avoid the onset of a persisting headache. This applies to patients with or without personal migraine history.

But which treatments should be prescribed? As there are no specific therapies for headache attributed to Covid-19, either in the acute or post-acute phase of the infection, clinicians must turn to existing therapies.

As with patients with migraine, patients with persistent headache post-Covid infection need a headache prevention strategy.

The strategy should be based on the following principles:

• treat headache
• treat comorbidities including mood disorders,  insomnia, and so on
• avoid complications such as medication overuse, which may be very common in these patients.

Acute medications

Despite the lack of specific literature on this matter, migraine-like phenotypes may respond to triptans and probably, where available, lasmiditan and gepants. These medications probably represent a therapeutic option for Covid patients with headache, but before prescribing them clinicians should carefully evaluate their use.

Before deciding on the prescription, clinicians should consider not only the medications’ most common contraindications, but also those that are related to Covid-19: the phase of the infection (acute/post-acute); the infection’s severity; and the presence of other Covid-related health problems. The concerns over the use of nonsteroidal anti-inflammatory medications (NSAIDs) and corticosteroids, raised when the pandemic first struck, have greatly dissipated.^8,9 Some patients with prolonged headache may benefit from a brief cycle of corticosteroids, similar to the treatment given to those patients with status migrainosus. Nerve blocks could also be considered.

Preventive medications

Drugs can be prescribed according to the headache phenotype too, but there are no published studies that specifically evaluate headache prevention treatments in patients with persistent headache post-infection. The case series mentioned earlier in this article recorded that patients whose headaches were treated with amitriptyline and onabotulinumtoxinA had reported variable treatment responses to this regimen, according to the patients’ characteristics.⁷

However, one important question regarding the safety of Covid patients with migraine – specifically patients on preventive treatments during the infection’s acute phase – has been somewhat resolved.

Medications such as renin-angiotensin system (RAS) blockers, suspected of possible involvement in the SARs-CoV-2 pathogenicity, seem to be safe.^8,10 And, in another multicenter Spanish study, researchers found that the use of anti-CGRP monoclonal antibodies did not seem to be associated with worse Covid-19 outcomes despite the possible implication of CGRP in modulating inflammatory responses during a viral infection.¹¹

The study of anti-CGRP monoclonal antibodies could be important in the future for another reason: To see whether these medications could be effective as a preventive treatment in patients with persistent headache after Covid-19, regardless of whether these patients have personal migraine history.

An interesting and important message to close this article. Although headache experienced in the infection’s acute phase could be extremely disabling for patients, the evidence points to the presence of headache as a marker of a better Covid-19 prognosis, in terms of a shorter infection period and a lower risk of mortality among hospitalized patients.^1,3,12  

This brief communication contains current information to help clinicians treat and inform their patients with Covid-sourced headache. Yet, we must keep in mind that the majority of the data reported here and published in the literature refer to studies conducted during the first wave of the pandemic. The emergence of new SARS-CoV-2 variants and vaccines have enormously changed the disease’s clinical presentation and course, so future studies are warranted to re-assess the validity of these findings under new conditions.

Edoardo Caronna, MD and Patricia Pozo-Rosich, MD, PhD,  Neurology Department, Hospital Universitari Vall d’Hebron, Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain; and Headache and Neurological Pain Research Group, Vall d’Hebron Research Institute, Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain. Dr. Pozo-Rosich also serves on the boards of the International Headache Society and Council of the European Headache Federation and is an editor for various peer-reviewed journals, including Cephalalgia and Headache.

Headache is a symptom of the coronavirus disease 2019 (Covid-19), caused by the novel, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the pandemic began, researchers have tried to describe, understand, and help clinicians manage headache in the setting of Covid-19.

The reason is simple: Headache is common, often debilitating, and difficult to treat.¹

Moreover, headache could manifest both in the acute phase of the infection and, once the infection has resolved, in the post-acute phase.¹ Therefore, it is critical for clinicians to know more about headache, as headache can be a common reason that patients seek help, both in the specialized and non-specialized medical care setting.

Definitions and manifestations

While the first step in such a communication would be to define headache attributed to Covid-19, no specific definition exists, as this is a new disease. Therefore, headache attributed to Covid-19 should be defined under the diagnostic criteria, as contained in the International Classification of Headache Disorders-3, as headache attributed to a systemic viral infection.² As this is a secondary headache appearing with an infection, the treating physician needs to rule out possible underlying meningitis and/or encephalitis in the diagnosis. Moreover, other secondary headaches (eg, cerebral venous thrombosis) may appear, so clinicians need to carefully evaluate patients with headache during Covid-19 to detect signs or symptoms that point to other etiologies.

It is also advisable to know the clinical manifestations of headache attributed to Covid-19. Studies published so far have observed two main phenotypes of headache in the acute phase of the infection: one resembles migraine, the other, a tension-type headache.^1,3 Although patients with history of migraine who contract Covid-19 report headache that is more similar to primary headache disorder,⁴ two relevant aspects should be considered. Namely, migraine-like features can be observed in patients without personal migraine history; and Covid-19 patients with such history may perceive that headache they experience in the infection’s acute phase differs from their usual experience, especially regarding increased severity or duration.^5,6 Of note, headache can be a prodromal symptom of the SARS-CoV-2 infection.¹

Evolution of a headache

 Because headache appearing after the acute phase of the infection can persist, often manifesting migraine-like features, it is inordinately helpful for clinicians to know its evolution.¹ This persistent headache, sometimes referred to as post-covid headache, is not aptly named because the post-covid headache is not just one type of headache, but instead can manifest as different headache types.

