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Keratotic Papule on the Abdomen
The Diagnosis: Hypergranulotic Dyscornification
Hypergranulotic dyscornification (HD) is a rarely reported reaction pattern present in benign solitary keratoses with only few reports to date. It may be an underrecognized reaction pattern based on the paucity of reported cases as well as the histologic similarities to other entities. It has been hypothesized that this pattern reflects an underlying keratin mutation or disorder of keratinization.1
Clinically, HD most commonly presents as a waxy, tan-colored, solitary keratosis generally found on the lower limbs, trunk, or back in individuals aged 20 to 60 years.1,2 Histopathology shows marked hyperkeratosis, papillomatosis, and clumped basophilic keratohyalin granules within the corneocytes with digitated epidermal hyperplasia. There is abnormal cornification across the entire lesion with papillomatosis and marked hypergranulosis.3 There often are homogeneous orthokeratotic mounds of large, dull, eosinophilic-staining anucleate keratinocytes that are sharply demarcated from the thickened granular layer.1,2 Within the spinous, granular, and corneal layers, there is a pale, gray-staining, basophilic, cytoplasmic substance intercellularly.1
Histopathologically, HD may be mistaken for several other entities both benign and malignant.1 Epidermolytic hyperkeratosis can be a genetic disorder, an incidental finding in a variety of skin conditions, or an isolated lesion.4 The genetic syndrome, caused by mutation in keratins 1 or 10, clinically presents with hyperkeratosis, erosions, blisters, and thickening of the epidermis, often with a corrugated appearance. Epidermal nevi findings often are seen in conjunction with histologic changes of epidermolytic hyperkeratosis caused by mutation. Solitary lesions also can resemble seborrheic keratosis or verruca. In all examples of epidermolytic hyperkeratosis, the histopathologic findings are identical.4 The granular layer is thickened, and coarse keratohyalin granules aggregate in the suprabasal cells.5 There is acantholysis with perinuclear vacuolization in the spinous and granular layers with characteristic pale cytoplasmic areas devoid of keratin filaments (Figure 1). The basal layer may be hyperproliferative.5
Irritated seborrheic keratosis presents as an exophytic, waxy, dark, sharply demarcated plaque with a stuck-on appearance.6 There is visible keratinization with comedolike openings, fissures and ridges, and scale; it also can contain milialike cysts. Histopathologically there is papillomatosis with prominent rete ridges, often including keratin pseudohorn cysts and squamous eddies. Enlarged capillaries can be seen in the dermal papillae. There is normal cytology with benign sheets of basaloid cells (Figure 2).7 Activating mutation in fibroblast growth factor receptor 3 leads to the growth and thickness of the epidermis that has been identified in these benign lesions.8
Verruca plana appears as a flesh-colored or reddish, warty, flat-topped papule that often forms clusters. Histopathologically it shows prominent hypergranulosis, thickened stratum spinosum, and vacuolized keratinocytes.9 The nuclei demonstrate a characteristic cytopathic effect of the virion, blurring the nuclear chromatin due to viral particle accumulation, known as koilocytes (Figure 3). The cause is the double-stranded DNA human papillomavirus types 2, 3, and 10.10
Bowen disease is a form of squamous cell carcinoma in situ characterized by an enlarging, well-demarcated, erythematous plaque with an irregular border and crusting or scaling. Histopathology reveals pleomorphic epidermal keratinization that becomes incorporated in the stratum corneum as parakeratotic nuclei. There is acanthosis, elongation of the rete ridges, and disorganized keratinocytes with atypia.11 The granular and spinous layers show an atypical honeycomb pattern with atypical cellular morphology (Figure 4).12 Bowen disease is a malignant lesion commonly found in older adults on sun-exposed skin that can evolve into invasive squamous cell carcinoma.
- Roy SF, Ko CJ, Moeckel GW, et al. Hypergranulotic dyscornification: 30 cases of a striking epithelial reaction pattern. J Cutan Pathol. 2019;46:742-747.
- Dohse L, Elston D, Lountzis N, et al. Benign hypergranulotic keratosis with dyscornification. J Am Acad Dermatol. 2010;62:AB52.
- Reichel M. Hypergranulotic dyscornification. Am J Dermatopathol. 1999;21:21-24.
- Kumar P, Kumar R, Kumar Mandal RK, et al. Systematized linear epidermolytic hyperkeratosis. Dermatol Online J. 2014;20:21248.
- Peter Rout D, Nair A, Gupta A, et al. Epidermolytic hyperkeratosis: clinical update. Clin Cosmet Investig Dermatol. 2019;12:333-344.
- Ingraffea A. Benign skin neoplasms. Facial Plast Surg Clin North Am. 2013;21:21-32.
- Braun R. Dermoscopy of pigmented seborrheic keratosis. Arch Dermatol. 2002;138:1556.
- Duperret EK, Oh SJ, McNeal A, et al. Activating FGFR3 mutations cause mild hyperplasia in human skin, but are insufficient to drive benign or malignant skin tumors. Cell Cycle. 2014;13:1551-1559.
- Liu H, Chen S, Zhang F, et al. Seborrheic keratosis or verruca plana? a pilot study with confocal laser scanning microscopy. Skin Res Technol. 2010;16:408-412.
- Prieto-Granada CN, Lobo AZC, Mihm MC. Skin infections. In: Kradin RL, ed. Diagnostic Pathology of Infectious Disease. Philadelphia, PA: Saunders Elsevier; 2010:519-616.
- DeCoste R, Moss P, Boutilier R, et al. Bowen disease with invasive mucin-secreting sweat gland differentiation: report of a case and review of the literature. J Cutan Pathol. 2019;46:425-430.
- Ulrich M, Kanitakis J, González S, et al. Evaluation of Bowen disease by in vivo reflectance confocal microscopy. Br J Dermatol. 2011;166:451-453.
The Diagnosis: Hypergranulotic Dyscornification
Hypergranulotic dyscornification (HD) is a rarely reported reaction pattern present in benign solitary keratoses with only few reports to date. It may be an underrecognized reaction pattern based on the paucity of reported cases as well as the histologic similarities to other entities. It has been hypothesized that this pattern reflects an underlying keratin mutation or disorder of keratinization.1
Clinically, HD most commonly presents as a waxy, tan-colored, solitary keratosis generally found on the lower limbs, trunk, or back in individuals aged 20 to 60 years.1,2 Histopathology shows marked hyperkeratosis, papillomatosis, and clumped basophilic keratohyalin granules within the corneocytes with digitated epidermal hyperplasia. There is abnormal cornification across the entire lesion with papillomatosis and marked hypergranulosis.3 There often are homogeneous orthokeratotic mounds of large, dull, eosinophilic-staining anucleate keratinocytes that are sharply demarcated from the thickened granular layer.1,2 Within the spinous, granular, and corneal layers, there is a pale, gray-staining, basophilic, cytoplasmic substance intercellularly.1
Histopathologically, HD may be mistaken for several other entities both benign and malignant.1 Epidermolytic hyperkeratosis can be a genetic disorder, an incidental finding in a variety of skin conditions, or an isolated lesion.4 The genetic syndrome, caused by mutation in keratins 1 or 10, clinically presents with hyperkeratosis, erosions, blisters, and thickening of the epidermis, often with a corrugated appearance. Epidermal nevi findings often are seen in conjunction with histologic changes of epidermolytic hyperkeratosis caused by mutation. Solitary lesions also can resemble seborrheic keratosis or verruca. In all examples of epidermolytic hyperkeratosis, the histopathologic findings are identical.4 The granular layer is thickened, and coarse keratohyalin granules aggregate in the suprabasal cells.5 There is acantholysis with perinuclear vacuolization in the spinous and granular layers with characteristic pale cytoplasmic areas devoid of keratin filaments (Figure 1). The basal layer may be hyperproliferative.5
Irritated seborrheic keratosis presents as an exophytic, waxy, dark, sharply demarcated plaque with a stuck-on appearance.6 There is visible keratinization with comedolike openings, fissures and ridges, and scale; it also can contain milialike cysts. Histopathologically there is papillomatosis with prominent rete ridges, often including keratin pseudohorn cysts and squamous eddies. Enlarged capillaries can be seen in the dermal papillae. There is normal cytology with benign sheets of basaloid cells (Figure 2).7 Activating mutation in fibroblast growth factor receptor 3 leads to the growth and thickness of the epidermis that has been identified in these benign lesions.8
Verruca plana appears as a flesh-colored or reddish, warty, flat-topped papule that often forms clusters. Histopathologically it shows prominent hypergranulosis, thickened stratum spinosum, and vacuolized keratinocytes.9 The nuclei demonstrate a characteristic cytopathic effect of the virion, blurring the nuclear chromatin due to viral particle accumulation, known as koilocytes (Figure 3). The cause is the double-stranded DNA human papillomavirus types 2, 3, and 10.10
Bowen disease is a form of squamous cell carcinoma in situ characterized by an enlarging, well-demarcated, erythematous plaque with an irregular border and crusting or scaling. Histopathology reveals pleomorphic epidermal keratinization that becomes incorporated in the stratum corneum as parakeratotic nuclei. There is acanthosis, elongation of the rete ridges, and disorganized keratinocytes with atypia.11 The granular and spinous layers show an atypical honeycomb pattern with atypical cellular morphology (Figure 4).12 Bowen disease is a malignant lesion commonly found in older adults on sun-exposed skin that can evolve into invasive squamous cell carcinoma.
The Diagnosis: Hypergranulotic Dyscornification
Hypergranulotic dyscornification (HD) is a rarely reported reaction pattern present in benign solitary keratoses with only few reports to date. It may be an underrecognized reaction pattern based on the paucity of reported cases as well as the histologic similarities to other entities. It has been hypothesized that this pattern reflects an underlying keratin mutation or disorder of keratinization.1
Clinically, HD most commonly presents as a waxy, tan-colored, solitary keratosis generally found on the lower limbs, trunk, or back in individuals aged 20 to 60 years.1,2 Histopathology shows marked hyperkeratosis, papillomatosis, and clumped basophilic keratohyalin granules within the corneocytes with digitated epidermal hyperplasia. There is abnormal cornification across the entire lesion with papillomatosis and marked hypergranulosis.3 There often are homogeneous orthokeratotic mounds of large, dull, eosinophilic-staining anucleate keratinocytes that are sharply demarcated from the thickened granular layer.1,2 Within the spinous, granular, and corneal layers, there is a pale, gray-staining, basophilic, cytoplasmic substance intercellularly.1
Histopathologically, HD may be mistaken for several other entities both benign and malignant.1 Epidermolytic hyperkeratosis can be a genetic disorder, an incidental finding in a variety of skin conditions, or an isolated lesion.4 The genetic syndrome, caused by mutation in keratins 1 or 10, clinically presents with hyperkeratosis, erosions, blisters, and thickening of the epidermis, often with a corrugated appearance. Epidermal nevi findings often are seen in conjunction with histologic changes of epidermolytic hyperkeratosis caused by mutation. Solitary lesions also can resemble seborrheic keratosis or verruca. In all examples of epidermolytic hyperkeratosis, the histopathologic findings are identical.4 The granular layer is thickened, and coarse keratohyalin granules aggregate in the suprabasal cells.5 There is acantholysis with perinuclear vacuolization in the spinous and granular layers with characteristic pale cytoplasmic areas devoid of keratin filaments (Figure 1). The basal layer may be hyperproliferative.5
Irritated seborrheic keratosis presents as an exophytic, waxy, dark, sharply demarcated plaque with a stuck-on appearance.6 There is visible keratinization with comedolike openings, fissures and ridges, and scale; it also can contain milialike cysts. Histopathologically there is papillomatosis with prominent rete ridges, often including keratin pseudohorn cysts and squamous eddies. Enlarged capillaries can be seen in the dermal papillae. There is normal cytology with benign sheets of basaloid cells (Figure 2).7 Activating mutation in fibroblast growth factor receptor 3 leads to the growth and thickness of the epidermis that has been identified in these benign lesions.8
Verruca plana appears as a flesh-colored or reddish, warty, flat-topped papule that often forms clusters. Histopathologically it shows prominent hypergranulosis, thickened stratum spinosum, and vacuolized keratinocytes.9 The nuclei demonstrate a characteristic cytopathic effect of the virion, blurring the nuclear chromatin due to viral particle accumulation, known as koilocytes (Figure 3). The cause is the double-stranded DNA human papillomavirus types 2, 3, and 10.10
Bowen disease is a form of squamous cell carcinoma in situ characterized by an enlarging, well-demarcated, erythematous plaque with an irregular border and crusting or scaling. Histopathology reveals pleomorphic epidermal keratinization that becomes incorporated in the stratum corneum as parakeratotic nuclei. There is acanthosis, elongation of the rete ridges, and disorganized keratinocytes with atypia.11 The granular and spinous layers show an atypical honeycomb pattern with atypical cellular morphology (Figure 4).12 Bowen disease is a malignant lesion commonly found in older adults on sun-exposed skin that can evolve into invasive squamous cell carcinoma.
- Roy SF, Ko CJ, Moeckel GW, et al. Hypergranulotic dyscornification: 30 cases of a striking epithelial reaction pattern. J Cutan Pathol. 2019;46:742-747.
- Dohse L, Elston D, Lountzis N, et al. Benign hypergranulotic keratosis with dyscornification. J Am Acad Dermatol. 2010;62:AB52.
- Reichel M. Hypergranulotic dyscornification. Am J Dermatopathol. 1999;21:21-24.
- Kumar P, Kumar R, Kumar Mandal RK, et al. Systematized linear epidermolytic hyperkeratosis. Dermatol Online J. 2014;20:21248.
- Peter Rout D, Nair A, Gupta A, et al. Epidermolytic hyperkeratosis: clinical update. Clin Cosmet Investig Dermatol. 2019;12:333-344.
- Ingraffea A. Benign skin neoplasms. Facial Plast Surg Clin North Am. 2013;21:21-32.
- Braun R. Dermoscopy of pigmented seborrheic keratosis. Arch Dermatol. 2002;138:1556.
- Duperret EK, Oh SJ, McNeal A, et al. Activating FGFR3 mutations cause mild hyperplasia in human skin, but are insufficient to drive benign or malignant skin tumors. Cell Cycle. 2014;13:1551-1559.
- Liu H, Chen S, Zhang F, et al. Seborrheic keratosis or verruca plana? a pilot study with confocal laser scanning microscopy. Skin Res Technol. 2010;16:408-412.
- Prieto-Granada CN, Lobo AZC, Mihm MC. Skin infections. In: Kradin RL, ed. Diagnostic Pathology of Infectious Disease. Philadelphia, PA: Saunders Elsevier; 2010:519-616.
- DeCoste R, Moss P, Boutilier R, et al. Bowen disease with invasive mucin-secreting sweat gland differentiation: report of a case and review of the literature. J Cutan Pathol. 2019;46:425-430.
- Ulrich M, Kanitakis J, González S, et al. Evaluation of Bowen disease by in vivo reflectance confocal microscopy. Br J Dermatol. 2011;166:451-453.
- Roy SF, Ko CJ, Moeckel GW, et al. Hypergranulotic dyscornification: 30 cases of a striking epithelial reaction pattern. J Cutan Pathol. 2019;46:742-747.
- Dohse L, Elston D, Lountzis N, et al. Benign hypergranulotic keratosis with dyscornification. J Am Acad Dermatol. 2010;62:AB52.
- Reichel M. Hypergranulotic dyscornification. Am J Dermatopathol. 1999;21:21-24.
- Kumar P, Kumar R, Kumar Mandal RK, et al. Systematized linear epidermolytic hyperkeratosis. Dermatol Online J. 2014;20:21248.
- Peter Rout D, Nair A, Gupta A, et al. Epidermolytic hyperkeratosis: clinical update. Clin Cosmet Investig Dermatol. 2019;12:333-344.
- Ingraffea A. Benign skin neoplasms. Facial Plast Surg Clin North Am. 2013;21:21-32.
- Braun R. Dermoscopy of pigmented seborrheic keratosis. Arch Dermatol. 2002;138:1556.
- Duperret EK, Oh SJ, McNeal A, et al. Activating FGFR3 mutations cause mild hyperplasia in human skin, but are insufficient to drive benign or malignant skin tumors. Cell Cycle. 2014;13:1551-1559.
- Liu H, Chen S, Zhang F, et al. Seborrheic keratosis or verruca plana? a pilot study with confocal laser scanning microscopy. Skin Res Technol. 2010;16:408-412.
- Prieto-Granada CN, Lobo AZC, Mihm MC. Skin infections. In: Kradin RL, ed. Diagnostic Pathology of Infectious Disease. Philadelphia, PA: Saunders Elsevier; 2010:519-616.
- DeCoste R, Moss P, Boutilier R, et al. Bowen disease with invasive mucin-secreting sweat gland differentiation: report of a case and review of the literature. J Cutan Pathol. 2019;46:425-430.
- Ulrich M, Kanitakis J, González S, et al. Evaluation of Bowen disease by in vivo reflectance confocal microscopy. Br J Dermatol. 2011;166:451-453.
A 59-year-old woman with a history of basal cell carcinoma, uterine and ovarian cancer, and verrucae presented with an asymptomatic 3-mm lesion on the left side of the lower abdomen. Physical examination revealed a waxy, tan-colored, solitary keratosis. A shave biopsy was performed. Histopathology showed hyperkeratosis, focal parakeratosis, papillomatosis, and marked hypergranulosis with pale gray cytoplasm of the spinous-layer keratinocytes.
