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Case reports illustrate heterogeneity of skin manifestations in COVID patients
Two infection.
It is not yet clear from these or other case reports which, if any, skin eruptions accompanying COVID-19 infections are caused by the virus, but the authors of the editorial, led by Lauren M. Madigan, MD, of the department of dermatology at the University of Utah, Salt Lake City, urged dermatologists to lead efforts to find out.
“To fully characterize skin manifestations, it may be necessary for dermatologists to evaluate these patients directly; comprehensive evaluation could reveal important morphologic clues, such as the subtle purpuric nature of skin lesions or the characteristic mucosal or ophthalmologic features of COVID-19,” the authors of the editorial stated.
So far, the patterns of skin symptoms, which have been identified in up to 20% of COVID-19–infected patients in some series, have been heterogeneous as demonstrated in the two published case reports.
In one case, a papulosquamous and erythematous periumbilical patch that appeared on the trunk in an elderly patient 1 day after hospital admission for acute respiratory distress rapidly evolved into a digitate papulosquamous eruption involving the upper arms, shoulder, and back. It was described as “clinically reminiscent” of pityriasis rosea by the authors, from the divisions of dermatology and venereology, pathology, intensive care, and the virology laboratory, of the Hôpital Cochin, Paris.
In the other, pruritic erythematous macules, papules, and petechiae affecting the buttocks, popliteal fossae, anterior thighs, and lower abdomen appeared 3 days after the onset of fever in a 48-year-old man hospitalized in Madrid. A biopsy demonstrated a superficial perivascular lymphocytic infiltrate with red cell extravasation and focal papillary edema, “along with focal parakeratosis and isolated dyskeratotic cells,” according to the authors of this report, from the department of dermatology at Ramon y Cajal University, Madrid.
It was unclear whether COVID-19 directly caused either skin eruption. In the patient with the digitate papulosquamous eruption, no virus could be isolated from the skin. Based on high levels of proinflammatory cytokines, it was hypothesized that the rash might have been secondary to an immune response. The rash resolved within a week, but the patient subsequently died of the infection.
In the second case, the petechial lesions, which developed before any treatment was initiated, were said to resemble those associated with other viruses, such as parvovirus B19. This led the investigators to speculate that SARS-CoV-2 “could affect the skin in a similar way,” even though other potential etiologies could not be excluded. Treated with a topical steroid and an oral antihistamine, the skin lesions resolved after 5 days. This patient was discharged after recovering from the respiratory illness after 12 days.
Like previously reported cutaneous eruptions associated with COVID-19 infection, these cases “raise more questions than they provide answers,” wrote the authors of the editorial, but the limited information currently available was the basis for encouraging dermatologists to get involved.
To participate, dermatologists need not necessarily be affiliated with an academic center, according to one of the editorial coauthors, Kanade Shinkai, MD, PhD, professor of dermatology at the University of California, San Francisco. She noted that any health professional is invited to submit cases of COVID-19–associated dermatoses to a registry set up by the American Academy of Dermatology.
It is hoped that cases captured in this registry will create sufficient data to allow clinically relevant patterns and etiologies to be characterized.
The need for data is clear to those on the front lines. Kirsten Lo Sicco, MD, associate director of the skin and cancer unit at New York University, reported that her center is already set up to collect data systematically. “At NYU, we are currently working on standardizing laboratory and histopathology work up for COVID-19 patients who present with various skin eruptions.”
The goal, she added, is “to better determine COVID-19 pathophysiology, systemic associations, patient outcomes, and potential therapeutics.”
“Presumably, many of the eruptions seen in the setting of COVID-19 infection are related,” Dr. Lo Sicco explained in an interview. However, skin complications of infection “may overlap with or be a result of other etiologies as well.”
While better testing for COVID-19 and more lesion biopsies will play a critical role in differentiating etiologies, “we must not overcall COVID-19–related skin eruptions and potentially overlook other diagnoses,” Dr. Lo Sicco said.
In recounting some challenges from the NYU experience so far, Dr. Lo Sicco described the difficulty of differentiating COVID-19–related skin eruptions from skin eruptions caused by treatments, such as antibiotics and antivirals, when the presentation is delayed.
“This is where collaboration with our dermatopathologists becomes important. Drug eruptions, viral exanthems, urticarial eruptions, vasculopathy, and vasculitis can all be differentiated on dermpath,” she said.
One early obstacle to the skin biopsies essential for these types of studies was the limited supply of personal protective equipment at many centers, including hospitals in New York. Biopsies could not be safely performed if supplies of masks and gowns were limited.
Recent evidence suggests that some of the more common morphologies, such as purpuric eruptions, livedo reticularis, and retiform purpura, are linked to the vasculopathy associated with COVID-19 infection, according to Dr. Lo Sicco, but this invites a new set of questions.
One is whether vasculopathies can be prevented with prophylactic anticoagulation. Many hospitalized COVID-19 patients are already receiving therapeutic anticoagulation, but Dr. Lo Sicco questioned whether prophylactic anticoagulation might improve prognosis for outpatients, such as those discharged or those never hospitalized. This is a strategy now being investigated.
Ultimately, she agreed with the thrust of the JAMA Dermatology editorial.
“Dermatologists are vital to determine if various morphologies, such as urticarial, vesicular, purpuric, or papulosquamous lesions, have any specific systemic implications or relate to differences in patient outcomes,” she said.
These are exactly the types of issues being actively investigated at her center.
Neither the authors of the case reports nor of the editorial reported any conflicts of interest.
SOURCEs: Madigan LM et al. JAMA Dermatol. 2020 Apr 30. doi:10.1001/jamadermatol.2020.1438; Diaz-Guimaraens B et al. JAMA Dermatol. 2020 Apr 30. doi: 10.1001/jamadermatol.2020.1741; Sanchez A et al. JAMA Dermatol. 2020 Apr 30. doi: 10.1001/jamadermatol.2020.1704.
Two infection.
It is not yet clear from these or other case reports which, if any, skin eruptions accompanying COVID-19 infections are caused by the virus, but the authors of the editorial, led by Lauren M. Madigan, MD, of the department of dermatology at the University of Utah, Salt Lake City, urged dermatologists to lead efforts to find out.
“To fully characterize skin manifestations, it may be necessary for dermatologists to evaluate these patients directly; comprehensive evaluation could reveal important morphologic clues, such as the subtle purpuric nature of skin lesions or the characteristic mucosal or ophthalmologic features of COVID-19,” the authors of the editorial stated.
So far, the patterns of skin symptoms, which have been identified in up to 20% of COVID-19–infected patients in some series, have been heterogeneous as demonstrated in the two published case reports.
In one case, a papulosquamous and erythematous periumbilical patch that appeared on the trunk in an elderly patient 1 day after hospital admission for acute respiratory distress rapidly evolved into a digitate papulosquamous eruption involving the upper arms, shoulder, and back. It was described as “clinically reminiscent” of pityriasis rosea by the authors, from the divisions of dermatology and venereology, pathology, intensive care, and the virology laboratory, of the Hôpital Cochin, Paris.
In the other, pruritic erythematous macules, papules, and petechiae affecting the buttocks, popliteal fossae, anterior thighs, and lower abdomen appeared 3 days after the onset of fever in a 48-year-old man hospitalized in Madrid. A biopsy demonstrated a superficial perivascular lymphocytic infiltrate with red cell extravasation and focal papillary edema, “along with focal parakeratosis and isolated dyskeratotic cells,” according to the authors of this report, from the department of dermatology at Ramon y Cajal University, Madrid.
It was unclear whether COVID-19 directly caused either skin eruption. In the patient with the digitate papulosquamous eruption, no virus could be isolated from the skin. Based on high levels of proinflammatory cytokines, it was hypothesized that the rash might have been secondary to an immune response. The rash resolved within a week, but the patient subsequently died of the infection.
In the second case, the petechial lesions, which developed before any treatment was initiated, were said to resemble those associated with other viruses, such as parvovirus B19. This led the investigators to speculate that SARS-CoV-2 “could affect the skin in a similar way,” even though other potential etiologies could not be excluded. Treated with a topical steroid and an oral antihistamine, the skin lesions resolved after 5 days. This patient was discharged after recovering from the respiratory illness after 12 days.
Like previously reported cutaneous eruptions associated with COVID-19 infection, these cases “raise more questions than they provide answers,” wrote the authors of the editorial, but the limited information currently available was the basis for encouraging dermatologists to get involved.
To participate, dermatologists need not necessarily be affiliated with an academic center, according to one of the editorial coauthors, Kanade Shinkai, MD, PhD, professor of dermatology at the University of California, San Francisco. She noted that any health professional is invited to submit cases of COVID-19–associated dermatoses to a registry set up by the American Academy of Dermatology.
It is hoped that cases captured in this registry will create sufficient data to allow clinically relevant patterns and etiologies to be characterized.
The need for data is clear to those on the front lines. Kirsten Lo Sicco, MD, associate director of the skin and cancer unit at New York University, reported that her center is already set up to collect data systematically. “At NYU, we are currently working on standardizing laboratory and histopathology work up for COVID-19 patients who present with various skin eruptions.”
The goal, she added, is “to better determine COVID-19 pathophysiology, systemic associations, patient outcomes, and potential therapeutics.”
“Presumably, many of the eruptions seen in the setting of COVID-19 infection are related,” Dr. Lo Sicco explained in an interview. However, skin complications of infection “may overlap with or be a result of other etiologies as well.”
While better testing for COVID-19 and more lesion biopsies will play a critical role in differentiating etiologies, “we must not overcall COVID-19–related skin eruptions and potentially overlook other diagnoses,” Dr. Lo Sicco said.
In recounting some challenges from the NYU experience so far, Dr. Lo Sicco described the difficulty of differentiating COVID-19–related skin eruptions from skin eruptions caused by treatments, such as antibiotics and antivirals, when the presentation is delayed.
“This is where collaboration with our dermatopathologists becomes important. Drug eruptions, viral exanthems, urticarial eruptions, vasculopathy, and vasculitis can all be differentiated on dermpath,” she said.
One early obstacle to the skin biopsies essential for these types of studies was the limited supply of personal protective equipment at many centers, including hospitals in New York. Biopsies could not be safely performed if supplies of masks and gowns were limited.
Recent evidence suggests that some of the more common morphologies, such as purpuric eruptions, livedo reticularis, and retiform purpura, are linked to the vasculopathy associated with COVID-19 infection, according to Dr. Lo Sicco, but this invites a new set of questions.
One is whether vasculopathies can be prevented with prophylactic anticoagulation. Many hospitalized COVID-19 patients are already receiving therapeutic anticoagulation, but Dr. Lo Sicco questioned whether prophylactic anticoagulation might improve prognosis for outpatients, such as those discharged or those never hospitalized. This is a strategy now being investigated.
Ultimately, she agreed with the thrust of the JAMA Dermatology editorial.
“Dermatologists are vital to determine if various morphologies, such as urticarial, vesicular, purpuric, or papulosquamous lesions, have any specific systemic implications or relate to differences in patient outcomes,” she said.
These are exactly the types of issues being actively investigated at her center.
Neither the authors of the case reports nor of the editorial reported any conflicts of interest.
SOURCEs: Madigan LM et al. JAMA Dermatol. 2020 Apr 30. doi:10.1001/jamadermatol.2020.1438; Diaz-Guimaraens B et al. JAMA Dermatol. 2020 Apr 30. doi: 10.1001/jamadermatol.2020.1741; Sanchez A et al. JAMA Dermatol. 2020 Apr 30. doi: 10.1001/jamadermatol.2020.1704.
Two infection.
It is not yet clear from these or other case reports which, if any, skin eruptions accompanying COVID-19 infections are caused by the virus, but the authors of the editorial, led by Lauren M. Madigan, MD, of the department of dermatology at the University of Utah, Salt Lake City, urged dermatologists to lead efforts to find out.
“To fully characterize skin manifestations, it may be necessary for dermatologists to evaluate these patients directly; comprehensive evaluation could reveal important morphologic clues, such as the subtle purpuric nature of skin lesions or the characteristic mucosal or ophthalmologic features of COVID-19,” the authors of the editorial stated.
So far, the patterns of skin symptoms, which have been identified in up to 20% of COVID-19–infected patients in some series, have been heterogeneous as demonstrated in the two published case reports.
In one case, a papulosquamous and erythematous periumbilical patch that appeared on the trunk in an elderly patient 1 day after hospital admission for acute respiratory distress rapidly evolved into a digitate papulosquamous eruption involving the upper arms, shoulder, and back. It was described as “clinically reminiscent” of pityriasis rosea by the authors, from the divisions of dermatology and venereology, pathology, intensive care, and the virology laboratory, of the Hôpital Cochin, Paris.
In the other, pruritic erythematous macules, papules, and petechiae affecting the buttocks, popliteal fossae, anterior thighs, and lower abdomen appeared 3 days after the onset of fever in a 48-year-old man hospitalized in Madrid. A biopsy demonstrated a superficial perivascular lymphocytic infiltrate with red cell extravasation and focal papillary edema, “along with focal parakeratosis and isolated dyskeratotic cells,” according to the authors of this report, from the department of dermatology at Ramon y Cajal University, Madrid.
It was unclear whether COVID-19 directly caused either skin eruption. In the patient with the digitate papulosquamous eruption, no virus could be isolated from the skin. Based on high levels of proinflammatory cytokines, it was hypothesized that the rash might have been secondary to an immune response. The rash resolved within a week, but the patient subsequently died of the infection.
In the second case, the petechial lesions, which developed before any treatment was initiated, were said to resemble those associated with other viruses, such as parvovirus B19. This led the investigators to speculate that SARS-CoV-2 “could affect the skin in a similar way,” even though other potential etiologies could not be excluded. Treated with a topical steroid and an oral antihistamine, the skin lesions resolved after 5 days. This patient was discharged after recovering from the respiratory illness after 12 days.
Like previously reported cutaneous eruptions associated with COVID-19 infection, these cases “raise more questions than they provide answers,” wrote the authors of the editorial, but the limited information currently available was the basis for encouraging dermatologists to get involved.
To participate, dermatologists need not necessarily be affiliated with an academic center, according to one of the editorial coauthors, Kanade Shinkai, MD, PhD, professor of dermatology at the University of California, San Francisco. She noted that any health professional is invited to submit cases of COVID-19–associated dermatoses to a registry set up by the American Academy of Dermatology.
It is hoped that cases captured in this registry will create sufficient data to allow clinically relevant patterns and etiologies to be characterized.
The need for data is clear to those on the front lines. Kirsten Lo Sicco, MD, associate director of the skin and cancer unit at New York University, reported that her center is already set up to collect data systematically. “At NYU, we are currently working on standardizing laboratory and histopathology work up for COVID-19 patients who present with various skin eruptions.”
The goal, she added, is “to better determine COVID-19 pathophysiology, systemic associations, patient outcomes, and potential therapeutics.”