 A recently published case series in Headache discussed three Covid patients who all experienced persistent headache during the infection’s post-acute phase.⁷ These patients experienced a migraine-like phenotype as have others with mild Covid-19, but their personal history of migraine, as well as their experience with Covid-19 related headache, were substantially different. Some patients had personal migraine history while others did not; some patients experienced no headache in the acute phase but did so in the post-acute phase; and the concomitant symptoms of the post-acute phase, such as insomnia, memory loss, dizziness, fatigue, and brain fog, were differentially expressed by patients.⁷ 

 This case series introduces the concept that patients with no prior history of migraine or any other primary headache disorder can develop a de novo headache because of their SARS-CoV-2 infection. Moreover, it could manifest as a new daily persistent headache. And patients with personal history of migraine may experience sudden chronification in their headache’s characteristics, rather than develop a new type of headache.⁷

 In another study, soon to be published in Cephalalgia, researchers observed that the median duration of headache in the acute phase is 2 weeks. This multicenter Spanish study, in which data on headache duration were available for 874 patients, found that 16% of these particular patients had persistent headache after 9 months. According to this study, headache that does not resolve within the first 3 months is less likely to do so later on.

Treatment

For clinicians, the significance of these findings is straightforward: Patients with headache experienced in the infection’s acute phase that does not seem to resolve post-infection requires continued medical attention. Patients should be monitored, carefully managed, and treated to avoid the onset of a persisting headache. This applies to patients with or without personal migraine history.

But which treatments should be prescribed? As there are no specific therapies for headache attributed to Covid-19, either in the acute or post-acute phase of the infection, clinicians must turn to existing therapies.

As with patients with migraine, patients with persistent headache post-Covid infection need a headache prevention strategy.

The strategy should be based on the following principles:

• treat headache
• treat comorbidities including mood disorders,  insomnia, and so on
• avoid complications such as medication overuse, which may be very common in these patients.

Acute medications

Despite the lack of specific literature on this matter, migraine-like phenotypes may respond to triptans and probably, where available, lasmiditan and gepants. These medications probably represent a therapeutic option for Covid patients with headache, but before prescribing them clinicians should carefully evaluate their use.

Before deciding on the prescription, clinicians should consider not only the medications’ most common contraindications, but also those that are related to Covid-19: the phase of the infection (acute/post-acute); the infection’s severity; and the presence of other Covid-related health problems. The concerns over the use of nonsteroidal anti-inflammatory medications (NSAIDs) and corticosteroids, raised when the pandemic first struck, have greatly dissipated.^8,9 Some patients with prolonged headache may benefit from a brief cycle of corticosteroids, similar to the treatment given to those patients with status migrainosus. Nerve blocks could also be considered.

Preventive medications

Drugs can be prescribed according to the headache phenotype too, but there are no published studies that specifically evaluate headache prevention treatments in patients with persistent headache post-infection. The case series mentioned earlier in this article recorded that patients whose headaches were treated with amitriptyline and onabotulinumtoxinA had reported variable treatment responses to this regimen, according to the patients’ characteristics.⁷

However, one important question regarding the safety of Covid patients with migraine – specifically patients on preventive treatments during the infection’s acute phase – has been somewhat resolved.

Medications such as renin-angiotensin system (RAS) blockers, suspected of possible involvement in the SARs-CoV-2 pathogenicity, seem to be safe.^8,10 And, in another multicenter Spanish study, researchers found that the use of anti-CGRP monoclonal antibodies did not seem to be associated with worse Covid-19 outcomes despite the possible implication of CGRP in modulating inflammatory responses during a viral infection.¹¹

The study of anti-CGRP monoclonal antibodies could be important in the future for another reason: To see whether these medications could be effective as a preventive treatment in patients with persistent headache after Covid-19, regardless of whether these patients have personal migraine history.

An interesting and important message to close this article. Although headache experienced in the infection’s acute phase could be extremely disabling for patients, the evidence points to the presence of headache as a marker of a better Covid-19 prognosis, in terms of a shorter infection period and a lower risk of mortality among hospitalized patients.^1,3,12  

This brief communication contains current information to help clinicians treat and inform their patients with Covid-sourced headache. Yet, we must keep in mind that the majority of the data reported here and published in the literature refer to studies conducted during the first wave of the pandemic. The emergence of new SARS-CoV-2 variants and vaccines have enormously changed the disease’s clinical presentation and course, so future studies are warranted to re-assess the validity of these findings under new conditions.

Edoardo Caronna, MD and Patricia Pozo-Rosich, MD, PhD,  Neurology Department, Hospital Universitari Vall d’Hebron, Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain; and Headache and Neurological Pain Research Group, Vall d’Hebron Research Institute, Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain. Dr. Pozo-Rosich also serves on the boards of the International Headache Society and Council of the European Headache Federation and is an editor for various peer-reviewed journals, including Cephalalgia and Headache.

Headache is a symptom of the coronavirus disease 2019 (Covid-19), caused by the novel, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the pandemic began, researchers have tried to describe, understand, and help clinicians manage headache in the setting of Covid-19.

The reason is simple: Headache is common, often debilitating, and difficult to treat.¹

Moreover, headache could manifest both in the acute phase of the infection and, once the infection has resolved, in the post-acute phase.¹ Therefore, it is critical for clinicians to know more about headache, as headache can be a common reason that patients seek help, both in the specialized and non-specialized medical care setting.

Definitions and manifestations

While the first step in such a communication would be to define headache attributed to Covid-19, no specific definition exists, as this is a new disease. Therefore, headache attributed to Covid-19 should be defined under the diagnostic criteria, as contained in the International Classification of Headache Disorders-3, as headache attributed to a systemic viral infection.² As this is a secondary headache appearing with an infection, the treating physician needs to rule out possible underlying meningitis and/or encephalitis in the diagnosis. Moreover, other secondary headaches (eg, cerebral venous thrombosis) may appear, so clinicians need to carefully evaluate patients with headache during Covid-19 to detect signs or symptoms that point to other etiologies.