Serum NfL in early MS can help predict clinical course
research suggests. The study showed that patients with higher sNfL within 5 years of MS diagnosis had a higher risk of long term-clinical disability and higher risk of developing progressive MS. The level of sNfL also predicted the rate of increase over time in the Expanded Disability Status Scale (EDSS).
Serum NfL levels can provide “useful information in both directions, adding to both an overall reassuring picture or worrying picture both at first presentation and then on subsequent visits,” said Simon Thebault, MBBCh, a neurology resident at the University of Ottawa and the Ottawa Hospital Research Institute, Canada.
This research was presented online as part of the 2020 American Academy of Neurology Science Highlights.
Prognostication from day one
Many studies have shown a correlation between MS disease activity (clinical relapses, EDSS progression, MRI lesions) and elevated sNfL. Other studies have also looked at the prognostic value of NfL in serum and cerebrospinal fluid (CSF), but the data are limited by the lack of long-term biobanked samples and subsequent follow-up, Dr. Thebault explained.
The new study took advantage of the Ottawa MS biobank, which contains carefully frozen and stored samples from more than 3,000 patients with MS going back up to 25 years.
The team identified patients with serum collected within 5 years of first MS symptom onset (baseline) who were followed for a median of 18.9 years (range 15.0 to 27.0 years). They quantified levels of sNfL in 67 patients and 37 matched controls.
In patients with MS, the median baseline sNfL level was 10.1 pg/mL – 38.5% higher than the median level in controls (7.26 pg/mL, P = 0.004).
The baseline sNfL level was “most helpful as a sensitive predictive marker to rule out disease progression,” the researchers reported in their meeting abstract.
Patients with baseline sNfL levels less than 7.62 pg/mL were 4.3 times less likely to develop significant disability (EDSS score ≥ 4; P = 0.001) and 7.1 times less likely to develop progressive MS by end of follow-up (P = 0.054).
The most rapid disease progression was seen in patients with the highest baseline NfL levels (3rd-tertile, > 13.2 pg/mL). Higher baseline sNfL level was associated with faster rate of EDSS progression even after adjusting for confounders of age, sex, and disease-modifying treatment.
“We were able to show that serum neurofilament levels collected very early in the disease, usually at the time of first diagnosis, were predictive of the clinical progression [by EDSS score] and the risk of evolving to secondary progressive MS on average 19 years later,” Dr. Thebault said. A baseline level less than 7.6 pg/mL was “reassuring.”
“Prognostication in MS from day one is important,” he emphasized.
“If we know someone is on a bad trajectory, neurologists might recommend more aggressive therapies up front. Equally, if a patient has a very reassuring picture, then maybe it is more appropriate to start with safer treatments [the so called ‘platform therapies’] that may serve a patient well for many years, as they did for many in the years before higher-efficacy therapies were available,” Dr. Thebault said.
“In the hands of an expert MS neurologist who understands both the pearls and pitfalls of this test ... serum neurofilament is already a useful clinical tool, and we have implemented it in our daily practice in Ottawa,” he concluded.
Noteworthy study
Commenting on the study, Asaff Harel, MD, neurologist at Lenox Hill Hospital in New York City, said the findings in this study are “noteworthy, as there is a relative lack of effective prognostic biomarkers in the field of MS.”
“It remains to be seen whether this improves risk stratification of patients above what can be achieved by looking at other prognostic factors, such as age, gender, baseline EDSS, and severity and frequency of relapses during early disease course,” Dr. Harel cautioned.
“This was a relatively small study and further research is necessary,” Dr. Harel added. It’s also worth noting, he said, that out of the 67 patients who met criteria to be included in the study (i.e., those with blood samples taken during “early MS,” more than 15 years ago), almost half were lost to follow-up, which could potentially open the study to error.
It is also “unclear whether early NfL level is a better prognostic marker than severity of early disease course and baseline EDSS, both of which were not addressed in the study, and this will be interesting to determine in the future,” Dr. Harel commented.
Funding for the study was provided by The Ottawa Hospital Pilot Project Grant. Thebault and Harel have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
research suggests. The study showed that patients with higher sNfL within 5 years of MS diagnosis had a higher risk of long term-clinical disability and higher risk of developing progressive MS. The level of sNfL also predicted the rate of increase over time in the Expanded Disability Status Scale (EDSS).
Serum NfL levels can provide “useful information in both directions, adding to both an overall reassuring picture or worrying picture both at first presentation and then on subsequent visits,” said Simon Thebault, MBBCh, a neurology resident at the University of Ottawa and the Ottawa Hospital Research Institute, Canada.
This research was presented online as part of the 2020 American Academy of Neurology Science Highlights.
Prognostication from day one
Many studies have shown a correlation between MS disease activity (clinical relapses, EDSS progression, MRI lesions) and elevated sNfL. Other studies have also looked at the prognostic value of NfL in serum and cerebrospinal fluid (CSF), but the data are limited by the lack of long-term biobanked samples and subsequent follow-up, Dr. Thebault explained.
The new study took advantage of the Ottawa MS biobank, which contains carefully frozen and stored samples from more than 3,000 patients with MS going back up to 25 years.
The team identified patients with serum collected within 5 years of first MS symptom onset (baseline) who were followed for a median of 18.9 years (range 15.0 to 27.0 years). They quantified levels of sNfL in 67 patients and 37 matched controls.
In patients with MS, the median baseline sNfL level was 10.1 pg/mL – 38.5% higher than the median level in controls (7.26 pg/mL, P = 0.004).
The baseline sNfL level was “most helpful as a sensitive predictive marker to rule out disease progression,” the researchers reported in their meeting abstract.
Patients with baseline sNfL levels less than 7.62 pg/mL were 4.3 times less likely to develop significant disability (EDSS score ≥ 4; P = 0.001) and 7.1 times less likely to develop progressive MS by end of follow-up (P = 0.054).
The most rapid disease progression was seen in patients with the highest baseline NfL levels (3rd-tertile, > 13.2 pg/mL). Higher baseline sNfL level was associated with faster rate of EDSS progression even after adjusting for confounders of age, sex, and disease-modifying treatment.
“We were able to show that serum neurofilament levels collected very early in the disease, usually at the time of first diagnosis, were predictive of the clinical progression [by EDSS score] and the risk of evolving to secondary progressive MS on average 19 years later,” Dr. Thebault said. A baseline level less than 7.6 pg/mL was “reassuring.”
“Prognostication in MS from day one is important,” he emphasized.
“If we know someone is on a bad trajectory, neurologists might recommend more aggressive therapies up front. Equally, if a patient has a very reassuring picture, then maybe it is more appropriate to start with safer treatments [the so called ‘platform therapies’] that may serve a patient well for many years, as they did for many in the years before higher-efficacy therapies were available,” Dr. Thebault said.
“In the hands of an expert MS neurologist who understands both the pearls and pitfalls of this test ... serum neurofilament is already a useful clinical tool, and we have implemented it in our daily practice in Ottawa,” he concluded.
Noteworthy study
Commenting on the study, Asaff Harel, MD, neurologist at Lenox Hill Hospital in New York City, said the findings in this study are “noteworthy, as there is a relative lack of effective prognostic biomarkers in the field of MS.”
“It remains to be seen whether this improves risk stratification of patients above what can be achieved by looking at other prognostic factors, such as age, gender, baseline EDSS, and severity and frequency of relapses during early disease course,” Dr. Harel cautioned.
“This was a relatively small study and further research is necessary,” Dr. Harel added. It’s also worth noting, he said, that out of the 67 patients who met criteria to be included in the study (i.e., those with blood samples taken during “early MS,” more than 15 years ago), almost half were lost to follow-up, which could potentially open the study to error.
It is also “unclear whether early NfL level is a better prognostic marker than severity of early disease course and baseline EDSS, both of which were not addressed in the study, and this will be interesting to determine in the future,” Dr. Harel commented.
Funding for the study was provided by The Ottawa Hospital Pilot Project Grant. Thebault and Harel have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
research suggests. The study showed that patients with higher sNfL within 5 years of MS diagnosis had a higher risk of long term-clinical disability and higher risk of developing progressive MS. The level of sNfL also predicted the rate of increase over time in the Expanded Disability Status Scale (EDSS).
Serum NfL levels can provide “useful information in both directions, adding to both an overall reassuring picture or worrying picture both at first presentation and then on subsequent visits,” said Simon Thebault, MBBCh, a neurology resident at the University of Ottawa and the Ottawa Hospital Research Institute, Canada.
This research was presented online as part of the 2020 American Academy of Neurology Science Highlights.
Prognostication from day one
Many studies have shown a correlation between MS disease activity (clinical relapses, EDSS progression, MRI lesions) and elevated sNfL. Other studies have also looked at the prognostic value of NfL in serum and cerebrospinal fluid (CSF), but the data are limited by the lack of long-term biobanked samples and subsequent follow-up, Dr. Thebault explained.
The new study took advantage of the Ottawa MS biobank, which contains carefully frozen and stored samples from more than 3,000 patients with MS going back up to 25 years.
The team identified patients with serum collected within 5 years of first MS symptom onset (baseline) who were followed for a median of 18.9 years (range 15.0 to 27.0 years). They quantified levels of sNfL in 67 patients and 37 matched controls.
In patients with MS, the median baseline sNfL level was 10.1 pg/mL – 38.5% higher than the median level in controls (7.26 pg/mL, P = 0.004).
The baseline sNfL level was “most helpful as a sensitive predictive marker to rule out disease progression,” the researchers reported in their meeting abstract.
Patients with baseline sNfL levels less than 7.62 pg/mL were 4.3 times less likely to develop significant disability (EDSS score ≥ 4; P = 0.001) and 7.1 times less likely to develop progressive MS by end of follow-up (P = 0.054).
The most rapid disease progression was seen in patients with the highest baseline NfL levels (3rd-tertile, > 13.2 pg/mL). Higher baseline sNfL level was associated with faster rate of EDSS progression even after adjusting for confounders of age, sex, and disease-modifying treatment.
“We were able to show that serum neurofilament levels collected very early in the disease, usually at the time of first diagnosis, were predictive of the clinical progression [by EDSS score] and the risk of evolving to secondary progressive MS on average 19 years later,” Dr. Thebault said. A baseline level less than 7.6 pg/mL was “reassuring.”
“Prognostication in MS from day one is important,” he emphasized.
“If we know someone is on a bad trajectory, neurologists might recommend more aggressive therapies up front. Equally, if a patient has a very reassuring picture, then maybe it is more appropriate to start with safer treatments [the so called ‘platform therapies’] that may serve a patient well for many years, as they did for many in the years before higher-efficacy therapies were available,” Dr. Thebault said.
“In the hands of an expert MS neurologist who understands both the pearls and pitfalls of this test ... serum neurofilament is already a useful clinical tool, and we have implemented it in our daily practice in Ottawa,” he concluded.
Noteworthy study
Commenting on the study, Asaff Harel, MD, neurologist at Lenox Hill Hospital in New York City, said the findings in this study are “noteworthy, as there is a relative lack of effective prognostic biomarkers in the field of MS.”
“It remains to be seen whether this improves risk stratification of patients above what can be achieved by looking at other prognostic factors, such as age, gender, baseline EDSS, and severity and frequency of relapses during early disease course,” Dr. Harel cautioned.
“This was a relatively small study and further research is necessary,” Dr. Harel added. It’s also worth noting, he said, that out of the 67 patients who met criteria to be included in the study (i.e., those with blood samples taken during “early MS,” more than 15 years ago), almost half were lost to follow-up, which could potentially open the study to error.
It is also “unclear whether early NfL level is a better prognostic marker than severity of early disease course and baseline EDSS, both of which were not addressed in the study, and this will be interesting to determine in the future,” Dr. Harel commented.
Funding for the study was provided by The Ottawa Hospital Pilot Project Grant. Thebault and Harel have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
COVID-19: Eight steps for getting ready to see patients again
After COVID-19 hit the Denver area, internist Jean Kutner, MD, and her clinical colleagues drastically reduced the number of patients they saw and kept a minimum number of people in the office. A small team sees patients who still require in-person visits on one side of the clinic; on the other side, another team conducts clinic-based telehealth visits. A rotating schedule allows for social distancing.
The rest of the practice’s physicians are home, conducting more virtual visits.
Dr. Kutner said she is looking forward to reopening her practice completely at some point. She said she realizes that the practice probably won’t be exactly the same as before.
“We have to embrace the fact that the way we practice medicine has fundamentally changed,” said Dr. Kutner, professor of medicine at the University of Colorado at Denver, Aurora, and incoming president of the Society of General Internal Medicine. She anticipates keeping many of these changes in place for the foreseeable future.
Nearly half of 2,600 primary care physicians who responded to a recent national survey said they were struggling to remain open during the crisis. Most have had to limit wellness/chronic-disease management visits, and nearly half reported that physicians or staff were out sick. Layoffs, furloughs, and reduced hours are commonplace; some practices were forced to shut down entirely.
Social distancing helps reduce the rates of hospitalizations and deaths.
For example, remote monitoring capabilities have reduced the need for in-person checks of vital signs, such as respiratory rate oxygenation, blood glucose levels, and heart rate. “We can’t go back,” she said.
Dr. Kutner sees the pandemic as an opportunity to innovate, to think about how primary practices can best utilize their resources, face-to-face time with patients, and when and how to best leverage virtual visits in a way that improves patient health. The goal, of course, is to meet the needs of the patients while keeping everyone safe.
Like many physicians in private practice, Dr. Kutner is concerned about revenue. She hopes the Centers for Medicare & Medicaid Services makes its temporary waivers permanent.
What you need to consider when planning to reopen your office
Physicians say their post-COVID-19 practices will look very different from their prepandemic practices. Many plan to maintain guidelines, such as those from the AAFP, long after the pandemic has peaked.
If you are starting to think about reopening, here are some major considerations.
1. Develop procedures and practices that will keep your patients and staff safe.
“When we return, the first thing we need to do is limit the number of patients in the waiting room,” said Clinton Coleman, MD, who practices internal medicine and nephrology in Teaneck, N.J. “No one is comfortable in a waiting room any longer,” said Dr. Coleman, chief of internal medicine at Holy Name Medical Center in Teaneck.
Careful planning is required to resume in-person care of patients requiring non-COVID-19 care, as well as all aspects of care, according to the CMS. Adequate staff, testing, supplies, and support services, such as pathology services, are just a few considerations. The CMS recommends that physicians “evaluate the necessity of the care based on clinical needs. Providers should prioritize surgical/procedural care and high-complexity chronic disease management; however, select preventive services may also be highly necessary.”
The American Medical Association recently unveiled a checklist for reopening. One key recommendation was for practices to select a date for reopening the office, ideally preceded by a “soft” or incremental reopening to ensure that new procedures are working. The AMA also recommends opening incrementally, continuing telehealth while also inviting patients back into the office.
2. Figure out how to safely see patients, particularly in your waiting areas and common spaces.
Logistic factors, such as managing patient flow, will change. Waiting rooms will be emptier; in some locations, patients may be asked to wait in their cars until an exam room is available.
The AMA also suggests limiting nonpatient visitors by posting the practice’s policy at the entrance and on the practice’s website. If service calls for repairs are needed, have those visitors come outside of normal operating hours.
Commonly shared objects such magazines or toys in pediatric offices will likely disappear. Wipes, hand sanitizers, and the wearing of masks will become even more commonplace. Those who suspect they’re ill or who have respiratory symptoms may be relegated to specific “sick visit” appointment times or taken to designated exam rooms, which will be thoroughly sanitized between patients.
3. Prepare for routine screening of staff and other facility workers.
According to recent CMS guidelines, you and your staff will need to undergo routine screening, as will others who work in the facility (housekeeping, delivery personnel, and anyone else who enters the area). This may mean regularly stocking screening tests and setting guidelines for what to do if one of your staff tests positive.
You may need to hire temporary workers if your staff tests positive. The CDC recommends at the very least understanding the minimum staffing requirements to ensure good patient care and a safe work environment. Consider adjusting staff schedules and rotating clinical personnel to positions that support patient care activities. You may also want to look into cross-training your office staff so that they can fill in or help out with each other’s responsibilities if one or more persons are ill.
Dr. Kutner is on board with these changes. “We don’t want to get rid of social distancing right away, because it will give us a new spike in cases – how do we figure out patient flow while honoring that?”
4. Develop a strategy for triaging and caring for a potential backlog of patients.
“Many of my partners are scared right now because they have no income except for emergencies,” said Andrew Gonzalez, MD, JD, MPH, a vascular surgeon and assistant professor of surgery at Indiana University, Indianapolis. Almost all nonemergency surgery has been put on hold.
“If we don’t operate, the practice makes no money,” he said. He thinks revenue will continue to be a problem as long as patients fear in-person consultations or undergoing surgery for nonacute problems such as hernias.
As restrictions ease, most physicians will face an enormous backlog of patients and will need to find new ways of triaging the most serious cases, he says. Telehealth will help, but Dr. Gonzalez predicts many of his colleagues will be working longer hours and on weekends to catch up. “Physicians are going to have to really think about ways of optimizing their time and workflow to be very efficient, because the backlog is going to prodigious.”
5. Anticipate changes in patient expectations.
This may entail your reconsidering tests and procedures you previously performed and considering developing new sources for some services, phasing some others out, and revising your current approach. It will most likely also mean that you make telemedicine and televisits a greater part of your practice.
