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A 4-year-old presented to our pediatric dermatology clinic for evaluation of asymptomatic "brown spots."
Capillary malformation-arteriovenous malformation syndrome
with or without arteriovenous malformations, as well as arteriovenous fistulas (AVFs). CM-AVM is an autosomal dominant disorder.1 CM-AVM type 1 is caused by mutations in the RASA1 gene, and CM-AVM type 2 is caused by mutations in the EPHB4 gene.2 Approximately 70% of patients with RASA1-associated CM-AVM syndrome and 80% of patients with EPHB4-associated CM-AVM syndrome have an affected parent, while the remainder have de novo variants.1
In patients with CM-AVM syndrome, CMs are often present at birth and more are typically acquired over time. CMs are characteristically 1-3 cm in diameter, round or oval, dull red or red-brown macules and patches with a blanched halo.3 Some CMs may be warm to touch indicating a possible underlying AVM or AVF.4 This can be confirmed by Doppler ultrasound, which would demonstrate increased arterial flow.4 CMs are most commonly located on the face and limbs and may present in isolation, but approximately one-third of patients have associated AVMs and AVFs.1,5 These high-flow vascular malformations may be present in skin, muscle, bone, brain, and/or spine and may be asymptomatic or lead to serious sequelae, including bleeding, congestive heart failure, and neurologic complications, such as migraine headaches, seizures, or even stroke.5 Symptoms from intracranial and spinal high-flow lesions usually present in early childhood and affect approximately 7% of patients.3
The diagnosis of CM-AVM should be suspected in an individual with numerous characteristic CMs and may be supported by the presence of AVMs and AVFs, family history of CM-AVM, and/or identification of RASA1 or EPHB4 mutation by molecular genetic testing.1,3 Although there are no consensus protocols for imaging CM-AVM patients, MRI of the brain and spine is recommended at diagnosis to identify underlying high-flow lesions.1 This may allow for early treatment before the development of symptoms.1 Any lesions identified on screening imaging may require regular surveillance, which is best determined by discussion with the radiologist.1 Although there are no reports of patients with negative results on screening imaging who later develop AVMs or AVFs, there should be a low threshold for repeat imaging in patients who develop new symptoms or physical exam findings.3,4
It has previously been suggested that the CMs in CM-AVM may actually represent early or small AVMs and pulsed-dye laser (PDL) treatment was not recommended because of concern for potential progression of lesions.4 However, a recent study demonstrated good response to PDL in patients with CM-AVM with no evidence of worsening or recurrence of lesions with long-term follow-up.6 Treatment of CMs that cause cosmetic concerns may be considered following discussion of risks and benefits with a dermatologist. Management of AVMs and AVFs requires a multidisciplinary team that, depending on location and symptoms of these features, may require the expertise of specialists such as neurosurgery, surgery, orthopedics, cardiology, and/or interventional radiology.1
Given the suspicion for CM-AVM in our patient, further workup was completed. A skin biopsy was consistent with CM. Genetic testing with the Vascular Malformations Panel, Sequencing and Deletion/Duplication revealed a pathogenic variant in the RASA1 gene and a variant of unknown clinical significance in the TEK gene. Parental genetic testing for the RASA1 mutation was negative, supporting a de novo mutation in the patient. CNS imaging showed a small developmental venous malformation in the brain that neurosurgery did not think was clinically significant. At the most recent follow-up at age 8 years, our patient had developed a few new small CMs but was otherwise well.
Dr. Leszczynska is trained in pediatrics and is the current dermatology research fellow at the University of Texas at Austin. Ms. Croce is a dermatology-trained pediatric nurse practitioner and PhD student at the University of Texas at Austin School of Nursing. Dr. Diaz is chief of pediatric dermatology at Dell Children’s Medical Center, Austin, assistant professor of pediatrics and medicine (dermatology), and dermatology residency associate program director at University of Texas at Austin . The authors have no relevant conflicts of interest to disclose. Donna Bilu Martin, MD, is the editor of this column.
References
1. Bayrak-Toydemir P, Stevenson D. Capillary Malformation-Arteriovenous Malformation Syndrome. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews®. Seattle: University of Washington, Seattle; February 22, 2011.
2.Yu J et al. Pediatr Dermatol. 2017 Sep;34(5):e227-30.
3. Orme CM et al. Pediatr Dermatol. 2013 Jul-Aug;30(4):409-15.
4. Weitz NA et al. Pediatr Dermatol. 2015 Jan-Feb;32(1):76-84.
5. Revencu N et al. Hum Mutat. 2013 Dec;34(12):1632-41.
6. Iznardo H et al. Pediatr Dermatol. 2020 Mar;37(2):342-44.
Capillary malformation-arteriovenous malformation syndrome
with or without arteriovenous malformations, as well as arteriovenous fistulas (AVFs). CM-AVM is an autosomal dominant disorder.1 CM-AVM type 1 is caused by mutations in the RASA1 gene, and CM-AVM type 2 is caused by mutations in the EPHB4 gene.2 Approximately 70% of patients with RASA1-associated CM-AVM syndrome and 80% of patients with EPHB4-associated CM-AVM syndrome have an affected parent, while the remainder have de novo variants.1
In patients with CM-AVM syndrome, CMs are often present at birth and more are typically acquired over time. CMs are characteristically 1-3 cm in diameter, round or oval, dull red or red-brown macules and patches with a blanched halo.3 Some CMs may be warm to touch indicating a possible underlying AVM or AVF.4 This can be confirmed by Doppler ultrasound, which would demonstrate increased arterial flow.4 CMs are most commonly located on the face and limbs and may present in isolation, but approximately one-third of patients have associated AVMs and AVFs.1,5 These high-flow vascular malformations may be present in skin, muscle, bone, brain, and/or spine and may be asymptomatic or lead to serious sequelae, including bleeding, congestive heart failure, and neurologic complications, such as migraine headaches, seizures, or even stroke.5 Symptoms from intracranial and spinal high-flow lesions usually present in early childhood and affect approximately 7% of patients.3
The diagnosis of CM-AVM should be suspected in an individual with numerous characteristic CMs and may be supported by the presence of AVMs and AVFs, family history of CM-AVM, and/or identification of RASA1 or EPHB4 mutation by molecular genetic testing.1,3 Although there are no consensus protocols for imaging CM-AVM patients, MRI of the brain and spine is recommended at diagnosis to identify underlying high-flow lesions.1 This may allow for early treatment before the development of symptoms.1 Any lesions identified on screening imaging may require regular surveillance, which is best determined by discussion with the radiologist.1 Although there are no reports of patients with negative results on screening imaging who later develop AVMs or AVFs, there should be a low threshold for repeat imaging in patients who develop new symptoms or physical exam findings.3,4
It has previously been suggested that the CMs in CM-AVM may actually represent early or small AVMs and pulsed-dye laser (PDL) treatment was not recommended because of concern for potential progression of lesions.4 However, a recent study demonstrated good response to PDL in patients with CM-AVM with no evidence of worsening or recurrence of lesions with long-term follow-up.6 Treatment of CMs that cause cosmetic concerns may be considered following discussion of risks and benefits with a dermatologist. Management of AVMs and AVFs requires a multidisciplinary team that, depending on location and symptoms of these features, may require the expertise of specialists such as neurosurgery, surgery, orthopedics, cardiology, and/or interventional radiology.1
Given the suspicion for CM-AVM in our patient, further workup was completed. A skin biopsy was consistent with CM. Genetic testing with the Vascular Malformations Panel, Sequencing and Deletion/Duplication revealed a pathogenic variant in the RASA1 gene and a variant of unknown clinical significance in the TEK gene. Parental genetic testing for the RASA1 mutation was negative, supporting a de novo mutation in the patient. CNS imaging showed a small developmental venous malformation in the brain that neurosurgery did not think was clinically significant. At the most recent follow-up at age 8 years, our patient had developed a few new small CMs but was otherwise well.
Dr. Leszczynska is trained in pediatrics and is the current dermatology research fellow at the University of Texas at Austin. Ms. Croce is a dermatology-trained pediatric nurse practitioner and PhD student at the University of Texas at Austin School of Nursing. Dr. Diaz is chief of pediatric dermatology at Dell Children’s Medical Center, Austin, assistant professor of pediatrics and medicine (dermatology), and dermatology residency associate program director at University of Texas at Austin . The authors have no relevant conflicts of interest to disclose. Donna Bilu Martin, MD, is the editor of this column.
References
1. Bayrak-Toydemir P, Stevenson D. Capillary Malformation-Arteriovenous Malformation Syndrome. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews®. Seattle: University of Washington, Seattle; February 22, 2011.
2.Yu J et al. Pediatr Dermatol. 2017 Sep;34(5):e227-30.