It is also advisable to know the clinical manifestations of headache attributed to Covid-19. Studies published so far have observed two main phenotypes of headache in the acute phase of the infection: one resembles migraine, the other, a tension-type headache.^1,3 Although patients with history of migraine who contract Covid-19 report headache that is more similar to primary headache disorder,⁴ two relevant aspects should be considered. Namely, migraine-like features can be observed in patients without personal migraine history; and Covid-19 patients with such history may perceive that headache they experience in the infection’s acute phase differs from their usual experience, especially regarding increased severity or duration.^5,6 Of note, headache can be a prodromal symptom of the SARS-CoV-2 infection.¹

Evolution of a headache

 Because headache appearing after the acute phase of the infection can persist, often manifesting migraine-like features, it is inordinately helpful for clinicians to know its evolution.¹ This persistent headache, sometimes referred to as post-covid headache, is not aptly named because the post-covid headache is not just one type of headache, but instead can manifest as different headache types.

 A recently published case series in Headache discussed three Covid patients who all experienced persistent headache during the infection’s post-acute phase.⁷ These patients experienced a migraine-like phenotype as have others with mild Covid-19, but their personal history of migraine, as well as their experience with Covid-19 related headache, were substantially different. Some patients had personal migraine history while others did not; some patients experienced no headache in the acute phase but did so in the post-acute phase; and the concomitant symptoms of the post-acute phase, such as insomnia, memory loss, dizziness, fatigue, and brain fog, were differentially expressed by patients.⁷ 

 This case series introduces the concept that patients with no prior history of migraine or any other primary headache disorder can develop a de novo headache because of their SARS-CoV-2 infection. Moreover, it could manifest as a new daily persistent headache. And patients with personal history of migraine may experience sudden chronification in their headache’s characteristics, rather than develop a new type of headache.⁷

 In another study, soon to be published in Cephalalgia, researchers observed that the median duration of headache in the acute phase is 2 weeks. This multicenter Spanish study, in which data on headache duration were available for 874 patients, found that 16% of these particular patients had persistent headache after 9 months. According to this study, headache that does not resolve within the first 3 months is less likely to do so later on.

Treatment

For clinicians, the significance of these findings is straightforward: Patients with headache experienced in the infection’s acute phase that does not seem to resolve post-infection requires continued medical attention. Patients should be monitored, carefully managed, and treated to avoid the onset of a persisting headache. This applies to patients with or without personal migraine history.

But which treatments should be prescribed? As there are no specific therapies for headache attributed to Covid-19, either in the acute or post-acute phase of the infection, clinicians must turn to existing therapies.

As with patients with migraine, patients with persistent headache post-Covid infection need a headache prevention strategy.

The strategy should be based on the following principles:

• treat headache
• treat comorbidities including mood disorders,  insomnia, and so on
• avoid complications such as medication overuse, which may be very common in these patients.

Acute medications

Despite the lack of specific literature on this matter, migraine-like phenotypes may respond to triptans and probably, where available, lasmiditan and gepants. These medications probably represent a therapeutic option for Covid patients with headache, but before prescribing them clinicians should carefully evaluate their use.

Before deciding on the prescription, clinicians should consider not only the medications’ most common contraindications, but also those that are related to Covid-19: the phase of the infection (acute/post-acute); the infection’s severity; and the presence of other Covid-related health problems. The concerns over the use of nonsteroidal anti-inflammatory medications (NSAIDs) and corticosteroids, raised when the pandemic first struck, have greatly dissipated.^8,9 Some patients with prolonged headache may benefit from a brief cycle of corticosteroids, similar to the treatment given to those patients with status migrainosus. Nerve blocks could also be considered.

Preventive medications

Drugs can be prescribed according to the headache phenotype too, but there are no published studies that specifically evaluate headache prevention treatments in patients with persistent headache post-infection. The case series mentioned earlier in this article recorded that patients whose headaches were treated with amitriptyline and onabotulinumtoxinA had reported variable treatment responses to this regimen, according to the patients’ characteristics.⁷

However, one important question regarding the safety of Covid patients with migraine – specifically patients on preventive treatments during the infection’s acute phase – has been somewhat resolved.

Medications such as renin-angiotensin system (RAS) blockers, suspected of possible involvement in the SARs-CoV-2 pathogenicity, seem to be safe.^8,10 And, in another multicenter Spanish study, researchers found that the use of anti-CGRP monoclonal antibodies did not seem to be associated with worse Covid-19 outcomes despite the possible implication of CGRP in modulating inflammatory responses during a viral infection.¹¹

The study of anti-CGRP monoclonal antibodies could be important in the future for another reason: To see whether these medications could be effective as a preventive treatment in patients with persistent headache after Covid-19, regardless of whether these patients have personal migraine history.

An interesting and important message to close this article. Although headache experienced in the infection’s acute phase could be extremely disabling for patients, the evidence points to the presence of headache as a marker of a better Covid-19 prognosis, in terms of a shorter infection period and a lower risk of mortality among hospitalized patients.^1,3,12  

This brief communication contains current information to help clinicians treat and inform their patients with Covid-sourced headache. Yet, we must keep in mind that the majority of the data reported here and published in the literature refer to studies conducted during the first wave of the pandemic. The emergence of new SARS-CoV-2 variants and vaccines have enormously changed the disease’s clinical presentation and course, so future studies are warranted to re-assess the validity of these findings under new conditions.

Patients with chronic lymphocytic leukemia (CLL) have increased risk for severe COVID-19 disease as well as mortality.

South_agency/Getty Images

Such patients are likely to have compromised immune systems, making them respond poorly to vaccines, as has been seen in studies involving pneumococcal, hepatitis B, and influenza A and B vaccination. 

In order to determine if vaccination against COVID-19 disease will be effective among these patients, researchers performed a study to determine the efficacy of a single COVID-19 vaccine in patients with CLL. They found that the response rate of patients with CLL to vaccination was significantly lower than that of healthy controls, according to the study published in Blood Advances.