Carolyn Kaloostian, MD, a family medicine and geriatric practitioner in Los Angeles, points to increased reliance on community agencies for conducting common office-based procedures, such as performing blood tests and taking ECGs and x-rays. “A lot of patients are using telemedicine or telephone visits and get the lab work or x-rays somewhere that’s less congested,” she said. To become sustainable, many of these changes will hinge on economics – whether and how they are reimbursed.
The pandemic will leave lasting effects in our health care delivery, according to Dr. Kaloostian. She is sure many of her colleagues’ and patients’ current experiences will be infused into future care. “I can’t say we’ll ever be back to normal, necessarily.”
Even if the CMS rolls back its telehealth waivers, some physicians, like Dr. Coleman, plan to continue using the technology extensively. He’s confident about the level of care he’s currently providing patients in his practice. It allows him to better manage many low-income patients who can’t access his office regularly. Not only does splitting his time between the clinic and telehealth allow him to be more available for more patients, he says it also empowers patients to take better care of themselves.
6. Consider a new way to conduct “check-in visits.”
One thing that will likely go by the wayside are “check-in” visits, or so-called “social visits,” those interval appointments that can just as easily be completed virtually. “Patients are going to ask why they need to drive 3 hours so you can tell them their incision looks fine from an operation you did 5 years ago,” Dr. Gonzalez said.
He’s concerned that some people will remain so fearful of the health care system that a formerly busy practice may see the pendulum swing in the opposite direction. If an aneurysm patient skips a visit, that person may also decide not to undergo a CT scan – and something preventable will be missed. “Not everybody has the option to stay away until they feel comfortable. They’re basically playing hot potato. And at some point, the music’s going to stop,” Dr. Gonzalez said.
The pandemic has prompted some very honest conversations with his patients about what truly needs to get done and what may be optional. “Everyone has now become a hyper-rational user of health care,” he said.
7. If you haven’t yet, consider becoming more involved with technology.
In addition to greater use of telehealth, Dr. Kaloostian, assistant professor of clinical family medicine at the University of Southern California, Los Angeles, foresees continued reliance upon technology such as smartphone apps that connect with a user’s smartwatch. This allows for more proactive, remote monitoring.
“For example, any time a patient is having recurrent nighttime trips to the bathroom, I’ll get pinged and know that,” she explained. It means she can reach out and ask about any changes before a fall occurs or a condition worsens. “It provides reassurance to the provider and to the patient that you’re doing all you can to keep an eye on them from afar.”
8. Update or reformulate your business plans.
Some physicians in smaller practices may have to temporarily or permanently rethink their situation. Those who have struggled or who have closed down and are considering reopening need to update their business plans. It may be safer economically to become part of a bigger group that is affiliated with an academic center or join a larger health care system that has more funds or resources.
In addition, Dr. Kaloostian suggests that primary care physicians become more flexible in the short term, perhaps working part time in an urgent care clinic or larger organization to gain additional sources of revenue until their own practice finances pick back up.
For offices that reopen, the AMA recommends contacting medical malpractice insurance carriers to check on possible liability concerns. Congress has provided certain protections for clinicians during this time, but malpractice carriers may have more information and may offer more coverage.
Dr. Coleman said a hybrid model of fewer in-person and more telehealth visits “will allow me to practice in a different way.” If the CMS reimposes prior restrictions, reimbursement may be affected initially, but that will likely change once insurers see the increased cost-effectiveness of this approach. Patients with minor complaints, those who need to have medications refilled, and patients with chronic diseases that need managing won’t have to deal with crowded waiting rooms, and it will help mitigate problems with infection control.
If there’s any upside to the pandemic, it’s an increase in attention given to advanced care planning, said Dr. Kutner. It’s something she hopes continues after everyone stops being in crisis mode. “We’re realizing how important it is to have these conversations and document people’s goals and values and code status,” she said.
Are offices likely to open soon?
An assumption that may or may not be valid is that a practice will remain viable and can return to former capacity. Prior to passage of the CARES Act on March 27, a survey from Kareo, a company in Irvine, California, that makes a technology platform for independent physician practices, found that 9% of respondents reported practice closures. Many more reported concern about potential closures as patient office visits plummet because of stay-at-home orders and other concerns.
By mid-April, a survey from the Primary Care Collaborative and the Larry A. Green Center found that 42% of practices had experienced layoffs and had furloughed staff. Most (85%) have seen dramatic decreases in patient volume.
“Reopening the economy or loosening physical distancing restrictions will be difficult when 20% of primary care practices predict closure within 4 weeks,” the survey concluded.
For the practices and the doctors who make it through this, we’re going to probably be better, stronger, and more efficient, Dr. Gonzalez predicts. This shock has uncovered a lot of weaknesses in the American health care system that doctors have known about and have been complaining about for a long time. It will take an open mind and lots of continued flexibility on the part of physicians, hospitals, health care systems, and the government for these changes to stick.
A version of this article originally appeared on Medscape.com.
After COVID-19 hit the Denver area, internist Jean Kutner, MD, and her clinical colleagues drastically reduced the number of patients they saw and kept a minimum number of people in the office. A small team sees patients who still require in-person visits on one side of the clinic; on the other side, another team conducts clinic-based telehealth visits. A rotating schedule allows for social distancing.
The rest of the practice’s physicians are home, conducting more virtual visits.
Dr. Kutner said she is looking forward to reopening her practice completely at some point. She said she realizes that the practice probably won’t be exactly the same as before.
“We have to embrace the fact that the way we practice medicine has fundamentally changed,” said Dr. Kutner, professor of medicine at the University of Colorado at Denver, Aurora, and incoming president of the Society of General Internal Medicine. She anticipates keeping many of these changes in place for the foreseeable future.
Nearly half of 2,600 primary care physicians who responded to a recent national survey said they were struggling to remain open during the crisis. Most have had to limit wellness/chronic-disease management visits, and nearly half reported that physicians or staff were out sick. Layoffs, furloughs, and reduced hours are commonplace; some practices were forced to shut down entirely.
Social distancing helps reduce the rates of hospitalizations and deaths.
For example, remote monitoring capabilities have reduced the need for in-person checks of vital signs, such as respiratory rate oxygenation, blood glucose levels, and heart rate. “We can’t go back,” she said.
Dr. Kutner sees the pandemic as an opportunity to innovate, to think about how primary practices can best utilize their resources, face-to-face time with patients, and when and how to best leverage virtual visits in a way that improves patient health. The goal, of course, is to meet the needs of the patients while keeping everyone safe.
Like many physicians in private practice, Dr. Kutner is concerned about revenue. She hopes the Centers for Medicare & Medicaid Services makes its temporary waivers permanent.
What you need to consider when planning to reopen your office
Physicians say their post-COVID-19 practices will look very different from their prepandemic practices. Many plan to maintain guidelines, such as those from the AAFP, long after the pandemic has peaked.
If you are starting to think about reopening, here are some major considerations.
1. Develop procedures and practices that will keep your patients and staff safe.
“When we return, the first thing we need to do is limit the number of patients in the waiting room,” said Clinton Coleman, MD, who practices internal medicine and nephrology in Teaneck, N.J. “No one is comfortable in a waiting room any longer,” said Dr. Coleman, chief of internal medicine at Holy Name Medical Center in Teaneck.
Careful planning is required to resume in-person care of patients requiring non-COVID-19 care, as well as all aspects of care, according to the CMS. Adequate staff, testing, supplies, and support services, such as pathology services, are just a few considerations. The CMS recommends that physicians “evaluate the necessity of the care based on clinical needs. Providers should prioritize surgical/procedural care and high-complexity chronic disease management; however, select preventive services may also be highly necessary.”
The American Medical Association recently unveiled a checklist for reopening. One key recommendation was for practices to select a date for reopening the office, ideally preceded by a “soft” or incremental reopening to ensure that new procedures are working. The AMA also recommends opening incrementally, continuing telehealth while also inviting patients back into the office.
2. Figure out how to safely see patients, particularly in your waiting areas and common spaces.
Logistic factors, such as managing patient flow, will change. Waiting rooms will be emptier; in some locations, patients may be asked to wait in their cars until an exam room is available.
The AMA also suggests limiting nonpatient visitors by posting the practice’s policy at the entrance and on the practice’s website. If service calls for repairs are needed, have those visitors come outside of normal operating hours.
Commonly shared objects such magazines or toys in pediatric offices will likely disappear. Wipes, hand sanitizers, and the wearing of masks will become even more commonplace. Those who suspect they’re ill or who have respiratory symptoms may be relegated to specific “sick visit” appointment times or taken to designated exam rooms, which will be thoroughly sanitized between patients.
3. Prepare for routine screening of staff and other facility workers.
According to recent CMS guidelines, you and your staff will need to undergo routine screening, as will others who work in the facility (housekeeping, delivery personnel, and anyone else who enters the area). This may mean regularly stocking screening tests and setting guidelines for what to do if one of your staff tests positive.
You may need to hire temporary workers if your staff tests positive. The CDC recommends at the very least understanding the minimum staffing requirements to ensure good patient care and a safe work environment. Consider adjusting staff schedules and rotating clinical personnel to positions that support patient care activities. You may also want to look into cross-training your office staff so that they can fill in or help out with each other’s responsibilities if one or more persons are ill.
Dr. Kutner is on board with these changes. “We don’t want to get rid of social distancing right away, because it will give us a new spike in cases – how do we figure out patient flow while honoring that?”
4. Develop a strategy for triaging and caring for a potential backlog of patients.
“Many of my partners are scared right now because they have no income except for emergencies,” said Andrew Gonzalez, MD, JD, MPH, a vascular surgeon and assistant professor of surgery at Indiana University, Indianapolis. Almost all nonemergency surgery has been put on hold.
“If we don’t operate, the practice makes no money,” he said. He thinks revenue will continue to be a problem as long as patients fear in-person consultations or undergoing surgery for nonacute problems such as hernias.
As restrictions ease, most physicians will face an enormous backlog of patients and will need to find new ways of triaging the most serious cases, he says. Telehealth will help, but Dr. Gonzalez predicts many of his colleagues will be working longer hours and on weekends to catch up. “Physicians are going to have to really think about ways of optimizing their time and workflow to be very efficient, because the backlog is going to prodigious.”
5. Anticipate changes in patient expectations.
This may entail your reconsidering tests and procedures you previously performed and considering developing new sources for some services, phasing some others out, and revising your current approach. It will most likely also mean that you make telemedicine and televisits a greater part of your practice.
Carolyn Kaloostian, MD, a family medicine and geriatric practitioner in Los Angeles, points to increased reliance on community agencies for conducting common office-based procedures, such as performing blood tests and taking ECGs and x-rays. “A lot of patients are using telemedicine or telephone visits and get the lab work or x-rays somewhere that’s less congested,” she said. To become sustainable, many of these changes will hinge on economics – whether and how they are reimbursed.
The pandemic will leave lasting effects in our health care delivery, according to Dr. Kaloostian. She is sure many of her colleagues’ and patients’ current experiences will be infused into future care. “I can’t say we’ll ever be back to normal, necessarily.”
Even if the CMS rolls back its telehealth waivers, some physicians, like Dr. Coleman, plan to continue using the technology extensively. He’s confident about the level of care he’s currently providing patients in his practice. It allows him to better manage many low-income patients who can’t access his office regularly. Not only does splitting his time between the clinic and telehealth allow him to be more available for more patients, he says it also empowers patients to take better care of themselves.
6. Consider a new way to conduct “check-in visits.”
One thing that will likely go by the wayside are “check-in” visits, or so-called “social visits,” those interval appointments that can just as easily be completed virtually. “Patients are going to ask why they need to drive 3 hours so you can tell them their incision looks fine from an operation you did 5 years ago,” Dr. Gonzalez said.
He’s concerned that some people will remain so fearful of the health care system that a formerly busy practice may see the pendulum swing in the opposite direction. If an aneurysm patient skips a visit, that person may also decide not to undergo a CT scan – and something preventable will be missed. “Not everybody has the option to stay away until they feel comfortable. They’re basically playing hot potato. And at some point, the music’s going to stop,” Dr. Gonzalez said.
The pandemic has prompted some very honest conversations with his patients about what truly needs to get done and what may be optional. “Everyone has now become a hyper-rational user of health care,” he said.
7. If you haven’t yet, consider becoming more involved with technology.
In addition to greater use of telehealth, Dr. Kaloostian, assistant professor of clinical family medicine at the University of Southern California, Los Angeles, foresees continued reliance upon technology such as smartphone apps that connect with a user’s smartwatch. This allows for more proactive, remote monitoring.
“For example, any time a patient is having recurrent nighttime trips to the bathroom, I’ll get pinged and know that,” she explained. It means she can reach out and ask about any changes before a fall occurs or a condition worsens. “It provides reassurance to the provider and to the patient that you’re doing all you can to keep an eye on them from afar.”
8. Update or reformulate your business plans.
Some physicians in smaller practices may have to temporarily or permanently rethink their situation. Those who have struggled or who have closed down and are considering reopening need to update their business plans. It may be safer economically to become part of a bigger group that is affiliated with an academic center or join a larger health care system that has more funds or resources.
In addition, Dr. Kaloostian suggests that primary care physicians become more flexible in the short term, perhaps working part time in an urgent care clinic or larger organization to gain additional sources of revenue until their own practice finances pick back up.
For offices that reopen, the AMA recommends contacting medical malpractice insurance carriers to check on possible liability concerns. Congress has provided certain protections for clinicians during this time, but malpractice carriers may have more information and may offer more coverage.
Dr. Coleman said a hybrid model of fewer in-person and more telehealth visits “will allow me to practice in a different way.” If the CMS reimposes prior restrictions, reimbursement may be affected initially, but that will likely change once insurers see the increased cost-effectiveness of this approach. Patients with minor complaints, those who need to have medications refilled, and patients with chronic diseases that need managing won’t have to deal with crowded waiting rooms, and it will help mitigate problems with infection control.
If there’s any upside to the pandemic, it’s an increase in attention given to advanced care planning, said Dr. Kutner. It’s something she hopes continues after everyone stops being in crisis mode. “We’re realizing how important it is to have these conversations and document people’s goals and values and code status,” she said.
Are offices likely to open soon?
An assumption that may or may not be valid is that a practice will remain viable and can return to former capacity. Prior to passage of the CARES Act on March 27, a survey from Kareo, a company in Irvine, California, that makes a technology platform for independent physician practices, found that 9% of respondents reported practice closures. Many more reported concern about potential closures as patient office visits plummet because of stay-at-home orders and other concerns.
By mid-April, a survey from the Primary Care Collaborative and the Larry A. Green Center found that 42% of practices had experienced layoffs and had furloughed staff. Most (85%) have seen dramatic decreases in patient volume.
“Reopening the economy or loosening physical distancing restrictions will be difficult when 20% of primary care practices predict closure within 4 weeks,” the survey concluded.
For the practices and the doctors who make it through this, we’re going to probably be better, stronger, and more efficient, Dr. Gonzalez predicts. This shock has uncovered a lot of weaknesses in the American health care system that doctors have known about and have been complaining about for a long time. It will take an open mind and lots of continued flexibility on the part of physicians, hospitals, health care systems, and the government for these changes to stick.
A version of this article originally appeared on Medscape.com.
After COVID-19 hit the Denver area, internist Jean Kutner, MD, and her clinical colleagues drastically reduced the number of patients they saw and kept a minimum number of people in the office. A small team sees patients who still require in-person visits on one side of the clinic; on the other side, another team conducts clinic-based telehealth visits. A rotating schedule allows for social distancing.
The rest of the practice’s physicians are home, conducting more virtual visits.
Dr. Kutner said she is looking forward to reopening her practice completely at some point. She said she realizes that the practice probably won’t be exactly the same as before.
“We have to embrace the fact that the way we practice medicine has fundamentally changed,” said Dr. Kutner, professor of medicine at the University of Colorado at Denver, Aurora, and incoming president of the Society of General Internal Medicine. She anticipates keeping many of these changes in place for the foreseeable future.
Nearly half of 2,600 primary care physicians who responded to a recent national survey said they were struggling to remain open during the crisis. Most have had to limit wellness/chronic-disease management visits, and nearly half reported that physicians or staff were out sick. Layoffs, furloughs, and reduced hours are commonplace; some practices were forced to shut down entirely.
Social distancing helps reduce the rates of hospitalizations and deaths.
For example, remote monitoring capabilities have reduced the need for in-person checks of vital signs, such as respiratory rate oxygenation, blood glucose levels, and heart rate. “We can’t go back,” she said.
Dr. Kutner sees the pandemic as an opportunity to innovate, to think about how primary practices can best utilize their resources, face-to-face time with patients, and when and how to best leverage virtual visits in a way that improves patient health. The goal, of course, is to meet the needs of the patients while keeping everyone safe.
Like many physicians in private practice, Dr. Kutner is concerned about revenue. She hopes the Centers for Medicare & Medicaid Services makes its temporary waivers permanent.
What you need to consider when planning to reopen your office
Physicians say their post-COVID-19 practices will look very different from their prepandemic practices. Many plan to maintain guidelines, such as those from the AAFP, long after the pandemic has peaked.
If you are starting to think about reopening, here are some major considerations.
1. Develop procedures and practices that will keep your patients and staff safe.
“When we return, the first thing we need to do is limit the number of patients in the waiting room,” said Clinton Coleman, MD, who practices internal medicine and nephrology in Teaneck, N.J. “No one is comfortable in a waiting room any longer,” said Dr. Coleman, chief of internal medicine at Holy Name Medical Center in Teaneck.