“Presumably, many of the eruptions seen in the setting of COVID-19 infection are related,” Dr. Lo Sicco explained in an interview. However, skin complications of infection “may overlap with or be a result of other etiologies as well.”
While better testing for COVID-19 and more lesion biopsies will play a critical role in differentiating etiologies, “we must not overcall COVID-19–related skin eruptions and potentially overlook other diagnoses,” Dr. Lo Sicco said.
In recounting some challenges from the NYU experience so far, Dr. Lo Sicco described the difficulty of differentiating COVID-19–related skin eruptions from skin eruptions caused by treatments, such as antibiotics and antivirals, when the presentation is delayed.
“This is where collaboration with our dermatopathologists becomes important. Drug eruptions, viral exanthems, urticarial eruptions, vasculopathy, and vasculitis can all be differentiated on dermpath,” she said.
One early obstacle to the skin biopsies essential for these types of studies was the limited supply of personal protective equipment at many centers, including hospitals in New York. Biopsies could not be safely performed if supplies of masks and gowns were limited.
Recent evidence suggests that some of the more common morphologies, such as purpuric eruptions, livedo reticularis, and retiform purpura, are linked to the vasculopathy associated with COVID-19 infection, according to Dr. Lo Sicco, but this invites a new set of questions.
One is whether vasculopathies can be prevented with prophylactic anticoagulation. Many hospitalized COVID-19 patients are already receiving therapeutic anticoagulation, but Dr. Lo Sicco questioned whether prophylactic anticoagulation might improve prognosis for outpatients, such as those discharged or those never hospitalized. This is a strategy now being investigated.
Ultimately, she agreed with the thrust of the JAMA Dermatology editorial.
“Dermatologists are vital to determine if various morphologies, such as urticarial, vesicular, purpuric, or papulosquamous lesions, have any specific systemic implications or relate to differences in patient outcomes,” she said.
These are exactly the types of issues being actively investigated at her center.
Neither the authors of the case reports nor of the editorial reported any conflicts of interest.
SOURCEs: Madigan LM et al. JAMA Dermatol. 2020 Apr 30. doi:10.1001/jamadermatol.2020.1438; Diaz-Guimaraens B et al. JAMA Dermatol. 2020 Apr 30. doi: 10.1001/jamadermatol.2020.1741; Sanchez A et al. JAMA Dermatol. 2020 Apr 30. doi: 10.1001/jamadermatol.2020.1704.
Diastolic dysfunction is a common risk factor for cognitive decline
a new study suggests. “We found people with worsening diastolic dysfunction have more white matter hyperintensities on brain imaging and greater difficulty with executive functioning, suggesting that diastolic dysfunction is a common modifiable risk factor for cognitive impairment,” said lead author Alicia S. Parker, MD. Dr. Parker is assistant professor of cognitive and behavioral neurology at the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, University of Texas Health, San Antonio.
“This is an entirely new finding. While there have been some small studies suggesting a link between diastolic dysfunction and a reduction in working memory, this is by far the largest dataset on this topic and the first study that has included brain imaging and neuropsychological measures,” she said.
“Diastolic dysfunction is very common in the older population, and we need to do more to find it and treat it to help prevent or reduce cognitive decline,” Dr. Parker added.
This research is being presented online as part of the 2020 American Academy of Neurology Science Highlights.
Dr. Parker explained that systolic dysfunction is known to have a major effect on cardiovascular outcomes and has been found to be associated with cognitive decline. Proposed mechanisms for cognitive decline in patients with systolic dysfunction include low cardiac output, embolic infarctions, and hypoxic changes, among others.
“There is increasing interest in analyzing the influence of diastolic dysfunction on cardiovascular outcomes, and the effects of diastolic dysfunction on cognition are not currently well delineated, which this study seeks to address,” she added.
“While these results are new, they are not surprising. In general, we are finding more and more that heart health is connected to brain health,” she commented.
Dr. Parker and her colleagues started the current research after noticing in clinic that among patients with significant diastolic dysfunction, there were often changes on brain MRI imaging, and the patients often had trouble with executive function. “The effect of diastolic dysfunction on cognition has not been well characterized, so we wanted to look at this,” she said.
The investigators analyzed data from the Framingham Heart Study Offspring Cohort at examination 8, collected between 2005 and 2008. The study sample included 1,438 individuals older than 55 years who had undergone neuropsychological assessment and echocardiographic diastolic measurement. Systolic measurements were normal for the participants, and they did not currently have dementia, stroke, or other neurologic illness.
Results showed that increasing E/E’ ratio (the ratio of mitral peak velocity of early filling to early diastolic mitral annular velocity) indicated increasing diastolic dysfunction and was associated with an increase in the incidence of mild cognitive impairment (hazard ratio, 1.29; 95% confidence interval, 1.01-1.66; P < .043).
An increased E/E’ ratio was associated with increased executive function impairment in the “similarities” (beta, –0.29; P < .002) and “phonemic fluency” (–1.28; P < .001) tasks.
Participants with moderate to severe diastolic dysfunction were more impaired with respect to both similarities (–0.62; P < .046) and phonemic fluency (–2.60; P < .023).
Data from 1,217 participants showed that among those with mild diastolic dysfunction, there was a trend toward an increase in white matter hyperintensities (0.11; P < .105). For participants with moderate to severe diastolic dysfunction, white matter hyperintensities were increased (0.30; P < 0.001).
The results were unchanged after the researchers adjusted for many other predictors of cognitive decline affecting diastolic function.
The researchers conclude: “As cerebral small vessel disease clinically presents with executive dysfunction, these results align well.” They add that replication in additional cohorts and analyses of cognition in treatment trials of diastolic dysfunction are warranted.
Earlier interventions
Commenting on the study, Marco R. Di Tullio, MD, professor of medicine and Columbia University Medical Center, New York City, who is also studying the relationship between subclinical cardiac abnormalities and cognition, said: “This is a promising area of research, as it might allow us to uncover novel risk factors for cognitive decline at an early stage, before the development of clinically manifest cardiac disease, which might allow earlier interventions to decrease or delay the onset of cognitive decline.”
Dr. Di Tullio added that he would like to know more about the interaction between diastolic dysfunction, MRI abnormalities, and cognitive impairment risk. “In this study, MRI abnormalities and cognitive impairment are treated as separate outcomes, with diastolic dysfunction being the exposure for each of them. An additional analysis of the association between diastolic dysfunction and cognitive impairment stratified by presence or absence of brain MRI findings would have been interesting.”
Dr. Parker responded that this is an area of investigation. “We suspect that our cognitive findings would not be explained by any one MRI measure, though a comprehensive examination of MRI findings would be of benefit. The thought that there may be a reversible cardiac abnormality that does not have a structural brain imaging correlate on MRI is an interesting possibility,” she said.
Dr. Di Tullio also pointed out that at present, there is no specific treatment for diastolic dysfunction other than to address some the conditions that predispose to it, such as hypertension and atrial fibrillation.
“We completely agree that specific treatments are an area of investigation and that treatment is therefore targeted at associated modifiable conditions,” Dr. Parker replied.
With regard to more specific estimates of the prevalence of diastolic dysfunction, Dr. Parker cites another Framingham analysis that involved 2,355 persons without any prevalent cardiovascular conditions. That study found that diastolic dysfunction was rare until 50 years of age and then gradually increased with age.
About 5% of people in their 50s had mild diastolic dysfunction, and about 3% had moderate to severe diastolic dysfunction. Among persons in their 60s, about 18% had mild and 5% had severe diastolic dysfunction. Among persons in their 70s, mild diastolic dysfunction occurred in 35%, and moderate to severe disease was present in 18%; and in persons older than 80 years, nearly half had mild and about 20% had moderate to severe diastolic dysfunction.
Dr. Parker has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
a new study suggests. “We found people with worsening diastolic dysfunction have more white matter hyperintensities on brain imaging and greater difficulty with executive functioning, suggesting that diastolic dysfunction is a common modifiable risk factor for cognitive impairment,” said lead author Alicia S. Parker, MD. Dr. Parker is assistant professor of cognitive and behavioral neurology at the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, University of Texas Health, San Antonio.
“This is an entirely new finding. While there have been some small studies suggesting a link between diastolic dysfunction and a reduction in working memory, this is by far the largest dataset on this topic and the first study that has included brain imaging and neuropsychological measures,” she said.
“Diastolic dysfunction is very common in the older population, and we need to do more to find it and treat it to help prevent or reduce cognitive decline,” Dr. Parker added.
This research is being presented online as part of the 2020 American Academy of Neurology Science Highlights.
Dr. Parker explained that systolic dysfunction is known to have a major effect on cardiovascular outcomes and has been found to be associated with cognitive decline. Proposed mechanisms for cognitive decline in patients with systolic dysfunction include low cardiac output, embolic infarctions, and hypoxic changes, among others.
“There is increasing interest in analyzing the influence of diastolic dysfunction on cardiovascular outcomes, and the effects of diastolic dysfunction on cognition are not currently well delineated, which this study seeks to address,” she added.
“While these results are new, they are not surprising. In general, we are finding more and more that heart health is connected to brain health,” she commented.
Dr. Parker and her colleagues started the current research after noticing in clinic that among patients with significant diastolic dysfunction, there were often changes on brain MRI imaging, and the patients often had trouble with executive function. “The effect of diastolic dysfunction on cognition has not been well characterized, so we wanted to look at this,” she said.
The investigators analyzed data from the Framingham Heart Study Offspring Cohort at examination 8, collected between 2005 and 2008. The study sample included 1,438 individuals older than 55 years who had undergone neuropsychological assessment and echocardiographic diastolic measurement. Systolic measurements were normal for the participants, and they did not currently have dementia, stroke, or other neurologic illness.
Results showed that increasing E/E’ ratio (the ratio of mitral peak velocity of early filling to early diastolic mitral annular velocity) indicated increasing diastolic dysfunction and was associated with an increase in the incidence of mild cognitive impairment (hazard ratio, 1.29; 95% confidence interval, 1.01-1.66; P < .043).
An increased E/E’ ratio was associated with increased executive function impairment in the “similarities” (beta, –0.29; P < .002) and “phonemic fluency” (–1.28; P < .001) tasks.
Participants with moderate to severe diastolic dysfunction were more impaired with respect to both similarities (–0.62; P < .046) and phonemic fluency (–2.60; P < .023).
Data from 1,217 participants showed that among those with mild diastolic dysfunction, there was a trend toward an increase in white matter hyperintensities (0.11; P < .105). For participants with moderate to severe diastolic dysfunction, white matter hyperintensities were increased (0.30; P < 0.001).
The results were unchanged after the researchers adjusted for many other predictors of cognitive decline affecting diastolic function.
The researchers conclude: “As cerebral small vessel disease clinically presents with executive dysfunction, these results align well.” They add that replication in additional cohorts and analyses of cognition in treatment trials of diastolic dysfunction are warranted.
Earlier interventions
Commenting on the study, Marco R. Di Tullio, MD, professor of medicine and Columbia University Medical Center, New York City, who is also studying the relationship between subclinical cardiac abnormalities and cognition, said: “This is a promising area of research, as it might allow us to uncover novel risk factors for cognitive decline at an early stage, before the development of clinically manifest cardiac disease, which might allow earlier interventions to decrease or delay the onset of cognitive decline.”
Dr. Di Tullio added that he would like to know more about the interaction between diastolic dysfunction, MRI abnormalities, and cognitive impairment risk. “In this study, MRI abnormalities and cognitive impairment are treated as separate outcomes, with diastolic dysfunction being the exposure for each of them. An additional analysis of the association between diastolic dysfunction and cognitive impairment stratified by presence or absence of brain MRI findings would have been interesting.”
Dr. Parker responded that this is an area of investigation. “We suspect that our cognitive findings would not be explained by any one MRI measure, though a comprehensive examination of MRI findings would be of benefit. The thought that there may be a reversible cardiac abnormality that does not have a structural brain imaging correlate on MRI is an interesting possibility,” she said.
Dr. Di Tullio also pointed out that at present, there is no specific treatment for diastolic dysfunction other than to address some the conditions that predispose to it, such as hypertension and atrial fibrillation.
“We completely agree that specific treatments are an area of investigation and that treatment is therefore targeted at associated modifiable conditions,” Dr. Parker replied.
With regard to more specific estimates of the prevalence of diastolic dysfunction, Dr. Parker cites another Framingham analysis that involved 2,355 persons without any prevalent cardiovascular conditions. That study found that diastolic dysfunction was rare until 50 years of age and then gradually increased with age.
About 5% of people in their 50s had mild diastolic dysfunction, and about 3% had moderate to severe diastolic dysfunction. Among persons in their 60s, about 18% had mild and 5% had severe diastolic dysfunction. Among persons in their 70s, mild diastolic dysfunction occurred in 35%, and moderate to severe disease was present in 18%; and in persons older than 80 years, nearly half had mild and about 20% had moderate to severe diastolic dysfunction.
Dr. Parker has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
a new study suggests. “We found people with worsening diastolic dysfunction have more white matter hyperintensities on brain imaging and greater difficulty with executive functioning, suggesting that diastolic dysfunction is a common modifiable risk factor for cognitive impairment,” said lead author Alicia S. Parker, MD. Dr. Parker is assistant professor of cognitive and behavioral neurology at the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, University of Texas Health, San Antonio.
“This is an entirely new finding. While there have been some small studies suggesting a link between diastolic dysfunction and a reduction in working memory, this is by far the largest dataset on this topic and the first study that has included brain imaging and neuropsychological measures,” she said.
“Diastolic dysfunction is very common in the older population, and we need to do more to find it and treat it to help prevent or reduce cognitive decline,” Dr. Parker added.
This research is being presented online as part of the 2020 American Academy of Neurology Science Highlights.
Dr. Parker explained that systolic dysfunction is known to have a major effect on cardiovascular outcomes and has been found to be associated with cognitive decline. Proposed mechanisms for cognitive decline in patients with systolic dysfunction include low cardiac output, embolic infarctions, and hypoxic changes, among others.
“There is increasing interest in analyzing the influence of diastolic dysfunction on cardiovascular outcomes, and the effects of diastolic dysfunction on cognition are not currently well delineated, which this study seeks to address,” she added.
“While these results are new, they are not surprising. In general, we are finding more and more that heart health is connected to brain health,” she commented.
Dr. Parker and her colleagues started the current research after noticing in clinic that among patients with significant diastolic dysfunction, there were often changes on brain MRI imaging, and the patients often had trouble with executive function. “The effect of diastolic dysfunction on cognition has not been well characterized, so we wanted to look at this,” she said.
The investigators analyzed data from the Framingham Heart Study Offspring Cohort at examination 8, collected between 2005 and 2008. The study sample included 1,438 individuals older than 55 years who had undergone neuropsychological assessment and echocardiographic diastolic measurement. Systolic measurements were normal for the participants, and they did not currently have dementia, stroke, or other neurologic illness.