3. Orme CM et al. Pediatr Dermatol. 2013 Jul-Aug;30(4):409-15.
4. Weitz NA et al. Pediatr Dermatol. 2015 Jan-Feb;32(1):76-84.
5. Revencu N et al. Hum Mutat. 2013 Dec;34(12):1632-41.
6. Iznardo H et al. Pediatr Dermatol. 2020 Mar;37(2):342-44.
Capillary malformation-arteriovenous malformation syndrome
with or without arteriovenous malformations, as well as arteriovenous fistulas (AVFs). CM-AVM is an autosomal dominant disorder.1 CM-AVM type 1 is caused by mutations in the RASA1 gene, and CM-AVM type 2 is caused by mutations in the EPHB4 gene.2 Approximately 70% of patients with RASA1-associated CM-AVM syndrome and 80% of patients with EPHB4-associated CM-AVM syndrome have an affected parent, while the remainder have de novo variants.1
In patients with CM-AVM syndrome, CMs are often present at birth and more are typically acquired over time. CMs are characteristically 1-3 cm in diameter, round or oval, dull red or red-brown macules and patches with a blanched halo.3 Some CMs may be warm to touch indicating a possible underlying AVM or AVF.4 This can be confirmed by Doppler ultrasound, which would demonstrate increased arterial flow.4 CMs are most commonly located on the face and limbs and may present in isolation, but approximately one-third of patients have associated AVMs and AVFs.1,5 These high-flow vascular malformations may be present in skin, muscle, bone, brain, and/or spine and may be asymptomatic or lead to serious sequelae, including bleeding, congestive heart failure, and neurologic complications, such as migraine headaches, seizures, or even stroke.5 Symptoms from intracranial and spinal high-flow lesions usually present in early childhood and affect approximately 7% of patients.3
The diagnosis of CM-AVM should be suspected in an individual with numerous characteristic CMs and may be supported by the presence of AVMs and AVFs, family history of CM-AVM, and/or identification of RASA1 or EPHB4 mutation by molecular genetic testing.1,3 Although there are no consensus protocols for imaging CM-AVM patients, MRI of the brain and spine is recommended at diagnosis to identify underlying high-flow lesions.1 This may allow for early treatment before the development of symptoms.1 Any lesions identified on screening imaging may require regular surveillance, which is best determined by discussion with the radiologist.1 Although there are no reports of patients with negative results on screening imaging who later develop AVMs or AVFs, there should be a low threshold for repeat imaging in patients who develop new symptoms or physical exam findings.3,4
It has previously been suggested that the CMs in CM-AVM may actually represent early or small AVMs and pulsed-dye laser (PDL) treatment was not recommended because of concern for potential progression of lesions.4 However, a recent study demonstrated good response to PDL in patients with CM-AVM with no evidence of worsening or recurrence of lesions with long-term follow-up.6 Treatment of CMs that cause cosmetic concerns may be considered following discussion of risks and benefits with a dermatologist. Management of AVMs and AVFs requires a multidisciplinary team that, depending on location and symptoms of these features, may require the expertise of specialists such as neurosurgery, surgery, orthopedics, cardiology, and/or interventional radiology.1
Given the suspicion for CM-AVM in our patient, further workup was completed. A skin biopsy was consistent with CM. Genetic testing with the Vascular Malformations Panel, Sequencing and Deletion/Duplication revealed a pathogenic variant in the RASA1 gene and a variant of unknown clinical significance in the TEK gene. Parental genetic testing for the RASA1 mutation was negative, supporting a de novo mutation in the patient. CNS imaging showed a small developmental venous malformation in the brain that neurosurgery did not think was clinically significant. At the most recent follow-up at age 8 years, our patient had developed a few new small CMs but was otherwise well.
Dr. Leszczynska is trained in pediatrics and is the current dermatology research fellow at the University of Texas at Austin. Ms. Croce is a dermatology-trained pediatric nurse practitioner and PhD student at the University of Texas at Austin School of Nursing. Dr. Diaz is chief of pediatric dermatology at Dell Children’s Medical Center, Austin, assistant professor of pediatrics and medicine (dermatology), and dermatology residency associate program director at University of Texas at Austin . The authors have no relevant conflicts of interest to disclose. Donna Bilu Martin, MD, is the editor of this column.
References
1. Bayrak-Toydemir P, Stevenson D. Capillary Malformation-Arteriovenous Malformation Syndrome. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews®. Seattle: University of Washington, Seattle; February 22, 2011.
2.Yu J et al. Pediatr Dermatol. 2017 Sep;34(5):e227-30.
3. Orme CM et al. Pediatr Dermatol. 2013 Jul-Aug;30(4):409-15.
4. Weitz NA et al. Pediatr Dermatol. 2015 Jan-Feb;32(1):76-84.
5. Revencu N et al. Hum Mutat. 2013 Dec;34(12):1632-41.
6. Iznardo H et al. Pediatr Dermatol. 2020 Mar;37(2):342-44.
RECIPE trial cooks up gout therapy improvement
Adding the immunomodulator mycophenolate mofetil (MMF) to therapy with pegloticase (Krystexxa) may improve outcomes in patients with refractory gout, results of the proof-of-concept RECIPE trial suggest.
In the phase 2 trial, 19 of 22 patients randomized to received pegloticase and MMF achieved the primary outcome of serum uric acid levels below 6 mg/dL at week 12, compared with 4 of 10 patients assigned to pegloticase and placebo, reported Puja Khanna MD, MPH, of the University of Michigan, Ann Arbor, and colleagues.
“The use of MMF was associated with statistically significant and clinically meaningful impact on the proportion of subjects who achieved and maintained a serum urate of less than 6 mg/dL. Short-term concomitant use of MMF with pegloticase was generally well tolerated, and the estimated rates of adverse events were comparable between the groups,” she said during the virtual annual meeting of the American College of Rheumatology.
Pegloticase is a pegylated recombinant form of porcine uricase that has been shown to be effective in the treatment of gout in patients for whom other therapies have failed.
The drug’s use is limited, however, by immunogenicity, with high antipegloticase antibody titers associated with a loss of response.
“The PEG portion of the molecule, the polyethylene glycol component, can initiate an immune response that would cause significant infusion reactions and preclude further use of the medication for our patients,” explained Suleman Bhana, MD, a rheumatologist with Crystal Run Healthcare in New York’s Hudson Valley, who was not involved in the study.
“By trying to attenuate that immune response by whatever means one can, that could reduce the risk of these infusion reactions and lead to longevity and continuing efficacy of the medication,” he said.
Study details
The RECIPE trial was designed to test whether concomitant immunomodulation could prolong the efficacy of pegloticase therapy by dampening immune reactions.
Investigators enrolled patients 18 years and older who met 2015 ACR/European League Against Rheumatism gout classification criteria and had chronic refractory disease, defined as having symptoms inadequately controlled with oral urate-lowering therapy or a contraindication to ULT.
A total of 42 patients from five rheumatology practices were screened, and 35 were randomized on a 3:1 basis. In the intention-to-treat analysis of the results, the investigators included 32 patients: 22 in the MMF/pegloticase group and 10 placebo-treated controls who had received at least one dose of pegloticase.
Men comprised approximately 90% of the patients in each study arm, with the mean patient age around 55 years. In both groups, patients had a median of one gout flare in the prior year, and a mean duration of gout of 13 years plus a few months.
The patients’ prior urate-lowering agents included allopurinol and febuxostat, and patients had received colchicine, NSAIDs, and corticosteroids for acute gout.
The mean serum urate levels at baseline were 8.9 mg/dL in the MMF group, and 9.8 mg/dL in the placebo group.
Patients were given either MMF 1 g twice daily or a placebo during a 2-week run-in, with the assigned medications continuing for the first 12 weeks concomitantly with pegloticase. The uricase was given intravenously at a dose of 8 mg every 2 weeks for a total of 12 infusions.
As noted before, 86% of patients in the MMF arm (19 of 22) reached the primary outcome of serum uric acid levels below 6 mg/dL by week 12, compared with 40% (4 of 10) in the placebo arm (P = .01).
Week 24 serum uric acid response, a secondary endpoint, was sustained in 68% of patients in the MMF arm, compared with 30% in the placebo arm (P = .03).
“We found no significant differences between the groups in the absolute change in serum urate from baseline to week 24, or from week 12 to 24. We also did not find any differences between the treatment arms for the PROMIS [Patient Reported Outcomes Measurement Information System] or for the Gout Impact Scale,” Dr. Khanna said.
The most commonly reported adverse events included gout flares in 13% of patients in the MMF group and 3% in the placebo group, cardiac disorders in 3% versus 2%, respectively, and gastrointestinal disorders in 9% versus 2%.
Adverse events that occurred only in the MMF group included infections (3%), musculoskeletal and connective tissue disorders (18%), and respiratory events.
Three patients in the placebo arm had infusion reactions, two of which occurred during the first infusion, and one during the second. One of the reactions was considered serious and required hospitalization, but all infusion reactions resolved and none were fatal. There were no infusion reactions in the MMF arm.
Maybe methotrexate instead?
“The efficacy data for mycophenolate in the RECIPE study are convincing, and suggest that this combination substantially increases the proportion of people who respond to pegloticase,” commented Nicola Dalbeth, MD, professor of medicine at the University of Auckland (New Zealand), who moderated the session where the RECIPE data were reported.
“Previous open-label studies of methotrexate with pegloticase [e.g., the MIRROR study] suggest that methotrexate is another effective option to increase the response to pegloticase. However, at this stage, placebo-controlled trials of methotrexate have not been reported. I think a key consideration will be safety, and which option [methotrexate vs. mycophenolate] is safer, noting that many patients with severe gout have important comorbidities, including chronic kidney disease, diabetes, and liver disease,” she said.
Dr. Bhana also noted that there are multiple factors that might determine the choice of MMF or methotrexate as an immunomodulatory partner for pegloticase.
“Some gout patients have chronic kidney disease or a variety of comorbidities – high uric acid can also cause kidney damage – and if they have a kidney illness, methotrexate may not be a safe medicine because there’s a risk of further toxicity that can lead to bone marrow suppression, which I have seen personally in patients, and in this case mycophenolate would be the preferred option,” he said.