Careful planning is required to resume in-person care of patients requiring non-COVID-19 care, as well as all aspects of care, according to the CMS. Adequate staff, testing, supplies, and support services, such as pathology services, are just a few considerations. The CMS recommends that physicians “evaluate the necessity of the care based on clinical needs. Providers should prioritize surgical/procedural care and high-complexity chronic disease management; however, select preventive services may also be highly necessary.”
The American Medical Association recently unveiled a checklist for reopening. One key recommendation was for practices to select a date for reopening the office, ideally preceded by a “soft” or incremental reopening to ensure that new procedures are working. The AMA also recommends opening incrementally, continuing telehealth while also inviting patients back into the office.
2. Figure out how to safely see patients, particularly in your waiting areas and common spaces.
Logistic factors, such as managing patient flow, will change. Waiting rooms will be emptier; in some locations, patients may be asked to wait in their cars until an exam room is available.
The AMA also suggests limiting nonpatient visitors by posting the practice’s policy at the entrance and on the practice’s website. If service calls for repairs are needed, have those visitors come outside of normal operating hours.
Commonly shared objects such magazines or toys in pediatric offices will likely disappear. Wipes, hand sanitizers, and the wearing of masks will become even more commonplace. Those who suspect they’re ill or who have respiratory symptoms may be relegated to specific “sick visit” appointment times or taken to designated exam rooms, which will be thoroughly sanitized between patients.
3. Prepare for routine screening of staff and other facility workers.
According to recent CMS guidelines, you and your staff will need to undergo routine screening, as will others who work in the facility (housekeeping, delivery personnel, and anyone else who enters the area). This may mean regularly stocking screening tests and setting guidelines for what to do if one of your staff tests positive.
You may need to hire temporary workers if your staff tests positive. The CDC recommends at the very least understanding the minimum staffing requirements to ensure good patient care and a safe work environment. Consider adjusting staff schedules and rotating clinical personnel to positions that support patient care activities. You may also want to look into cross-training your office staff so that they can fill in or help out with each other’s responsibilities if one or more persons are ill.
Dr. Kutner is on board with these changes. “We don’t want to get rid of social distancing right away, because it will give us a new spike in cases – how do we figure out patient flow while honoring that?”
4. Develop a strategy for triaging and caring for a potential backlog of patients.
“Many of my partners are scared right now because they have no income except for emergencies,” said Andrew Gonzalez, MD, JD, MPH, a vascular surgeon and assistant professor of surgery at Indiana University, Indianapolis. Almost all nonemergency surgery has been put on hold.
“If we don’t operate, the practice makes no money,” he said. He thinks revenue will continue to be a problem as long as patients fear in-person consultations or undergoing surgery for nonacute problems such as hernias.
As restrictions ease, most physicians will face an enormous backlog of patients and will need to find new ways of triaging the most serious cases, he says. Telehealth will help, but Dr. Gonzalez predicts many of his colleagues will be working longer hours and on weekends to catch up. “Physicians are going to have to really think about ways of optimizing their time and workflow to be very efficient, because the backlog is going to prodigious.”
5. Anticipate changes in patient expectations.
This may entail your reconsidering tests and procedures you previously performed and considering developing new sources for some services, phasing some others out, and revising your current approach. It will most likely also mean that you make telemedicine and televisits a greater part of your practice.
Carolyn Kaloostian, MD, a family medicine and geriatric practitioner in Los Angeles, points to increased reliance on community agencies for conducting common office-based procedures, such as performing blood tests and taking ECGs and x-rays. “A lot of patients are using telemedicine or telephone visits and get the lab work or x-rays somewhere that’s less congested,” she said. To become sustainable, many of these changes will hinge on economics – whether and how they are reimbursed.
The pandemic will leave lasting effects in our health care delivery, according to Dr. Kaloostian. She is sure many of her colleagues’ and patients’ current experiences will be infused into future care. “I can’t say we’ll ever be back to normal, necessarily.”
Even if the CMS rolls back its telehealth waivers, some physicians, like Dr. Coleman, plan to continue using the technology extensively. He’s confident about the level of care he’s currently providing patients in his practice. It allows him to better manage many low-income patients who can’t access his office regularly. Not only does splitting his time between the clinic and telehealth allow him to be more available for more patients, he says it also empowers patients to take better care of themselves.
6. Consider a new way to conduct “check-in visits.”
One thing that will likely go by the wayside are “check-in” visits, or so-called “social visits,” those interval appointments that can just as easily be completed virtually. “Patients are going to ask why they need to drive 3 hours so you can tell them their incision looks fine from an operation you did 5 years ago,” Dr. Gonzalez said.
He’s concerned that some people will remain so fearful of the health care system that a formerly busy practice may see the pendulum swing in the opposite direction. If an aneurysm patient skips a visit, that person may also decide not to undergo a CT scan – and something preventable will be missed. “Not everybody has the option to stay away until they feel comfortable. They’re basically playing hot potato. And at some point, the music’s going to stop,” Dr. Gonzalez said.
The pandemic has prompted some very honest conversations with his patients about what truly needs to get done and what may be optional. “Everyone has now become a hyper-rational user of health care,” he said.
7. If you haven’t yet, consider becoming more involved with technology.
In addition to greater use of telehealth, Dr. Kaloostian, assistant professor of clinical family medicine at the University of Southern California, Los Angeles, foresees continued reliance upon technology such as smartphone apps that connect with a user’s smartwatch. This allows for more proactive, remote monitoring.
“For example, any time a patient is having recurrent nighttime trips to the bathroom, I’ll get pinged and know that,” she explained. It means she can reach out and ask about any changes before a fall occurs or a condition worsens. “It provides reassurance to the provider and to the patient that you’re doing all you can to keep an eye on them from afar.”
8. Update or reformulate your business plans.
Some physicians in smaller practices may have to temporarily or permanently rethink their situation. Those who have struggled or who have closed down and are considering reopening need to update their business plans. It may be safer economically to become part of a bigger group that is affiliated with an academic center or join a larger health care system that has more funds or resources.
In addition, Dr. Kaloostian suggests that primary care physicians become more flexible in the short term, perhaps working part time in an urgent care clinic or larger organization to gain additional sources of revenue until their own practice finances pick back up.
For offices that reopen, the AMA recommends contacting medical malpractice insurance carriers to check on possible liability concerns. Congress has provided certain protections for clinicians during this time, but malpractice carriers may have more information and may offer more coverage.
Dr. Coleman said a hybrid model of fewer in-person and more telehealth visits “will allow me to practice in a different way.” If the CMS reimposes prior restrictions, reimbursement may be affected initially, but that will likely change once insurers see the increased cost-effectiveness of this approach. Patients with minor complaints, those who need to have medications refilled, and patients with chronic diseases that need managing won’t have to deal with crowded waiting rooms, and it will help mitigate problems with infection control.
If there’s any upside to the pandemic, it’s an increase in attention given to advanced care planning, said Dr. Kutner. It’s something she hopes continues after everyone stops being in crisis mode. “We’re realizing how important it is to have these conversations and document people’s goals and values and code status,” she said.
Are offices likely to open soon?
An assumption that may or may not be valid is that a practice will remain viable and can return to former capacity. Prior to passage of the CARES Act on March 27, a survey from Kareo, a company in Irvine, California, that makes a technology platform for independent physician practices, found that 9% of respondents reported practice closures. Many more reported concern about potential closures as patient office visits plummet because of stay-at-home orders and other concerns.
By mid-April, a survey from the Primary Care Collaborative and the Larry A. Green Center found that 42% of practices had experienced layoffs and had furloughed staff. Most (85%) have seen dramatic decreases in patient volume.
“Reopening the economy or loosening physical distancing restrictions will be difficult when 20% of primary care practices predict closure within 4 weeks,” the survey concluded.
For the practices and the doctors who make it through this, we’re going to probably be better, stronger, and more efficient, Dr. Gonzalez predicts. This shock has uncovered a lot of weaknesses in the American health care system that doctors have known about and have been complaining about for a long time. It will take an open mind and lots of continued flexibility on the part of physicians, hospitals, health care systems, and the government for these changes to stick.
A version of this article originally appeared on Medscape.com.
Adolescent obesity, diabetes linked to atherosclerotic signs
published online in the Journal of the American Heart Association.
significantly greater than their normal-weight peers, according to a longitudinal studyThe study evaluated 448 adolescents over 5 years for changes in a variety of metrics to determine changes in arterial structure, including carotid intima media thickness (cIMT), carotid-femoral pulse-wave velocity (PWV), and augmentation index (Aix). The average age of the study group was 17.6 years. The three study groups broke down accordingly: 141 with normal weight, 156 with obesity, and 151 with type 2 diabetes. Patients were evaluated at baseline and 5 years later.
“The presence of obesity and especially type 2 diabetes in adolescents accelerates the early vascular aging process associated with several key risk factors,” wrote Justin R. Ryder, PhD, an assistant professor of pediatrics at the University of Minnesota, Minneapolis, and colleagues.
The researchers also noted that systolic hypertension was associated with changes in cIMT and arterial stiffness comparable to obesity and diabetes. “These data add further evidence underscoring the importance of efforts targeting prevention and treatment of obesity, type 2 diabetes, and elevated blood pressure among youth, with a goal of delaying and/or preventing the progression of early vascular aging,” Dr. Ryder and colleagues wrote.
Obese patients, when compared with normal-weight participants, had the following average increases: common cIMT by 0.05 mm, bulb cIMT by 0.02 mm, internal cIMT by 0.03 mm, and PWV carotid-femoral by 0.38 m/sec, all statistically significant differences. Patients with diabetes, compared with normal-weight participants, registered the following average increases: common cIMT by 0.05 mm, bulb cIMT by 0.06 mm, internal cIMT by 0.04 mm, Aix by 4.67%, and PWV carotid-femoral by 0.74 m/sec. All differences were highly significant at P less than .001.
The results also showed that higher baseline systolic blood pressure was associated with significantly greater average increases in the following factors: common cIMT by 0.007 mm, bulb cIMT by 0.009 mm, internal cIMT by 0.008 mm, and PWV carotid-femoral by 0.66 m/sec.
Drilling down into the data, the study reported that males had greater increases in bulb cIMT and incremental elastic modulus as well as reduced Aix, compared with females. Nonwhites also had greater increases in bulb cIMT than did whites. Age was associated with greater increases in bulb and internal cIMT and Aix.
“Our data support the concept that male sex is an independent and primary risk factor for accelerated early vascular aging,” Dr. Ryder and colleagues wrote. The study also determined that type 2 diabetes is a more prominent risk factor than obesity for early vascular aging.
The size of the study population, specifically adolescents with diabetes, is a study strength, Dr. Ryder and colleagues noted. Other strengths they pointed to are the 5-year duration and the robust panel of noninvasive measures, although not using hard cardiovascular outcomes is an acknowledged limitation.
“It should also be noted that many of the youth with type 2 diabetes were on medications for glycemic control, lipids, and/or blood pressure regulation,” Dr. Ryder and colleagues wrote. “Despite this, the vascular profiles worsened over time.”
The study showed “a really significant change” in the carotid anatomy in adolescents with obesity and type 2 diabetes over 5 years, Robert Eckel, MD, professor at the University of Colorado Anschutz Medical Campus, Aurora, said in an interview. “Notably, the PWV is not just anatomy; now we’re talking about function. In other words, the augmentation index and PWV will assess the compliance of the artery.”
The findings suggest that atherosclerosis begins with thickening of the arterial walls. “The question is, is thickness reversible?” Dr. Eckel said. “It’s probably not very reversible, so these are early changes that ultimately in the middle years or latter years are associated with major cardiovascular disease.”
They key lesson from the study, Dr. Eckel noted, is to “prevent obesity. If you prevent obesity in the teenage years, you basically prevent diabetes.”
Dr. Ryder disclosed receiving support from Boehringer Ingelheim in the form of drug/placebo. The National Institutes of Health provided funding. Dr. Eckel has no relevant relationships to disclose.
SOURCE: Ryder JR et al. J Am Heart Assoc. 2020 May 6:e014891. doi: 10.1161/JAHA.119.014891.
published online in the Journal of the American Heart Association.
significantly greater than their normal-weight peers, according to a longitudinal studyThe study evaluated 448 adolescents over 5 years for changes in a variety of metrics to determine changes in arterial structure, including carotid intima media thickness (cIMT), carotid-femoral pulse-wave velocity (PWV), and augmentation index (Aix). The average age of the study group was 17.6 years. The three study groups broke down accordingly: 141 with normal weight, 156 with obesity, and 151 with type 2 diabetes. Patients were evaluated at baseline and 5 years later.
“The presence of obesity and especially type 2 diabetes in adolescents accelerates the early vascular aging process associated with several key risk factors,” wrote Justin R. Ryder, PhD, an assistant professor of pediatrics at the University of Minnesota, Minneapolis, and colleagues.
The researchers also noted that systolic hypertension was associated with changes in cIMT and arterial stiffness comparable to obesity and diabetes. “These data add further evidence underscoring the importance of efforts targeting prevention and treatment of obesity, type 2 diabetes, and elevated blood pressure among youth, with a goal of delaying and/or preventing the progression of early vascular aging,” Dr. Ryder and colleagues wrote.
Obese patients, when compared with normal-weight participants, had the following average increases: common cIMT by 0.05 mm, bulb cIMT by 0.02 mm, internal cIMT by 0.03 mm, and PWV carotid-femoral by 0.38 m/sec, all statistically significant differences. Patients with diabetes, compared with normal-weight participants, registered the following average increases: common cIMT by 0.05 mm, bulb cIMT by 0.06 mm, internal cIMT by 0.04 mm, Aix by 4.67%, and PWV carotid-femoral by 0.74 m/sec. All differences were highly significant at P less than .001.
The results also showed that higher baseline systolic blood pressure was associated with significantly greater average increases in the following factors: common cIMT by 0.007 mm, bulb cIMT by 0.009 mm, internal cIMT by 0.008 mm, and PWV carotid-femoral by 0.66 m/sec.
Drilling down into the data, the study reported that males had greater increases in bulb cIMT and incremental elastic modulus as well as reduced Aix, compared with females. Nonwhites also had greater increases in bulb cIMT than did whites. Age was associated with greater increases in bulb and internal cIMT and Aix.
“Our data support the concept that male sex is an independent and primary risk factor for accelerated early vascular aging,” Dr. Ryder and colleagues wrote. The study also determined that type 2 diabetes is a more prominent risk factor than obesity for early vascular aging.
The size of the study population, specifically adolescents with diabetes, is a study strength, Dr. Ryder and colleagues noted. Other strengths they pointed to are the 5-year duration and the robust panel of noninvasive measures, although not using hard cardiovascular outcomes is an acknowledged limitation.
“It should also be noted that many of the youth with type 2 diabetes were on medications for glycemic control, lipids, and/or blood pressure regulation,” Dr. Ryder and colleagues wrote. “Despite this, the vascular profiles worsened over time.”
The study showed “a really significant change” in the carotid anatomy in adolescents with obesity and type 2 diabetes over 5 years, Robert Eckel, MD, professor at the University of Colorado Anschutz Medical Campus, Aurora, said in an interview. “Notably, the PWV is not just anatomy; now we’re talking about function. In other words, the augmentation index and PWV will assess the compliance of the artery.”
The findings suggest that atherosclerosis begins with thickening of the arterial walls. “The question is, is thickness reversible?” Dr. Eckel said. “It’s probably not very reversible, so these are early changes that ultimately in the middle years or latter years are associated with major cardiovascular disease.”
They key lesson from the study, Dr. Eckel noted, is to “prevent obesity. If you prevent obesity in the teenage years, you basically prevent diabetes.”
Dr. Ryder disclosed receiving support from Boehringer Ingelheim in the form of drug/placebo. The National Institutes of Health provided funding. Dr. Eckel has no relevant relationships to disclose.
SOURCE: Ryder JR et al. J Am Heart Assoc. 2020 May 6:e014891. doi: 10.1161/JAHA.119.014891.
published online in the Journal of the American Heart Association.
significantly greater than their normal-weight peers, according to a longitudinal studyThe study evaluated 448 adolescents over 5 years for changes in a variety of metrics to determine changes in arterial structure, including carotid intima media thickness (cIMT), carotid-femoral pulse-wave velocity (PWV), and augmentation index (Aix). The average age of the study group was 17.6 years. The three study groups broke down accordingly: 141 with normal weight, 156 with obesity, and 151 with type 2 diabetes. Patients were evaluated at baseline and 5 years later.
“The presence of obesity and especially type 2 diabetes in adolescents accelerates the early vascular aging process associated with several key risk factors,” wrote Justin R. Ryder, PhD, an assistant professor of pediatrics at the University of Minnesota, Minneapolis, and colleagues.
The researchers also noted that systolic hypertension was associated with changes in cIMT and arterial stiffness comparable to obesity and diabetes. “These data add further evidence underscoring the importance of efforts targeting prevention and treatment of obesity, type 2 diabetes, and elevated blood pressure among youth, with a goal of delaying and/or preventing the progression of early vascular aging,” Dr. Ryder and colleagues wrote.
Obese patients, when compared with normal-weight participants, had the following average increases: common cIMT by 0.05 mm, bulb cIMT by 0.02 mm, internal cIMT by 0.03 mm, and PWV carotid-femoral by 0.38 m/sec, all statistically significant differences. Patients with diabetes, compared with normal-weight participants, registered the following average increases: common cIMT by 0.05 mm, bulb cIMT by 0.06 mm, internal cIMT by 0.04 mm, Aix by 4.67%, and PWV carotid-femoral by 0.74 m/sec. All differences were highly significant at P less than .001.