Study details

The study (NCT04746092) assessed the humoral immune responses to BNT162b2 mRNA COVID-19 (Pfizer) vaccination in adult patients with CLL and compared responses with those obtained in age-matched healthy controls. Patients received two vaccine doses, 21 days apart, and antibody titers were measured 2-3 weeks after administration of the second dose, according to Yair Herishanu, MD, of the Tel-Aviv Sourasky Medical Center, Tel Aviv University, and colleagues.

Troubling results

The researchers found an antibody-mediated response to the BNT162b2 mRNA COVID-19 vaccine in only 66 of 167 (39.5%) of all patients with CLL. The response rate of 52 of these responding patients with CLL to the vaccine was significantly lower than that occurring in 52 age- and sex-matched healthy controls (52% vs. 100%, respectively; adjusted odds ratio, 0.010; 95% confidence interval, 0.001-0.162; P < .001). 

Among the patients with CLL, the response rate was highest in those who obtained clinical remission after treatment (79.2%), followed by 55.2% in treatment-naive patients, and it was only 16% in patients under treatment at the time of vaccination. 

In patients treated with either BTK inhibitors or venetoclax with and without anti-CD20 antibody, response rates were low (16.0% and 13.6%, respectively). In particular, none of the patients exposed to anti-CD20 antibodies less than 12 months prior to vaccination responded, according to the researchers.

Multivariate analysis showed that the independent predictors of a vaccine response were age (65 years or younger; odds ratio, 3.17; P = .025), sex (women; OR, 3.66; P = .006), lack of active therapy (including treatment naive and previously treated patients; OR 6.59; P < .001), IgG levels 550 mg/dL or greater (OR, 3.70; P = .037), and IgM levels 40mg/dL or greater (OR, 2.92; P = .017). 

Within a median follow-up period of 75 days since the first vaccine dose, none of the CLL patients developed COVID-19 infection, the researchers reported.

“Vaccinated patients with CLL should continue to adhere to masking, social distancing, and vaccination of their close contacts should be strongly recommended. Serological tests after the second injection of the COVID-19 vaccine can provide valuable information to the individual patient and perhaps, may be integrated in future clinical decisions,” the researchers concluded.

The study was sponsored by the Tel-Aviv Sourasky Medical Center. The authors reported that they had no conflicts of interest. 

mlesney@mdedge.com 

Patients with chronic lymphocytic leukemia (CLL) have increased risk for severe COVID-19 disease as well as mortality.

South_agency/Getty Images

Such patients are likely to have compromised immune systems, making them respond poorly to vaccines, as has been seen in studies involving pneumococcal, hepatitis B, and influenza A and B vaccination. 

In order to determine if vaccination against COVID-19 disease will be effective among these patients, researchers performed a study to determine the efficacy of a single COVID-19 vaccine in patients with CLL. They found that the response rate of patients with CLL to vaccination was significantly lower than that of healthy controls, according to the study published in Blood Advances.

Study details

The study (NCT04746092) assessed the humoral immune responses to BNT162b2 mRNA COVID-19 (Pfizer) vaccination in adult patients with CLL and compared responses with those obtained in age-matched healthy controls. Patients received two vaccine doses, 21 days apart, and antibody titers were measured 2-3 weeks after administration of the second dose, according to Yair Herishanu, MD, of the Tel-Aviv Sourasky Medical Center, Tel Aviv University, and colleagues.

Troubling results

The researchers found an antibody-mediated response to the BNT162b2 mRNA COVID-19 vaccine in only 66 of 167 (39.5%) of all patients with CLL. The response rate of 52 of these responding patients with CLL to the vaccine was significantly lower than that occurring in 52 age- and sex-matched healthy controls (52% vs. 100%, respectively; adjusted odds ratio, 0.010; 95% confidence interval, 0.001-0.162; P < .001). 

Among the patients with CLL, the response rate was highest in those who obtained clinical remission after treatment (79.2%), followed by 55.2% in treatment-naive patients, and it was only 16% in patients under treatment at the time of vaccination. 

In patients treated with either BTK inhibitors or venetoclax with and without anti-CD20 antibody, response rates were low (16.0% and 13.6%, respectively). In particular, none of the patients exposed to anti-CD20 antibodies less than 12 months prior to vaccination responded, according to the researchers.

Multivariate analysis showed that the independent predictors of a vaccine response were age (65 years or younger; odds ratio, 3.17; P = .025), sex (women; OR, 3.66; P = .006), lack of active therapy (including treatment naive and previously treated patients; OR 6.59; P < .001), IgG levels 550 mg/dL or greater (OR, 3.70; P = .037), and IgM levels 40mg/dL or greater (OR, 2.92; P = .017). 

Within a median follow-up period of 75 days since the first vaccine dose, none of the CLL patients developed COVID-19 infection, the researchers reported.

“Vaccinated patients with CLL should continue to adhere to masking, social distancing, and vaccination of their close contacts should be strongly recommended. Serological tests after the second injection of the COVID-19 vaccine can provide valuable information to the individual patient and perhaps, may be integrated in future clinical decisions,” the researchers concluded.

The study was sponsored by the Tel-Aviv Sourasky Medical Center. The authors reported that they had no conflicts of interest. 

mlesney@mdedge.com 

Patients with chronic lymphocytic leukemia (CLL) have increased risk for severe COVID-19 disease as well as mortality.

South_agency/Getty Images

Such patients are likely to have compromised immune systems, making them respond poorly to vaccines, as has been seen in studies involving pneumococcal, hepatitis B, and influenza A and B vaccination. 

In order to determine if vaccination against COVID-19 disease will be effective among these patients, researchers performed a study to determine the efficacy of a single COVID-19 vaccine in patients with CLL. They found that the response rate of patients with CLL to vaccination was significantly lower than that of healthy controls, according to the study published in Blood Advances.