The study was sponsored by the University of Alabama at Birmingham, with collaboration from the University of Michigan, as well as the National Institute of Arthritis and Musculoskeletal and Skin Diseases and Horizon, which makes pegloticase. Dr. Khanna disclosed grant and research support from Dyve, Selecta, and Sobi, and consulting for Sobi and Horizon. Dr. Dalbeth disclosed relationships with AstraZeneca, AbbVie, Arthrosi, Dyve, Selecta, and Janssen. Dr. Bhana disclosed nonbranded consulting work for Horizon.
SOURCE: Khanna P et al. Arthritis Rheumatol. 2020;72(suppl 10), Abstract 0952.
Adding the immunomodulator mycophenolate mofetil (MMF) to therapy with pegloticase (Krystexxa) may improve outcomes in patients with refractory gout, results of the proof-of-concept RECIPE trial suggest.
In the phase 2 trial, 19 of 22 patients randomized to received pegloticase and MMF achieved the primary outcome of serum uric acid levels below 6 mg/dL at week 12, compared with 4 of 10 patients assigned to pegloticase and placebo, reported Puja Khanna MD, MPH, of the University of Michigan, Ann Arbor, and colleagues.
“The use of MMF was associated with statistically significant and clinically meaningful impact on the proportion of subjects who achieved and maintained a serum urate of less than 6 mg/dL. Short-term concomitant use of MMF with pegloticase was generally well tolerated, and the estimated rates of adverse events were comparable between the groups,” she said during the virtual annual meeting of the American College of Rheumatology.
Pegloticase is a pegylated recombinant form of porcine uricase that has been shown to be effective in the treatment of gout in patients for whom other therapies have failed.
The drug’s use is limited, however, by immunogenicity, with high antipegloticase antibody titers associated with a loss of response.
“The PEG portion of the molecule, the polyethylene glycol component, can initiate an immune response that would cause significant infusion reactions and preclude further use of the medication for our patients,” explained Suleman Bhana, MD, a rheumatologist with Crystal Run Healthcare in New York’s Hudson Valley, who was not involved in the study.
“By trying to attenuate that immune response by whatever means one can, that could reduce the risk of these infusion reactions and lead to longevity and continuing efficacy of the medication,” he said.
Study details
The RECIPE trial was designed to test whether concomitant immunomodulation could prolong the efficacy of pegloticase therapy by dampening immune reactions.
Investigators enrolled patients 18 years and older who met 2015 ACR/European League Against Rheumatism gout classification criteria and had chronic refractory disease, defined as having symptoms inadequately controlled with oral urate-lowering therapy or a contraindication to ULT.
A total of 42 patients from five rheumatology practices were screened, and 35 were randomized on a 3:1 basis. In the intention-to-treat analysis of the results, the investigators included 32 patients: 22 in the MMF/pegloticase group and 10 placebo-treated controls who had received at least one dose of pegloticase.
Men comprised approximately 90% of the patients in each study arm, with the mean patient age around 55 years. In both groups, patients had a median of one gout flare in the prior year, and a mean duration of gout of 13 years plus a few months.
The patients’ prior urate-lowering agents included allopurinol and febuxostat, and patients had received colchicine, NSAIDs, and corticosteroids for acute gout.
The mean serum urate levels at baseline were 8.9 mg/dL in the MMF group, and 9.8 mg/dL in the placebo group.
Patients were given either MMF 1 g twice daily or a placebo during a 2-week run-in, with the assigned medications continuing for the first 12 weeks concomitantly with pegloticase. The uricase was given intravenously at a dose of 8 mg every 2 weeks for a total of 12 infusions.
As noted before, 86% of patients in the MMF arm (19 of 22) reached the primary outcome of serum uric acid levels below 6 mg/dL by week 12, compared with 40% (4 of 10) in the placebo arm (P = .01).
Week 24 serum uric acid response, a secondary endpoint, was sustained in 68% of patients in the MMF arm, compared with 30% in the placebo arm (P = .03).
“We found no significant differences between the groups in the absolute change in serum urate from baseline to week 24, or from week 12 to 24. We also did not find any differences between the treatment arms for the PROMIS [Patient Reported Outcomes Measurement Information System] or for the Gout Impact Scale,” Dr. Khanna said.
The most commonly reported adverse events included gout flares in 13% of patients in the MMF group and 3% in the placebo group, cardiac disorders in 3% versus 2%, respectively, and gastrointestinal disorders in 9% versus 2%.
Adverse events that occurred only in the MMF group included infections (3%), musculoskeletal and connective tissue disorders (18%), and respiratory events.
Three patients in the placebo arm had infusion reactions, two of which occurred during the first infusion, and one during the second. One of the reactions was considered serious and required hospitalization, but all infusion reactions resolved and none were fatal. There were no infusion reactions in the MMF arm.
Maybe methotrexate instead?
“The efficacy data for mycophenolate in the RECIPE study are convincing, and suggest that this combination substantially increases the proportion of people who respond to pegloticase,” commented Nicola Dalbeth, MD, professor of medicine at the University of Auckland (New Zealand), who moderated the session where the RECIPE data were reported.
“Previous open-label studies of methotrexate with pegloticase [e.g., the MIRROR study] suggest that methotrexate is another effective option to increase the response to pegloticase. However, at this stage, placebo-controlled trials of methotrexate have not been reported. I think a key consideration will be safety, and which option [methotrexate vs. mycophenolate] is safer, noting that many patients with severe gout have important comorbidities, including chronic kidney disease, diabetes, and liver disease,” she said.
Dr. Bhana also noted that there are multiple factors that might determine the choice of MMF or methotrexate as an immunomodulatory partner for pegloticase.
“Some gout patients have chronic kidney disease or a variety of comorbidities – high uric acid can also cause kidney damage – and if they have a kidney illness, methotrexate may not be a safe medicine because there’s a risk of further toxicity that can lead to bone marrow suppression, which I have seen personally in patients, and in this case mycophenolate would be the preferred option,” he said.
The study was sponsored by the University of Alabama at Birmingham, with collaboration from the University of Michigan, as well as the National Institute of Arthritis and Musculoskeletal and Skin Diseases and Horizon, which makes pegloticase. Dr. Khanna disclosed grant and research support from Dyve, Selecta, and Sobi, and consulting for Sobi and Horizon. Dr. Dalbeth disclosed relationships with AstraZeneca, AbbVie, Arthrosi, Dyve, Selecta, and Janssen. Dr. Bhana disclosed nonbranded consulting work for Horizon.
SOURCE: Khanna P et al. Arthritis Rheumatol. 2020;72(suppl 10), Abstract 0952.
Adding the immunomodulator mycophenolate mofetil (MMF) to therapy with pegloticase (Krystexxa) may improve outcomes in patients with refractory gout, results of the proof-of-concept RECIPE trial suggest.
In the phase 2 trial, 19 of 22 patients randomized to received pegloticase and MMF achieved the primary outcome of serum uric acid levels below 6 mg/dL at week 12, compared with 4 of 10 patients assigned to pegloticase and placebo, reported Puja Khanna MD, MPH, of the University of Michigan, Ann Arbor, and colleagues.
“The use of MMF was associated with statistically significant and clinically meaningful impact on the proportion of subjects who achieved and maintained a serum urate of less than 6 mg/dL. Short-term concomitant use of MMF with pegloticase was generally well tolerated, and the estimated rates of adverse events were comparable between the groups,” she said during the virtual annual meeting of the American College of Rheumatology.
Pegloticase is a pegylated recombinant form of porcine uricase that has been shown to be effective in the treatment of gout in patients for whom other therapies have failed.
The drug’s use is limited, however, by immunogenicity, with high antipegloticase antibody titers associated with a loss of response.
“The PEG portion of the molecule, the polyethylene glycol component, can initiate an immune response that would cause significant infusion reactions and preclude further use of the medication for our patients,” explained Suleman Bhana, MD, a rheumatologist with Crystal Run Healthcare in New York’s Hudson Valley, who was not involved in the study.
“By trying to attenuate that immune response by whatever means one can, that could reduce the risk of these infusion reactions and lead to longevity and continuing efficacy of the medication,” he said.
Study details
The RECIPE trial was designed to test whether concomitant immunomodulation could prolong the efficacy of pegloticase therapy by dampening immune reactions.
Investigators enrolled patients 18 years and older who met 2015 ACR/European League Against Rheumatism gout classification criteria and had chronic refractory disease, defined as having symptoms inadequately controlled with oral urate-lowering therapy or a contraindication to ULT.
A total of 42 patients from five rheumatology practices were screened, and 35 were randomized on a 3:1 basis. In the intention-to-treat analysis of the results, the investigators included 32 patients: 22 in the MMF/pegloticase group and 10 placebo-treated controls who had received at least one dose of pegloticase.
Men comprised approximately 90% of the patients in each study arm, with the mean patient age around 55 years. In both groups, patients had a median of one gout flare in the prior year, and a mean duration of gout of 13 years plus a few months.
The patients’ prior urate-lowering agents included allopurinol and febuxostat, and patients had received colchicine, NSAIDs, and corticosteroids for acute gout.
The mean serum urate levels at baseline were 8.9 mg/dL in the MMF group, and 9.8 mg/dL in the placebo group.
Patients were given either MMF 1 g twice daily or a placebo during a 2-week run-in, with the assigned medications continuing for the first 12 weeks concomitantly with pegloticase. The uricase was given intravenously at a dose of 8 mg every 2 weeks for a total of 12 infusions.
As noted before, 86% of patients in the MMF arm (19 of 22) reached the primary outcome of serum uric acid levels below 6 mg/dL by week 12, compared with 40% (4 of 10) in the placebo arm (P = .01).
Week 24 serum uric acid response, a secondary endpoint, was sustained in 68% of patients in the MMF arm, compared with 30% in the placebo arm (P = .03).