The results also showed that higher baseline systolic blood pressure was associated with significantly greater average increases in the following factors: common cIMT by 0.007 mm, bulb cIMT by 0.009 mm, internal cIMT by 0.008 mm, and PWV carotid-femoral by 0.66 m/sec.
Drilling down into the data, the study reported that males had greater increases in bulb cIMT and incremental elastic modulus as well as reduced Aix, compared with females. Nonwhites also had greater increases in bulb cIMT than did whites. Age was associated with greater increases in bulb and internal cIMT and Aix.
“Our data support the concept that male sex is an independent and primary risk factor for accelerated early vascular aging,” Dr. Ryder and colleagues wrote. The study also determined that type 2 diabetes is a more prominent risk factor than obesity for early vascular aging.
The size of the study population, specifically adolescents with diabetes, is a study strength, Dr. Ryder and colleagues noted. Other strengths they pointed to are the 5-year duration and the robust panel of noninvasive measures, although not using hard cardiovascular outcomes is an acknowledged limitation.
“It should also be noted that many of the youth with type 2 diabetes were on medications for glycemic control, lipids, and/or blood pressure regulation,” Dr. Ryder and colleagues wrote. “Despite this, the vascular profiles worsened over time.”
The study showed “a really significant change” in the carotid anatomy in adolescents with obesity and type 2 diabetes over 5 years, Robert Eckel, MD, professor at the University of Colorado Anschutz Medical Campus, Aurora, said in an interview. “Notably, the PWV is not just anatomy; now we’re talking about function. In other words, the augmentation index and PWV will assess the compliance of the artery.”
The findings suggest that atherosclerosis begins with thickening of the arterial walls. “The question is, is thickness reversible?” Dr. Eckel said. “It’s probably not very reversible, so these are early changes that ultimately in the middle years or latter years are associated with major cardiovascular disease.”
They key lesson from the study, Dr. Eckel noted, is to “prevent obesity. If you prevent obesity in the teenage years, you basically prevent diabetes.”
Dr. Ryder disclosed receiving support from Boehringer Ingelheim in the form of drug/placebo. The National Institutes of Health provided funding. Dr. Eckel has no relevant relationships to disclose.
SOURCE: Ryder JR et al. J Am Heart Assoc. 2020 May 6:e014891. doi: 10.1161/JAHA.119.014891.
FROM JOURNAL OF THE AMERICAN HEART ASSOCIATION
In COVID-19 era: Infusion centers shuffle services
It’s anything but business as usual for clinicians who oversee office-based infusion centers, as they scramble to maintain services for patients considered to be at heightened risk for severe illness should they become infected with COVID-19.
“For many reasons, the guidance for patients right now is that they stay on their medications,” Max I. Hamburger, MD, a managing partner at Rheumatology Associates of Long Island (N.Y.), said in an interview. “Some have decided to stop the drug, and then they call us up to tell us that they’re flaring. The beginning of a flare is tiredness and other things. Now they’re worried: Are they tired because of the disease, or are they tired because they have COVID-19?”
With five offices located in a region considered to be the epicenter of the COVID-19 pandemic in the United States, Dr. Hamburger and his colleagues are hypervigilant about screening patients for symptoms of the virus before they visit one of the three practice locations that provide infusion services. This starts with an automated phone system that reminds patients of their appointment time. “Part of that robocall now has some questions like, ‘Do you have any symptoms of COVID-19?’ ‘Are you running a fever?’ ” The infusion nurses are also calling the patients in advance of their appointment to check on their status. “When they get to the office location, we ask them again about their general health and check their temperature,” said Dr. Hamburger. “We’re doing everything we can to talk to them about their own state of health and to question them about what I call extended paranoia: like, ‘Who are you living with?’ ‘Who are you hanging out with?’... We do everything we can to see if there’s anybody who might have had the slightest [contact with someone who has COVID-19]. Because if I lose my infusion nurse, then I’m up the creek.”
The infusion nurse wears scrubs, a face mask, and latex gloves. She and her staff are using hand sanitizer and cleaning infusion equipment with sanitizing wipes as one might do in a surgical setting. “Every surface is wiped down between patients, and the nurse is changing gloves between patients,” said Dr. Hamburger, who was founding president of the New York State Rheumatology Society before retiring from that post in 2017. “Getting masks has been tough. We’re doing the best we can there. We’re not gloving patients but we’re masking patients.”
As noted in guidance from the American College of Rheumatology and other medical organizations, following the Center for Disease Control and Prevention’s recommendation to stay at home during the pandemic has jump-started conversations between physicians and their patients about modifying the time interval between infusions. “If they have been doing well for the last 9 months, we’re having a conversation such as ‘Maybe instead of getting your Orencia every 4 weeks, maybe we’ll push it out to 5 weeks, or maybe we’ll push the Enbrel out to 10 days and the Humira out 3 weeks, et cetera,” Dr. Hamburger said. “One has to be very careful about when you do that, because you don’t want the patient to flare up because it’s hard to get them in, but it is a natural opportunity to look at this. We’re seeing how we can optimize the dose, but I don’t want to send the message that we’re doing this because it changes the patient’s outcome, because there’s zero evidence that it’s a good thing to do in terms of resistance.”
At the infusion centers operated by the Johns Hopkins division of gastroenterology and hepatology, Baltimore, clinicians are not increasing the time interval between infusions for patients at this time. “We’re keeping them as they are, to prevent any flare-ups. Our main goal is to keep patients in remission and out of the hospital,” said Alyssa M. Parian, MD, medical director of the infusion center and associate director of the university’s GI department. “With Remicade specifically, there’s also the risk of developing antibodies if you delay treatment, so we’re basically keeping everyone on track. We’re not recommending a switch from infusions to injectables, and we also are not speeding up infusions, either. Before this pandemic happened, we had already tried to decrease all Remicade infusions from 2 hours to 1 hour for patient satisfaction. The Entyvio is a pretty quick, 30-minute infusion.”
To accommodate patients during this era of physical distancing measures recommended by the CDC, Dr. Parian and her infusion nurse manager Elisheva Weiser converted one of their two outpatient GI centers into an infusion-only suite with 12 individual clinic rooms. As soon as patients exit the second-floor elevator, they encounter a workstation prior to entering the office where they are screened for COVID-19 symptoms and their temperature is taken. “If any symptoms or temperature comes back positive, we’re asking them to postpone their treatment and consider COVID testing,” she said.Instead of one nurse looking after four patients in one room during infusion therapy, now one nurse looks after two patients who are in rooms next to each other. All patients and all staff wear masks while in the center. “We always have physician oversight at our infusion centers,” Dr. Parian said. “We are trying to maintain a ‘COVID-free zone.’ Therefore, no physicians who have served in a hospital ward are allowed in the infusion suite because we don’t want any carriers of COVID-19. Same with the nurses. Additionally, we limit the staff within the suite to only those who are essential and don’t allow anyone to perform telemedicine or urgent clinic visits in this location. Our infusion center staff are on a strict protocol to not come in with any symptoms at all. They are asked to take their temperature before coming in to work.”
She and her colleagues drew from recommendations from the joint GI society message on COVID-19, the Crohn’s and Colitis Foundation, and the International Organization for the Study of Inflammatory Bowel Disease to inform their approach in serving patients during this unprecedented time. “We went as conservative as possible because these are immunosuppressed patients,” she said. One patient on her panel who receives an infusion every 8 weeks tested positive for COVID-19 between infusions, but was not hospitalized. Dr. Parian said that person will be treated only 14 days after all symptoms disappear. “That person will wear a mask and will be infused in a separate room,” she said.
AGA provides up-to-date news, resources and research COVID-19 to help the GI community navigate the coronavirus pandemic. Learn more at https://www.gastro.org/covid-
It’s anything but business as usual for clinicians who oversee office-based infusion centers, as they scramble to maintain services for patients considered to be at heightened risk for severe illness should they become infected with COVID-19.
“For many reasons, the guidance for patients right now is that they stay on their medications,” Max I. Hamburger, MD, a managing partner at Rheumatology Associates of Long Island (N.Y.), said in an interview. “Some have decided to stop the drug, and then they call us up to tell us that they’re flaring. The beginning of a flare is tiredness and other things. Now they’re worried: Are they tired because of the disease, or are they tired because they have COVID-19?”
With five offices located in a region considered to be the epicenter of the COVID-19 pandemic in the United States, Dr. Hamburger and his colleagues are hypervigilant about screening patients for symptoms of the virus before they visit one of the three practice locations that provide infusion services. This starts with an automated phone system that reminds patients of their appointment time. “Part of that robocall now has some questions like, ‘Do you have any symptoms of COVID-19?’ ‘Are you running a fever?’ ” The infusion nurses are also calling the patients in advance of their appointment to check on their status. “When they get to the office location, we ask them again about their general health and check their temperature,” said Dr. Hamburger. “We’re doing everything we can to talk to them about their own state of health and to question them about what I call extended paranoia: like, ‘Who are you living with?’ ‘Who are you hanging out with?’... We do everything we can to see if there’s anybody who might have had the slightest [contact with someone who has COVID-19]. Because if I lose my infusion nurse, then I’m up the creek.”
The infusion nurse wears scrubs, a face mask, and latex gloves. She and her staff are using hand sanitizer and cleaning infusion equipment with sanitizing wipes as one might do in a surgical setting. “Every surface is wiped down between patients, and the nurse is changing gloves between patients,” said Dr. Hamburger, who was founding president of the New York State Rheumatology Society before retiring from that post in 2017. “Getting masks has been tough. We’re doing the best we can there. We’re not gloving patients but we’re masking patients.”
As noted in guidance from the American College of Rheumatology and other medical organizations, following the Center for Disease Control and Prevention’s recommendation to stay at home during the pandemic has jump-started conversations between physicians and their patients about modifying the time interval between infusions. “If they have been doing well for the last 9 months, we’re having a conversation such as ‘Maybe instead of getting your Orencia every 4 weeks, maybe we’ll push it out to 5 weeks, or maybe we’ll push the Enbrel out to 10 days and the Humira out 3 weeks, et cetera,” Dr. Hamburger said. “One has to be very careful about when you do that, because you don’t want the patient to flare up because it’s hard to get them in, but it is a natural opportunity to look at this. We’re seeing how we can optimize the dose, but I don’t want to send the message that we’re doing this because it changes the patient’s outcome, because there’s zero evidence that it’s a good thing to do in terms of resistance.”
At the infusion centers operated by the Johns Hopkins division of gastroenterology and hepatology, Baltimore, clinicians are not increasing the time interval between infusions for patients at this time. “We’re keeping them as they are, to prevent any flare-ups. Our main goal is to keep patients in remission and out of the hospital,” said Alyssa M. Parian, MD, medical director of the infusion center and associate director of the university’s GI department. “With Remicade specifically, there’s also the risk of developing antibodies if you delay treatment, so we’re basically keeping everyone on track. We’re not recommending a switch from infusions to injectables, and we also are not speeding up infusions, either. Before this pandemic happened, we had already tried to decrease all Remicade infusions from 2 hours to 1 hour for patient satisfaction. The Entyvio is a pretty quick, 30-minute infusion.”
To accommodate patients during this era of physical distancing measures recommended by the CDC, Dr. Parian and her infusion nurse manager Elisheva Weiser converted one of their two outpatient GI centers into an infusion-only suite with 12 individual clinic rooms. As soon as patients exit the second-floor elevator, they encounter a workstation prior to entering the office where they are screened for COVID-19 symptoms and their temperature is taken. “If any symptoms or temperature comes back positive, we’re asking them to postpone their treatment and consider COVID testing,” she said.Instead of one nurse looking after four patients in one room during infusion therapy, now one nurse looks after two patients who are in rooms next to each other. All patients and all staff wear masks while in the center. “We always have physician oversight at our infusion centers,” Dr. Parian said. “We are trying to maintain a ‘COVID-free zone.’ Therefore, no physicians who have served in a hospital ward are allowed in the infusion suite because we don’t want any carriers of COVID-19. Same with the nurses. Additionally, we limit the staff within the suite to only those who are essential and don’t allow anyone to perform telemedicine or urgent clinic visits in this location. Our infusion center staff are on a strict protocol to not come in with any symptoms at all. They are asked to take their temperature before coming in to work.”
She and her colleagues drew from recommendations from the joint GI society message on COVID-19, the Crohn’s and Colitis Foundation, and the International Organization for the Study of Inflammatory Bowel Disease to inform their approach in serving patients during this unprecedented time. “We went as conservative as possible because these are immunosuppressed patients,” she said. One patient on her panel who receives an infusion every 8 weeks tested positive for COVID-19 between infusions, but was not hospitalized. Dr. Parian said that person will be treated only 14 days after all symptoms disappear. “That person will wear a mask and will be infused in a separate room,” she said.
AGA provides up-to-date news, resources and research COVID-19 to help the GI community navigate the coronavirus pandemic. Learn more at https://www.gastro.org/covid-
It’s anything but business as usual for clinicians who oversee office-based infusion centers, as they scramble to maintain services for patients considered to be at heightened risk for severe illness should they become infected with COVID-19.
“For many reasons, the guidance for patients right now is that they stay on their medications,” Max I. Hamburger, MD, a managing partner at Rheumatology Associates of Long Island (N.Y.), said in an interview. “Some have decided to stop the drug, and then they call us up to tell us that they’re flaring. The beginning of a flare is tiredness and other things. Now they’re worried: Are they tired because of the disease, or are they tired because they have COVID-19?”
With five offices located in a region considered to be the epicenter of the COVID-19 pandemic in the United States, Dr. Hamburger and his colleagues are hypervigilant about screening patients for symptoms of the virus before they visit one of the three practice locations that provide infusion services. This starts with an automated phone system that reminds patients of their appointment time. “Part of that robocall now has some questions like, ‘Do you have any symptoms of COVID-19?’ ‘Are you running a fever?’ ” The infusion nurses are also calling the patients in advance of their appointment to check on their status. “When they get to the office location, we ask them again about their general health and check their temperature,” said Dr. Hamburger. “We’re doing everything we can to talk to them about their own state of health and to question them about what I call extended paranoia: like, ‘Who are you living with?’ ‘Who are you hanging out with?’... We do everything we can to see if there’s anybody who might have had the slightest [contact with someone who has COVID-19]. Because if I lose my infusion nurse, then I’m up the creek.”
The infusion nurse wears scrubs, a face mask, and latex gloves. She and her staff are using hand sanitizer and cleaning infusion equipment with sanitizing wipes as one might do in a surgical setting. “Every surface is wiped down between patients, and the nurse is changing gloves between patients,” said Dr. Hamburger, who was founding president of the New York State Rheumatology Society before retiring from that post in 2017. “Getting masks has been tough. We’re doing the best we can there. We’re not gloving patients but we’re masking patients.”
As noted in guidance from the American College of Rheumatology and other medical organizations, following the Center for Disease Control and Prevention’s recommendation to stay at home during the pandemic has jump-started conversations between physicians and their patients about modifying the time interval between infusions. “If they have been doing well for the last 9 months, we’re having a conversation such as ‘Maybe instead of getting your Orencia every 4 weeks, maybe we’ll push it out to 5 weeks, or maybe we’ll push the Enbrel out to 10 days and the Humira out 3 weeks, et cetera,” Dr. Hamburger said. “One has to be very careful about when you do that, because you don’t want the patient to flare up because it’s hard to get them in, but it is a natural opportunity to look at this. We’re seeing how we can optimize the dose, but I don’t want to send the message that we’re doing this because it changes the patient’s outcome, because there’s zero evidence that it’s a good thing to do in terms of resistance.”
At the infusion centers operated by the Johns Hopkins division of gastroenterology and hepatology, Baltimore, clinicians are not increasing the time interval between infusions for patients at this time. “We’re keeping them as they are, to prevent any flare-ups. Our main goal is to keep patients in remission and out of the hospital,” said Alyssa M. Parian, MD, medical director of the infusion center and associate director of the university’s GI department. “With Remicade specifically, there’s also the risk of developing antibodies if you delay treatment, so we’re basically keeping everyone on track. We’re not recommending a switch from infusions to injectables, and we also are not speeding up infusions, either. Before this pandemic happened, we had already tried to decrease all Remicade infusions from 2 hours to 1 hour for patient satisfaction. The Entyvio is a pretty quick, 30-minute infusion.”
To accommodate patients during this era of physical distancing measures recommended by the CDC, Dr. Parian and her infusion nurse manager Elisheva Weiser converted one of their two outpatient GI centers into an infusion-only suite with 12 individual clinic rooms. As soon as patients exit the second-floor elevator, they encounter a workstation prior to entering the office where they are screened for COVID-19 symptoms and their temperature is taken. “If any symptoms or temperature comes back positive, we’re asking them to postpone their treatment and consider COVID testing,” she said.Instead of one nurse looking after four patients in one room during infusion therapy, now one nurse looks after two patients who are in rooms next to each other. All patients and all staff wear masks while in the center. “We always have physician oversight at our infusion centers,” Dr. Parian said. “We are trying to maintain a ‘COVID-free zone.’ Therefore, no physicians who have served in a hospital ward are allowed in the infusion suite because we don’t want any carriers of COVID-19. Same with the nurses. Additionally, we limit the staff within the suite to only those who are essential and don’t allow anyone to perform telemedicine or urgent clinic visits in this location. Our infusion center staff are on a strict protocol to not come in with any symptoms at all. They are asked to take their temperature before coming in to work.”