Results showed that increasing E/E’ ratio (the ratio of mitral peak velocity of early filling to early diastolic mitral annular velocity) indicated increasing diastolic dysfunction and was associated with an increase in the incidence of mild cognitive impairment (hazard ratio, 1.29; 95% confidence interval, 1.01-1.66; P < .043).
An increased E/E’ ratio was associated with increased executive function impairment in the “similarities” (beta, –0.29; P < .002) and “phonemic fluency” (–1.28; P < .001) tasks.
Participants with moderate to severe diastolic dysfunction were more impaired with respect to both similarities (–0.62; P < .046) and phonemic fluency (–2.60; P < .023).
Data from 1,217 participants showed that among those with mild diastolic dysfunction, there was a trend toward an increase in white matter hyperintensities (0.11; P < .105). For participants with moderate to severe diastolic dysfunction, white matter hyperintensities were increased (0.30; P < 0.001).
The results were unchanged after the researchers adjusted for many other predictors of cognitive decline affecting diastolic function.
The researchers conclude: “As cerebral small vessel disease clinically presents with executive dysfunction, these results align well.” They add that replication in additional cohorts and analyses of cognition in treatment trials of diastolic dysfunction are warranted.
Earlier interventions
Commenting on the study, Marco R. Di Tullio, MD, professor of medicine and Columbia University Medical Center, New York City, who is also studying the relationship between subclinical cardiac abnormalities and cognition, said: “This is a promising area of research, as it might allow us to uncover novel risk factors for cognitive decline at an early stage, before the development of clinically manifest cardiac disease, which might allow earlier interventions to decrease or delay the onset of cognitive decline.”
Dr. Di Tullio added that he would like to know more about the interaction between diastolic dysfunction, MRI abnormalities, and cognitive impairment risk. “In this study, MRI abnormalities and cognitive impairment are treated as separate outcomes, with diastolic dysfunction being the exposure for each of them. An additional analysis of the association between diastolic dysfunction and cognitive impairment stratified by presence or absence of brain MRI findings would have been interesting.”
Dr. Parker responded that this is an area of investigation. “We suspect that our cognitive findings would not be explained by any one MRI measure, though a comprehensive examination of MRI findings would be of benefit. The thought that there may be a reversible cardiac abnormality that does not have a structural brain imaging correlate on MRI is an interesting possibility,” she said.
Dr. Di Tullio also pointed out that at present, there is no specific treatment for diastolic dysfunction other than to address some the conditions that predispose to it, such as hypertension and atrial fibrillation.
“We completely agree that specific treatments are an area of investigation and that treatment is therefore targeted at associated modifiable conditions,” Dr. Parker replied.
With regard to more specific estimates of the prevalence of diastolic dysfunction, Dr. Parker cites another Framingham analysis that involved 2,355 persons without any prevalent cardiovascular conditions. That study found that diastolic dysfunction was rare until 50 years of age and then gradually increased with age.
About 5% of people in their 50s had mild diastolic dysfunction, and about 3% had moderate to severe diastolic dysfunction. Among persons in their 60s, about 18% had mild and 5% had severe diastolic dysfunction. Among persons in their 70s, mild diastolic dysfunction occurred in 35%, and moderate to severe disease was present in 18%; and in persons older than 80 years, nearly half had mild and about 20% had moderate to severe diastolic dysfunction.
Dr. Parker has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
FDA tightens requirements for COVID-19 antibody tests
The U.S. Food and Drug Administration is tightening requirements for companies that develop COVID-19 antibody tests in an effort to combat fraud and better regulate the frenzy of tests coming to market.
The updated policy, announced May 4, requires commercial antibody test developers to apply for Emergency Use Authorization (EUA) from the FDA under a tight time frame and also provides specific performance threshold recommendations for test specificity and sensitivity. The revised requirements follow a March 16 policy that allowed developers to validate their own tests and bring them to market without an agency review. More than 100 coronavirus antibody tests have since entered the market, fueling a congressional investigation into the accuracy of tests.
When the March policy was issued, FDA Commissioner Stephen M. Hahn, MD, said it was critical for the FDA to provide regulatory flexibility for serology test developers, given the nature of the COVID-19 public health emergency and an understanding that the tests were not meant to be used as the sole basis for COVID-19 diagnosis.
“As FDA has authorized more antibody tests and validation data has become available, including through the capability at [the National Cancer Institute] the careful balancing of risks and benefits has shifted to the approach we have outlined today and our policy update,” Dr. Hahn said during a May 4 press conference.
The new approach requires all commercial manufacturers to submit EUA requests with their validation data within 10 business days from the date they notified the FDA of their validation testing or from the date of the May 4 policy, whichever is later. Additionally, the FDA has provided specific performance threshold recommendations for specificity and sensitivity for all serology test developers.
In a statement released May 4, FDA leaders acknowledged the widespread fraud that is occurring in connection to antibody tests entering the market.
“We unfortunately see unscrupulous actors marketing fraudulent test kits and using the pandemic as an opportunity to take advantage of Americans’ anxiety,” wrote Anand Shah, MD, FDA deputy commissioner for medical and scientific affairs in a joint statement with Jeff E. Shuren, MD, director for the FDA’s Center for Devices and Radiological Health. “Some test developers have falsely claimed their serological tests are FDA approved or authorized. Others have falsely claimed that their tests can diagnose COVID-19 or that they are for at-home testing, which would fall outside of the policies outlined in our March 16 guidance, as well as the updated guidance.”
At the same time, FDA officials said they are aware of a “concerning number” of commercial serology tests that are being inappropriately marketed, including for diagnostic use, or that are performing poorly based on an independent evaluation by the National Institutes of Health, according to the May 4 statement.
In addition to tightening its requirements for test developers, the FDA also is introducing a more streamlined process to support EUA submissions and review. Two voluntary EUA templates for antibody tests are now available – one for commercial manufacturers and one for Clinical Laboratory Improvement Amendments-certified high-complexity labs seeking FDA authorization. The templates will facilitate the preparation and submission of EUA requests and can be used by any interested developer, according to the FDA.
To date, 12 antibody tests have been authorized under an individual EUA, and more than 200 antibody tests are currently the subject of a pre-EUA or EUA review, according to the FDA.
Many unknowns remain about antibody tests and how they might help researchers and clinicians understand and/or potentially treat COVID-19. Antibody tests may be able to provide information on disease prevalence and frequency of asymptomatic infection, as well as identify potential donors of “convalescent plasma,” an approach in which blood plasma containing antibodies from a recovered individual serves as a therapy for an infected patient with severe disease, Dr. Shah wrote in the May 4 statement.
“There are a lot of unanswered questions about this particular issue,” Dr. Hahn said during the press conference. “We need the data because we need to understand this particular aspect of the disease and put it as part of the puzzle around COVID-19.”
The U.S. Food and Drug Administration is tightening requirements for companies that develop COVID-19 antibody tests in an effort to combat fraud and better regulate the frenzy of tests coming to market.
The updated policy, announced May 4, requires commercial antibody test developers to apply for Emergency Use Authorization (EUA) from the FDA under a tight time frame and also provides specific performance threshold recommendations for test specificity and sensitivity. The revised requirements follow a March 16 policy that allowed developers to validate their own tests and bring them to market without an agency review. More than 100 coronavirus antibody tests have since entered the market, fueling a congressional investigation into the accuracy of tests.
When the March policy was issued, FDA Commissioner Stephen M. Hahn, MD, said it was critical for the FDA to provide regulatory flexibility for serology test developers, given the nature of the COVID-19 public health emergency and an understanding that the tests were not meant to be used as the sole basis for COVID-19 diagnosis.
“As FDA has authorized more antibody tests and validation data has become available, including through the capability at [the National Cancer Institute] the careful balancing of risks and benefits has shifted to the approach we have outlined today and our policy update,” Dr. Hahn said during a May 4 press conference.
The new approach requires all commercial manufacturers to submit EUA requests with their validation data within 10 business days from the date they notified the FDA of their validation testing or from the date of the May 4 policy, whichever is later. Additionally, the FDA has provided specific performance threshold recommendations for specificity and sensitivity for all serology test developers.
In a statement released May 4, FDA leaders acknowledged the widespread fraud that is occurring in connection to antibody tests entering the market.
“We unfortunately see unscrupulous actors marketing fraudulent test kits and using the pandemic as an opportunity to take advantage of Americans’ anxiety,” wrote Anand Shah, MD, FDA deputy commissioner for medical and scientific affairs in a joint statement with Jeff E. Shuren, MD, director for the FDA’s Center for Devices and Radiological Health. “Some test developers have falsely claimed their serological tests are FDA approved or authorized. Others have falsely claimed that their tests can diagnose COVID-19 or that they are for at-home testing, which would fall outside of the policies outlined in our March 16 guidance, as well as the updated guidance.”
At the same time, FDA officials said they are aware of a “concerning number” of commercial serology tests that are being inappropriately marketed, including for diagnostic use, or that are performing poorly based on an independent evaluation by the National Institutes of Health, according to the May 4 statement.
In addition to tightening its requirements for test developers, the FDA also is introducing a more streamlined process to support EUA submissions and review. Two voluntary EUA templates for antibody tests are now available – one for commercial manufacturers and one for Clinical Laboratory Improvement Amendments-certified high-complexity labs seeking FDA authorization. The templates will facilitate the preparation and submission of EUA requests and can be used by any interested developer, according to the FDA.
To date, 12 antibody tests have been authorized under an individual EUA, and more than 200 antibody tests are currently the subject of a pre-EUA or EUA review, according to the FDA.
Many unknowns remain about antibody tests and how they might help researchers and clinicians understand and/or potentially treat COVID-19. Antibody tests may be able to provide information on disease prevalence and frequency of asymptomatic infection, as well as identify potential donors of “convalescent plasma,” an approach in which blood plasma containing antibodies from a recovered individual serves as a therapy for an infected patient with severe disease, Dr. Shah wrote in the May 4 statement.
“There are a lot of unanswered questions about this particular issue,” Dr. Hahn said during the press conference. “We need the data because we need to understand this particular aspect of the disease and put it as part of the puzzle around COVID-19.”
The U.S. Food and Drug Administration is tightening requirements for companies that develop COVID-19 antibody tests in an effort to combat fraud and better regulate the frenzy of tests coming to market.
The updated policy, announced May 4, requires commercial antibody test developers to apply for Emergency Use Authorization (EUA) from the FDA under a tight time frame and also provides specific performance threshold recommendations for test specificity and sensitivity. The revised requirements follow a March 16 policy that allowed developers to validate their own tests and bring them to market without an agency review. More than 100 coronavirus antibody tests have since entered the market, fueling a congressional investigation into the accuracy of tests.
When the March policy was issued, FDA Commissioner Stephen M. Hahn, MD, said it was critical for the FDA to provide regulatory flexibility for serology test developers, given the nature of the COVID-19 public health emergency and an understanding that the tests were not meant to be used as the sole basis for COVID-19 diagnosis.
“As FDA has authorized more antibody tests and validation data has become available, including through the capability at [the National Cancer Institute] the careful balancing of risks and benefits has shifted to the approach we have outlined today and our policy update,” Dr. Hahn said during a May 4 press conference.
The new approach requires all commercial manufacturers to submit EUA requests with their validation data within 10 business days from the date they notified the FDA of their validation testing or from the date of the May 4 policy, whichever is later. Additionally, the FDA has provided specific performance threshold recommendations for specificity and sensitivity for all serology test developers.
In a statement released May 4, FDA leaders acknowledged the widespread fraud that is occurring in connection to antibody tests entering the market.
“We unfortunately see unscrupulous actors marketing fraudulent test kits and using the pandemic as an opportunity to take advantage of Americans’ anxiety,” wrote Anand Shah, MD, FDA deputy commissioner for medical and scientific affairs in a joint statement with Jeff E. Shuren, MD, director for the FDA’s Center for Devices and Radiological Health. “Some test developers have falsely claimed their serological tests are FDA approved or authorized. Others have falsely claimed that their tests can diagnose COVID-19 or that they are for at-home testing, which would fall outside of the policies outlined in our March 16 guidance, as well as the updated guidance.”
At the same time, FDA officials said they are aware of a “concerning number” of commercial serology tests that are being inappropriately marketed, including for diagnostic use, or that are performing poorly based on an independent evaluation by the National Institutes of Health, according to the May 4 statement.
In addition to tightening its requirements for test developers, the FDA also is introducing a more streamlined process to support EUA submissions and review. Two voluntary EUA templates for antibody tests are now available – one for commercial manufacturers and one for Clinical Laboratory Improvement Amendments-certified high-complexity labs seeking FDA authorization. The templates will facilitate the preparation and submission of EUA requests and can be used by any interested developer, according to the FDA.
To date, 12 antibody tests have been authorized under an individual EUA, and more than 200 antibody tests are currently the subject of a pre-EUA or EUA review, according to the FDA.
Many unknowns remain about antibody tests and how they might help researchers and clinicians understand and/or potentially treat COVID-19. Antibody tests may be able to provide information on disease prevalence and frequency of asymptomatic infection, as well as identify potential donors of “convalescent plasma,” an approach in which blood plasma containing antibodies from a recovered individual serves as a therapy for an infected patient with severe disease, Dr. Shah wrote in the May 4 statement.
“There are a lot of unanswered questions about this particular issue,” Dr. Hahn said during the press conference. “We need the data because we need to understand this particular aspect of the disease and put it as part of the puzzle around COVID-19.”
Adding mechanical to pharma prophylaxis does not cut DVT incidence
Background: Critically ill patients have a high risk of venous thromboembolism (VTE) during their hospitalizations, and it is standard of care to prophylax against this complication by either pharmacological or mechanical means.
Study design: Prospective, randomized, controlled trial (Pneumatic Compression for Preventing Venous Thromboembolism [PREVENT]).
Setting: Multicenter study involving 20 ICUs in Saudi Arabia, Canada, Australia, and India.
Synopsis: The study monitored 2,003 medical and surgical ICU patients on pharmacological thromboprophylaxis (unfractionated or low-molecular-weight heparin) after receiving either adjunctive pneumatic compression or pharmacological thromboprophylaxis alone. The primary outcome was incident (newly diagnosed) proximal lower-limb DVT detected by twice-weekly venous ultrasonography until ICU discharge, death, attainment of full mobility, or trial day 28, whichever occurred first. Key secondary outcomes included the occurrence of any lower-limb DVTs and pulmonary embolism. Intermittent pneumatic compression was used a median of 22 hours daily. The incidence of proximal lower limb DVT did not differ in the two groups and was relatively low (4%) in the control group. There were also no differences in the groups in the composite VTE, death at 28 days, or any other secondary outcomes studied.
The main limitation of the study was the low incidence of primary outcomes in the control group, which reduced the power of the study.
Bottom line: Based on the PREVENT trial, adjunctive intermittent pneumatic compression provided no additional benefit to pharmacological prophylaxis in the prevention of incident proximal lower-limb DVT.
Citation: Arabi Y et al. Adjunctive intermittent pneumatic compression for venous thromboprophylaxis. N Eng J Med. 2019 Feb 18. doi: 10.1056/NEJMoa1816150.