Study details

The study (NCT04746092) assessed the humoral immune responses to BNT162b2 mRNA COVID-19 (Pfizer) vaccination in adult patients with CLL and compared responses with those obtained in age-matched healthy controls. Patients received two vaccine doses, 21 days apart, and antibody titers were measured 2-3 weeks after administration of the second dose, according to Yair Herishanu, MD, of the Tel-Aviv Sourasky Medical Center, Tel Aviv University, and colleagues.

Troubling results

The researchers found an antibody-mediated response to the BNT162b2 mRNA COVID-19 vaccine in only 66 of 167 (39.5%) of all patients with CLL. The response rate of 52 of these responding patients with CLL to the vaccine was significantly lower than that occurring in 52 age- and sex-matched healthy controls (52% vs. 100%, respectively; adjusted odds ratio, 0.010; 95% confidence interval, 0.001-0.162; P < .001). 

Among the patients with CLL, the response rate was highest in those who obtained clinical remission after treatment (79.2%), followed by 55.2% in treatment-naive patients, and it was only 16% in patients under treatment at the time of vaccination. 

In patients treated with either BTK inhibitors or venetoclax with and without anti-CD20 antibody, response rates were low (16.0% and 13.6%, respectively). In particular, none of the patients exposed to anti-CD20 antibodies less than 12 months prior to vaccination responded, according to the researchers.

Multivariate analysis showed that the independent predictors of a vaccine response were age (65 years or younger; odds ratio, 3.17; P = .025), sex (women; OR, 3.66; P = .006), lack of active therapy (including treatment naive and previously treated patients; OR 6.59; P < .001), IgG levels 550 mg/dL or greater (OR, 3.70; P = .037), and IgM levels 40mg/dL or greater (OR, 2.92; P = .017). 

Within a median follow-up period of 75 days since the first vaccine dose, none of the CLL patients developed COVID-19 infection, the researchers reported.

“Vaccinated patients with CLL should continue to adhere to masking, social distancing, and vaccination of their close contacts should be strongly recommended. Serological tests after the second injection of the COVID-19 vaccine can provide valuable information to the individual patient and perhaps, may be integrated in future clinical decisions,” the researchers concluded.

The study was sponsored by the Tel-Aviv Sourasky Medical Center. The authors reported that they had no conflicts of interest. 

mlesney@mdedge.com 

Mohs micrographic surgery (MMS) entails multiple time-consuming surgical and histological examinations for each patient. As surgical stages are performed and histological sections are processed, an efficient communication method among providers, medical assistants, histotechnologists, and patients is necessary to avoid delays. To address these and other communication issues, providers have focused on ways to increase clinic efficiency and improve patient-reported outcomes by utilizing new or repurposed communication technologies in their Mohs practice. 

Prior reports have highlighted the utility of hands-free headsets that allow real-time communication among staff members as a means of increasing clinic efficiency and decreasing patient wait times.^1-4 These systems may mediate a more rapid turnover between stages by mitigating the need for surgeons and support staff to assemble within a designated workspace.^1,3,4 However, there is no single or standardized communication method that best suits all surgical suites and MMS practices. Our study aimed to identify the current communication strategies employed by Mohs surgeons and thereby ascertain which method(s) portend(s) the highest benefit in average daily time savings and provider-perceived patient satisfaction.

Materials and Methods

Survey Instrument
A new 10-question electronic survey was published on the SurveyMonkey website, and a link to the survey was provided in a quarterly email that originated from the American College of Mohs Surgery and was distributed to all 1735 active members. Responses were obtained from January 2019 to February 2019.

Statistical Analysis
A statistical analysis was done to determine any significant associations among the providers’ responses. P<.05 was used to determine statistical significance. A Cochran-Armitage test for trend was used to identify significant associations between the number of rooms and the communication systems that were used. Thus, 7 total tests—1 for each device (whiteboard, light system, flag system, wired intercom, wireless intercom, walkie-talkie, or headset)—were conducted. The Cochran-Armitage test also was used to determine whether the probability of using the device was affected by the number of stations/surgical rooms that were attended by the Mohs surgeons. To determine whether the communication devices used were associated with higher patient satisfaction, a χ² test was conducted for each device (7 total tests), testing the categories of using that device (yes/no) and patient satisfaction (yes/no). A Fisher exact test of independence was used in any case where the proportion for the device and patient satisfaction was 25% or higher. To determine whether the communication method was associated with increased time savings, 7 total Cochran-Armitage tests were conducted, 1 for each device. A logistic regression model was used to determine whether there was a significant association between the number of stations and the likelihood of reporting patient satisfaction.

Results

Eighty-eight surgeons responded to the survey, with a response rate of 5% (88/1735). A total of 55 surgeons completed the survey in its entirety and were included in the data analysis. The most commonly used communication mediums were whiteboards (29/55 [53%]), followed by a flag system (16/55 [29%]) and a light system (13/55 [24%]). Most Mohs surgeons (52/55 [95%]) used the communication media to communicate with their staff only, and 76% (42/55) of Mohs surgeons believed that their communication media contributed to higher patient satisfaction. Overall, 58% (32/55) of Mohs surgeons stated that their communication media saved more than 15 minutes (on average) per day. The use of a whiteboard and/or flag system was reported as the least efficient method, with average daily time savings of 13 minutes. With the introduction of newer technology (wired or wireless intercoms, headsets, walkie-talkies, or internal messaging systems such as Skype) to the whiteboard and/or flag system, the time savings increased by 10 minutes per day. Nearly 25% (14/55) of surgeons utilized more than 1 communication system.

As the number of stations in an MMS suite increased, the probability of using a whiteboard to track the progress of the cases decreased. There were no statistically significant associations identified between the number of stations and the use of other communication devices (ie, flag system, light system, wireless intercom, wired intercom, walkie-talkie, headset). The stratified percentages of the amount of time savings for each communication modality are presented in the Figure (whiteboards and headsets were excluded because they did not increase time savings). The use of a light system was the only communication modality found to be statistically associated with an increase in provider-reported time savings (P=.0482; Figure). In addition, our analysis did not show an improvement in provider-reported patient satisfaction with any of the current systems used in MMS clinics.