She and her colleagues drew from recommendations from the joint GI society message on COVID-19, the Crohn’s and Colitis Foundation, and the International Organization for the Study of Inflammatory Bowel Disease to inform their approach in serving patients during this unprecedented time. “We went as conservative as possible because these are immunosuppressed patients,” she said. One patient on her panel who receives an infusion every 8 weeks tested positive for COVID-19 between infusions, but was not hospitalized. Dr. Parian said that person will be treated only 14 days after all symptoms disappear. “That person will wear a mask and will be infused in a separate room,” she said.
AGA provides up-to-date news, resources and research COVID-19 to help the GI community navigate the coronavirus pandemic. Learn more at https://www.gastro.org/covid-
More guidance on inpatient management of blood glucose in COVID-19
“The glycemic management of many COVID-19–positive patients with diabetes is proving extremely complex, with huge fluctuations in glucose control and the need for very high doses of insulin,” says Diabetes UK’s National Diabetes Inpatient COVID Response Team.
“Intravenous infusion pumps, also required for inotropes, are at a premium and there may be the need to consider the use of subcutaneous or intramuscular insulin protocols,” they note.
Updated as of April 29, all of the information of the National Diabetes Inpatient COVID Response Team is available on the Diabetes UK website.
The new inpatient management graphic adds more detail to the previous “front-door” guidance, as reported by Medscape Medical News.
The document stressed that, as well as identifying patients with known diabetes, it is imperative that all newly admitted patients with COVID-19 are evaluated for diabetes, as the infection is known to cause new-onset diabetes.
Subcutaneous insulin dosing
The new graphic gives extensive details on subcutaneous insulin dosing in place of variable rate intravenous insulin when infusion pumps are not available, and when the patient has a glucose level above 12 mmol/L (216 mg/dL) but does not have DKA or hyperosmolar hyperglycemic state.
However, the advice is not intended for people with COVID-19 causing severe insulin resistance in the intensive care unit.
The other new guidance graphic on managing DKA or hyperosmolar state in people with COVID-19 using subcutaneous insulin is also intended for situations where intravenous infusion isn’t available.
Seek help from specialist diabetes team when needed
This is not to be used for mixed DKA/hyperosmolar state or for patients who are pregnant, have severe metabolic derangement, other significant comorbidity, or impaired consciousness, however.
For those situations, the advice is to seek help from a specialist diabetes team, says Diabetes UK.
Specialist teams will be available to answer diabetes queries, both by signposting to relevant existing local documents and also by providing patient-specific advice.
Indeed, NHS England recommends that such a team be available in every hospital, with a lead consultant designated each day to co-ordinate these services who must be free of other clinical duties when doing so. The role involves co-ordination of the whole service from the emergency department through to liaison with other specialties and managers.
Also newly updated is a page with extensive information for patients, including advice for staying at home, medication use, self-isolating, shielding, hospital and doctor appointments, need for urgent medical advice, and going to the hospital.
It also covers how coronavirus can affect people with diabetes, children and school, pregnancy, work situations, and tips for picking up prescriptions.
Another, shorter document with COVID-19 advice for patients has been posted by the JDRF and Beyond Type 1 Alliance.
It has also been endorsed by the American Diabetes Association, Harvard Medical School, and International Society for Pediatric and Adolescent Diabetes, in partnership with many other professional organizations, including the International Diabetes Federation, American Association of Clinical Endocrinologists, and Association of Diabetes Care & Education Specialists.
The shorter document covers topics such as personal hygiene, distancing, diabetes management, and seeking treatment, as well as links to other resources on what to do when health insurance is lost and legal rights.
This article first appeared on Medscape.com.
“The glycemic management of many COVID-19–positive patients with diabetes is proving extremely complex, with huge fluctuations in glucose control and the need for very high doses of insulin,” says Diabetes UK’s National Diabetes Inpatient COVID Response Team.
“Intravenous infusion pumps, also required for inotropes, are at a premium and there may be the need to consider the use of subcutaneous or intramuscular insulin protocols,” they note.
Updated as of April 29, all of the information of the National Diabetes Inpatient COVID Response Team is available on the Diabetes UK website.
The new inpatient management graphic adds more detail to the previous “front-door” guidance, as reported by Medscape Medical News.
The document stressed that, as well as identifying patients with known diabetes, it is imperative that all newly admitted patients with COVID-19 are evaluated for diabetes, as the infection is known to cause new-onset diabetes.
Subcutaneous insulin dosing
The new graphic gives extensive details on subcutaneous insulin dosing in place of variable rate intravenous insulin when infusion pumps are not available, and when the patient has a glucose level above 12 mmol/L (216 mg/dL) but does not have DKA or hyperosmolar hyperglycemic state.
However, the advice is not intended for people with COVID-19 causing severe insulin resistance in the intensive care unit.
The other new guidance graphic on managing DKA or hyperosmolar state in people with COVID-19 using subcutaneous insulin is also intended for situations where intravenous infusion isn’t available.
Seek help from specialist diabetes team when needed
This is not to be used for mixed DKA/hyperosmolar state or for patients who are pregnant, have severe metabolic derangement, other significant comorbidity, or impaired consciousness, however.
For those situations, the advice is to seek help from a specialist diabetes team, says Diabetes UK.
Specialist teams will be available to answer diabetes queries, both by signposting to relevant existing local documents and also by providing patient-specific advice.
Indeed, NHS England recommends that such a team be available in every hospital, with a lead consultant designated each day to co-ordinate these services who must be free of other clinical duties when doing so. The role involves co-ordination of the whole service from the emergency department through to liaison with other specialties and managers.
Also newly updated is a page with extensive information for patients, including advice for staying at home, medication use, self-isolating, shielding, hospital and doctor appointments, need for urgent medical advice, and going to the hospital.
It also covers how coronavirus can affect people with diabetes, children and school, pregnancy, work situations, and tips for picking up prescriptions.
Another, shorter document with COVID-19 advice for patients has been posted by the JDRF and Beyond Type 1 Alliance.
It has also been endorsed by the American Diabetes Association, Harvard Medical School, and International Society for Pediatric and Adolescent Diabetes, in partnership with many other professional organizations, including the International Diabetes Federation, American Association of Clinical Endocrinologists, and Association of Diabetes Care & Education Specialists.
The shorter document covers topics such as personal hygiene, distancing, diabetes management, and seeking treatment, as well as links to other resources on what to do when health insurance is lost and legal rights.
This article first appeared on Medscape.com.
“The glycemic management of many COVID-19–positive patients with diabetes is proving extremely complex, with huge fluctuations in glucose control and the need for very high doses of insulin,” says Diabetes UK’s National Diabetes Inpatient COVID Response Team.
“Intravenous infusion pumps, also required for inotropes, are at a premium and there may be the need to consider the use of subcutaneous or intramuscular insulin protocols,” they note.
Updated as of April 29, all of the information of the National Diabetes Inpatient COVID Response Team is available on the Diabetes UK website.
The new inpatient management graphic adds more detail to the previous “front-door” guidance, as reported by Medscape Medical News.
The document stressed that, as well as identifying patients with known diabetes, it is imperative that all newly admitted patients with COVID-19 are evaluated for diabetes, as the infection is known to cause new-onset diabetes.
Subcutaneous insulin dosing
The new graphic gives extensive details on subcutaneous insulin dosing in place of variable rate intravenous insulin when infusion pumps are not available, and when the patient has a glucose level above 12 mmol/L (216 mg/dL) but does not have DKA or hyperosmolar hyperglycemic state.
However, the advice is not intended for people with COVID-19 causing severe insulin resistance in the intensive care unit.
The other new guidance graphic on managing DKA or hyperosmolar state in people with COVID-19 using subcutaneous insulin is also intended for situations where intravenous infusion isn’t available.
Seek help from specialist diabetes team when needed
This is not to be used for mixed DKA/hyperosmolar state or for patients who are pregnant, have severe metabolic derangement, other significant comorbidity, or impaired consciousness, however.
For those situations, the advice is to seek help from a specialist diabetes team, says Diabetes UK.
Specialist teams will be available to answer diabetes queries, both by signposting to relevant existing local documents and also by providing patient-specific advice.
Indeed, NHS England recommends that such a team be available in every hospital, with a lead consultant designated each day to co-ordinate these services who must be free of other clinical duties when doing so. The role involves co-ordination of the whole service from the emergency department through to liaison with other specialties and managers.
Also newly updated is a page with extensive information for patients, including advice for staying at home, medication use, self-isolating, shielding, hospital and doctor appointments, need for urgent medical advice, and going to the hospital.
It also covers how coronavirus can affect people with diabetes, children and school, pregnancy, work situations, and tips for picking up prescriptions.
Another, shorter document with COVID-19 advice for patients has been posted by the JDRF and Beyond Type 1 Alliance.
It has also been endorsed by the American Diabetes Association, Harvard Medical School, and International Society for Pediatric and Adolescent Diabetes, in partnership with many other professional organizations, including the International Diabetes Federation, American Association of Clinical Endocrinologists, and Association of Diabetes Care & Education Specialists.
The shorter document covers topics such as personal hygiene, distancing, diabetes management, and seeking treatment, as well as links to other resources on what to do when health insurance is lost and legal rights.
This article first appeared on Medscape.com.
Results from 11 AHA-funded COVID-19 studies expected within months
Work is set to start in June, with findings reported in as few as 6 months. The Cleveland Clinic will coordinate the efforts, collecting and disseminating the findings.
There were more than 750 research proposals in less than a month after the association announced its COVID-19 and Its Cardiovascular Impact Rapid Response Grant initiative.
“We were just blown away and so impressed to see this level of interest and commitment from the teams submitting such thorough proposals so quickly,” AHA President Robert Harrington, MD, chair of the department of medicine at Stanford (Calif.) University, said in a press statement. “There’s so much we don’t know about this unique coronavirus, and we continue to see emerging complications affecting both heart and brain health for which we desperately need answers and we need them quickly.”
The projects include the following:
- A Comprehensive Assessment of Arterial and Venous Thrombotic Complications in Patients with COVID-19, led by Columbia University, New York City.
- Repurposing Drugs for Treatment of Cardiomyopathy Caused by Coronavirus-2 (SARS-CoV-2), led by Brigham and Women’s Hospital and Harvard Medical School, Boston.
- Risk of Severe Morbidity and Mortality of Coronavirus Disease 2019 (COVID-19) Among Patients Taking Antihypertensive Medications, led by Kaiser Permanente Southern California.
- Deep Learning Using Chest Radiographs to Predict COVID-19 Cardiopulmonary Risk, led by Massachusetts General Hospital, Boston.
- Cardiovascular Outcomes and Biomarker Titrated Corticosteroid Dosing for SARS COV-2 (COVID-19): A Randomized Controlled Trial, led by the Mayo Clinic, Rochester Minn.
- Outcomes for Patients With Hypertension, Diabetes, and Heart Disease in the Coronavirus Pandemic: Impact of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Treatment, led by Stanford University.
- Rapid COVID-19-on-A-Chip to Screen Competitive Targets for SARS-CoV-2 Spike Binding Sites, led by University of California, Los Angeles.
- COVID-19 Infection, African American Women and Cardiovascular Health, led by University of California, San Francisco.
- Myocardial Virus and Gene Expression in SARS CoV-2 Positive Patients with Clinically Important Myocardial Dysfunction, led by the University of Colorado, Aurora.
- The Role of the Platelet in Mediating Cardiovascular Disease in SARS-CoV-2 Infection, led by the University of Massachusetts, Worcester.
- Harnessing Glycomics to Understand Myocardial Injury in COVID-19, led by the University of Nebraska Medical Center, Omaha.
The AHA also awarded $800,000 for short-term projects to members of its new Health Technologies & Innovation Strategically Focused Research Network.
Cincinnati Children’s Hospital will assess the use of ejection fraction to triage COVID-19 patients; Johns Hopkins University, Baltimore, will assess smartphones for “virtual check-in” for stroke symptoms; Stanford will assess digital tracking of COVID-19 patients with cardiovascular complications; and the University of Michigan, Ann Arbor, will assess a system to track physiological and cardiovascular consequences of the infection.
Work is set to start in June, with findings reported in as few as 6 months. The Cleveland Clinic will coordinate the efforts, collecting and disseminating the findings.
There were more than 750 research proposals in less than a month after the association announced its COVID-19 and Its Cardiovascular Impact Rapid Response Grant initiative.
“We were just blown away and so impressed to see this level of interest and commitment from the teams submitting such thorough proposals so quickly,” AHA President Robert Harrington, MD, chair of the department of medicine at Stanford (Calif.) University, said in a press statement. “There’s so much we don’t know about this unique coronavirus, and we continue to see emerging complications affecting both heart and brain health for which we desperately need answers and we need them quickly.”
The projects include the following:
- A Comprehensive Assessment of Arterial and Venous Thrombotic Complications in Patients with COVID-19, led by Columbia University, New York City.
- Repurposing Drugs for Treatment of Cardiomyopathy Caused by Coronavirus-2 (SARS-CoV-2), led by Brigham and Women’s Hospital and Harvard Medical School, Boston.
- Risk of Severe Morbidity and Mortality of Coronavirus Disease 2019 (COVID-19) Among Patients Taking Antihypertensive Medications, led by Kaiser Permanente Southern California.
- Deep Learning Using Chest Radiographs to Predict COVID-19 Cardiopulmonary Risk, led by Massachusetts General Hospital, Boston.
- Cardiovascular Outcomes and Biomarker Titrated Corticosteroid Dosing for SARS COV-2 (COVID-19): A Randomized Controlled Trial, led by the Mayo Clinic, Rochester Minn.
- Outcomes for Patients With Hypertension, Diabetes, and Heart Disease in the Coronavirus Pandemic: Impact of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Treatment, led by Stanford University.
- Rapid COVID-19-on-A-Chip to Screen Competitive Targets for SARS-CoV-2 Spike Binding Sites, led by University of California, Los Angeles.
- COVID-19 Infection, African American Women and Cardiovascular Health, led by University of California, San Francisco.
- Myocardial Virus and Gene Expression in SARS CoV-2 Positive Patients with Clinically Important Myocardial Dysfunction, led by the University of Colorado, Aurora.
- The Role of the Platelet in Mediating Cardiovascular Disease in SARS-CoV-2 Infection, led by the University of Massachusetts, Worcester.
- Harnessing Glycomics to Understand Myocardial Injury in COVID-19, led by the University of Nebraska Medical Center, Omaha.
The AHA also awarded $800,000 for short-term projects to members of its new Health Technologies & Innovation Strategically Focused Research Network.
Cincinnati Children’s Hospital will assess the use of ejection fraction to triage COVID-19 patients; Johns Hopkins University, Baltimore, will assess smartphones for “virtual check-in” for stroke symptoms; Stanford will assess digital tracking of COVID-19 patients with cardiovascular complications; and the University of Michigan, Ann Arbor, will assess a system to track physiological and cardiovascular consequences of the infection.
Work is set to start in June, with findings reported in as few as 6 months. The Cleveland Clinic will coordinate the efforts, collecting and disseminating the findings.
There were more than 750 research proposals in less than a month after the association announced its COVID-19 and Its Cardiovascular Impact Rapid Response Grant initiative.
“We were just blown away and so impressed to see this level of interest and commitment from the teams submitting such thorough proposals so quickly,” AHA President Robert Harrington, MD, chair of the department of medicine at Stanford (Calif.) University, said in a press statement. “There’s so much we don’t know about this unique coronavirus, and we continue to see emerging complications affecting both heart and brain health for which we desperately need answers and we need them quickly.”
The projects include the following:
- A Comprehensive Assessment of Arterial and Venous Thrombotic Complications in Patients with COVID-19, led by Columbia University, New York City.
- Repurposing Drugs for Treatment of Cardiomyopathy Caused by Coronavirus-2 (SARS-CoV-2), led by Brigham and Women’s Hospital and Harvard Medical School, Boston.
- Risk of Severe Morbidity and Mortality of Coronavirus Disease 2019 (COVID-19) Among Patients Taking Antihypertensive Medications, led by Kaiser Permanente Southern California.
- Deep Learning Using Chest Radiographs to Predict COVID-19 Cardiopulmonary Risk, led by Massachusetts General Hospital, Boston.
- Cardiovascular Outcomes and Biomarker Titrated Corticosteroid Dosing for SARS COV-2 (COVID-19): A Randomized Controlled Trial, led by the Mayo Clinic, Rochester Minn.
- Outcomes for Patients With Hypertension, Diabetes, and Heart Disease in the Coronavirus Pandemic: Impact of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Treatment, led by Stanford University.
- Rapid COVID-19-on-A-Chip to Screen Competitive Targets for SARS-CoV-2 Spike Binding Sites, led by University of California, Los Angeles.
- COVID-19 Infection, African American Women and Cardiovascular Health, led by University of California, San Francisco.
- Myocardial Virus and Gene Expression in SARS CoV-2 Positive Patients with Clinically Important Myocardial Dysfunction, led by the University of Colorado, Aurora.
- The Role of the Platelet in Mediating Cardiovascular Disease in SARS-CoV-2 Infection, led by the University of Massachusetts, Worcester.
- Harnessing Glycomics to Understand Myocardial Injury in COVID-19, led by the University of Nebraska Medical Center, Omaha.
The AHA also awarded $800,000 for short-term projects to members of its new Health Technologies & Innovation Strategically Focused Research Network.