Dr. Sekaran is a hospitalist at Massachusetts General Hospital.
Background: Critically ill patients have a high risk of venous thromboembolism (VTE) during their hospitalizations, and it is standard of care to prophylax against this complication by either pharmacological or mechanical means.
Study design: Prospective, randomized, controlled trial (Pneumatic Compression for Preventing Venous Thromboembolism [PREVENT]).
Setting: Multicenter study involving 20 ICUs in Saudi Arabia, Canada, Australia, and India.
Synopsis: The study monitored 2,003 medical and surgical ICU patients on pharmacological thromboprophylaxis (unfractionated or low-molecular-weight heparin) after receiving either adjunctive pneumatic compression or pharmacological thromboprophylaxis alone. The primary outcome was incident (newly diagnosed) proximal lower-limb DVT detected by twice-weekly venous ultrasonography until ICU discharge, death, attainment of full mobility, or trial day 28, whichever occurred first. Key secondary outcomes included the occurrence of any lower-limb DVTs and pulmonary embolism. Intermittent pneumatic compression was used a median of 22 hours daily. The incidence of proximal lower limb DVT did not differ in the two groups and was relatively low (4%) in the control group. There were also no differences in the groups in the composite VTE, death at 28 days, or any other secondary outcomes studied.
The main limitation of the study was the low incidence of primary outcomes in the control group, which reduced the power of the study.
Bottom line: Based on the PREVENT trial, adjunctive intermittent pneumatic compression provided no additional benefit to pharmacological prophylaxis in the prevention of incident proximal lower-limb DVT.
Citation: Arabi Y et al. Adjunctive intermittent pneumatic compression for venous thromboprophylaxis. N Eng J Med. 2019 Feb 18. doi: 10.1056/NEJMoa1816150.
Dr. Sekaran is a hospitalist at Massachusetts General Hospital.
Background: Critically ill patients have a high risk of venous thromboembolism (VTE) during their hospitalizations, and it is standard of care to prophylax against this complication by either pharmacological or mechanical means.
Study design: Prospective, randomized, controlled trial (Pneumatic Compression for Preventing Venous Thromboembolism [PREVENT]).
Setting: Multicenter study involving 20 ICUs in Saudi Arabia, Canada, Australia, and India.
Synopsis: The study monitored 2,003 medical and surgical ICU patients on pharmacological thromboprophylaxis (unfractionated or low-molecular-weight heparin) after receiving either adjunctive pneumatic compression or pharmacological thromboprophylaxis alone. The primary outcome was incident (newly diagnosed) proximal lower-limb DVT detected by twice-weekly venous ultrasonography until ICU discharge, death, attainment of full mobility, or trial day 28, whichever occurred first. Key secondary outcomes included the occurrence of any lower-limb DVTs and pulmonary embolism. Intermittent pneumatic compression was used a median of 22 hours daily. The incidence of proximal lower limb DVT did not differ in the two groups and was relatively low (4%) in the control group. There were also no differences in the groups in the composite VTE, death at 28 days, or any other secondary outcomes studied.
The main limitation of the study was the low incidence of primary outcomes in the control group, which reduced the power of the study.
Bottom line: Based on the PREVENT trial, adjunctive intermittent pneumatic compression provided no additional benefit to pharmacological prophylaxis in the prevention of incident proximal lower-limb DVT.
Citation: Arabi Y et al. Adjunctive intermittent pneumatic compression for venous thromboprophylaxis. N Eng J Med. 2019 Feb 18. doi: 10.1056/NEJMoa1816150.
Dr. Sekaran is a hospitalist at Massachusetts General Hospital.
Hydroxychloroquine-triggered QTc-interval prolongations mount in COVID-19 patients
The potential for serious arrhythmias from hydroxychloroquine treatment of COVID-19 patients received further documentation from a pair of studies released on May 1, casting further doubt on whether the uncertain benefit from this or related drugs to infected patients is worth the clear risks the agents pose.
A report from 90 confirmed COVID-19 patients treated with hydroxychloroquine at one Boston hospital during March-April 2020 identified a significantly prolonged, corrected QT (QTc) interval of at least 500 msec in 18 patients (20%), which included 10 patients whose QTc rose by at least 60 msec above baseline, and a total of 21 patients (23%) having a notable prolongation (JAMA Cardiol. 2020 May 4. doi: 10.1001/jamacardio.2020.1834). This series included one patient who developed torsades de pointes following treatment with hydroxychloroquine and azithromycin, “which to our knowledge has yet to be reported elsewhere in the literature,” the report said.
The second report, from a single center in Lyon, France, included 40 confirmed COVID-19 patients treated with hydroxychloroquine during 2 weeks in late March, and found that 37 (93%) had some increase in the QTc interval, including 14 patients (36%) with an increase of at least 60 msec, and 7 patients (18%) whose QTc rose to at least 500 msec (JAMA Cardiol. 2020 May. doi: 10.1001/jamacardio.2020.1787). However, none of the 40 patients in this series developed an identified ventricular arrhythmia. All patients in both studies received hydroxychloroquine for at least 1 day, and roughly half the patients in each series also received concurrent azithromycin, another drug that can prolong the QTc interval and that has been frequently used in combination with hydroxychloroquine as an unproven COVID-19 treatment cocktail.
These two reports, as well as prior report from Brazil on COVID-19 patients treated with chloroquine diphosphate (JAMA Netw Open. 2020;3[4]:e208857), “underscore the potential risk associated with widespread use of hydroxychloroquine and the combination of hydroxychloroquine and azithromycin in ambulatory patients with known or suspected COVID-19. Understanding whether this risk is worth taking in the absence of evidence of therapeutic efficacy creates a knowledge gap that needs to be addressed,” wrote Robert O. Bonow, MD, a professor of medicine at Northwestern University in Chicago, and coauthors in an editorial that accompanied the two reports (JAMA Cardiol. 2020 May 4;doi: 10.1001/jamacardio.2020.1782). The editorial cited two recently-begun prospective trials, ORCHID and RECOVERY, that are more systematically assessing the safety and efficacy of hydroxychloroquine treatment in COVID-19 patients.
The findings lend further support to a Safety Communication from the U.S. Food and Drug Administration on April 24 that reminded clinicians that the Emergency Use Authorization for hydroxychloroquine and chloroquine in COVID-19 patients that the FDA issued on March 28 applied to only certain hospitalized patients or those enrolled in clinical trials. The Safety Communication also said that agency was aware of reports of adverse arrhythmia events when COVID-19 patients received these drugs outside a hospital setting as well as uninfected people who had received one of these drugs for preventing infection.
In addition, leaders of the American College of Cardiology, the American Heart Association, and the Heart Rhythm Society on April 10 issued a summary of considerations when using hydroxychloroquine and azithromycin to treat COVID-19 patients, and noted that a way to minimized the risk from these drugs is to withhold them from patients with a QTc interval of 500 msec or greater at baseline (J Am Coll Cardiol. 2020 Apr 10. doi: 10.1016/j.jacc.2020.04.016). The summary also highlighted the need for regular ECG monitoring of COVID-19 patients who receive drugs that can prolong the QTc interval, and recommended withdrawing treatment from patients when their QTc exceeds the 500 msec threshold.
None of the authors of the two reports and editorial had relevant commercial disclosures.
The potential for serious arrhythmias from hydroxychloroquine treatment of COVID-19 patients received further documentation from a pair of studies released on May 1, casting further doubt on whether the uncertain benefit from this or related drugs to infected patients is worth the clear risks the agents pose.
A report from 90 confirmed COVID-19 patients treated with hydroxychloroquine at one Boston hospital during March-April 2020 identified a significantly prolonged, corrected QT (QTc) interval of at least 500 msec in 18 patients (20%), which included 10 patients whose QTc rose by at least 60 msec above baseline, and a total of 21 patients (23%) having a notable prolongation (JAMA Cardiol. 2020 May 4. doi: 10.1001/jamacardio.2020.1834). This series included one patient who developed torsades de pointes following treatment with hydroxychloroquine and azithromycin, “which to our knowledge has yet to be reported elsewhere in the literature,” the report said.
The second report, from a single center in Lyon, France, included 40 confirmed COVID-19 patients treated with hydroxychloroquine during 2 weeks in late March, and found that 37 (93%) had some increase in the QTc interval, including 14 patients (36%) with an increase of at least 60 msec, and 7 patients (18%) whose QTc rose to at least 500 msec (JAMA Cardiol. 2020 May. doi: 10.1001/jamacardio.2020.1787). However, none of the 40 patients in this series developed an identified ventricular arrhythmia. All patients in both studies received hydroxychloroquine for at least 1 day, and roughly half the patients in each series also received concurrent azithromycin, another drug that can prolong the QTc interval and that has been frequently used in combination with hydroxychloroquine as an unproven COVID-19 treatment cocktail.
These two reports, as well as prior report from Brazil on COVID-19 patients treated with chloroquine diphosphate (JAMA Netw Open. 2020;3[4]:e208857), “underscore the potential risk associated with widespread use of hydroxychloroquine and the combination of hydroxychloroquine and azithromycin in ambulatory patients with known or suspected COVID-19. Understanding whether this risk is worth taking in the absence of evidence of therapeutic efficacy creates a knowledge gap that needs to be addressed,” wrote Robert O. Bonow, MD, a professor of medicine at Northwestern University in Chicago, and coauthors in an editorial that accompanied the two reports (JAMA Cardiol. 2020 May 4;doi: 10.1001/jamacardio.2020.1782). The editorial cited two recently-begun prospective trials, ORCHID and RECOVERY, that are more systematically assessing the safety and efficacy of hydroxychloroquine treatment in COVID-19 patients.
The findings lend further support to a Safety Communication from the U.S. Food and Drug Administration on April 24 that reminded clinicians that the Emergency Use Authorization for hydroxychloroquine and chloroquine in COVID-19 patients that the FDA issued on March 28 applied to only certain hospitalized patients or those enrolled in clinical trials. The Safety Communication also said that agency was aware of reports of adverse arrhythmia events when COVID-19 patients received these drugs outside a hospital setting as well as uninfected people who had received one of these drugs for preventing infection.
In addition, leaders of the American College of Cardiology, the American Heart Association, and the Heart Rhythm Society on April 10 issued a summary of considerations when using hydroxychloroquine and azithromycin to treat COVID-19 patients, and noted that a way to minimized the risk from these drugs is to withhold them from patients with a QTc interval of 500 msec or greater at baseline (J Am Coll Cardiol. 2020 Apr 10. doi: 10.1016/j.jacc.2020.04.016). The summary also highlighted the need for regular ECG monitoring of COVID-19 patients who receive drugs that can prolong the QTc interval, and recommended withdrawing treatment from patients when their QTc exceeds the 500 msec threshold.
None of the authors of the two reports and editorial had relevant commercial disclosures.
The potential for serious arrhythmias from hydroxychloroquine treatment of COVID-19 patients received further documentation from a pair of studies released on May 1, casting further doubt on whether the uncertain benefit from this or related drugs to infected patients is worth the clear risks the agents pose.
A report from 90 confirmed COVID-19 patients treated with hydroxychloroquine at one Boston hospital during March-April 2020 identified a significantly prolonged, corrected QT (QTc) interval of at least 500 msec in 18 patients (20%), which included 10 patients whose QTc rose by at least 60 msec above baseline, and a total of 21 patients (23%) having a notable prolongation (JAMA Cardiol. 2020 May 4. doi: 10.1001/jamacardio.2020.1834). This series included one patient who developed torsades de pointes following treatment with hydroxychloroquine and azithromycin, “which to our knowledge has yet to be reported elsewhere in the literature,” the report said.
The second report, from a single center in Lyon, France, included 40 confirmed COVID-19 patients treated with hydroxychloroquine during 2 weeks in late March, and found that 37 (93%) had some increase in the QTc interval, including 14 patients (36%) with an increase of at least 60 msec, and 7 patients (18%) whose QTc rose to at least 500 msec (JAMA Cardiol. 2020 May. doi: 10.1001/jamacardio.2020.1787). However, none of the 40 patients in this series developed an identified ventricular arrhythmia. All patients in both studies received hydroxychloroquine for at least 1 day, and roughly half the patients in each series also received concurrent azithromycin, another drug that can prolong the QTc interval and that has been frequently used in combination with hydroxychloroquine as an unproven COVID-19 treatment cocktail.
These two reports, as well as prior report from Brazil on COVID-19 patients treated with chloroquine diphosphate (JAMA Netw Open. 2020;3[4]:e208857), “underscore the potential risk associated with widespread use of hydroxychloroquine and the combination of hydroxychloroquine and azithromycin in ambulatory patients with known or suspected COVID-19. Understanding whether this risk is worth taking in the absence of evidence of therapeutic efficacy creates a knowledge gap that needs to be addressed,” wrote Robert O. Bonow, MD, a professor of medicine at Northwestern University in Chicago, and coauthors in an editorial that accompanied the two reports (JAMA Cardiol. 2020 May 4;doi: 10.1001/jamacardio.2020.1782). The editorial cited two recently-begun prospective trials, ORCHID and RECOVERY, that are more systematically assessing the safety and efficacy of hydroxychloroquine treatment in COVID-19 patients.
The findings lend further support to a Safety Communication from the U.S. Food and Drug Administration on April 24 that reminded clinicians that the Emergency Use Authorization for hydroxychloroquine and chloroquine in COVID-19 patients that the FDA issued on March 28 applied to only certain hospitalized patients or those enrolled in clinical trials. The Safety Communication also said that agency was aware of reports of adverse arrhythmia events when COVID-19 patients received these drugs outside a hospital setting as well as uninfected people who had received one of these drugs for preventing infection.
In addition, leaders of the American College of Cardiology, the American Heart Association, and the Heart Rhythm Society on April 10 issued a summary of considerations when using hydroxychloroquine and azithromycin to treat COVID-19 patients, and noted that a way to minimized the risk from these drugs is to withhold them from patients with a QTc interval of 500 msec or greater at baseline (J Am Coll Cardiol. 2020 Apr 10. doi: 10.1016/j.jacc.2020.04.016). The summary also highlighted the need for regular ECG monitoring of COVID-19 patients who receive drugs that can prolong the QTc interval, and recommended withdrawing treatment from patients when their QTc exceeds the 500 msec threshold.
None of the authors of the two reports and editorial had relevant commercial disclosures.
FROM JAMA CARDIOLOGY
COVID-19: To have and to hold ... in quarantine
Tips for marriage survival during a pandemic
Most married couples vowed to stay with their partners during sickness and health, but none of us vowed to remain trapped with our loved ones behind the same four walls, all day, every day, for an unknown period of time. We didn’t sign up for this! Some romantics may be titillated by the prospect, while more independent partners may panic at the mere thought of spending all day and night with their loved ones.
Because of the swift implementation of the lifestyle-altering restrictions, couples did not have ample time to mentally and physically prepare. A lack of preparation and loss of control heightens our emotions. It can make couples more susceptible to engage in unhealthy styles of communication and destructive behaviors that are harmful to their relationships.