“We found no significant differences between the groups in the absolute change in serum urate from baseline to week 24, or from week 12 to 24. We also did not find any differences between the treatment arms for the PROMIS [Patient Reported Outcomes Measurement Information System] or for the Gout Impact Scale,” Dr. Khanna said.
The most commonly reported adverse events included gout flares in 13% of patients in the MMF group and 3% in the placebo group, cardiac disorders in 3% versus 2%, respectively, and gastrointestinal disorders in 9% versus 2%.
Adverse events that occurred only in the MMF group included infections (3%), musculoskeletal and connective tissue disorders (18%), and respiratory events.
Three patients in the placebo arm had infusion reactions, two of which occurred during the first infusion, and one during the second. One of the reactions was considered serious and required hospitalization, but all infusion reactions resolved and none were fatal. There were no infusion reactions in the MMF arm.
Maybe methotrexate instead?
“The efficacy data for mycophenolate in the RECIPE study are convincing, and suggest that this combination substantially increases the proportion of people who respond to pegloticase,” commented Nicola Dalbeth, MD, professor of medicine at the University of Auckland (New Zealand), who moderated the session where the RECIPE data were reported.
“Previous open-label studies of methotrexate with pegloticase [e.g., the MIRROR study] suggest that methotrexate is another effective option to increase the response to pegloticase. However, at this stage, placebo-controlled trials of methotrexate have not been reported. I think a key consideration will be safety, and which option [methotrexate vs. mycophenolate] is safer, noting that many patients with severe gout have important comorbidities, including chronic kidney disease, diabetes, and liver disease,” she said.
Dr. Bhana also noted that there are multiple factors that might determine the choice of MMF or methotrexate as an immunomodulatory partner for pegloticase.
“Some gout patients have chronic kidney disease or a variety of comorbidities – high uric acid can also cause kidney damage – and if they have a kidney illness, methotrexate may not be a safe medicine because there’s a risk of further toxicity that can lead to bone marrow suppression, which I have seen personally in patients, and in this case mycophenolate would be the preferred option,” he said.
The study was sponsored by the University of Alabama at Birmingham, with collaboration from the University of Michigan, as well as the National Institute of Arthritis and Musculoskeletal and Skin Diseases and Horizon, which makes pegloticase. Dr. Khanna disclosed grant and research support from Dyve, Selecta, and Sobi, and consulting for Sobi and Horizon. Dr. Dalbeth disclosed relationships with AstraZeneca, AbbVie, Arthrosi, Dyve, Selecta, and Janssen. Dr. Bhana disclosed nonbranded consulting work for Horizon.
SOURCE: Khanna P et al. Arthritis Rheumatol. 2020;72(suppl 10), Abstract 0952.
FROM ACR 2020
A high proportion of SARS-CoV-2–infected university students are asymptomatic
Many individuals infected with SARS-CoV-2 never become symptomatic. In a South Korean study, these infected individuals remained asymptomatic for a prolonged period while maintaining the same viral load as symptomatic patients, suggesting that they are just as infectious.1 A narrative review found high rates of asymptomatic disease in several younger populations, including women in an obstetric ward (88%), the crew of an aircraft carrier (58%), and prisoners (96%).2 However, there is no published research on the percentage of university students who are asymptomatic.
Methods
The University of Georgia (UGA) began classes on August 20, 2020. Shortly before the beginning of classes, UGA implemented a surveillance program for asymptomatic students, faculty, and staff, testing 300 to 450 people per day. Initially, during Weeks 1 and 2 of data collection, anyone could choose to be tested. In Weeks 3 and 4, students, faculty, and staff were randomly invited to participate.
Over the 4-week period beginning on August 17, we calculated the percent of positive cases in surveillance testing and applied this percentage to the entire UGA student population (n = 38,920) to estimate the total number of asymptomatic COVID-19 students each week.3 Data for symptomatic cases were also reported by the university on a weekly basis. This included positive tests from the University Health Center, as well as voluntary reporting using a smartphone app from other sites.
Positive tests in symptomatic individuals were not stratified by student vs nonstudent until Week 3; students comprised 95% of positive symptomatic reports in Week 3 and 99% in Week 4, so we conservatively estimated that 95% of symptomatic cases in Weeks 1 and 2 were students. These data were used to estimate the percentage of SARS-CoV-2–positive students who were asymptomatic.
Results
Our results are summarized in the table. The percentage of asymptomatic students testing positive in surveillance testing was 3.4% in Week 1 and rose steadily to 9% by Week 4. We estimated that there were 1303 asymptomatic cases among students in Week 1, increasing to 3487 asymptomatic positive students on campus by Week 4. The estimated percentage of asymptomatic students infected with SARS-CoV-2 ranged from 73% to 92.5% by week and was 81.1% overall.
Discussion
During the reporting period from August 17 to September 13, the 7-day moving average of new cases in Clarke County (home of UGA) increased from 30 to 83 per 100,000 persons/day (https://dph.georgia.gov/covid-19-daily-status-report). During this period, there were large increases in the number of infected students, more than 80% of whom were asymptomatic. With the assumption that anyone could be infected even if asymptomatic, these numbers highlight the importance for infection control to prevent potential spread within a community by taking universal precautions such as wearing a mask, following physical distancing guidelines, and handwashing.
Limitations. First, reporting of positive tests in symptomatic individuals is highly encouraged but not required. The large drop in symptomatic positive test reports between Weeks 3 and 4, with no change in test positivity in surveillance of asymptomatic students (8.9% vs 9%), suggests that students may have chosen to be tested elsewhere in conjunction with evaluation of their symptoms and/or not reported positive tests, possibly to avoid mandatory isolation and other restrictions on their activities. Further evidence to support no change in actual infection rates comes from testing for virus in wastewater, which also remained unchanged.4
Continue to: Second, each week's surveillance...
Second, each week’s surveillance population is not a true random sample, so extrapolating this estimate to the full student population could over- or undercount asymptomatic cases depending on the direction of bias (ie, healthy volunteer bias vs test avoidance by those with high-risk behaviors).
Finally, some students who were positive in surveillance testing may have been presymptomatic, rather than asymptomatic.
In conclusion, we estimate that approximately 80% of students infected with SARS-CoV-2 are asymptomatic. This is consistent with other studies in young adult populations.2
Mark H. Ebell, MD, MS
Cassie Chupp, MPH
Michelle Bentivegna, MPH
Department of Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens
ebell@uga.edu
The authors reported no potential conflict of interest relevant to this article.
1. Lee S, Kim T, Lee E, et al. Clinical course and molecular viral shedding among asymptomatic and symptomatic patients with SARS-CoV-2 infection in a community treatment center in the Republic of Korea [published online ahead of print August 6, 2020]. JAMA Intern Med. doi:10.1001/jamainternmed.2020.3862
2. Oran DP, Topol EJ. Prevalence of asymptomatic SARS-CoV-2 infection : a narrative review. Ann Intern Med. 2020;173:362-367.
3. UGA by the Numbers. University of Georgia Web site. www.uga.edu/facts.php. Updated August 2020. Accessed October 20, 2020.
4. Lott M, Norfolk W, Robertson M, et al. Wastewater surveillance for SARS-CoV-2 in Athens, GA. COVID-19 Portal: Center for the Ecology of Infectious Diseases, University of Georgia Web site. www.covid19.uga.edu/wastewater-athens.html. Updated October 15, 2020. Accessed October 20, 2020.
Many individuals infected with SARS-CoV-2 never become symptomatic. In a South Korean study, these infected individuals remained asymptomatic for a prolonged period while maintaining the same viral load as symptomatic patients, suggesting that they are just as infectious.1 A narrative review found high rates of asymptomatic disease in several younger populations, including women in an obstetric ward (88%), the crew of an aircraft carrier (58%), and prisoners (96%).2 However, there is no published research on the percentage of university students who are asymptomatic.
Methods
The University of Georgia (UGA) began classes on August 20, 2020. Shortly before the beginning of classes, UGA implemented a surveillance program for asymptomatic students, faculty, and staff, testing 300 to 450 people per day. Initially, during Weeks 1 and 2 of data collection, anyone could choose to be tested. In Weeks 3 and 4, students, faculty, and staff were randomly invited to participate.
Over the 4-week period beginning on August 17, we calculated the percent of positive cases in surveillance testing and applied this percentage to the entire UGA student population (n = 38,920) to estimate the total number of asymptomatic COVID-19 students each week.3 Data for symptomatic cases were also reported by the university on a weekly basis. This included positive tests from the University Health Center, as well as voluntary reporting using a smartphone app from other sites.
Positive tests in symptomatic individuals were not stratified by student vs nonstudent until Week 3; students comprised 95% of positive symptomatic reports in Week 3 and 99% in Week 4, so we conservatively estimated that 95% of symptomatic cases in Weeks 1 and 2 were students. These data were used to estimate the percentage of SARS-CoV-2–positive students who were asymptomatic.
Results
Our results are summarized in the table. The percentage of asymptomatic students testing positive in surveillance testing was 3.4% in Week 1 and rose steadily to 9% by Week 4. We estimated that there were 1303 asymptomatic cases among students in Week 1, increasing to 3487 asymptomatic positive students on campus by Week 4. The estimated percentage of asymptomatic students infected with SARS-CoV-2 ranged from 73% to 92.5% by week and was 81.1% overall.
Discussion
During the reporting period from August 17 to September 13, the 7-day moving average of new cases in Clarke County (home of UGA) increased from 30 to 83 per 100,000 persons/day (https://dph.georgia.gov/covid-19-daily-status-report). During this period, there were large increases in the number of infected students, more than 80% of whom were asymptomatic. With the assumption that anyone could be infected even if asymptomatic, these numbers highlight the importance for infection control to prevent potential spread within a community by taking universal precautions such as wearing a mask, following physical distancing guidelines, and handwashing.