Comment

The process of transmitting information among the medical team during MMS is a complex interplay involving the relay of crucial information, with many opportunities for the introduction of distraction and error. Despite numerous improvements in the efficiency of the preparation of histological specimens and implementation of various time-saving and tissue-saving surgical interventions, relatively little attention has been given to address the sometimes chaotic and challenging process of organizing results from each stage of multiple patients in an MMS surgical suite.⁵

As demonstrated by our survey, incorporation of a light-based system into an MMS clinic may improve workplace efficiency by decreasing the redundant use of support staff and allowing Mohs surgeons to transition from one station to the next seamlessly. Light-based communication systems provide an immediate notification for support staff via color-coded and/or numerically coded indicators on input switches located outside and inside the examination/surgery rooms. The switch indicators can be depressed with minimal disruption from station to station, thereby foregoing the need to interrupt an ongoing excision or closure to convey the status of the case. These systems may then permit enhanced clinic and workflow efficiency, which may help to shorten patient wait times.

Conclusion

Our study supports the use of light-based communication systems in MMS suites to improve efficiency in the clinic. Based on our analysis, light-based communication methods were significantly associated with improved time savings (P=.0482). Our study did not show an improvement in provider-reported satisfaction with any of the current systems used in MMS clinics. We hope that this information will help guide providers in implementing new communication techniques to improve clinic efficiency. 



Acknowledgments
The authors would like to thank Ms. Kathy Kyler (Oklahoma City, Oklahoma) for her assistance in preparing this manuscript. Support for Dr. Chen and Mr. Stubblefield was provided through National Institutes of Health, National Institute of General Medical Sciences [Grant 2U54GM104938-06, PI Judith James].

Mohs micrographic surgery (MMS) entails multiple time-consuming surgical and histological examinations for each patient. As surgical stages are performed and histological sections are processed, an efficient communication method among providers, medical assistants, histotechnologists, and patients is necessary to avoid delays. To address these and other communication issues, providers have focused on ways to increase clinic efficiency and improve patient-reported outcomes by utilizing new or repurposed communication technologies in their Mohs practice. 

Prior reports have highlighted the utility of hands-free headsets that allow real-time communication among staff members as a means of increasing clinic efficiency and decreasing patient wait times.^1-4 These systems may mediate a more rapid turnover between stages by mitigating the need for surgeons and support staff to assemble within a designated workspace.^1,3,4 However, there is no single or standardized communication method that best suits all surgical suites and MMS practices. Our study aimed to identify the current communication strategies employed by Mohs surgeons and thereby ascertain which method(s) portend(s) the highest benefit in average daily time savings and provider-perceived patient satisfaction.

Materials and Methods

Survey Instrument
A new 10-question electronic survey was published on the SurveyMonkey website, and a link to the survey was provided in a quarterly email that originated from the American College of Mohs Surgery and was distributed to all 1735 active members. Responses were obtained from January 2019 to February 2019.

Statistical Analysis
A statistical analysis was done to determine any significant associations among the providers’ responses. P<.05 was used to determine statistical significance. A Cochran-Armitage test for trend was used to identify significant associations between the number of rooms and the communication systems that were used. Thus, 7 total tests—1 for each device (whiteboard, light system, flag system, wired intercom, wireless intercom, walkie-talkie, or headset)—were conducted. The Cochran-Armitage test also was used to determine whether the probability of using the device was affected by the number of stations/surgical rooms that were attended by the Mohs surgeons. To determine whether the communication devices used were associated with higher patient satisfaction, a χ² test was conducted for each device (7 total tests), testing the categories of using that device (yes/no) and patient satisfaction (yes/no). A Fisher exact test of independence was used in any case where the proportion for the device and patient satisfaction was 25% or higher. To determine whether the communication method was associated with increased time savings, 7 total Cochran-Armitage tests were conducted, 1 for each device. A logistic regression model was used to determine whether there was a significant association between the number of stations and the likelihood of reporting patient satisfaction.

Results

Eighty-eight surgeons responded to the survey, with a response rate of 5% (88/1735). A total of 55 surgeons completed the survey in its entirety and were included in the data analysis. The most commonly used communication mediums were whiteboards (29/55 [53%]), followed by a flag system (16/55 [29%]) and a light system (13/55 [24%]). Most Mohs surgeons (52/55 [95%]) used the communication media to communicate with their staff only, and 76% (42/55) of Mohs surgeons believed that their communication media contributed to higher patient satisfaction. Overall, 58% (32/55) of Mohs surgeons stated that their communication media saved more than 15 minutes (on average) per day. The use of a whiteboard and/or flag system was reported as the least efficient method, with average daily time savings of 13 minutes. With the introduction of newer technology (wired or wireless intercoms, headsets, walkie-talkies, or internal messaging systems such as Skype) to the whiteboard and/or flag system, the time savings increased by 10 minutes per day. Nearly 25% (14/55) of surgeons utilized more than 1 communication system.

As the number of stations in an MMS suite increased, the probability of using a whiteboard to track the progress of the cases decreased. There were no statistically significant associations identified between the number of stations and the use of other communication devices (ie, flag system, light system, wireless intercom, wired intercom, walkie-talkie, headset). The stratified percentages of the amount of time savings for each communication modality are presented in the Figure (whiteboards and headsets were excluded because they did not increase time savings). The use of a light system was the only communication modality found to be statistically associated with an increase in provider-reported time savings (P=.0482; Figure). In addition, our analysis did not show an improvement in provider-reported patient satisfaction with any of the current systems used in MMS clinics.