There are psychological reasons that “absence makes the heart grow fonder.” Distance from your partner is not just a clever way to make your partner appreciate and desire you more. It is human nature to habituate to what is part of your daily life. For instance, when your partner is away from you while on a work trip, you may find the first night or two alone relaxing; but by day 3, you begin to miss your partner’s hugs and kisses, smell, and touch. And after many days apart, you may even miss the incessant nagging that secretly motivates you. Physical distance from our partners essentially gives us the ability to long for and appreciate each other. Our brains are wired to pay more attention to things that are novel and exciting and less interested in what is in our everyday lives.
Separation gives us the ability to miss our partners, while quarantine does the complete opposite.
To avoid contemplating how to murder one’s spouse before quarantine ends, partners can strengthen their relationships by using the strategies I’ve outlined below, which are loosely based on dialectical behavior therapy (DBT). These strategies can be useful for anyone – providers and patients alike – going through these struggles.
Dialectical behavior therapy was developed by psychologist Marsha Linehan PhD, to help regulate emotions for people diagnosed with borderline personality disorder. These skills help to identify thoughts and feelings, to accept one’s inner emotional world and outward behaviors. The idea is that, once you can recognize and accept, then change is possible. The “dialectic” in dialectical behavior therapy implies that one is attempting to find a balance between acceptance and change. All of us can benefit from these skills, especially emotionally volatile couples who are trapped together in quarantine.
Radically accept what is uncertain in your lives
Radical acceptance is a practice used in DBT in situations that are out of our control, such as the COVID-19 pandemic. Radically accept that you and your partner are trapped in quarantine without attempting to place blame on our government, your spouse, your boss, and even yourself. Radical acceptance is exactly what the name implies. Accept your current situation for what it is and not what you hoped it to be.
Accept the unknown and unanswered questions such as when will this quarantine end? Will there be a summer camp? Will I get back to my office this summer? Will my children even return to school in the fall? The acceptance of what is out of your control will ultimately decrease your mental time spent worrying and obsessing about the uncertainties of your post-quarantine life and instead provide you more time to be present with your spouse.
Remain mindful during all communication with your spouse. To stay in the moment, you need to be aware of your bodily reactions to distress and notice when your heart rate increases, breathing becomes more shallow, stomach muscles tighten, and when your thoughts become more negative. Mindfulness skills enable us to use physiological changes in our body to become aware of our emotions. You can use your partner’s nonverbal body language and tone of voice to gauge that person’s emotional reactivity.
The practice of mindfulness leads to an increased emotional intelligence. The goal is to have enough self-awareness and emotional understanding of your partner and enough empathy to know when a conversation is becoming too emotionally charged and to let it go and back off. Mindfulness is not nagging your partner to remember to change the heating unit filters with a reminder of what happened years ago when this wasn’t done promptly – without first checking in to make sure your partner is emotionally ready for this type of conversation.
When we have strong emotions, we are using the more primitive parts of our brain that induce a fight or flight reaction. These emotional reactions overshadow the more advanced prefrontal region of our brain that stores our rational thoughts and reasoning skills, a concept identified by psychologist Daniel Goleman as “emotional hijacking.”
Use distress tolerance skills to deal with negative emotions
Distress tolerance is an individual’s ability to manage feelings in response to stress. Distress tolerance skills are aimed at helping one manage intense emotions without worsening a situation by engaging in behaviors that are destructive and may exacerbate the problem. The goal is to tolerate the stress while with your partner and not respond negatively or in a way that is harmful to the integrity of your relationship.
To prioritize your relationship, this may mean that you choose not to react negatively when your partner makes a passive-aggressive comment on how you spent your day during quarantine since you still have a pile of laundry on your bedroom floor and overflowing dishes in the kitchen sink. A high level of distress tolerance will enable you to not overreact or withdraw from your spouse when flooded with emotions of anger or sadness.
Distraction techniques are a type of distress tolerance skill. You can engage in activities that keep you distracted and require your full attention. When things get heated between you and your spouse during quarantine, try to obtain some distance from each other to cool down and engage in an activity that involves your full concentration.
Many of us have been surprised by our hidden talents that were discovered during the quarantine. Use the time away from your partner to distract yourself with your new passion for writing, baking, organizing, and even your newfound love of balloon artistry. Do an activity that engages your mind and provides you the necessary physical and mental time away from your partner to deescalate. You can always revisit the initial cause of the conflict when both you and your partner are not emotionally charged. You can also distract yourself with self-soothing tactics such as taking a warm bath or a reading good book. Perhaps distract yourself by giving back to others and spending time planning a drive-by surprise party for your sister’s birthday next month. It can be helpful to distract yourself by comparing yourself to others less fortunate than you or a time in your life when you and your partner were struggling much worse than now, to provide perspective. The goal is not to add to your distress but instead, provide yourself a sense of perspective.
Use interpersonal effectiveness skills to establish a healthy relationship
Be gentle in all your communications with your partner, think about your spouse’s perspective, show empathy and interest in what your partner has to say by your verbal communication or body language, such as maintaining eye contact, and offer recognitional cues, such as “uh-huh” and “oh, really.” Avoid communication that is at all invalidating. Never start a sentence with “YOU” while having heated conversations with your spouse; instead, use “I feel” statements. This type of communication avoids the blame game that gets many couples into trouble.
Instead, communicate how you feel while not necessarily blaming your spouse but rather expressing your emotions. This will ultimately lead to less defensive communication from your partner. Remember that not all communication is for the sole purpose of communicating. Much of the time, communication is used as an attempt for one partner to connect with the other partner. Couples may say that they have difficulty with communication when it is not the communication that is the issue but instead the underlying disconnect of the couple.
This disconnect usually manifests while couples are communicating, and therefore, can be misconstrued as solely a communication issue by the couple. When your partner asks you to stop staring at your phone during dinner, it is not necessarily that your spouse is attempting to control you or wants to engage in some deep conversation, but more likely a bid to try to connect with you. Your partner is attempting to tell you that he or she feels disconnected, misses you, and wants to reconnect.
Provide validation and acceptance to your partner
Focus on your partner’s strengths and accept the weaknesses. Accept that your partner is scattered, disorganized, and takes at least 20 minutes to find the phone and keys every morning. Remember that during your courtship days, you found your partner’s flighty attributes to be endearing. Do the same for your strengths and weaknesses.
Accept that the pandemic is unpredictable and that you may need to strengthen your ability to be flexible and more adaptable. This will ultimately lead to feeling less disappointment by your partner and more accepting of shortcomings. Acceptance of your imperfections will improve your sense of worth and confidence and lessen negative emotions, such as guilt, regret, and shame.
Accept the fact that, as similar as we all are, we use different methods to recharge ourselves. In contrast, your spouse needs alone time without distractions to reboot mentally and prepare for the following day. In the pre-pandemic world, if there were a mismatch in what a couple needed to feel rejuvenated, they could independently compensate and search for fulfillment outside of the home. Before stay-at-home orders were rolled out throughout the country, spouses had ample opportunities to spend time away from their partners at work, dinner with friends, or while squeezing in a 7 p.m. yoga sculpt class – barely getting home in time to kiss our children goodnight – with a few minutes to spare to engage in mundane conversation with our partners before our nighttime routine of TV commenced. Unfortunately, COVID-19 has made it very hard for couples to carve out that time for compensatory activities outside of the home.
Remember that you are a team
Remind yourself of the reason why you initially fell in love with your partner. Teammates do not keep score or compete with one another. They support each other when one player is not feeling well, and they make sacrifices for the betterment of the team.
Your marriage vows included “through sickness and health” and now should include “through quarantine.”
Dr. Abraham is a psychiatrist in private practice in Philadelphia. She has no disclosures.
Tips for marriage survival during a pandemic
Tips for marriage survival during a pandemic
Most married couples vowed to stay with their partners during sickness and health, but none of us vowed to remain trapped with our loved ones behind the same four walls, all day, every day, for an unknown period of time. We didn’t sign up for this! Some romantics may be titillated by the prospect, while more independent partners may panic at the mere thought of spending all day and night with their loved ones.
Because of the swift implementation of the lifestyle-altering restrictions, couples did not have ample time to mentally and physically prepare. A lack of preparation and loss of control heightens our emotions. It can make couples more susceptible to engage in unhealthy styles of communication and destructive behaviors that are harmful to their relationships.
There are psychological reasons that “absence makes the heart grow fonder.” Distance from your partner is not just a clever way to make your partner appreciate and desire you more. It is human nature to habituate to what is part of your daily life. For instance, when your partner is away from you while on a work trip, you may find the first night or two alone relaxing; but by day 3, you begin to miss your partner’s hugs and kisses, smell, and touch. And after many days apart, you may even miss the incessant nagging that secretly motivates you. Physical distance from our partners essentially gives us the ability to long for and appreciate each other. Our brains are wired to pay more attention to things that are novel and exciting and less interested in what is in our everyday lives.
Separation gives us the ability to miss our partners, while quarantine does the complete opposite.
To avoid contemplating how to murder one’s spouse before quarantine ends, partners can strengthen their relationships by using the strategies I’ve outlined below, which are loosely based on dialectical behavior therapy (DBT). These strategies can be useful for anyone – providers and patients alike – going through these struggles.
Dialectical behavior therapy was developed by psychologist Marsha Linehan PhD, to help regulate emotions for people diagnosed with borderline personality disorder. These skills help to identify thoughts and feelings, to accept one’s inner emotional world and outward behaviors. The idea is that, once you can recognize and accept, then change is possible. The “dialectic” in dialectical behavior therapy implies that one is attempting to find a balance between acceptance and change. All of us can benefit from these skills, especially emotionally volatile couples who are trapped together in quarantine.
Radically accept what is uncertain in your lives
Radical acceptance is a practice used in DBT in situations that are out of our control, such as the COVID-19 pandemic. Radically accept that you and your partner are trapped in quarantine without attempting to place blame on our government, your spouse, your boss, and even yourself. Radical acceptance is exactly what the name implies. Accept your current situation for what it is and not what you hoped it to be.
Accept the unknown and unanswered questions such as when will this quarantine end? Will there be a summer camp? Will I get back to my office this summer? Will my children even return to school in the fall? The acceptance of what is out of your control will ultimately decrease your mental time spent worrying and obsessing about the uncertainties of your post-quarantine life and instead provide you more time to be present with your spouse.
Remain mindful during all communication with your spouse. To stay in the moment, you need to be aware of your bodily reactions to distress and notice when your heart rate increases, breathing becomes more shallow, stomach muscles tighten, and when your thoughts become more negative. Mindfulness skills enable us to use physiological changes in our body to become aware of our emotions. You can use your partner’s nonverbal body language and tone of voice to gauge that person’s emotional reactivity.
The practice of mindfulness leads to an increased emotional intelligence. The goal is to have enough self-awareness and emotional understanding of your partner and enough empathy to know when a conversation is becoming too emotionally charged and to let it go and back off. Mindfulness is not nagging your partner to remember to change the heating unit filters with a reminder of what happened years ago when this wasn’t done promptly – without first checking in to make sure your partner is emotionally ready for this type of conversation.
When we have strong emotions, we are using the more primitive parts of our brain that induce a fight or flight reaction. These emotional reactions overshadow the more advanced prefrontal region of our brain that stores our rational thoughts and reasoning skills, a concept identified by psychologist Daniel Goleman as “emotional hijacking.”
Use distress tolerance skills to deal with negative emotions
Distress tolerance is an individual’s ability to manage feelings in response to stress. Distress tolerance skills are aimed at helping one manage intense emotions without worsening a situation by engaging in behaviors that are destructive and may exacerbate the problem. The goal is to tolerate the stress while with your partner and not respond negatively or in a way that is harmful to the integrity of your relationship.
To prioritize your relationship, this may mean that you choose not to react negatively when your partner makes a passive-aggressive comment on how you spent your day during quarantine since you still have a pile of laundry on your bedroom floor and overflowing dishes in the kitchen sink. A high level of distress tolerance will enable you to not overreact or withdraw from your spouse when flooded with emotions of anger or sadness.
Distraction techniques are a type of distress tolerance skill. You can engage in activities that keep you distracted and require your full attention. When things get heated between you and your spouse during quarantine, try to obtain some distance from each other to cool down and engage in an activity that involves your full concentration.
Many of us have been surprised by our hidden talents that were discovered during the quarantine. Use the time away from your partner to distract yourself with your new passion for writing, baking, organizing, and even your newfound love of balloon artistry. Do an activity that engages your mind and provides you the necessary physical and mental time away from your partner to deescalate. You can always revisit the initial cause of the conflict when both you and your partner are not emotionally charged. You can also distract yourself with self-soothing tactics such as taking a warm bath or a reading good book. Perhaps distract yourself by giving back to others and spending time planning a drive-by surprise party for your sister’s birthday next month. It can be helpful to distract yourself by comparing yourself to others less fortunate than you or a time in your life when you and your partner were struggling much worse than now, to provide perspective. The goal is not to add to your distress but instead, provide yourself a sense of perspective.
Use interpersonal effectiveness skills to establish a healthy relationship
Be gentle in all your communications with your partner, think about your spouse’s perspective, show empathy and interest in what your partner has to say by your verbal communication or body language, such as maintaining eye contact, and offer recognitional cues, such as “uh-huh” and “oh, really.” Avoid communication that is at all invalidating. Never start a sentence with “YOU” while having heated conversations with your spouse; instead, use “I feel” statements. This type of communication avoids the blame game that gets many couples into trouble.
Instead, communicate how you feel while not necessarily blaming your spouse but rather expressing your emotions. This will ultimately lead to less defensive communication from your partner. Remember that not all communication is for the sole purpose of communicating. Much of the time, communication is used as an attempt for one partner to connect with the other partner. Couples may say that they have difficulty with communication when it is not the communication that is the issue but instead the underlying disconnect of the couple.
This disconnect usually manifests while couples are communicating, and therefore, can be misconstrued as solely a communication issue by the couple. When your partner asks you to stop staring at your phone during dinner, it is not necessarily that your spouse is attempting to control you or wants to engage in some deep conversation, but more likely a bid to try to connect with you. Your partner is attempting to tell you that he or she feels disconnected, misses you, and wants to reconnect.
Provide validation and acceptance to your partner
Focus on your partner’s strengths and accept the weaknesses. Accept that your partner is scattered, disorganized, and takes at least 20 minutes to find the phone and keys every morning. Remember that during your courtship days, you found your partner’s flighty attributes to be endearing. Do the same for your strengths and weaknesses.
Accept that the pandemic is unpredictable and that you may need to strengthen your ability to be flexible and more adaptable. This will ultimately lead to feeling less disappointment by your partner and more accepting of shortcomings. Acceptance of your imperfections will improve your sense of worth and confidence and lessen negative emotions, such as guilt, regret, and shame.