Limitations. First, reporting of positive tests in symptomatic individuals is highly encouraged but not required. The large drop in symptomatic positive test reports between Weeks 3 and 4, with no change in test positivity in surveillance of asymptomatic students (8.9% vs 9%), suggests that students may have chosen to be tested elsewhere in conjunction with evaluation of their symptoms and/or not reported positive tests, possibly to avoid mandatory isolation and other restrictions on their activities. Further evidence to support no change in actual infection rates comes from testing for virus in wastewater, which also remained unchanged.4
Continue to: Second, each week's surveillance...
Second, each week’s surveillance population is not a true random sample, so extrapolating this estimate to the full student population could over- or undercount asymptomatic cases depending on the direction of bias (ie, healthy volunteer bias vs test avoidance by those with high-risk behaviors).
Finally, some students who were positive in surveillance testing may have been presymptomatic, rather than asymptomatic.
In conclusion, we estimate that approximately 80% of students infected with SARS-CoV-2 are asymptomatic. This is consistent with other studies in young adult populations.2
Mark H. Ebell, MD, MS
Cassie Chupp, MPH
Michelle Bentivegna, MPH
Department of Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens
ebell@uga.edu
The authors reported no potential conflict of interest relevant to this article.
Many individuals infected with SARS-CoV-2 never become symptomatic. In a South Korean study, these infected individuals remained asymptomatic for a prolonged period while maintaining the same viral load as symptomatic patients, suggesting that they are just as infectious.1 A narrative review found high rates of asymptomatic disease in several younger populations, including women in an obstetric ward (88%), the crew of an aircraft carrier (58%), and prisoners (96%).2 However, there is no published research on the percentage of university students who are asymptomatic.
Methods
The University of Georgia (UGA) began classes on August 20, 2020. Shortly before the beginning of classes, UGA implemented a surveillance program for asymptomatic students, faculty, and staff, testing 300 to 450 people per day. Initially, during Weeks 1 and 2 of data collection, anyone could choose to be tested. In Weeks 3 and 4, students, faculty, and staff were randomly invited to participate.
Over the 4-week period beginning on August 17, we calculated the percent of positive cases in surveillance testing and applied this percentage to the entire UGA student population (n = 38,920) to estimate the total number of asymptomatic COVID-19 students each week.3 Data for symptomatic cases were also reported by the university on a weekly basis. This included positive tests from the University Health Center, as well as voluntary reporting using a smartphone app from other sites.
Positive tests in symptomatic individuals were not stratified by student vs nonstudent until Week 3; students comprised 95% of positive symptomatic reports in Week 3 and 99% in Week 4, so we conservatively estimated that 95% of symptomatic cases in Weeks 1 and 2 were students. These data were used to estimate the percentage of SARS-CoV-2–positive students who were asymptomatic.
Results
Our results are summarized in the table. The percentage of asymptomatic students testing positive in surveillance testing was 3.4% in Week 1 and rose steadily to 9% by Week 4. We estimated that there were 1303 asymptomatic cases among students in Week 1, increasing to 3487 asymptomatic positive students on campus by Week 4. The estimated percentage of asymptomatic students infected with SARS-CoV-2 ranged from 73% to 92.5% by week and was 81.1% overall.
Discussion
During the reporting period from August 17 to September 13, the 7-day moving average of new cases in Clarke County (home of UGA) increased from 30 to 83 per 100,000 persons/day (https://dph.georgia.gov/covid-19-daily-status-report). During this period, there were large increases in the number of infected students, more than 80% of whom were asymptomatic. With the assumption that anyone could be infected even if asymptomatic, these numbers highlight the importance for infection control to prevent potential spread within a community by taking universal precautions such as wearing a mask, following physical distancing guidelines, and handwashing.
Limitations. First, reporting of positive tests in symptomatic individuals is highly encouraged but not required. The large drop in symptomatic positive test reports between Weeks 3 and 4, with no change in test positivity in surveillance of asymptomatic students (8.9% vs 9%), suggests that students may have chosen to be tested elsewhere in conjunction with evaluation of their symptoms and/or not reported positive tests, possibly to avoid mandatory isolation and other restrictions on their activities. Further evidence to support no change in actual infection rates comes from testing for virus in wastewater, which also remained unchanged.4
Continue to: Second, each week's surveillance...
Second, each week’s surveillance population is not a true random sample, so extrapolating this estimate to the full student population could over- or undercount asymptomatic cases depending on the direction of bias (ie, healthy volunteer bias vs test avoidance by those with high-risk behaviors).
Finally, some students who were positive in surveillance testing may have been presymptomatic, rather than asymptomatic.
In conclusion, we estimate that approximately 80% of students infected with SARS-CoV-2 are asymptomatic. This is consistent with other studies in young adult populations.2
Mark H. Ebell, MD, MS
Cassie Chupp, MPH
Michelle Bentivegna, MPH
Department of Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens
ebell@uga.edu
The authors reported no potential conflict of interest relevant to this article.
1. Lee S, Kim T, Lee E, et al. Clinical course and molecular viral shedding among asymptomatic and symptomatic patients with SARS-CoV-2 infection in a community treatment center in the Republic of Korea [published online ahead of print August 6, 2020]. JAMA Intern Med. doi:10.1001/jamainternmed.2020.3862
2. Oran DP, Topol EJ. Prevalence of asymptomatic SARS-CoV-2 infection : a narrative review. Ann Intern Med. 2020;173:362-367.
3. UGA by the Numbers. University of Georgia Web site. www.uga.edu/facts.php. Updated August 2020. Accessed October 20, 2020.
4. Lott M, Norfolk W, Robertson M, et al. Wastewater surveillance for SARS-CoV-2 in Athens, GA. COVID-19 Portal: Center for the Ecology of Infectious Diseases, University of Georgia Web site. www.covid19.uga.edu/wastewater-athens.html. Updated October 15, 2020. Accessed October 20, 2020.
1. Lee S, Kim T, Lee E, et al. Clinical course and molecular viral shedding among asymptomatic and symptomatic patients with SARS-CoV-2 infection in a community treatment center in the Republic of Korea [published online ahead of print August 6, 2020]. JAMA Intern Med. doi:10.1001/jamainternmed.2020.3862
2. Oran DP, Topol EJ. Prevalence of asymptomatic SARS-CoV-2 infection : a narrative review. Ann Intern Med. 2020;173:362-367.
3. UGA by the Numbers. University of Georgia Web site. www.uga.edu/facts.php. Updated August 2020. Accessed October 20, 2020.
4. Lott M, Norfolk W, Robertson M, et al. Wastewater surveillance for SARS-CoV-2 in Athens, GA. COVID-19 Portal: Center for the Ecology of Infectious Diseases, University of Georgia Web site. www.covid19.uga.edu/wastewater-athens.html. Updated October 15, 2020. Accessed October 20, 2020.
Whales, seals, and dolphins: Will SARS-CoV-2–contaminated wastewater prove a killer?
Zoonoses are no respecter of biological boundaries and are notorious for crossing genus and even higher taxonomic boundaries. SARS-CoV-2 is no exception, the current outbreak most probably having originated in bats, a common source of human-affecting zoonoses throughout history. But it is not a one-way street, and the virus has been shown to spread from infected humans to a variety of other land mammals, including our domesticated animals and kept zoo species.
A recent troubling report, however, has indicated that sea mammals may be part of a next wave of likely candidates for infection, put at risk by the current human pandemic and environmental degradation on a global scale, according to a the results of a genomic analysis of four major groups of sea mammals.
Researchers Sabateeshan Mathavarajah and colleagues from Dalhousie University, Halifax, N.S., examined the sequences of the ACE2 receptors in the various marine mammal species. The ACE2 receptor has recently been identified as the SARS-CoV-2 receptor, which allows for infection.
The researchers examined genomic databases of the marine species to determine if their ACE2 receptor sequences indicated the potential for high, medium, or low susceptibility to infection, as reported in Science of the Total Environment. Database analysis was performed for four groups: Cetacea (whales and dolphins), Pinnepidia (seals), Sirenia (sea cows), and Fissipedia (sea otters and polar bears).
The researchers defined susceptibility values based on comparable binding with the receptor and came up with the following subgroups: higher than human, high (resembles human ACE2), medium (resembles cat ACE2), and low (resembles dog ACE2). It has yet to be established if these marine mammals actually are infected with SARS-CoV-2 and what the impact of such an infection might have on animal health or humans who come in contact with infected animals.
They also cross-referenced for the level of species endangerment and with maps of potential wastewater contamination for certain areas that species came in contact with, using Alaska as the model.
Populations in danger
The researchers found 15 species that are already at risk globally that fall under the categories of near threatened, vulnerable, endangered, and critically endangered that were predicted to be medium to higher susceptibility to the SARS-CoV-2 virus than humans. Cross infection is of particular concern because other coronaviruses have been shown to have severe and lethal effects among many of these species.
Among the potentially impacted species were the near threatened–status Antarctic Mink whale and the stellar sea lion; the vulnerable sperm whale, northern fur seal, and Atlantic walrus; the endangered northern and southern sea otters, the North Pacific right whale, and the Amazon River dolphin; and the critically threatened Baiji and Vaquita dolphin species.