Comment

The process of transmitting information among the medical team during MMS is a complex interplay involving the relay of crucial information, with many opportunities for the introduction of distraction and error. Despite numerous improvements in the efficiency of the preparation of histological specimens and implementation of various time-saving and tissue-saving surgical interventions, relatively little attention has been given to address the sometimes chaotic and challenging process of organizing results from each stage of multiple patients in an MMS surgical suite.⁵

As demonstrated by our survey, incorporation of a light-based system into an MMS clinic may improve workplace efficiency by decreasing the redundant use of support staff and allowing Mohs surgeons to transition from one station to the next seamlessly. Light-based communication systems provide an immediate notification for support staff via color-coded and/or numerically coded indicators on input switches located outside and inside the examination/surgery rooms. The switch indicators can be depressed with minimal disruption from station to station, thereby foregoing the need to interrupt an ongoing excision or closure to convey the status of the case. These systems may then permit enhanced clinic and workflow efficiency, which may help to shorten patient wait times.

Conclusion

Our study supports the use of light-based communication systems in MMS suites to improve efficiency in the clinic. Based on our analysis, light-based communication methods were significantly associated with improved time savings (P=.0482). Our study did not show an improvement in provider-reported satisfaction with any of the current systems used in MMS clinics. We hope that this information will help guide providers in implementing new communication techniques to improve clinic efficiency. 



Acknowledgments
The authors would like to thank Ms. Kathy Kyler (Oklahoma City, Oklahoma) for her assistance in preparing this manuscript. Support for Dr. Chen and Mr. Stubblefield was provided through National Institutes of Health, National Institute of General Medical Sciences [Grant 2U54GM104938-06, PI Judith James].

Mohs micrographic surgery (MMS) entails multiple time-consuming surgical and histological examinations for each patient. As surgical stages are performed and histological sections are processed, an efficient communication method among providers, medical assistants, histotechnologists, and patients is necessary to avoid delays. To address these and other communication issues, providers have focused on ways to increase clinic efficiency and improve patient-reported outcomes by utilizing new or repurposed communication technologies in their Mohs practice. 

Prior reports have highlighted the utility of hands-free headsets that allow real-time communication among staff members as a means of increasing clinic efficiency and decreasing patient wait times.^1-4 These systems may mediate a more rapid turnover between stages by mitigating the need for surgeons and support staff to assemble within a designated workspace.^1,3,4 However, there is no single or standardized communication method that best suits all surgical suites and MMS practices. Our study aimed to identify the current communication strategies employed by Mohs surgeons and thereby ascertain which method(s) portend(s) the highest benefit in average daily time savings and provider-perceived patient satisfaction.

Materials and Methods

Survey Instrument
A new 10-question electronic survey was published on the SurveyMonkey website, and a link to the survey was provided in a quarterly email that originated from the American College of Mohs Surgery and was distributed to all 1735 active members. Responses were obtained from January 2019 to February 2019.

Statistical Analysis
A statistical analysis was done to determine any significant associations among the providers’ responses. P<.05 was used to determine statistical significance. A Cochran-Armitage test for trend was used to identify significant associations between the number of rooms and the communication systems that were used. Thus, 7 total tests—1 for each device (whiteboard, light system, flag system, wired intercom, wireless intercom, walkie-talkie, or headset)—were conducted. The Cochran-Armitage test also was used to determine whether the probability of using the device was affected by the number of stations/surgical rooms that were attended by the Mohs surgeons. To determine whether the communication devices used were associated with higher patient satisfaction, a χ² test was conducted for each device (7 total tests), testing the categories of using that device (yes/no) and patient satisfaction (yes/no). A Fisher exact test of independence was used in any case where the proportion for the device and patient satisfaction was 25% or higher. To determine whether the communication method was associated with increased time savings, 7 total Cochran-Armitage tests were conducted, 1 for each device. A logistic regression model was used to determine whether there was a significant association between the number of stations and the likelihood of reporting patient satisfaction.

Results

Eighty-eight surgeons responded to the survey, with a response rate of 5% (88/1735). A total of 55 surgeons completed the survey in its entirety and were included in the data analysis. The most commonly used communication mediums were whiteboards (29/55 [53%]), followed by a flag system (16/55 [29%]) and a light system (13/55 [24%]). Most Mohs surgeons (52/55 [95%]) used the communication media to communicate with their staff only, and 76% (42/55) of Mohs surgeons believed that their communication media contributed to higher patient satisfaction. Overall, 58% (32/55) of Mohs surgeons stated that their communication media saved more than 15 minutes (on average) per day. The use of a whiteboard and/or flag system was reported as the least efficient method, with average daily time savings of 13 minutes. With the introduction of newer technology (wired or wireless intercoms, headsets, walkie-talkies, or internal messaging systems such as Skype) to the whiteboard and/or flag system, the time savings increased by 10 minutes per day. Nearly 25% (14/55) of surgeons utilized more than 1 communication system.

As the number of stations in an MMS suite increased, the probability of using a whiteboard to track the progress of the cases decreased. There were no statistically significant associations identified between the number of stations and the use of other communication devices (ie, flag system, light system, wireless intercom, wired intercom, walkie-talkie, headset). The stratified percentages of the amount of time savings for each communication modality are presented in the Figure (whiteboards and headsets were excluded because they did not increase time savings). The use of a light system was the only communication modality found to be statistically associated with an increase in provider-reported time savings (P=.0482; Figure). In addition, our analysis did not show an improvement in provider-reported patient satisfaction with any of the current systems used in MMS clinics.