Accept the fact that, as similar as we all are, we use different methods to recharge ourselves. In contrast, your spouse needs alone time without distractions to reboot mentally and prepare for the following day. In the pre-pandemic world, if there were a mismatch in what a couple needed to feel rejuvenated, they could independently compensate and search for fulfillment outside of the home. Before stay-at-home orders were rolled out throughout the country, spouses had ample opportunities to spend time away from their partners at work, dinner with friends, or while squeezing in a 7 p.m. yoga sculpt class – barely getting home in time to kiss our children goodnight – with a few minutes to spare to engage in mundane conversation with our partners before our nighttime routine of TV commenced. Unfortunately, COVID-19 has made it very hard for couples to carve out that time for compensatory activities outside of the home.
Remember that you are a team
Remind yourself of the reason why you initially fell in love with your partner. Teammates do not keep score or compete with one another. They support each other when one player is not feeling well, and they make sacrifices for the betterment of the team.
Your marriage vows included “through sickness and health” and now should include “through quarantine.”
Dr. Abraham is a psychiatrist in private practice in Philadelphia. She has no disclosures.
Most married couples vowed to stay with their partners during sickness and health, but none of us vowed to remain trapped with our loved ones behind the same four walls, all day, every day, for an unknown period of time. We didn’t sign up for this! Some romantics may be titillated by the prospect, while more independent partners may panic at the mere thought of spending all day and night with their loved ones.
Because of the swift implementation of the lifestyle-altering restrictions, couples did not have ample time to mentally and physically prepare. A lack of preparation and loss of control heightens our emotions. It can make couples more susceptible to engage in unhealthy styles of communication and destructive behaviors that are harmful to their relationships.
There are psychological reasons that “absence makes the heart grow fonder.” Distance from your partner is not just a clever way to make your partner appreciate and desire you more. It is human nature to habituate to what is part of your daily life. For instance, when your partner is away from you while on a work trip, you may find the first night or two alone relaxing; but by day 3, you begin to miss your partner’s hugs and kisses, smell, and touch. And after many days apart, you may even miss the incessant nagging that secretly motivates you. Physical distance from our partners essentially gives us the ability to long for and appreciate each other. Our brains are wired to pay more attention to things that are novel and exciting and less interested in what is in our everyday lives.
Separation gives us the ability to miss our partners, while quarantine does the complete opposite.
To avoid contemplating how to murder one’s spouse before quarantine ends, partners can strengthen their relationships by using the strategies I’ve outlined below, which are loosely based on dialectical behavior therapy (DBT). These strategies can be useful for anyone – providers and patients alike – going through these struggles.
Dialectical behavior therapy was developed by psychologist Marsha Linehan PhD, to help regulate emotions for people diagnosed with borderline personality disorder. These skills help to identify thoughts and feelings, to accept one’s inner emotional world and outward behaviors. The idea is that, once you can recognize and accept, then change is possible. The “dialectic” in dialectical behavior therapy implies that one is attempting to find a balance between acceptance and change. All of us can benefit from these skills, especially emotionally volatile couples who are trapped together in quarantine.
Radically accept what is uncertain in your lives
Radical acceptance is a practice used in DBT in situations that are out of our control, such as the COVID-19 pandemic. Radically accept that you and your partner are trapped in quarantine without attempting to place blame on our government, your spouse, your boss, and even yourself. Radical acceptance is exactly what the name implies. Accept your current situation for what it is and not what you hoped it to be.
Accept the unknown and unanswered questions such as when will this quarantine end? Will there be a summer camp? Will I get back to my office this summer? Will my children even return to school in the fall? The acceptance of what is out of your control will ultimately decrease your mental time spent worrying and obsessing about the uncertainties of your post-quarantine life and instead provide you more time to be present with your spouse.
Remain mindful during all communication with your spouse. To stay in the moment, you need to be aware of your bodily reactions to distress and notice when your heart rate increases, breathing becomes more shallow, stomach muscles tighten, and when your thoughts become more negative. Mindfulness skills enable us to use physiological changes in our body to become aware of our emotions. You can use your partner’s nonverbal body language and tone of voice to gauge that person’s emotional reactivity.
The practice of mindfulness leads to an increased emotional intelligence. The goal is to have enough self-awareness and emotional understanding of your partner and enough empathy to know when a conversation is becoming too emotionally charged and to let it go and back off. Mindfulness is not nagging your partner to remember to change the heating unit filters with a reminder of what happened years ago when this wasn’t done promptly – without first checking in to make sure your partner is emotionally ready for this type of conversation.
When we have strong emotions, we are using the more primitive parts of our brain that induce a fight or flight reaction. These emotional reactions overshadow the more advanced prefrontal region of our brain that stores our rational thoughts and reasoning skills, a concept identified by psychologist Daniel Goleman as “emotional hijacking.”
Use distress tolerance skills to deal with negative emotions
Distress tolerance is an individual’s ability to manage feelings in response to stress. Distress tolerance skills are aimed at helping one manage intense emotions without worsening a situation by engaging in behaviors that are destructive and may exacerbate the problem. The goal is to tolerate the stress while with your partner and not respond negatively or in a way that is harmful to the integrity of your relationship.
To prioritize your relationship, this may mean that you choose not to react negatively when your partner makes a passive-aggressive comment on how you spent your day during quarantine since you still have a pile of laundry on your bedroom floor and overflowing dishes in the kitchen sink. A high level of distress tolerance will enable you to not overreact or withdraw from your spouse when flooded with emotions of anger or sadness.
Distraction techniques are a type of distress tolerance skill. You can engage in activities that keep you distracted and require your full attention. When things get heated between you and your spouse during quarantine, try to obtain some distance from each other to cool down and engage in an activity that involves your full concentration.
Many of us have been surprised by our hidden talents that were discovered during the quarantine. Use the time away from your partner to distract yourself with your new passion for writing, baking, organizing, and even your newfound love of balloon artistry. Do an activity that engages your mind and provides you the necessary physical and mental time away from your partner to deescalate. You can always revisit the initial cause of the conflict when both you and your partner are not emotionally charged. You can also distract yourself with self-soothing tactics such as taking a warm bath or a reading good book. Perhaps distract yourself by giving back to others and spending time planning a drive-by surprise party for your sister’s birthday next month. It can be helpful to distract yourself by comparing yourself to others less fortunate than you or a time in your life when you and your partner were struggling much worse than now, to provide perspective. The goal is not to add to your distress but instead, provide yourself a sense of perspective.
Use interpersonal effectiveness skills to establish a healthy relationship
Be gentle in all your communications with your partner, think about your spouse’s perspective, show empathy and interest in what your partner has to say by your verbal communication or body language, such as maintaining eye contact, and offer recognitional cues, such as “uh-huh” and “oh, really.” Avoid communication that is at all invalidating. Never start a sentence with “YOU” while having heated conversations with your spouse; instead, use “I feel” statements. This type of communication avoids the blame game that gets many couples into trouble.
Instead, communicate how you feel while not necessarily blaming your spouse but rather expressing your emotions. This will ultimately lead to less defensive communication from your partner. Remember that not all communication is for the sole purpose of communicating. Much of the time, communication is used as an attempt for one partner to connect with the other partner. Couples may say that they have difficulty with communication when it is not the communication that is the issue but instead the underlying disconnect of the couple.
This disconnect usually manifests while couples are communicating, and therefore, can be misconstrued as solely a communication issue by the couple. When your partner asks you to stop staring at your phone during dinner, it is not necessarily that your spouse is attempting to control you or wants to engage in some deep conversation, but more likely a bid to try to connect with you. Your partner is attempting to tell you that he or she feels disconnected, misses you, and wants to reconnect.
Provide validation and acceptance to your partner
Focus on your partner’s strengths and accept the weaknesses. Accept that your partner is scattered, disorganized, and takes at least 20 minutes to find the phone and keys every morning. Remember that during your courtship days, you found your partner’s flighty attributes to be endearing. Do the same for your strengths and weaknesses.
Accept that the pandemic is unpredictable and that you may need to strengthen your ability to be flexible and more adaptable. This will ultimately lead to feeling less disappointment by your partner and more accepting of shortcomings. Acceptance of your imperfections will improve your sense of worth and confidence and lessen negative emotions, such as guilt, regret, and shame.
Accept the fact that, as similar as we all are, we use different methods to recharge ourselves. In contrast, your spouse needs alone time without distractions to reboot mentally and prepare for the following day. In the pre-pandemic world, if there were a mismatch in what a couple needed to feel rejuvenated, they could independently compensate and search for fulfillment outside of the home. Before stay-at-home orders were rolled out throughout the country, spouses had ample opportunities to spend time away from their partners at work, dinner with friends, or while squeezing in a 7 p.m. yoga sculpt class – barely getting home in time to kiss our children goodnight – with a few minutes to spare to engage in mundane conversation with our partners before our nighttime routine of TV commenced. Unfortunately, COVID-19 has made it very hard for couples to carve out that time for compensatory activities outside of the home.
Remember that you are a team
Remind yourself of the reason why you initially fell in love with your partner. Teammates do not keep score or compete with one another. They support each other when one player is not feeling well, and they make sacrifices for the betterment of the team.
Your marriage vows included “through sickness and health” and now should include “through quarantine.”
Dr. Abraham is a psychiatrist in private practice in Philadelphia. She has no disclosures.
FDA authorizes emergency use of remdesivir for COVID-19
The investigational antiviral drug, manufactured by Gilead Sciences Inc., was shown in a preliminary analysis of a National Institutes of Health (NIH) clinical trial to shorten recovery time in some patients, according to information presented during a White House press conference earlier this week. However, the results of the trial have not been published and little is known about how safe and effective it is in treating people in the hospital with COVID-19.
The emergency use authorization (EUA) designation means remdesivir can be distributed in the United States and administered intravenously by healthcare providers, as appropriate to treat severe disease. Those with severe disease, the FDA said in a press release, are patients with low blood oxygen levels or those who need oxygen therapy or more intensive support such as a mechanical ventilator.
“There’s tremendous interest among all parties to identify and arm ourselves with medicines to combat COVID-19, and through our Coronavirus Treatment Acceleration Program, the FDA is working around-the-clock and using every tool at our disposal to speed these efforts,” FDA Commissioner Stephen M. Hahn, MD, said in a statement.
The FDA writes, “Based on evaluation of the emergency use authorization criteria and the scientific evidence available, it was determined that it is reasonable to believe that remdesivir may be effective in treating COVID-19, and that, given there are no adequate, approved, or available alternative treatments, the known and potential benefits to treat this serious or life-threatening virus currently outweigh the known and potential risks of the drug’s use.”
The drug must be administered intravenously and the optimal dosing and duration are not yet known, the company said in a press release issued May 1.
In addition, Gilead advises that infusion-related reactions and liver transaminase elevations have been seen in patients treated with the drug.
“If signs and symptoms of a clinically significant infusion reaction occur, immediately discontinue administration of remdesivir and initiate appropriate treatment. Patients should have appropriate clinical and laboratory monitoring to aid in early detection of any potential adverse events. Monitor renal and hepatic function prior to initiating and daily during therapy with remdesivir; additionally monitor serum chemistries and hematology daily during therapy,” the company said.
Before granting the emergency use authorization, the FDA had allowed for study of the drug in clinical trials, as well as expanded access use for individual patients and through a multipatient expanded access program coordinated by Gilead.
“The EUA will be effective until the declaration that circumstances exist justifying the authorization of the emergency use of drugs and biologics for prevention and treatment of COVID-19 is terminated and may be revised or revoked if it is determined the EUA no longer meets the statutory criteria for issuance,” the FDA said.
This article first appeared on Medscape.com.
The investigational antiviral drug, manufactured by Gilead Sciences Inc., was shown in a preliminary analysis of a National Institutes of Health (NIH) clinical trial to shorten recovery time in some patients, according to information presented during a White House press conference earlier this week. However, the results of the trial have not been published and little is known about how safe and effective it is in treating people in the hospital with COVID-19.
The emergency use authorization (EUA) designation means remdesivir can be distributed in the United States and administered intravenously by healthcare providers, as appropriate to treat severe disease. Those with severe disease, the FDA said in a press release, are patients with low blood oxygen levels or those who need oxygen therapy or more intensive support such as a mechanical ventilator.
“There’s tremendous interest among all parties to identify and arm ourselves with medicines to combat COVID-19, and through our Coronavirus Treatment Acceleration Program, the FDA is working around-the-clock and using every tool at our disposal to speed these efforts,” FDA Commissioner Stephen M. Hahn, MD, said in a statement.
The FDA writes, “Based on evaluation of the emergency use authorization criteria and the scientific evidence available, it was determined that it is reasonable to believe that remdesivir may be effective in treating COVID-19, and that, given there are no adequate, approved, or available alternative treatments, the known and potential benefits to treat this serious or life-threatening virus currently outweigh the known and potential risks of the drug’s use.”
The drug must be administered intravenously and the optimal dosing and duration are not yet known, the company said in a press release issued May 1.
In addition, Gilead advises that infusion-related reactions and liver transaminase elevations have been seen in patients treated with the drug.
“If signs and symptoms of a clinically significant infusion reaction occur, immediately discontinue administration of remdesivir and initiate appropriate treatment. Patients should have appropriate clinical and laboratory monitoring to aid in early detection of any potential adverse events. Monitor renal and hepatic function prior to initiating and daily during therapy with remdesivir; additionally monitor serum chemistries and hematology daily during therapy,” the company said.
Before granting the emergency use authorization, the FDA had allowed for study of the drug in clinical trials, as well as expanded access use for individual patients and through a multipatient expanded access program coordinated by Gilead.
“The EUA will be effective until the declaration that circumstances exist justifying the authorization of the emergency use of drugs and biologics for prevention and treatment of COVID-19 is terminated and may be revised or revoked if it is determined the EUA no longer meets the statutory criteria for issuance,” the FDA said.
This article first appeared on Medscape.com.
The investigational antiviral drug, manufactured by Gilead Sciences Inc., was shown in a preliminary analysis of a National Institutes of Health (NIH) clinical trial to shorten recovery time in some patients, according to information presented during a White House press conference earlier this week. However, the results of the trial have not been published and little is known about how safe and effective it is in treating people in the hospital with COVID-19.
The emergency use authorization (EUA) designation means remdesivir can be distributed in the United States and administered intravenously by healthcare providers, as appropriate to treat severe disease. Those with severe disease, the FDA said in a press release, are patients with low blood oxygen levels or those who need oxygen therapy or more intensive support such as a mechanical ventilator.
“There’s tremendous interest among all parties to identify and arm ourselves with medicines to combat COVID-19, and through our Coronavirus Treatment Acceleration Program, the FDA is working around-the-clock and using every tool at our disposal to speed these efforts,” FDA Commissioner Stephen M. Hahn, MD, said in a statement.
The FDA writes, “Based on evaluation of the emergency use authorization criteria and the scientific evidence available, it was determined that it is reasonable to believe that remdesivir may be effective in treating COVID-19, and that, given there are no adequate, approved, or available alternative treatments, the known and potential benefits to treat this serious or life-threatening virus currently outweigh the known and potential risks of the drug’s use.”