Pollution risks
In Alaska, as of Aug. 7th, 2020, there were 4,221 confirmed cases of COVID-19 and this number continues to rise, according to the researchers. Since there is a diversity of marine mammals in Alaska and their populations are well documented, they compared this information with available data on the wastewater treatment plants in the state. They were thus able to determine the potential geographic locations and species at high risk for transmission of SARS-CoV-2 via wastewater effluent.
Among their findings, the city of Cold Bay discharges wastewater into Cold Bay, where there are Northern sea otter populations that are predicted to be highly susceptible to the virus. Beluga whales are also predicted to have high susceptibility and they can be found in Bristol Bay near Naknek, a city which relies only on lagoon treatment prior to the discharge of wastewater effluent; the city of Dillingham discharges wastewater into the Nushagak River where beluga whales are found. In Palmer, wastewater effluent flows into the Talkeetna River, which is a tributary to the Susitna River and home to two species predicted to have high susceptibility, beluga whales and harbor seals, the authors added.
Based on these results, the researchers predicted that there was likely a significant risk to sea mammals across the globe, especially where less-adequate treatment facilities and high population densities may lead to greater wastewater contamination.
“Given the proximity of marine animals to high-risk environments where viral spill over is likely, we must act with foresight to protect marine mammal species predicted to be at risk and mitigate the environmental impact of the COVID-19 pandemic,” the researchers concluded.
The authors reported that they had no disclosures.
SOURCE: Mathavarajah S et al. Sci Total Environ. 2020 Oct 29. doi: 10.1016/j.scitotenv.2020.143346.
Zoonoses are no respecter of biological boundaries and are notorious for crossing genus and even higher taxonomic boundaries. SARS-CoV-2 is no exception, the current outbreak most probably having originated in bats, a common source of human-affecting zoonoses throughout history. But it is not a one-way street, and the virus has been shown to spread from infected humans to a variety of other land mammals, including our domesticated animals and kept zoo species.
A recent troubling report, however, has indicated that sea mammals may be part of a next wave of likely candidates for infection, put at risk by the current human pandemic and environmental degradation on a global scale, according to a the results of a genomic analysis of four major groups of sea mammals.
Researchers Sabateeshan Mathavarajah and colleagues from Dalhousie University, Halifax, N.S., examined the sequences of the ACE2 receptors in the various marine mammal species. The ACE2 receptor has recently been identified as the SARS-CoV-2 receptor, which allows for infection.
The researchers examined genomic databases of the marine species to determine if their ACE2 receptor sequences indicated the potential for high, medium, or low susceptibility to infection, as reported in Science of the Total Environment. Database analysis was performed for four groups: Cetacea (whales and dolphins), Pinnepidia (seals), Sirenia (sea cows), and Fissipedia (sea otters and polar bears).
The researchers defined susceptibility values based on comparable binding with the receptor and came up with the following subgroups: higher than human, high (resembles human ACE2), medium (resembles cat ACE2), and low (resembles dog ACE2). It has yet to be established if these marine mammals actually are infected with SARS-CoV-2 and what the impact of such an infection might have on animal health or humans who come in contact with infected animals.
They also cross-referenced for the level of species endangerment and with maps of potential wastewater contamination for certain areas that species came in contact with, using Alaska as the model.
Populations in danger
The researchers found 15 species that are already at risk globally that fall under the categories of near threatened, vulnerable, endangered, and critically endangered that were predicted to be medium to higher susceptibility to the SARS-CoV-2 virus than humans. Cross infection is of particular concern because other coronaviruses have been shown to have severe and lethal effects among many of these species.
Among the potentially impacted species were the near threatened–status Antarctic Mink whale and the stellar sea lion; the vulnerable sperm whale, northern fur seal, and Atlantic walrus; the endangered northern and southern sea otters, the North Pacific right whale, and the Amazon River dolphin; and the critically threatened Baiji and Vaquita dolphin species.
Pollution risks
In Alaska, as of Aug. 7th, 2020, there were 4,221 confirmed cases of COVID-19 and this number continues to rise, according to the researchers. Since there is a diversity of marine mammals in Alaska and their populations are well documented, they compared this information with available data on the wastewater treatment plants in the state. They were thus able to determine the potential geographic locations and species at high risk for transmission of SARS-CoV-2 via wastewater effluent.
Among their findings, the city of Cold Bay discharges wastewater into Cold Bay, where there are Northern sea otter populations that are predicted to be highly susceptible to the virus. Beluga whales are also predicted to have high susceptibility and they can be found in Bristol Bay near Naknek, a city which relies only on lagoon treatment prior to the discharge of wastewater effluent; the city of Dillingham discharges wastewater into the Nushagak River where beluga whales are found. In Palmer, wastewater effluent flows into the Talkeetna River, which is a tributary to the Susitna River and home to two species predicted to have high susceptibility, beluga whales and harbor seals, the authors added.
Based on these results, the researchers predicted that there was likely a significant risk to sea mammals across the globe, especially where less-adequate treatment facilities and high population densities may lead to greater wastewater contamination.
“Given the proximity of marine animals to high-risk environments where viral spill over is likely, we must act with foresight to protect marine mammal species predicted to be at risk and mitigate the environmental impact of the COVID-19 pandemic,” the researchers concluded.
The authors reported that they had no disclosures.
SOURCE: Mathavarajah S et al. Sci Total Environ. 2020 Oct 29. doi: 10.1016/j.scitotenv.2020.143346.
Zoonoses are no respecter of biological boundaries and are notorious for crossing genus and even higher taxonomic boundaries. SARS-CoV-2 is no exception, the current outbreak most probably having originated in bats, a common source of human-affecting zoonoses throughout history. But it is not a one-way street, and the virus has been shown to spread from infected humans to a variety of other land mammals, including our domesticated animals and kept zoo species.
A recent troubling report, however, has indicated that sea mammals may be part of a next wave of likely candidates for infection, put at risk by the current human pandemic and environmental degradation on a global scale, according to a the results of a genomic analysis of four major groups of sea mammals.
Researchers Sabateeshan Mathavarajah and colleagues from Dalhousie University, Halifax, N.S., examined the sequences of the ACE2 receptors in the various marine mammal species. The ACE2 receptor has recently been identified as the SARS-CoV-2 receptor, which allows for infection.
The researchers examined genomic databases of the marine species to determine if their ACE2 receptor sequences indicated the potential for high, medium, or low susceptibility to infection, as reported in Science of the Total Environment. Database analysis was performed for four groups: Cetacea (whales and dolphins), Pinnepidia (seals), Sirenia (sea cows), and Fissipedia (sea otters and polar bears).
The researchers defined susceptibility values based on comparable binding with the receptor and came up with the following subgroups: higher than human, high (resembles human ACE2), medium (resembles cat ACE2), and low (resembles dog ACE2). It has yet to be established if these marine mammals actually are infected with SARS-CoV-2 and what the impact of such an infection might have on animal health or humans who come in contact with infected animals.
They also cross-referenced for the level of species endangerment and with maps of potential wastewater contamination for certain areas that species came in contact with, using Alaska as the model.
Populations in danger
The researchers found 15 species that are already at risk globally that fall under the categories of near threatened, vulnerable, endangered, and critically endangered that were predicted to be medium to higher susceptibility to the SARS-CoV-2 virus than humans. Cross infection is of particular concern because other coronaviruses have been shown to have severe and lethal effects among many of these species.
Among the potentially impacted species were the near threatened–status Antarctic Mink whale and the stellar sea lion; the vulnerable sperm whale, northern fur seal, and Atlantic walrus; the endangered northern and southern sea otters, the North Pacific right whale, and the Amazon River dolphin; and the critically threatened Baiji and Vaquita dolphin species.
Pollution risks
In Alaska, as of Aug. 7th, 2020, there were 4,221 confirmed cases of COVID-19 and this number continues to rise, according to the researchers. Since there is a diversity of marine mammals in Alaska and their populations are well documented, they compared this information with available data on the wastewater treatment plants in the state. They were thus able to determine the potential geographic locations and species at high risk for transmission of SARS-CoV-2 via wastewater effluent.
Among their findings, the city of Cold Bay discharges wastewater into Cold Bay, where there are Northern sea otter populations that are predicted to be highly susceptible to the virus. Beluga whales are also predicted to have high susceptibility and they can be found in Bristol Bay near Naknek, a city which relies only on lagoon treatment prior to the discharge of wastewater effluent; the city of Dillingham discharges wastewater into the Nushagak River where beluga whales are found. In Palmer, wastewater effluent flows into the Talkeetna River, which is a tributary to the Susitna River and home to two species predicted to have high susceptibility, beluga whales and harbor seals, the authors added.
Based on these results, the researchers predicted that there was likely a significant risk to sea mammals across the globe, especially where less-adequate treatment facilities and high population densities may lead to greater wastewater contamination.
“Given the proximity of marine animals to high-risk environments where viral spill over is likely, we must act with foresight to protect marine mammal species predicted to be at risk and mitigate the environmental impact of the COVID-19 pandemic,” the researchers concluded.
The authors reported that they had no disclosures.
SOURCE: Mathavarajah S et al. Sci Total Environ. 2020 Oct 29. doi: 10.1016/j.scitotenv.2020.143346.
FROM SCIENCE OF THE TOTAL ENVIRONMENT
Increasing ear pain and headache
A previously healthy 12-year-old boy with normal development presented to his primary care physician (PCP) with a 1-week history of moderate ear pain. He was given a diagnosis of acute otitis media (AOM) and prescribed a 7-day course of amoxicillin. Although the child’s history was otherwise unremarkable, the mother reported that she’d had a deep venous thrombosis and pulmonary embolism a year earlier.