Cincinnati Children’s Hospital will assess the use of ejection fraction to triage COVID-19 patients; Johns Hopkins University, Baltimore, will assess smartphones for “virtual check-in” for stroke symptoms; Stanford will assess digital tracking of COVID-19 patients with cardiovascular complications; and the University of Michigan, Ann Arbor, will assess a system to track physiological and cardiovascular consequences of the infection.
COVID-19–associated coagulopathy
Coronavirus disease 2019 (COVID-19) is a viral illness caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), currently causing a pandemic affecting many countries around the world, beginning in December 2019 and spreading rapidly on a global scale since. Globally, its burden has been increasing rapidly, with more than 1.2 million people testing positive for the illness and 123,000 people losing their lives, as per April 15th’s WHO COVID-19 Situation Report.1 These numbers are increasing with each passing day. Clinically, SARS-CoV-2 has a highly variable course, ranging from mild disease manifested as a self-limited illness (seen in younger and healthier patients) to severe pneumonia/ARDS and multiorgan failure with intravascular coagulopathy.2
In this article, we intend to investigate and establish a comprehensive review of COVID-19–associated coagulopathy mechanisms, laboratory findings, and current management guidelines put forth by various societies globally.
Mechanism of coagulopathy
COVID-19–associated coagulopathy has been shown to predispose to both arterial and venous thrombosis through excessive inflammation and hypoxia, leading to activation of the coagulation cascade and consumption of coagulation factors, resulting in microvascular thrombosis.3 Though the exact pathophysiology for the activation of this cascade is not known, the proposed mechanism has been: endothelial damage triggering platelet activation within the lung, leading to aggregation, thrombosis, and consumption of platelets in the lung.2,5,6
Fox et al. noted similar coagulopathy findings of four deceased COVID-19 patients. Autopsy results concluded that the dominant process was diffuse alveolar damage, notable CD4+ aggregates around thrombosed small vessels, significant associated hemorrhage, and thrombotic microangiopathy restricted to the lungs. The proposed mechanism was the activation of megakaryocytes, possibly native to the lung, with platelet aggregation, formation of platelet-rich clots, and fibrin deposition playing a major role.4
It has been noted that diabetic patients are at an increased risk of vascular events and hypercoagulability with COVID-19.7 COVID-19 can also cause livedo reticularis and acrocyanosis because of the microthrombosis in the cutaneous vasculature secondary to underlying coagulopathy, as reported in a case report of two U.S. patients with COVID-19.8
Clinical and laboratory abnormalities
A recent study reported from Netherlands by Klok et al. analyzed 184 ICU patients with COVID-19 pneumonia and concluded that the cumulative incidence of acute pulmonary embolism (PE), deep vein thrombosis (DVT), ischemic stroke, MI, or systemic arterial embolism was 31% (95% confidence interval, 20%-41%). PE was the most frequent thrombotic complication and was noted in 81% of patients. Coagulopathy, defined as spontaneous prolongation of prothrombin time (PT) > 3s or activated partial thromboplastin time (aPTT) > 5s, was reported as an independent predictor of thrombotic complications.3
Hematologic abnormalities that were noted in COVID-19 coagulopathy include: decreased platelet counts, decreased fibrinogen levels, elevated PT/INR, elevated partial thromboplastin time (PTT), and elevated d-dimer.9,10 In a retrospective analysis9 by Tang et al., 71.4% of nonsurvivors and 0.6% of survivors had met the criteria of disseminated intravascular coagulation (DIC) during their hospital stay. Nonsurvivors of COVID-19 had statistically significant elevation of d-dimer levels, FDP levels, PT, and aPTT, when compared to survivors (P < .05). The overall mortality in this study was reported as 11.5%.9 In addition, elevated d-dimer, fibrin and fibrinogen degradation product (FDP) levels and longer PT and aPTT were associated with poor prognosis.
Thus, d-dimer, PT, and platelet count should be measured in all patients who present with COVID-19 infection. We can also suggest that in patients with markedly elevated d-dimer (three- to fourfold increase), admission to hospital should be considered even in the absence of severe clinical symptoms.11
COVID-19 coagulopathy management
In a retrospective study9 of 449 patients with severe COVID-19 from Wuhan, China, by Tang et al., 99 patients mainly received low-weight molecular heparin (LMWH) for 7 days or longer. No difference in 28-day mortality was noted between heparin users and nonusers (30.3% vs. 29.7%; P = .910). A lower 28-day mortality rate was noted in heparin patients with sepsis-induced coagulopathy score of ≥4.0 (40.0% vs. 64.2%; P = .029) or a d-dimer level greater than sixfold of upper limit of normal, compared with nonusers of heparin.12
Another small study of seven COVID-19 patients with acroischemia in China demonstrated that administering LMWH was successful at decreasing the d-dimer and fibrinogen degradation product levels but noted no significant improvement in clinical symptoms.13
Recently, the International Society of Thrombosis and Hemostasis and American Society of Hematology published recommendations and guidelines regarding the recognition and management of coagulopathy in COVID-19.11 Prophylactic anticoagulation therapy with LMWH was recommended in all hospitalized patients with COVID-19, provided there was an absence of any contraindications (active bleeding, platelet count less than 25 x 109/L and fibrinogen less than 0.5 g/dL). Anticoagulation with LMWH was associated with better prognosis in severe COVID-19 patients and in COVID-19 patients with markedly elevated d-dimer, as it also has anti-inflammatory effects.12 This anti-inflammatory property of heparin has been documented in previous studies but the underlying mechanism is unknown and more research is required.14,15
Despite coagulopathy being noticed with cases of COVID-19, bleeding has been a rare finding in COVID-19 infections. If bleeding is noted, recommendations were made to keep platelet levels greater than 50 x109/L, fibrinogen less than 2.0 g/L, and INR [international normalized ratio] greater than 1.5.11 Mechanical thromboprophylaxis should be used when pharmacologic thromboprophylaxis is contraindicated.16
COVID-19 patients with new diagnoses of venous thromboembolism (VTE) or atrial fibrillation should be prescribed therapeutic anticoagulation. Patients who are already on anticoagulation for VTE or atrial fibrillation should continue their therapy unless the platelet count is less than 30-50x109/L or if the fibrinogen is less than 1.0 g/L.16
Conclusion
Coagulopathies associated with COVID-19 infections have been documented in several studies around the world, and it has been shown to be fatal in some cases. Despite documentation, the mechanism behind this coagulopathy is not well understood. Because of the potentially lethal complications associated with coagulopathies, early recognition and anticoagulation is imperative to improve clinical outcomes. These results are very preliminary: More studies are required to understand the role of anticoagulation and its effect on the morbidity and mortality associated with COVID-19–associated coagulopathy.
Dr. Yeruva is a board-certified hematologist/medical oncologist with WellSpan Health and clinical assistant professor of internal medicine, Penn State University, Hershey. Mr. Henderson is a third-year graduate-entry medical student at the Royal College of Surgeons in Ireland with interests in family medicine, dermatology, and tropical diseases. Dr. Al-Tawfiq is a consultant of internal medicine & infectious diseases, and the director of quality at Johns Hopkins Aramco Healthcare in Dhahran, Saudi Arabia, an adjunct associate professor of infectious diseases, molecular medicine and clinical pharmacology at Johns Hopkins University School of Medicine, and adjunct associate professor at Indiana University School of Medicine, Indianapolis. Dr. Tirupathi is the medical director of Keystone Infectious Diseases/HIV in Chambersburg, Pa., and currently chair of infection prevention at Wellspan Chambersburg and Waynesboro (Pa.) Hospitals. He also is the lead physician for antibiotic stewardship at these hospitals.
References
1. World Health Organization. Coronavirus disease (COVID-2019) situation reports.
2. Lippi G et al. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis. Clin Chim Acta. 2020 Mar 13. 506:145-8. doi: 10.1016/j.cca.2020.03.022.
3. Klok FA et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Throm Res. 2020;18(4):844-7. doi: 10.1016/j.thromres.2020.04.013.
4. Fox S et al. Pulmonary and cardiac pathology in Covid-19: The first autopsy series from New Orleans. MedRxiv. 2020 Apr 10. doi: 10.1101/2020.04.06.20050575.
5. Yang M et al. Thrombocytopenia in patients with severe acute respiratory syndrome (review). Hematology 2013 Sep 4. doi: 10.1080/1024533040002617.
6. Giannis D et al. Coagulation disorders in coronavirus infected patients: COVID-19, SARS-CoV-1, MERS-CoV and lessons from the past. J Clin Virol. 2020 June. doi: 10.1016/j.jcv.2020.104362.
7. Guo W et al. Diabetes is a risk factor for the progression and prognosis of COVID-19. Diabetes Metab Res Rev. 2020 Mar 31. doi: 10.1002/dmrr.3319.
8. Manalo IF et al. A dermatologic manifestation of COVID-19: Transient livedo reticularis. J Am Acad Dermat. 2020 Apr. doi: 10.1016/j.jaad.2020.04.018.
9. Tang N et al. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020 Feb 19. doi: 10.1111/jth.14768, 18: 844-847.
10. Huang C et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020 Jan 24. doi: 10.1016/S0140-6736(20)30183-5.
11. Thachil J et al. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost. 2020 Mar 25. doi: 10.1111/JTH.14810.
12. Tang N et al. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 2020 Mar 27. doi: 10.1111/JTH.14817.
13. Zhang Y et al. Clinical and coagulation characteristics of 7 patients with critical COVID-2019 pneumonia and acro-ischemia. Zhonghua Xue Ye Xue Za Zhi. 2020 Mar 28. doi: 10.3760/cma.j.issn.0253-2727.2020.0006.
14. Poterucha TJ et al. More than an anticoagulant: Do heparins have direct anti-inflammatory effects? Thromb Haemost. 2017. doi: 10.1160/TH16-08-0620.
15. Mousavi S et al. Anti-inflammatory effects of heparin and its derivatives: A systematic review. Adv Pharmacol Pharm Sci. 2015 May 12. doi: 10.1155/2015/507151.
16. Kreuziger L et al. COVID-19 and VTE/anticoagulation: Frequently asked questions. American Society of Hematology. 2020 Apr 17.
Coronavirus disease 2019 (COVID-19) is a viral illness caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), currently causing a pandemic affecting many countries around the world, beginning in December 2019 and spreading rapidly on a global scale since. Globally, its burden has been increasing rapidly, with more than 1.2 million people testing positive for the illness and 123,000 people losing their lives, as per April 15th’s WHO COVID-19 Situation Report.1 These numbers are increasing with each passing day. Clinically, SARS-CoV-2 has a highly variable course, ranging from mild disease manifested as a self-limited illness (seen in younger and healthier patients) to severe pneumonia/ARDS and multiorgan failure with intravascular coagulopathy.2
In this article, we intend to investigate and establish a comprehensive review of COVID-19–associated coagulopathy mechanisms, laboratory findings, and current management guidelines put forth by various societies globally.
Mechanism of coagulopathy
COVID-19–associated coagulopathy has been shown to predispose to both arterial and venous thrombosis through excessive inflammation and hypoxia, leading to activation of the coagulation cascade and consumption of coagulation factors, resulting in microvascular thrombosis.3 Though the exact pathophysiology for the activation of this cascade is not known, the proposed mechanism has been: endothelial damage triggering platelet activation within the lung, leading to aggregation, thrombosis, and consumption of platelets in the lung.2,5,6
Fox et al. noted similar coagulopathy findings of four deceased COVID-19 patients. Autopsy results concluded that the dominant process was diffuse alveolar damage, notable CD4+ aggregates around thrombosed small vessels, significant associated hemorrhage, and thrombotic microangiopathy restricted to the lungs. The proposed mechanism was the activation of megakaryocytes, possibly native to the lung, with platelet aggregation, formation of platelet-rich clots, and fibrin deposition playing a major role.4
It has been noted that diabetic patients are at an increased risk of vascular events and hypercoagulability with COVID-19.7 COVID-19 can also cause livedo reticularis and acrocyanosis because of the microthrombosis in the cutaneous vasculature secondary to underlying coagulopathy, as reported in a case report of two U.S. patients with COVID-19.8
Clinical and laboratory abnormalities
A recent study reported from Netherlands by Klok et al. analyzed 184 ICU patients with COVID-19 pneumonia and concluded that the cumulative incidence of acute pulmonary embolism (PE), deep vein thrombosis (DVT), ischemic stroke, MI, or systemic arterial embolism was 31% (95% confidence interval, 20%-41%). PE was the most frequent thrombotic complication and was noted in 81% of patients. Coagulopathy, defined as spontaneous prolongation of prothrombin time (PT) > 3s or activated partial thromboplastin time (aPTT) > 5s, was reported as an independent predictor of thrombotic complications.3
Hematologic abnormalities that were noted in COVID-19 coagulopathy include: decreased platelet counts, decreased fibrinogen levels, elevated PT/INR, elevated partial thromboplastin time (PTT), and elevated d-dimer.9,10 In a retrospective analysis9 by Tang et al., 71.4% of nonsurvivors and 0.6% of survivors had met the criteria of disseminated intravascular coagulation (DIC) during their hospital stay. Nonsurvivors of COVID-19 had statistically significant elevation of d-dimer levels, FDP levels, PT, and aPTT, when compared to survivors (P < .05). The overall mortality in this study was reported as 11.5%.9 In addition, elevated d-dimer, fibrin and fibrinogen degradation product (FDP) levels and longer PT and aPTT were associated with poor prognosis.
Thus, d-dimer, PT, and platelet count should be measured in all patients who present with COVID-19 infection. We can also suggest that in patients with markedly elevated d-dimer (three- to fourfold increase), admission to hospital should be considered even in the absence of severe clinical symptoms.11
COVID-19 coagulopathy management
In a retrospective study9 of 449 patients with severe COVID-19 from Wuhan, China, by Tang et al., 99 patients mainly received low-weight molecular heparin (LMWH) for 7 days or longer. No difference in 28-day mortality was noted between heparin users and nonusers (30.3% vs. 29.7%; P = .910). A lower 28-day mortality rate was noted in heparin patients with sepsis-induced coagulopathy score of ≥4.0 (40.0% vs. 64.2%; P = .029) or a d-dimer level greater than sixfold of upper limit of normal, compared with nonusers of heparin.12
Another small study of seven COVID-19 patients with acroischemia in China demonstrated that administering LMWH was successful at decreasing the d-dimer and fibrinogen degradation product levels but noted no significant improvement in clinical symptoms.13
Recently, the International Society of Thrombosis and Hemostasis and American Society of Hematology published recommendations and guidelines regarding the recognition and management of coagulopathy in COVID-19.11 Prophylactic anticoagulation therapy with LMWH was recommended in all hospitalized patients with COVID-19, provided there was an absence of any contraindications (active bleeding, platelet count less than 25 x 109/L and fibrinogen less than 0.5 g/dL). Anticoagulation with LMWH was associated with better prognosis in severe COVID-19 patients and in COVID-19 patients with markedly elevated d-dimer, as it also has anti-inflammatory effects.12 This anti-inflammatory property of heparin has been documented in previous studies but the underlying mechanism is unknown and more research is required.14,15
Despite coagulopathy being noticed with cases of COVID-19, bleeding has been a rare finding in COVID-19 infections. If bleeding is noted, recommendations were made to keep platelet levels greater than 50 x109/L, fibrinogen less than 2.0 g/L, and INR [international normalized ratio] greater than 1.5.11 Mechanical thromboprophylaxis should be used when pharmacologic thromboprophylaxis is contraindicated.16
COVID-19 patients with new diagnoses of venous thromboembolism (VTE) or atrial fibrillation should be prescribed therapeutic anticoagulation. Patients who are already on anticoagulation for VTE or atrial fibrillation should continue their therapy unless the platelet count is less than 30-50x109/L or if the fibrinogen is less than 1.0 g/L.16
Conclusion
Coagulopathies associated with COVID-19 infections have been documented in several studies around the world, and it has been shown to be fatal in some cases. Despite documentation, the mechanism behind this coagulopathy is not well understood. Because of the potentially lethal complications associated with coagulopathies, early recognition and anticoagulation is imperative to improve clinical outcomes. These results are very preliminary: More studies are required to understand the role of anticoagulation and its effect on the morbidity and mortality associated with COVID-19–associated coagulopathy.
Dr. Yeruva is a board-certified hematologist/medical oncologist with WellSpan Health and clinical assistant professor of internal medicine, Penn State University, Hershey. Mr. Henderson is a third-year graduate-entry medical student at the Royal College of Surgeons in Ireland with interests in family medicine, dermatology, and tropical diseases. Dr. Al-Tawfiq is a consultant of internal medicine & infectious diseases, and the director of quality at Johns Hopkins Aramco Healthcare in Dhahran, Saudi Arabia, an adjunct associate professor of infectious diseases, molecular medicine and clinical pharmacology at Johns Hopkins University School of Medicine, and adjunct associate professor at Indiana University School of Medicine, Indianapolis. Dr. Tirupathi is the medical director of Keystone Infectious Diseases/HIV in Chambersburg, Pa., and currently chair of infection prevention at Wellspan Chambersburg and Waynesboro (Pa.) Hospitals. He also is the lead physician for antibiotic stewardship at these hospitals.
References
1. World Health Organization. Coronavirus disease (COVID-2019) situation reports.
2. Lippi G et al. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis. Clin Chim Acta. 2020 Mar 13. 506:145-8. doi: 10.1016/j.cca.2020.03.022.
3. Klok FA et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Throm Res. 2020;18(4):844-7. doi: 10.1016/j.thromres.2020.04.013.