The drug must be administered intravenously and the optimal dosing and duration are not yet known, the company said in a press release issued May 1.
In addition, Gilead advises that infusion-related reactions and liver transaminase elevations have been seen in patients treated with the drug.
“If signs and symptoms of a clinically significant infusion reaction occur, immediately discontinue administration of remdesivir and initiate appropriate treatment. Patients should have appropriate clinical and laboratory monitoring to aid in early detection of any potential adverse events. Monitor renal and hepatic function prior to initiating and daily during therapy with remdesivir; additionally monitor serum chemistries and hematology daily during therapy,” the company said.
Before granting the emergency use authorization, the FDA had allowed for study of the drug in clinical trials, as well as expanded access use for individual patients and through a multipatient expanded access program coordinated by Gilead.
“The EUA will be effective until the declaration that circumstances exist justifying the authorization of the emergency use of drugs and biologics for prevention and treatment of COVID-19 is terminated and may be revised or revoked if it is determined the EUA no longer meets the statutory criteria for issuance,” the FDA said.
This article first appeared on Medscape.com.
Out-of-hospital cardiac arrests soar during COVID-19 in Italy
Out-of-hospital cardiac arrests increased 58% during the peak of the COVID-19 outbreak in the hard-hit region of Lombardy, Italy, compared with the same period last year, a new analysis shows.
During the first 40 days of the outbreak beginning Feb. 21, four provinces in northern Italy reported 362 cases of out-of-hospital cardiac arrest compared with 229 during the same period in 2019.
The increases in these provinces varied in magnitude from 18% in Mantua, where there were 1,688 confirmed COVID-19 cases, to 187% in Lodi, which had 2,116 COVID-19 cases. The Cremona province, which had the highest number of COVID-19 cases at 3,869, saw a 143% increase in out-of-hospital cardiac arrests.
The mortality rate in the field was 14.9 percentage points higher in 2020 than in 2019 among patients in whom resuscitation was attempted by emergency medical services (EMS), Enrico Baldi, MD, University of Pavia, Italy, and colleagues reported in a letter April 29 in the New England Journal of Medicine.
“The sex and age of the patients were similar in the 2020 and 2019 periods, but in 2020, the incidence of out-of-hospital cardiac arrest due to a medical cause was 6.5 percentage points higher, the incidence of out-of-hospital cardiac arrest at home was 7.3 percentage points higher, and the incidence of unwitnessed cardiac arrest was 11.3 percentage points higher,” the authors wrote.
Patients were also less likely to receive cardiopulmonary resuscitation from bystanders in 2020 vs 2019 (–15.6 percentage points) and were more likely to die before reaching the hospital when resuscitation was attempted by EMS (+14.9 percentage points).
Among all patients, the death rate in the field increased 11.4 percentage points during the outbreak, from 77.3% in 2019 to 88.7% in 2020.
The cumulative incidence of out-of-hospital cardiac arrest in 2020 was “strongly associated” with the cumulative incidence of COVID-19 (Spearman rank correlation coefficient, 0.87; 95% confidence interval, 0.83-0.91) and the spike in cases “followed the time course of the COVID-19 outbreak,” the researchers noted.
A total of 103 patients, who arrested out of hospital and were diagnosed with or suspected of having COVID-19, “account for 77.4% of the increase in cases of out-of-hospital cardiac arrest observed in these provinces in 2020,” the investigators noted.
As the pandemic has taken hold, hospitals and physicians across the United States are also voicing concerns about the drop in the number of patients presenting with myocardial infarction (MI) or stroke.
Nearly one-third of Americans (29%) report having delayed or avoided medical care because of concerns of catching COVID-19, according to a new poll released April 28 from the American College of Emergency Physicians (ACEP) and Morning Consult, a global data research firm.
Despite many emergency departments reporting a decline in patient volume, 74% of respondents said they were worried about hospital wait times and overcrowding. Another 59% expressed concerns about being turned away from the hospital or doctor’s office.
At the same time, the survey found strong support for emergency physicians and 73% of respondents said they were concerned about overstressing the health care system.
The drop-off in Americans seeking care for MI and strokes nationally prompted eight professional societies – including ACEP, the American Heart Association, and the Association of Black Cardiologists – to issue a joint statement urging those experiencing symptoms to call 911 and seek care for these life-threatening events.
The authors have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Out-of-hospital cardiac arrests increased 58% during the peak of the COVID-19 outbreak in the hard-hit region of Lombardy, Italy, compared with the same period last year, a new analysis shows.
During the first 40 days of the outbreak beginning Feb. 21, four provinces in northern Italy reported 362 cases of out-of-hospital cardiac arrest compared with 229 during the same period in 2019.
The increases in these provinces varied in magnitude from 18% in Mantua, where there were 1,688 confirmed COVID-19 cases, to 187% in Lodi, which had 2,116 COVID-19 cases. The Cremona province, which had the highest number of COVID-19 cases at 3,869, saw a 143% increase in out-of-hospital cardiac arrests.
The mortality rate in the field was 14.9 percentage points higher in 2020 than in 2019 among patients in whom resuscitation was attempted by emergency medical services (EMS), Enrico Baldi, MD, University of Pavia, Italy, and colleagues reported in a letter April 29 in the New England Journal of Medicine.
“The sex and age of the patients were similar in the 2020 and 2019 periods, but in 2020, the incidence of out-of-hospital cardiac arrest due to a medical cause was 6.5 percentage points higher, the incidence of out-of-hospital cardiac arrest at home was 7.3 percentage points higher, and the incidence of unwitnessed cardiac arrest was 11.3 percentage points higher,” the authors wrote.
Patients were also less likely to receive cardiopulmonary resuscitation from bystanders in 2020 vs 2019 (–15.6 percentage points) and were more likely to die before reaching the hospital when resuscitation was attempted by EMS (+14.9 percentage points).
Among all patients, the death rate in the field increased 11.4 percentage points during the outbreak, from 77.3% in 2019 to 88.7% in 2020.
The cumulative incidence of out-of-hospital cardiac arrest in 2020 was “strongly associated” with the cumulative incidence of COVID-19 (Spearman rank correlation coefficient, 0.87; 95% confidence interval, 0.83-0.91) and the spike in cases “followed the time course of the COVID-19 outbreak,” the researchers noted.
A total of 103 patients, who arrested out of hospital and were diagnosed with or suspected of having COVID-19, “account for 77.4% of the increase in cases of out-of-hospital cardiac arrest observed in these provinces in 2020,” the investigators noted.
As the pandemic has taken hold, hospitals and physicians across the United States are also voicing concerns about the drop in the number of patients presenting with myocardial infarction (MI) or stroke.
Nearly one-third of Americans (29%) report having delayed or avoided medical care because of concerns of catching COVID-19, according to a new poll released April 28 from the American College of Emergency Physicians (ACEP) and Morning Consult, a global data research firm.
Despite many emergency departments reporting a decline in patient volume, 74% of respondents said they were worried about hospital wait times and overcrowding. Another 59% expressed concerns about being turned away from the hospital or doctor’s office.
At the same time, the survey found strong support for emergency physicians and 73% of respondents said they were concerned about overstressing the health care system.
The drop-off in Americans seeking care for MI and strokes nationally prompted eight professional societies – including ACEP, the American Heart Association, and the Association of Black Cardiologists – to issue a joint statement urging those experiencing symptoms to call 911 and seek care for these life-threatening events.
The authors have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Out-of-hospital cardiac arrests increased 58% during the peak of the COVID-19 outbreak in the hard-hit region of Lombardy, Italy, compared with the same period last year, a new analysis shows.
During the first 40 days of the outbreak beginning Feb. 21, four provinces in northern Italy reported 362 cases of out-of-hospital cardiac arrest compared with 229 during the same period in 2019.
The increases in these provinces varied in magnitude from 18% in Mantua, where there were 1,688 confirmed COVID-19 cases, to 187% in Lodi, which had 2,116 COVID-19 cases. The Cremona province, which had the highest number of COVID-19 cases at 3,869, saw a 143% increase in out-of-hospital cardiac arrests.
The mortality rate in the field was 14.9 percentage points higher in 2020 than in 2019 among patients in whom resuscitation was attempted by emergency medical services (EMS), Enrico Baldi, MD, University of Pavia, Italy, and colleagues reported in a letter April 29 in the New England Journal of Medicine.
“The sex and age of the patients were similar in the 2020 and 2019 periods, but in 2020, the incidence of out-of-hospital cardiac arrest due to a medical cause was 6.5 percentage points higher, the incidence of out-of-hospital cardiac arrest at home was 7.3 percentage points higher, and the incidence of unwitnessed cardiac arrest was 11.3 percentage points higher,” the authors wrote.
Patients were also less likely to receive cardiopulmonary resuscitation from bystanders in 2020 vs 2019 (–15.6 percentage points) and were more likely to die before reaching the hospital when resuscitation was attempted by EMS (+14.9 percentage points).
Among all patients, the death rate in the field increased 11.4 percentage points during the outbreak, from 77.3% in 2019 to 88.7% in 2020.
The cumulative incidence of out-of-hospital cardiac arrest in 2020 was “strongly associated” with the cumulative incidence of COVID-19 (Spearman rank correlation coefficient, 0.87; 95% confidence interval, 0.83-0.91) and the spike in cases “followed the time course of the COVID-19 outbreak,” the researchers noted.
A total of 103 patients, who arrested out of hospital and were diagnosed with or suspected of having COVID-19, “account for 77.4% of the increase in cases of out-of-hospital cardiac arrest observed in these provinces in 2020,” the investigators noted.
As the pandemic has taken hold, hospitals and physicians across the United States are also voicing concerns about the drop in the number of patients presenting with myocardial infarction (MI) or stroke.
Nearly one-third of Americans (29%) report having delayed or avoided medical care because of concerns of catching COVID-19, according to a new poll released April 28 from the American College of Emergency Physicians (ACEP) and Morning Consult, a global data research firm.
Despite many emergency departments reporting a decline in patient volume, 74% of respondents said they were worried about hospital wait times and overcrowding. Another 59% expressed concerns about being turned away from the hospital or doctor’s office.
At the same time, the survey found strong support for emergency physicians and 73% of respondents said they were concerned about overstressing the health care system.
The drop-off in Americans seeking care for MI and strokes nationally prompted eight professional societies – including ACEP, the American Heart Association, and the Association of Black Cardiologists – to issue a joint statement urging those experiencing symptoms to call 911 and seek care for these life-threatening events.
The authors have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Excess cancer deaths predicted as care is disrupted by COVID-19
The majority of patients who have cancer or are suspected of having cancer are not accessing healthcare services in the United Kingdom or the United States because of the COVID-19 pandemic, the first report of its kind estimates.
As a result, there will be an excess of deaths among patients who have cancer and multiple comorbidities in both countries during the current coronavirus emergency, the report warns.
The authors calculate that there will be 6,270 excess deaths among cancer patients 1 year from now in England and 33,890 excess deaths among cancer patients in the United States. (In the United States, the estimated excess number of deaths applies only to patients older than 40 years, they note.)
“The recorded underlying cause of these excess deaths may be cancer, COVID-19, or comorbidity (such as myocardial infarction),” Alvina Lai, PhD, University College London, United Kingdom, and colleagues observe.
“Our data have highlighted how cancer patients with multimorbidity are a particularly at-risk group during the current pandemic,” they emphasize.
The study was published on ResearchGate as a preprint and has not undergone peer review.
Commenting on the study on the UK Science Media Center, several experts emphasized the lack of peer review, noting that interpretation of these data needs to be further refined on the basis of that input. One expert suggested that there are “substantial uncertainties that this paper does not adequately communicate.” But others argued that this topic was important enough to warrant early release of the data.
Chris Bunce, PhD, University of Birmingham, United Kingdom, said this study represents “a highly valuable contribution.”
“It is universally accepted that early diagnosis and treatment and adherence to treatment regimens saves lives,” he pointed out.
“Therefore, these COVID-19-related impacts will cost lives,” Bunce said.
“And if this information is to influence cancer care and guide policy during the COVID-19 crisis, then it is important that the findings are disseminated and discussed immediately, warranting their release ahead of peer view,” he added.
In a Medscape UK commentary, oncologist Karol Sikora, MD, PhD, argues that “restarting cancer services can’t come soon enough.”
“Resonably Argued Numerical Estimate”
“It’s well known that there have been considerable changes in the provision of health care for many conditions, including cancers, as a result of all the measures to deal with the COVID-19 crisis,” said Kevin McConway, PhD, professor emeritus of applied statistics, the Open University, Milton Keynes, United Kingdom.
“It seems inevitable that there will be increased deaths in cancer patients if they are infected with the virus or because of changes in the health services available to them, and quite possibly also from socio-economic effects of the responses to the crisis,” he continued.
“This study is the first that I have seen that produces a reasonably argued numerical estimate of the number of excess deaths of people with cancer arising from these factors in the UK and the USA,” he added.
Declines in Urgent Referrals and Chemo Attendance
For the study, the team used DATA-CAN, the UK National Health Data Research Hub for Cancer, to assess weekly returns for urgent cancer referrals for early diagnosis and also chemotherapy attendances for hospitals in Leeds, London, and Northern Ireland going back to 2018.
The data revealed that there have been major declines in chemotherapy attendances. There has been, on average, a 60% decrease from prepandemic levels in eight hospitals in the three regions that were assessed.
Urgent cancer referrals have dropped by an average of 76% compared to prepandemic levels in the three regions.
On the conservative assumption that the COVID-19 pandemic will only affect patients with newly diagnosed cancer (incident cases), the researchers estimate that the proportion of the population affected by the emergency (PAE) is 40% and that the relative impact of the emergency (RIE) is 1.5.
PAE is a summary measure of exposure to the adverse health consequences of the emergency; RIE is a summary measure of the combined impact on mortality of infection, health service change, physical distancing, and economic downturn, the authors explain.
Comorbidities Common
“Comorbidities were common in people with cancer,” the study authors note. For example, more than one quarter of the study population had at least one comorbidity; more than 14% had two.
For incident cancers, the number of excess deaths steadily increased in conjunction with an increase in the number of comorbidities, such that more than 80% of deaths occurred in patients with one or more comorbidities.
“When considering both prevalent and incident cancers together with a COVID-19 PAE of 40%, we estimated 17,991 excess deaths at a RIE of 1.5; 78.1% of these deaths occur in patients with ≥1 comorbidities,” the authors report.
“The excess risk of death in people living with cancer during the COVID-19 emergency may be due not only to COVID-19 infection, but also to the unintended health consequences of changes in health service provision, the physical or psychological effects of social distancing, and economic upheaval,” they state.
“This is the first study demonstrating profound recent changes in cancer care delivery in multiple centers,” the authors observe.
Lai has disclosed no relevant financial relationships. Several coauthors have various relationships with industry, as listed in their article. The commentators have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
The majority of patients who have cancer or are suspected of having cancer are not accessing healthcare services in the United Kingdom or the United States because of the COVID-19 pandemic, the first report of its kind estimates.