The boy continued to experience intermittent left ear pain 2 weeks after completing his antibiotic treatment, leading the PCP to refer him to an otolaryngologist. An examination by the otolaryngologist revealed a cloudy, bulging tympanic membrane. The patient was prescribed amoxicillin/clavulanate and ofloxacin ear drops.
Two days later, he was admitted to the emergency department (ED) due to worsening left ear pain and a new-onset left-sided headache. His left tympanic membrane was normal, with no tenderness or erythema of the mastoid. His vital signs were normal. He was afebrile and discharged home.
A week later, he returned to the ED with worsening ear pain and severe persistent headache, which was localized in the left occipital, left frontal, and retro-orbital regions. He denied light or sound sensitivity, nausea, vomiting, or increased lacrimation. He was tearful on examination due to the pain. He had no meningismus and normal fundi. A neurologic examination was nonlateralizing. Laboratory tests showed a normal complete blood count but increased C-reactive protein at 113 mg/dL (normal, < 0.3 mg/dL) and an erythrocyte sedimentation rate of 88 mm/hr (normal, 0-20 mm/hr).
Magnetic resonance imaging was ordered (FIGURES 1A and 1B), and Neurosurgery and Otolaryngology were consulted.
WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?
Dx: Acute mastoiditis with epidural abscess
The contrast-enhanced cranial MRI scan (FIGURE 1A) revealed a case of acute mastoiditis with fluid in the left mastoid (blue arrow) and a large epidural abscess in the left posterior fossa (green arrow). The normal right mastoid was air-filled (yellow arrow). The T2-weighted MRI scan (FIGURE 1B) showed mild dilatation of the lateral ventricles (blue arrow) secondary to compression on the fourth ventricle by mass effect from the epidural abscess.
Acute mastoiditis—a complication of AOM—is an inflammatory process of mastoid air cells, which are contiguous to the middle ear cleft. In one large study of 61,783 inpatient children admitted with AOM, acute mastoiditis was reported as the most common complication in 1505 (2.4%) of the cases.1 The 2000-2012 national estimated incidence rate of pediatric mastoiditis has ranged from a high of 2.7 per 100,000 population in 2006 to a low of 1.8 per 100,000 in 2012.2 Clinical features of mastoiditis include localized mastoid tenderness, swelling, erythema, fluctuance, protrusion of the auricle, and ear pain.3
The clinical presentation of epidural abscess can be subtle with fever, headache, neck pain, and changes in mental status developing over several days.1 Focal deficits and seizures are relatively uncommon. In a review of 308 children with acute mastoiditis (3 with an epidural abscess), high-grade fever and high absolute neutrophil count and C-reactive protein levels were associated with the development of complications of mastoiditis, including hearing loss, sinus venous thrombosis, intracranial abscess, and cranial nerve palsies.4
Venous sinus thrombosis was part of the differential
When we were caring for this patient, the differential diagnosis included a cranial extension of AOM. Venous sinus thrombosis was also considered, given the family history of a hypercoagulable state. The patient did not have any features suggesting primary headache syndromes, such as migraine, tension type, or cluster headache.
The differential for a patient complaining of ear pain also includes postauricular lymphadenopathy, mumps, periauricular cellulitis (with and without otitis externa), perichondritis of the auricle, and tumors involving the mastoid bone.4
Continue to: Imaging and treatment
Imaging and treatment
Imaging of temporal bone is not recommended to make a diagnosis of mastoiditis in children with characteristic clinical findings. When imaging is needed, contrast-enhanced computed tomography (CT) is best to help visualize changes in temporal bone. If intracranial complications are suspected, cranial MRI with contrast or cranial CT with contrast can be ordered (depending on availability).5
Conservative management with intravenous antimicrobial therapy and middle ear drainage with myringotomy is indicated for a child with uncomplicated acute or subacute mastoiditis. For patients with suppurative extracranial or intracranial complications, aggressive surgical management is needed.5
Treatment for this patient included craniotomy, evacuation of the epidural abscess, and mastoidectomy. A culture obtained from the abscess showed Streptococcus intermedius. He was treated with broad-spectrum antibiotics, including ceftriaxone, vancomycin, and metronidazole. Within a week of surgery, he was discharged from the hospital and continued antibiotic treatment for 6 weeks via a peripherally inserted central catheter line.
1. Lavin JM, Rusher T, Shah RK. Complications of pediatric otitis media. Otolaryngol Head Neck Surg. 2016;154:366-370.
2. King LM, Bartoces M, Hersh AL, et al. National incidence of pediatric mastoiditis in the United States, 2000-2012: creating a baseline for public health surveillance. Pediatr Infect Dis J. 2019;38:e14-e16.
3. Pang LH, Barakate MS, Havas TE. Mastoiditis in a paediatric population: a review of 11 years’ experience in management. Int J Pediatr Otorhinolaryngol. 2009;73:1520.
4. Bilavsky E, Yarden-Bilavsky H, Samra Z, et al. Clinical, laboratory, and microbiological differences between children with simple or complicated mastoiditis. Int J Pediatr Otorhinolaryngol. 2009;73:1270-1273.
5. Chesney J, Black A, Choo D. What is the best practice for acute mastoiditis in children? Laryngoscope. 2014;124:1057-1059.
A previously healthy 12-year-old boy with normal development presented to his primary care physician (PCP) with a 1-week history of moderate ear pain. He was given a diagnosis of acute otitis media (AOM) and prescribed a 7-day course of amoxicillin. Although the child’s history was otherwise unremarkable, the mother reported that she’d had a deep venous thrombosis and pulmonary embolism a year earlier.
The boy continued to experience intermittent left ear pain 2 weeks after completing his antibiotic treatment, leading the PCP to refer him to an otolaryngologist. An examination by the otolaryngologist revealed a cloudy, bulging tympanic membrane. The patient was prescribed amoxicillin/clavulanate and ofloxacin ear drops.
Two days later, he was admitted to the emergency department (ED) due to worsening left ear pain and a new-onset left-sided headache. His left tympanic membrane was normal, with no tenderness or erythema of the mastoid. His vital signs were normal. He was afebrile and discharged home.
A week later, he returned to the ED with worsening ear pain and severe persistent headache, which was localized in the left occipital, left frontal, and retro-orbital regions. He denied light or sound sensitivity, nausea, vomiting, or increased lacrimation. He was tearful on examination due to the pain. He had no meningismus and normal fundi. A neurologic examination was nonlateralizing. Laboratory tests showed a normal complete blood count but increased C-reactive protein at 113 mg/dL (normal, < 0.3 mg/dL) and an erythrocyte sedimentation rate of 88 mm/hr (normal, 0-20 mm/hr).
Magnetic resonance imaging was ordered (FIGURES 1A and 1B), and Neurosurgery and Otolaryngology were consulted.
WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?
Dx: Acute mastoiditis with epidural abscess
The contrast-enhanced cranial MRI scan (FIGURE 1A) revealed a case of acute mastoiditis with fluid in the left mastoid (blue arrow) and a large epidural abscess in the left posterior fossa (green arrow). The normal right mastoid was air-filled (yellow arrow). The T2-weighted MRI scan (FIGURE 1B) showed mild dilatation of the lateral ventricles (blue arrow) secondary to compression on the fourth ventricle by mass effect from the epidural abscess.
Acute mastoiditis—a complication of AOM—is an inflammatory process of mastoid air cells, which are contiguous to the middle ear cleft. In one large study of 61,783 inpatient children admitted with AOM, acute mastoiditis was reported as the most common complication in 1505 (2.4%) of the cases.1 The 2000-2012 national estimated incidence rate of pediatric mastoiditis has ranged from a high of 2.7 per 100,000 population in 2006 to a low of 1.8 per 100,000 in 2012.2 Clinical features of mastoiditis include localized mastoid tenderness, swelling, erythema, fluctuance, protrusion of the auricle, and ear pain.3
The clinical presentation of epidural abscess can be subtle with fever, headache, neck pain, and changes in mental status developing over several days.1 Focal deficits and seizures are relatively uncommon. In a review of 308 children with acute mastoiditis (3 with an epidural abscess), high-grade fever and high absolute neutrophil count and C-reactive protein levels were associated with the development of complications of mastoiditis, including hearing loss, sinus venous thrombosis, intracranial abscess, and cranial nerve palsies.4
Venous sinus thrombosis was part of the differential
When we were caring for this patient, the differential diagnosis included a cranial extension of AOM. Venous sinus thrombosis was also considered, given the family history of a hypercoagulable state. The patient did not have any features suggesting primary headache syndromes, such as migraine, tension type, or cluster headache.
The differential for a patient complaining of ear pain also includes postauricular lymphadenopathy, mumps, periauricular cellulitis (with and without otitis externa), perichondritis of the auricle, and tumors involving the mastoid bone.4
Continue to: Imaging and treatment
Imaging and treatment
Imaging of temporal bone is not recommended to make a diagnosis of mastoiditis in children with characteristic clinical findings. When imaging is needed, contrast-enhanced computed tomography (CT) is best to help visualize changes in temporal bone. If intracranial complications are suspected, cranial MRI with contrast or cranial CT with contrast can be ordered (depending on availability).5
Conservative management with intravenous antimicrobial therapy and middle ear drainage with myringotomy is indicated for a child with uncomplicated acute or subacute mastoiditis. For patients with suppurative extracranial or intracranial complications, aggressive surgical management is needed.5
Treatment for this patient included craniotomy, evacuation of the epidural abscess, and mastoidectomy. A culture obtained from the abscess showed Streptococcus intermedius. He was treated with broad-spectrum antibiotics, including ceftriaxone, vancomycin, and metronidazole. Within a week of surgery, he was discharged from the hospital and continued antibiotic treatment for 6 weeks via a peripherally inserted central catheter line.