Comment

The process of transmitting information among the medical team during MMS is a complex interplay involving the relay of crucial information, with many opportunities for the introduction of distraction and error. Despite numerous improvements in the efficiency of the preparation of histological specimens and implementation of various time-saving and tissue-saving surgical interventions, relatively little attention has been given to address the sometimes chaotic and challenging process of organizing results from each stage of multiple patients in an MMS surgical suite.⁵

As demonstrated by our survey, incorporation of a light-based system into an MMS clinic may improve workplace efficiency by decreasing the redundant use of support staff and allowing Mohs surgeons to transition from one station to the next seamlessly. Light-based communication systems provide an immediate notification for support staff via color-coded and/or numerically coded indicators on input switches located outside and inside the examination/surgery rooms. The switch indicators can be depressed with minimal disruption from station to station, thereby foregoing the need to interrupt an ongoing excision or closure to convey the status of the case. These systems may then permit enhanced clinic and workflow efficiency, which may help to shorten patient wait times.

Conclusion

Our study supports the use of light-based communication systems in MMS suites to improve efficiency in the clinic. Based on our analysis, light-based communication methods were significantly associated with improved time savings (P=.0482). Our study did not show an improvement in provider-reported satisfaction with any of the current systems used in MMS clinics. We hope that this information will help guide providers in implementing new communication techniques to improve clinic efficiency. 



Acknowledgments
The authors would like to thank Ms. Kathy Kyler (Oklahoma City, Oklahoma) for her assistance in preparing this manuscript. Support for Dr. Chen and Mr. Stubblefield was provided through National Institutes of Health, National Institute of General Medical Sciences [Grant 2U54GM104938-06, PI Judith James].

Key findings in metastatic breast cancer, presented at the ASCO 2020 Virtual Annual Meeting, ranged across all tumor subtypes.

Arguably, the top news in breast cancer was a plenary presentation addressing the role of locoregional therapy in advanced disease. Dr. Harold Burstein, of Dana-Farber Cancer Institute, comments that this study indicates systemic therapy as the mainstay treatment for woman with newly diagnosed advanced disease and a tumor in the breast.

In triple-negative breast cancer, Dr. Burstein highlights two studies. The KEYNOTE-355 study validates the addition of a checkpoint inhibitor in first-line therapy in women whose tumors are PD-L1 positive. The intriguing results of the SWOG S1416 trial, Dr. Burstein comments, suggest the use of PARP inhibition may extend beyond BRCA1 and BRCA2 breast cancers.

In HER2-positive breast cancer, an update of the HER2CLIMB study indicates that the combination of tucatinib, trastuzumab, and capecitabine continues to benefit women with HER2-positive disease. Dr. Burstein expects this combination will be a new standard of care, particularly in women with brain metastases.

As for ER-positive breast cancer, Dr. Burstein reviews the BYLieve trial. Results of this study suggest alpelisib has activity in women with a PIK3CA mutation who have already received a CDK4/6 inhibitor.

Harold J. Burstein, Md, PhD

Professor, Department of Medicine, Harvard Medical School; Institute Physician, Dana-Farber Cancer Institute, Boston, Massachusetts. Harold J. Burstein, MD, PhD, has disclosed no relevant financial relationships.

Key findings in metastatic breast cancer, presented at the ASCO 2020 Virtual Annual Meeting, ranged across all tumor subtypes.

Arguably, the top news in breast cancer was a plenary presentation addressing the role of locoregional therapy in advanced disease. Dr. Harold Burstein, of Dana-Farber Cancer Institute, comments that this study indicates systemic therapy as the mainstay treatment for woman with newly diagnosed advanced disease and a tumor in the breast.

In triple-negative breast cancer, Dr. Burstein highlights two studies. The KEYNOTE-355 study validates the addition of a checkpoint inhibitor in first-line therapy in women whose tumors are PD-L1 positive. The intriguing results of the SWOG S1416 trial, Dr. Burstein comments, suggest the use of PARP inhibition may extend beyond BRCA1 and BRCA2 breast cancers.

In HER2-positive breast cancer, an update of the HER2CLIMB study indicates that the combination of tucatinib, trastuzumab, and capecitabine continues to benefit women with HER2-positive disease. Dr. Burstein expects this combination will be a new standard of care, particularly in women with brain metastases.

As for ER-positive breast cancer, Dr. Burstein reviews the BYLieve trial. Results of this study suggest alpelisib has activity in women with a PIK3CA mutation who have already received a CDK4/6 inhibitor.

Harold J. Burstein, Md, PhD

Professor, Department of Medicine, Harvard Medical School; Institute Physician, Dana-Farber Cancer Institute, Boston, Massachusetts. Harold J. Burstein, MD, PhD, has disclosed no relevant financial relationships.

Key findings in metastatic breast cancer, presented at the ASCO 2020 Virtual Annual Meeting, ranged across all tumor subtypes.

Arguably, the top news in breast cancer was a plenary presentation addressing the role of locoregional therapy in advanced disease. Dr. Harold Burstein, of Dana-Farber Cancer Institute, comments that this study indicates systemic therapy as the mainstay treatment for woman with newly diagnosed advanced disease and a tumor in the breast.

In triple-negative breast cancer, Dr. Burstein highlights two studies. The KEYNOTE-355 study validates the addition of a checkpoint inhibitor in first-line therapy in women whose tumors are PD-L1 positive. The intriguing results of the SWOG S1416 trial, Dr. Burstein comments, suggest the use of PARP inhibition may extend beyond BRCA1 and BRCA2 breast cancers.

In HER2-positive breast cancer, an update of the HER2CLIMB study indicates that the combination of tucatinib, trastuzumab, and capecitabine continues to benefit women with HER2-positive disease. Dr. Burstein expects this combination will be a new standard of care, particularly in women with brain metastases.

As for ER-positive breast cancer, Dr. Burstein reviews the BYLieve trial. Results of this study suggest alpelisib has activity in women with a PIK3CA mutation who have already received a CDK4/6 inhibitor.

Harold J. Burstein, Md, PhD

Professor, Department of Medicine, Harvard Medical School; Institute Physician, Dana-Farber Cancer Institute, Boston, Massachusetts. Harold J. Burstein, MD, PhD, has disclosed no relevant financial relationships.