As a result, there will be an excess of deaths among patients who have cancer and multiple comorbidities in both countries during the current coronavirus emergency, the report warns.
The authors calculate that there will be 6,270 excess deaths among cancer patients 1 year from now in England and 33,890 excess deaths among cancer patients in the United States. (In the United States, the estimated excess number of deaths applies only to patients older than 40 years, they note.)
“The recorded underlying cause of these excess deaths may be cancer, COVID-19, or comorbidity (such as myocardial infarction),” Alvina Lai, PhD, University College London, United Kingdom, and colleagues observe.
“Our data have highlighted how cancer patients with multimorbidity are a particularly at-risk group during the current pandemic,” they emphasize.
The study was published on ResearchGate as a preprint and has not undergone peer review.
Commenting on the study on the UK Science Media Center, several experts emphasized the lack of peer review, noting that interpretation of these data needs to be further refined on the basis of that input. One expert suggested that there are “substantial uncertainties that this paper does not adequately communicate.” But others argued that this topic was important enough to warrant early release of the data.
Chris Bunce, PhD, University of Birmingham, United Kingdom, said this study represents “a highly valuable contribution.”
“It is universally accepted that early diagnosis and treatment and adherence to treatment regimens saves lives,” he pointed out.
“Therefore, these COVID-19-related impacts will cost lives,” Bunce said.
“And if this information is to influence cancer care and guide policy during the COVID-19 crisis, then it is important that the findings are disseminated and discussed immediately, warranting their release ahead of peer view,” he added.
In a Medscape UK commentary, oncologist Karol Sikora, MD, PhD, argues that “restarting cancer services can’t come soon enough.”
“Resonably Argued Numerical Estimate”
“It’s well known that there have been considerable changes in the provision of health care for many conditions, including cancers, as a result of all the measures to deal with the COVID-19 crisis,” said Kevin McConway, PhD, professor emeritus of applied statistics, the Open University, Milton Keynes, United Kingdom.
“It seems inevitable that there will be increased deaths in cancer patients if they are infected with the virus or because of changes in the health services available to them, and quite possibly also from socio-economic effects of the responses to the crisis,” he continued.
“This study is the first that I have seen that produces a reasonably argued numerical estimate of the number of excess deaths of people with cancer arising from these factors in the UK and the USA,” he added.
Declines in Urgent Referrals and Chemo Attendance
For the study, the team used DATA-CAN, the UK National Health Data Research Hub for Cancer, to assess weekly returns for urgent cancer referrals for early diagnosis and also chemotherapy attendances for hospitals in Leeds, London, and Northern Ireland going back to 2018.
The data revealed that there have been major declines in chemotherapy attendances. There has been, on average, a 60% decrease from prepandemic levels in eight hospitals in the three regions that were assessed.
Urgent cancer referrals have dropped by an average of 76% compared to prepandemic levels in the three regions.
On the conservative assumption that the COVID-19 pandemic will only affect patients with newly diagnosed cancer (incident cases), the researchers estimate that the proportion of the population affected by the emergency (PAE) is 40% and that the relative impact of the emergency (RIE) is 1.5.
PAE is a summary measure of exposure to the adverse health consequences of the emergency; RIE is a summary measure of the combined impact on mortality of infection, health service change, physical distancing, and economic downturn, the authors explain.
Comorbidities Common
“Comorbidities were common in people with cancer,” the study authors note. For example, more than one quarter of the study population had at least one comorbidity; more than 14% had two.
For incident cancers, the number of excess deaths steadily increased in conjunction with an increase in the number of comorbidities, such that more than 80% of deaths occurred in patients with one or more comorbidities.
“When considering both prevalent and incident cancers together with a COVID-19 PAE of 40%, we estimated 17,991 excess deaths at a RIE of 1.5; 78.1% of these deaths occur in patients with ≥1 comorbidities,” the authors report.
“The excess risk of death in people living with cancer during the COVID-19 emergency may be due not only to COVID-19 infection, but also to the unintended health consequences of changes in health service provision, the physical or psychological effects of social distancing, and economic upheaval,” they state.
“This is the first study demonstrating profound recent changes in cancer care delivery in multiple centers,” the authors observe.
Lai has disclosed no relevant financial relationships. Several coauthors have various relationships with industry, as listed in their article. The commentators have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
The majority of patients who have cancer or are suspected of having cancer are not accessing healthcare services in the United Kingdom or the United States because of the COVID-19 pandemic, the first report of its kind estimates.
As a result, there will be an excess of deaths among patients who have cancer and multiple comorbidities in both countries during the current coronavirus emergency, the report warns.
The authors calculate that there will be 6,270 excess deaths among cancer patients 1 year from now in England and 33,890 excess deaths among cancer patients in the United States. (In the United States, the estimated excess number of deaths applies only to patients older than 40 years, they note.)
“The recorded underlying cause of these excess deaths may be cancer, COVID-19, or comorbidity (such as myocardial infarction),” Alvina Lai, PhD, University College London, United Kingdom, and colleagues observe.
“Our data have highlighted how cancer patients with multimorbidity are a particularly at-risk group during the current pandemic,” they emphasize.
The study was published on ResearchGate as a preprint and has not undergone peer review.
Commenting on the study on the UK Science Media Center, several experts emphasized the lack of peer review, noting that interpretation of these data needs to be further refined on the basis of that input. One expert suggested that there are “substantial uncertainties that this paper does not adequately communicate.” But others argued that this topic was important enough to warrant early release of the data.
Chris Bunce, PhD, University of Birmingham, United Kingdom, said this study represents “a highly valuable contribution.”
“It is universally accepted that early diagnosis and treatment and adherence to treatment regimens saves lives,” he pointed out.
“Therefore, these COVID-19-related impacts will cost lives,” Bunce said.
“And if this information is to influence cancer care and guide policy during the COVID-19 crisis, then it is important that the findings are disseminated and discussed immediately, warranting their release ahead of peer view,” he added.
In a Medscape UK commentary, oncologist Karol Sikora, MD, PhD, argues that “restarting cancer services can’t come soon enough.”
“Resonably Argued Numerical Estimate”
“It’s well known that there have been considerable changes in the provision of health care for many conditions, including cancers, as a result of all the measures to deal with the COVID-19 crisis,” said Kevin McConway, PhD, professor emeritus of applied statistics, the Open University, Milton Keynes, United Kingdom.
“It seems inevitable that there will be increased deaths in cancer patients if they are infected with the virus or because of changes in the health services available to them, and quite possibly also from socio-economic effects of the responses to the crisis,” he continued.
“This study is the first that I have seen that produces a reasonably argued numerical estimate of the number of excess deaths of people with cancer arising from these factors in the UK and the USA,” he added.
Declines in Urgent Referrals and Chemo Attendance
For the study, the team used DATA-CAN, the UK National Health Data Research Hub for Cancer, to assess weekly returns for urgent cancer referrals for early diagnosis and also chemotherapy attendances for hospitals in Leeds, London, and Northern Ireland going back to 2018.
The data revealed that there have been major declines in chemotherapy attendances. There has been, on average, a 60% decrease from prepandemic levels in eight hospitals in the three regions that were assessed.
Urgent cancer referrals have dropped by an average of 76% compared to prepandemic levels in the three regions.
On the conservative assumption that the COVID-19 pandemic will only affect patients with newly diagnosed cancer (incident cases), the researchers estimate that the proportion of the population affected by the emergency (PAE) is 40% and that the relative impact of the emergency (RIE) is 1.5.
PAE is a summary measure of exposure to the adverse health consequences of the emergency; RIE is a summary measure of the combined impact on mortality of infection, health service change, physical distancing, and economic downturn, the authors explain.
Comorbidities Common
“Comorbidities were common in people with cancer,” the study authors note. For example, more than one quarter of the study population had at least one comorbidity; more than 14% had two.
For incident cancers, the number of excess deaths steadily increased in conjunction with an increase in the number of comorbidities, such that more than 80% of deaths occurred in patients with one or more comorbidities.
“When considering both prevalent and incident cancers together with a COVID-19 PAE of 40%, we estimated 17,991 excess deaths at a RIE of 1.5; 78.1% of these deaths occur in patients with ≥1 comorbidities,” the authors report.
“The excess risk of death in people living with cancer during the COVID-19 emergency may be due not only to COVID-19 infection, but also to the unintended health consequences of changes in health service provision, the physical or psychological effects of social distancing, and economic upheaval,” they state.
“This is the first study demonstrating profound recent changes in cancer care delivery in multiple centers,” the authors observe.
Lai has disclosed no relevant financial relationships. Several coauthors have various relationships with industry, as listed in their article. The commentators have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
New tetracycline antibiotic effective in acute bacterial skin and skin-structure infections
Background: Acute bacterial skin and skin-structure infections (ABSSSIs) continue to account for substantial morbidity and health care burden, with the emergence of drug-resistant pathogens further complicating their management. Omadacycline is a new once-daily tetracycline with in vitro activity against a wide range of causative agents of ABSSSI, including Streptococcus pyogenes, Staphylococcus aureus (including methicillin-resistant strains, or MRSA), and Enterococcus spp.
Study design: Phase 3, randomized, double-blind, double-dummy, placebo-controlled trial.
Setting: A total of 55 sites in the United States, Peru, South Africa, and Europe.
Synopsis: The trial recruited 645 adults with a qualifying ABSSSI (such as wound infection, cellulitis or erysipelas, or major abscess) with evidence of an inflammatory response (white blood cell count at least 10,000 cells/mm3 or 4,000 cells/mm3 and below, immature neutrophils at least 15%, lymphatic involvement, or oral or rectal temperature greater than 38.0° C or less than 36.0° C). Exclusion criteria included infections associated with chronic skin lesions and clinically significant liver or renal insufficiency or immunocompromised state. All patients received either omadacycline or linezolid IV with the option to switch to the oral preparation of the respective drugs after at least 3 days of therapy.
Omadacycline was noninferior to moxifloxacin with respect to early clinical response (84.8% vs. 85.5%, respectively) and posttreatment clinical response rates (86.1% vs. 83.6%). Efficacy was similar for methicillin-susceptible or methicillin-resistant Staphylococcus aureus, the most common isolated pathogens. Frequency of adverse events (primarily gastrointestinal) was also similar in the two groups. Mean duration of IV therapy was 4.4 days, and mean duration of oral therapy was 5.5 days in the omadacycline group.
Bottom line: Omadacycline provides similar clinical benefit as linezolid in the treatment of ABSSSIs.
Citation: O’Riordan W et al. Omadacycline for acute bacterial skin and skin-structure infections. N Eng J Med. 2019;380:528-38.
Dr. Manian is a core educator faculty member in the department of medicine at Massachusetts General Hospital and an associate professor of medicine at Harvard Medical School, Boston.
Background: Acute bacterial skin and skin-structure infections (ABSSSIs) continue to account for substantial morbidity and health care burden, with the emergence of drug-resistant pathogens further complicating their management. Omadacycline is a new once-daily tetracycline with in vitro activity against a wide range of causative agents of ABSSSI, including Streptococcus pyogenes, Staphylococcus aureus (including methicillin-resistant strains, or MRSA), and Enterococcus spp.
Study design: Phase 3, randomized, double-blind, double-dummy, placebo-controlled trial.
Setting: A total of 55 sites in the United States, Peru, South Africa, and Europe.
Synopsis: The trial recruited 645 adults with a qualifying ABSSSI (such as wound infection, cellulitis or erysipelas, or major abscess) with evidence of an inflammatory response (white blood cell count at least 10,000 cells/mm3 or 4,000 cells/mm3 and below, immature neutrophils at least 15%, lymphatic involvement, or oral or rectal temperature greater than 38.0° C or less than 36.0° C). Exclusion criteria included infections associated with chronic skin lesions and clinically significant liver or renal insufficiency or immunocompromised state. All patients received either omadacycline or linezolid IV with the option to switch to the oral preparation of the respective drugs after at least 3 days of therapy.
Omadacycline was noninferior to moxifloxacin with respect to early clinical response (84.8% vs. 85.5%, respectively) and posttreatment clinical response rates (86.1% vs. 83.6%). Efficacy was similar for methicillin-susceptible or methicillin-resistant Staphylococcus aureus, the most common isolated pathogens. Frequency of adverse events (primarily gastrointestinal) was also similar in the two groups. Mean duration of IV therapy was 4.4 days, and mean duration of oral therapy was 5.5 days in the omadacycline group.
Bottom line: Omadacycline provides similar clinical benefit as linezolid in the treatment of ABSSSIs.
Citation: O’Riordan W et al. Omadacycline for acute bacterial skin and skin-structure infections. N Eng J Med. 2019;380:528-38.
Dr. Manian is a core educator faculty member in the department of medicine at Massachusetts General Hospital and an associate professor of medicine at Harvard Medical School, Boston.
Background: Acute bacterial skin and skin-structure infections (ABSSSIs) continue to account for substantial morbidity and health care burden, with the emergence of drug-resistant pathogens further complicating their management. Omadacycline is a new once-daily tetracycline with in vitro activity against a wide range of causative agents of ABSSSI, including Streptococcus pyogenes, Staphylococcus aureus (including methicillin-resistant strains, or MRSA), and Enterococcus spp.
Study design: Phase 3, randomized, double-blind, double-dummy, placebo-controlled trial.
Setting: A total of 55 sites in the United States, Peru, South Africa, and Europe.
Synopsis: The trial recruited 645 adults with a qualifying ABSSSI (such as wound infection, cellulitis or erysipelas, or major abscess) with evidence of an inflammatory response (white blood cell count at least 10,000 cells/mm3 or 4,000 cells/mm3 and below, immature neutrophils at least 15%, lymphatic involvement, or oral or rectal temperature greater than 38.0° C or less than 36.0° C). Exclusion criteria included infections associated with chronic skin lesions and clinically significant liver or renal insufficiency or immunocompromised state. All patients received either omadacycline or linezolid IV with the option to switch to the oral preparation of the respective drugs after at least 3 days of therapy.
Omadacycline was noninferior to moxifloxacin with respect to early clinical response (84.8% vs. 85.5%, respectively) and posttreatment clinical response rates (86.1% vs. 83.6%). Efficacy was similar for methicillin-susceptible or methicillin-resistant Staphylococcus aureus, the most common isolated pathogens. Frequency of adverse events (primarily gastrointestinal) was also similar in the two groups. Mean duration of IV therapy was 4.4 days, and mean duration of oral therapy was 5.5 days in the omadacycline group.
Bottom line: Omadacycline provides similar clinical benefit as linezolid in the treatment of ABSSSIs.
Citation: O’Riordan W et al. Omadacycline for acute bacterial skin and skin-structure infections. N Eng J Med. 2019;380:528-38.
Dr. Manian is a core educator faculty member in the department of medicine at Massachusetts General Hospital and an associate professor of medicine at Harvard Medical School, Boston.