4. Fox S et al. Pulmonary and cardiac pathology in Covid-19: The first autopsy series from New Orleans. MedRxiv. 2020 Apr 10. doi: 10.1101/2020.04.06.20050575.
5. Yang M et al. Thrombocytopenia in patients with severe acute respiratory syndrome (review). Hematology 2013 Sep 4. doi: 10.1080/1024533040002617.
6. Giannis D et al. Coagulation disorders in coronavirus infected patients: COVID-19, SARS-CoV-1, MERS-CoV and lessons from the past. J Clin Virol. 2020 June. doi: 10.1016/j.jcv.2020.104362.
7. Guo W et al. Diabetes is a risk factor for the progression and prognosis of COVID-19. Diabetes Metab Res Rev. 2020 Mar 31. doi: 10.1002/dmrr.3319.
8. Manalo IF et al. A dermatologic manifestation of COVID-19: Transient livedo reticularis. J Am Acad Dermat. 2020 Apr. doi: 10.1016/j.jaad.2020.04.018.
9. Tang N et al. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020 Feb 19. doi: 10.1111/jth.14768, 18: 844-847.
10. Huang C et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020 Jan 24. doi: 10.1016/S0140-6736(20)30183-5.
11. Thachil J et al. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost. 2020 Mar 25. doi: 10.1111/JTH.14810.
12. Tang N et al. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 2020 Mar 27. doi: 10.1111/JTH.14817.
13. Zhang Y et al. Clinical and coagulation characteristics of 7 patients with critical COVID-2019 pneumonia and acro-ischemia. Zhonghua Xue Ye Xue Za Zhi. 2020 Mar 28. doi: 10.3760/cma.j.issn.0253-2727.2020.0006.
14. Poterucha TJ et al. More than an anticoagulant: Do heparins have direct anti-inflammatory effects? Thromb Haemost. 2017. doi: 10.1160/TH16-08-0620.
15. Mousavi S et al. Anti-inflammatory effects of heparin and its derivatives: A systematic review. Adv Pharmacol Pharm Sci. 2015 May 12. doi: 10.1155/2015/507151.
16. Kreuziger L et al. COVID-19 and VTE/anticoagulation: Frequently asked questions. American Society of Hematology. 2020 Apr 17.
Coronavirus disease 2019 (COVID-19) is a viral illness caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), currently causing a pandemic affecting many countries around the world, beginning in December 2019 and spreading rapidly on a global scale since. Globally, its burden has been increasing rapidly, with more than 1.2 million people testing positive for the illness and 123,000 people losing their lives, as per April 15th’s WHO COVID-19 Situation Report.1 These numbers are increasing with each passing day. Clinically, SARS-CoV-2 has a highly variable course, ranging from mild disease manifested as a self-limited illness (seen in younger and healthier patients) to severe pneumonia/ARDS and multiorgan failure with intravascular coagulopathy.2
In this article, we intend to investigate and establish a comprehensive review of COVID-19–associated coagulopathy mechanisms, laboratory findings, and current management guidelines put forth by various societies globally.
Mechanism of coagulopathy
COVID-19–associated coagulopathy has been shown to predispose to both arterial and venous thrombosis through excessive inflammation and hypoxia, leading to activation of the coagulation cascade and consumption of coagulation factors, resulting in microvascular thrombosis.3 Though the exact pathophysiology for the activation of this cascade is not known, the proposed mechanism has been: endothelial damage triggering platelet activation within the lung, leading to aggregation, thrombosis, and consumption of platelets in the lung.2,5,6
Fox et al. noted similar coagulopathy findings of four deceased COVID-19 patients. Autopsy results concluded that the dominant process was diffuse alveolar damage, notable CD4+ aggregates around thrombosed small vessels, significant associated hemorrhage, and thrombotic microangiopathy restricted to the lungs. The proposed mechanism was the activation of megakaryocytes, possibly native to the lung, with platelet aggregation, formation of platelet-rich clots, and fibrin deposition playing a major role.4
It has been noted that diabetic patients are at an increased risk of vascular events and hypercoagulability with COVID-19.7 COVID-19 can also cause livedo reticularis and acrocyanosis because of the microthrombosis in the cutaneous vasculature secondary to underlying coagulopathy, as reported in a case report of two U.S. patients with COVID-19.8
Clinical and laboratory abnormalities
A recent study reported from Netherlands by Klok et al. analyzed 184 ICU patients with COVID-19 pneumonia and concluded that the cumulative incidence of acute pulmonary embolism (PE), deep vein thrombosis (DVT), ischemic stroke, MI, or systemic arterial embolism was 31% (95% confidence interval, 20%-41%). PE was the most frequent thrombotic complication and was noted in 81% of patients. Coagulopathy, defined as spontaneous prolongation of prothrombin time (PT) > 3s or activated partial thromboplastin time (aPTT) > 5s, was reported as an independent predictor of thrombotic complications.3
Hematologic abnormalities that were noted in COVID-19 coagulopathy include: decreased platelet counts, decreased fibrinogen levels, elevated PT/INR, elevated partial thromboplastin time (PTT), and elevated d-dimer.9,10 In a retrospective analysis9 by Tang et al., 71.4% of nonsurvivors and 0.6% of survivors had met the criteria of disseminated intravascular coagulation (DIC) during their hospital stay. Nonsurvivors of COVID-19 had statistically significant elevation of d-dimer levels, FDP levels, PT, and aPTT, when compared to survivors (P < .05). The overall mortality in this study was reported as 11.5%.9 In addition, elevated d-dimer, fibrin and fibrinogen degradation product (FDP) levels and longer PT and aPTT were associated with poor prognosis.
Thus, d-dimer, PT, and platelet count should be measured in all patients who present with COVID-19 infection. We can also suggest that in patients with markedly elevated d-dimer (three- to fourfold increase), admission to hospital should be considered even in the absence of severe clinical symptoms.11
COVID-19 coagulopathy management
In a retrospective study9 of 449 patients with severe COVID-19 from Wuhan, China, by Tang et al., 99 patients mainly received low-weight molecular heparin (LMWH) for 7 days or longer. No difference in 28-day mortality was noted between heparin users and nonusers (30.3% vs. 29.7%; P = .910). A lower 28-day mortality rate was noted in heparin patients with sepsis-induced coagulopathy score of ≥4.0 (40.0% vs. 64.2%; P = .029) or a d-dimer level greater than sixfold of upper limit of normal, compared with nonusers of heparin.12
Another small study of seven COVID-19 patients with acroischemia in China demonstrated that administering LMWH was successful at decreasing the d-dimer and fibrinogen degradation product levels but noted no significant improvement in clinical symptoms.13
Recently, the International Society of Thrombosis and Hemostasis and American Society of Hematology published recommendations and guidelines regarding the recognition and management of coagulopathy in COVID-19.11 Prophylactic anticoagulation therapy with LMWH was recommended in all hospitalized patients with COVID-19, provided there was an absence of any contraindications (active bleeding, platelet count less than 25 x 109/L and fibrinogen less than 0.5 g/dL). Anticoagulation with LMWH was associated with better prognosis in severe COVID-19 patients and in COVID-19 patients with markedly elevated d-dimer, as it also has anti-inflammatory effects.12 This anti-inflammatory property of heparin has been documented in previous studies but the underlying mechanism is unknown and more research is required.14,15
Despite coagulopathy being noticed with cases of COVID-19, bleeding has been a rare finding in COVID-19 infections. If bleeding is noted, recommendations were made to keep platelet levels greater than 50 x109/L, fibrinogen less than 2.0 g/L, and INR [international normalized ratio] greater than 1.5.11 Mechanical thromboprophylaxis should be used when pharmacologic thromboprophylaxis is contraindicated.16
COVID-19 patients with new diagnoses of venous thromboembolism (VTE) or atrial fibrillation should be prescribed therapeutic anticoagulation. Patients who are already on anticoagulation for VTE or atrial fibrillation should continue their therapy unless the platelet count is less than 30-50x109/L or if the fibrinogen is less than 1.0 g/L.16
Conclusion
Coagulopathies associated with COVID-19 infections have been documented in several studies around the world, and it has been shown to be fatal in some cases. Despite documentation, the mechanism behind this coagulopathy is not well understood. Because of the potentially lethal complications associated with coagulopathies, early recognition and anticoagulation is imperative to improve clinical outcomes. These results are very preliminary: More studies are required to understand the role of anticoagulation and its effect on the morbidity and mortality associated with COVID-19–associated coagulopathy.
Dr. Yeruva is a board-certified hematologist/medical oncologist with WellSpan Health and clinical assistant professor of internal medicine, Penn State University, Hershey. Mr. Henderson is a third-year graduate-entry medical student at the Royal College of Surgeons in Ireland with interests in family medicine, dermatology, and tropical diseases. Dr. Al-Tawfiq is a consultant of internal medicine & infectious diseases, and the director of quality at Johns Hopkins Aramco Healthcare in Dhahran, Saudi Arabia, an adjunct associate professor of infectious diseases, molecular medicine and clinical pharmacology at Johns Hopkins University School of Medicine, and adjunct associate professor at Indiana University School of Medicine, Indianapolis. Dr. Tirupathi is the medical director of Keystone Infectious Diseases/HIV in Chambersburg, Pa., and currently chair of infection prevention at Wellspan Chambersburg and Waynesboro (Pa.) Hospitals. He also is the lead physician for antibiotic stewardship at these hospitals.
References
1. World Health Organization. Coronavirus disease (COVID-2019) situation reports.
2. Lippi G et al. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis. Clin Chim Acta. 2020 Mar 13. 506:145-8. doi: 10.1016/j.cca.2020.03.022.
3. Klok FA et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Throm Res. 2020;18(4):844-7. doi: 10.1016/j.thromres.2020.04.013.
4. Fox S et al. Pulmonary and cardiac pathology in Covid-19: The first autopsy series from New Orleans. MedRxiv. 2020 Apr 10. doi: 10.1101/2020.04.06.20050575.
5. Yang M et al. Thrombocytopenia in patients with severe acute respiratory syndrome (review). Hematology 2013 Sep 4. doi: 10.1080/1024533040002617.
6. Giannis D et al. Coagulation disorders in coronavirus infected patients: COVID-19, SARS-CoV-1, MERS-CoV and lessons from the past. J Clin Virol. 2020 June. doi: 10.1016/j.jcv.2020.104362.
7. Guo W et al. Diabetes is a risk factor for the progression and prognosis of COVID-19. Diabetes Metab Res Rev. 2020 Mar 31. doi: 10.1002/dmrr.3319.
8. Manalo IF et al. A dermatologic manifestation of COVID-19: Transient livedo reticularis. J Am Acad Dermat. 2020 Apr. doi: 10.1016/j.jaad.2020.04.018.
9. Tang N et al. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020 Feb 19. doi: 10.1111/jth.14768, 18: 844-847.
10. Huang C et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020 Jan 24. doi: 10.1016/S0140-6736(20)30183-5.
11. Thachil J et al. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost. 2020 Mar 25. doi: 10.1111/JTH.14810.
12. Tang N et al. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 2020 Mar 27. doi: 10.1111/JTH.14817.
13. Zhang Y et al. Clinical and coagulation characteristics of 7 patients with critical COVID-2019 pneumonia and acro-ischemia. Zhonghua Xue Ye Xue Za Zhi. 2020 Mar 28. doi: 10.3760/cma.j.issn.0253-2727.2020.0006.
14. Poterucha TJ et al. More than an anticoagulant: Do heparins have direct anti-inflammatory effects? Thromb Haemost. 2017. doi: 10.1160/TH16-08-0620.
15. Mousavi S et al. Anti-inflammatory effects of heparin and its derivatives: A systematic review. Adv Pharmacol Pharm Sci. 2015 May 12. doi: 10.1155/2015/507151.
16. Kreuziger L et al. COVID-19 and VTE/anticoagulation: Frequently asked questions. American Society of Hematology. 2020 Apr 17.
IV-to-oral antibiotics can benefit patients with MRSA bloodstream infection
Background: Methicillin-resistant Staphylococcus aureus bloodstream infections carry a high risk of morbidity and relapse with most published guidelines recommending prolonged courses of IV antibiotics to ensure complete clearance of the infection. However, long-term IV antibiotic therapy may also be costly and is not without its own complications. An equally effective IV-to-oral antibiotic therapy would be welcome.
Study design: Retrospective cohort study.
Setting: A single academic center in the United States.
Synopsis: The investigators reviewed data from 492 adults with at least one positive blood culture for MRSA who had not yet completed their antibiotic course at the time of discharge during the index hospitalization but were sufficiently stable to complete outpatient antibiotic treatment. Of this cohort, 70 patients were switched to oral antibiotic therapy on discharge, while the rest received OPAT. The primary outcome was clinical failure, a 90-day composite measure of MRSA bloodstream infection recurrence, deep MRSA infection, or all-cause mortality. The most commonly used oral antibiotics were linezolid, trimethoprim/sulfamethoxazole, and clindamycin, all with high bioavailability. Endovascular infection was present in 21.5% of the study population. After propensity score adjustment for covariates, patients who received oral antibiotics had a nonsignificant reduction in the rate of clinical failure (hazard ratio, 0.379; 95% CI, 0.131-1.101).
Limitations of the study included its observational design with potential for significant residual confounding despite the propensity score–adjusted analysis, its single-center setting, the low frequency of endovascular infections, and the uncertainty in how the loss of patients to follow-up might have affected the results.
Bottom line: Selected patients with MRSA BSI may be successfully treated with sequential IV-to-oral antibiotic therapy.
Citation: Jorgensen SCJ et al. Sequential intravenous-to-oral outpatient antibiotic therapy for MRSA bacteraemia: One step closer. J Antimicrob Chemother. 2019 Feb;74(2):489-98.
Dr. Torres is a hospitalist at Massachusetts General Hospital.
Background: Methicillin-resistant Staphylococcus aureus bloodstream infections carry a high risk of morbidity and relapse with most published guidelines recommending prolonged courses of IV antibiotics to ensure complete clearance of the infection. However, long-term IV antibiotic therapy may also be costly and is not without its own complications. An equally effective IV-to-oral antibiotic therapy would be welcome.
Study design: Retrospective cohort study.
Setting: A single academic center in the United States.
Synopsis: The investigators reviewed data from 492 adults with at least one positive blood culture for MRSA who had not yet completed their antibiotic course at the time of discharge during the index hospitalization but were sufficiently stable to complete outpatient antibiotic treatment. Of this cohort, 70 patients were switched to oral antibiotic therapy on discharge, while the rest received OPAT. The primary outcome was clinical failure, a 90-day composite measure of MRSA bloodstream infection recurrence, deep MRSA infection, or all-cause mortality. The most commonly used oral antibiotics were linezolid, trimethoprim/sulfamethoxazole, and clindamycin, all with high bioavailability. Endovascular infection was present in 21.5% of the study population. After propensity score adjustment for covariates, patients who received oral antibiotics had a nonsignificant reduction in the rate of clinical failure (hazard ratio, 0.379; 95% CI, 0.131-1.101).
Limitations of the study included its observational design with potential for significant residual confounding despite the propensity score–adjusted analysis, its single-center setting, the low frequency of endovascular infections, and the uncertainty in how the loss of patients to follow-up might have affected the results.
Bottom line: Selected patients with MRSA BSI may be successfully treated with sequential IV-to-oral antibiotic therapy.
Citation: Jorgensen SCJ et al. Sequential intravenous-to-oral outpatient antibiotic therapy for MRSA bacteraemia: One step closer. J Antimicrob Chemother. 2019 Feb;74(2):489-98.
Dr. Torres is a hospitalist at Massachusetts General Hospital.
Background: Methicillin-resistant Staphylococcus aureus bloodstream infections carry a high risk of morbidity and relapse with most published guidelines recommending prolonged courses of IV antibiotics to ensure complete clearance of the infection. However, long-term IV antibiotic therapy may also be costly and is not without its own complications. An equally effective IV-to-oral antibiotic therapy would be welcome.
Study design: Retrospective cohort study.
Setting: A single academic center in the United States.
Synopsis: The investigators reviewed data from 492 adults with at least one positive blood culture for MRSA who had not yet completed their antibiotic course at the time of discharge during the index hospitalization but were sufficiently stable to complete outpatient antibiotic treatment. Of this cohort, 70 patients were switched to oral antibiotic therapy on discharge, while the rest received OPAT. The primary outcome was clinical failure, a 90-day composite measure of MRSA bloodstream infection recurrence, deep MRSA infection, or all-cause mortality. The most commonly used oral antibiotics were linezolid, trimethoprim/sulfamethoxazole, and clindamycin, all with high bioavailability. Endovascular infection was present in 21.5% of the study population. After propensity score adjustment for covariates, patients who received oral antibiotics had a nonsignificant reduction in the rate of clinical failure (hazard ratio, 0.379; 95% CI, 0.131-1.101).
Limitations of the study included its observational design with potential for significant residual confounding despite the propensity score–adjusted analysis, its single-center setting, the low frequency of endovascular infections, and the uncertainty in how the loss of patients to follow-up might have affected the results.
Bottom line: Selected patients with MRSA BSI may be successfully treated with sequential IV-to-oral antibiotic therapy.
Citation: Jorgensen SCJ et al. Sequential intravenous-to-oral outpatient antibiotic therapy for MRSA bacteraemia: One step closer. J Antimicrob Chemother. 2019 Feb;74(2):489-98.
Dr. Torres is a hospitalist at Massachusetts General Hospital.