A previously healthy 12-year-old boy with normal development presented to his primary care physician (PCP) with a 1-week history of moderate ear pain. He was given a diagnosis of acute otitis media (AOM) and prescribed a 7-day course of amoxicillin. Although the child’s history was otherwise unremarkable, the mother reported that she’d had a deep venous thrombosis and pulmonary embolism a year earlier.
The boy continued to experience intermittent left ear pain 2 weeks after completing his antibiotic treatment, leading the PCP to refer him to an otolaryngologist. An examination by the otolaryngologist revealed a cloudy, bulging tympanic membrane. The patient was prescribed amoxicillin/clavulanate and ofloxacin ear drops.
Two days later, he was admitted to the emergency department (ED) due to worsening left ear pain and a new-onset left-sided headache. His left tympanic membrane was normal, with no tenderness or erythema of the mastoid. His vital signs were normal. He was afebrile and discharged home.
A week later, he returned to the ED with worsening ear pain and severe persistent headache, which was localized in the left occipital, left frontal, and retro-orbital regions. He denied light or sound sensitivity, nausea, vomiting, or increased lacrimation. He was tearful on examination due to the pain. He had no meningismus and normal fundi. A neurologic examination was nonlateralizing. Laboratory tests showed a normal complete blood count but increased C-reactive protein at 113 mg/dL (normal, < 0.3 mg/dL) and an erythrocyte sedimentation rate of 88 mm/hr (normal, 0-20 mm/hr).
Magnetic resonance imaging was ordered (FIGURES 1A and 1B), and Neurosurgery and Otolaryngology were consulted.
WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?
Dx: Acute mastoiditis with epidural abscess
The contrast-enhanced cranial MRI scan (FIGURE 1A) revealed a case of acute mastoiditis with fluid in the left mastoid (blue arrow) and a large epidural abscess in the left posterior fossa (green arrow). The normal right mastoid was air-filled (yellow arrow). The T2-weighted MRI scan (FIGURE 1B) showed mild dilatation of the lateral ventricles (blue arrow) secondary to compression on the fourth ventricle by mass effect from the epidural abscess.
Acute mastoiditis—a complication of AOM—is an inflammatory process of mastoid air cells, which are contiguous to the middle ear cleft. In one large study of 61,783 inpatient children admitted with AOM, acute mastoiditis was reported as the most common complication in 1505 (2.4%) of the cases.1 The 2000-2012 national estimated incidence rate of pediatric mastoiditis has ranged from a high of 2.7 per 100,000 population in 2006 to a low of 1.8 per 100,000 in 2012.2 Clinical features of mastoiditis include localized mastoid tenderness, swelling, erythema, fluctuance, protrusion of the auricle, and ear pain.3
The clinical presentation of epidural abscess can be subtle with fever, headache, neck pain, and changes in mental status developing over several days.1 Focal deficits and seizures are relatively uncommon. In a review of 308 children with acute mastoiditis (3 with an epidural abscess), high-grade fever and high absolute neutrophil count and C-reactive protein levels were associated with the development of complications of mastoiditis, including hearing loss, sinus venous thrombosis, intracranial abscess, and cranial nerve palsies.4
Venous sinus thrombosis was part of the differential
When we were caring for this patient, the differential diagnosis included a cranial extension of AOM. Venous sinus thrombosis was also considered, given the family history of a hypercoagulable state. The patient did not have any features suggesting primary headache syndromes, such as migraine, tension type, or cluster headache.
The differential for a patient complaining of ear pain also includes postauricular lymphadenopathy, mumps, periauricular cellulitis (with and without otitis externa), perichondritis of the auricle, and tumors involving the mastoid bone.4
Continue to: Imaging and treatment
Imaging and treatment
Imaging of temporal bone is not recommended to make a diagnosis of mastoiditis in children with characteristic clinical findings. When imaging is needed, contrast-enhanced computed tomography (CT) is best to help visualize changes in temporal bone. If intracranial complications are suspected, cranial MRI with contrast or cranial CT with contrast can be ordered (depending on availability).5
Conservative management with intravenous antimicrobial therapy and middle ear drainage with myringotomy is indicated for a child with uncomplicated acute or subacute mastoiditis. For patients with suppurative extracranial or intracranial complications, aggressive surgical management is needed.5
Treatment for this patient included craniotomy, evacuation of the epidural abscess, and mastoidectomy. A culture obtained from the abscess showed Streptococcus intermedius. He was treated with broad-spectrum antibiotics, including ceftriaxone, vancomycin, and metronidazole. Within a week of surgery, he was discharged from the hospital and continued antibiotic treatment for 6 weeks via a peripherally inserted central catheter line.
1. Lavin JM, Rusher T, Shah RK. Complications of pediatric otitis media. Otolaryngol Head Neck Surg. 2016;154:366-370.
2. King LM, Bartoces M, Hersh AL, et al. National incidence of pediatric mastoiditis in the United States, 2000-2012: creating a baseline for public health surveillance. Pediatr Infect Dis J. 2019;38:e14-e16.
3. Pang LH, Barakate MS, Havas TE. Mastoiditis in a paediatric population: a review of 11 years’ experience in management. Int J Pediatr Otorhinolaryngol. 2009;73:1520.
4. Bilavsky E, Yarden-Bilavsky H, Samra Z, et al. Clinical, laboratory, and microbiological differences between children with simple or complicated mastoiditis. Int J Pediatr Otorhinolaryngol. 2009;73:1270-1273.
5. Chesney J, Black A, Choo D. What is the best practice for acute mastoiditis in children? Laryngoscope. 2014;124:1057-1059.
1. Lavin JM, Rusher T, Shah RK. Complications of pediatric otitis media. Otolaryngol Head Neck Surg. 2016;154:366-370.
2. King LM, Bartoces M, Hersh AL, et al. National incidence of pediatric mastoiditis in the United States, 2000-2012: creating a baseline for public health surveillance. Pediatr Infect Dis J. 2019;38:e14-e16.
3. Pang LH, Barakate MS, Havas TE. Mastoiditis in a paediatric population: a review of 11 years’ experience in management. Int J Pediatr Otorhinolaryngol. 2009;73:1520.
4. Bilavsky E, Yarden-Bilavsky H, Samra Z, et al. Clinical, laboratory, and microbiological differences between children with simple or complicated mastoiditis. Int J Pediatr Otorhinolaryngol. 2009;73:1270-1273.
5. Chesney J, Black A, Choo D. What is the best practice for acute mastoiditis in children? Laryngoscope. 2014;124:1057-1059.
Five pediatric heart health practices that may be unnecessary
the American Academy of Pediatrics explained in guidance released Nov. 2.
The AAP Section on Cardiology and Cardiac Surgery developed the recommendations as part of the Choosing Wisely campaign after reviewing evidence pertaining to practices common during pediatric visits, such as routinely ordering an electrocardiogram (ECG) as part of a sports exam.
The guidance lets physicians know what is not necessary or not indicated, with noted exceptions, Christopher S. Snyder, MD, chair of the section, said in an interview.
In all cases, family history is key, said Dr. Snyder, who is also chief of the division of pediatric cardiology at University Hospitals Cleveland Medical Center. That means taking the time necessary to ask about aunts, uncles, and all first-degree relatives, not just asking the single question of whether a patient has a family history of cardiac problems.
The following are the targeted practices and the AAP’s guidance on each.
ECG for sports participation
A screening ECG should not be ordered as part of a routine sports entry examination in otherwise healthy patients who have no symptoms and no personal or family history of cardiac disease, the committee says.
Some medical societies argue that all children who participate in sports should have an ECG, but, Dr. Snyder said, “Currently there are no data that support that, especially in the United States.”
ECGs often yield false positive findings, he noted: “About 10% of them will say the child is a little abnormal.”
That can be a particular problem in places with few or no pediatric cardiologists because kids can become sidelined from sports without access to experts who could clear them.
“In the U.S.,” he said, “we believe that the preparticipation physical exam and screening, which is routine for all high school athletes for sure and most athletes who compete in sports, is currently good enough.”
However, he warned, patients with a family history of heart disease need to see a pediatric cardiologist and “those patients need an ECG.”
The test is not perfect, though, he noted: “You could get your screening, go home, get a fever, COVID, something like that, and come back and have myocarditis and drop dead.”
ECG before ADHD therapy
Similarly, a screening ECG is not routinely needed before initiating therapy for ADHD in asymptomatic, otherwise healthy children who have no personal or family history of cardiac disease, according to the new guidance.
Dr. Snyder said that it has become routine for children to undergo an ECG before ADHD therapy, but evidence doesn’t support the practice, and with the rise in the number of ADHD diagnoses, the tests have increasingly become a burden.
Twenty years ago, the prevalence of ADHD was 3%-4%, Dr. Snyder said. It is now almost threefold higher.
The AAP committee points out that, when ECG abnormalities are identified, they rarely lead to a change in ADHD therapy. Additionally, the typical stimulants used to treat ADHD “have never shown any major effect on the heart,” Dr. Snyder said.
“Black box warnings have been put on these medications, but nothing has been found in the very routine stimulants in normal, routine doses to warrant an ECG,” he said.
Echocardiogram for syncope
The committee says routine use of echocardiograms for children with syncope is unnecessary unless a child has a concerning history or ECG abnormalities.
Most patient who have true syncope or are passing out or fainting are diagnosed through thorough family history, Dr. Snyder said.
“The vast majority of those need an ECG to rule out one other cause that can do this and a physical exam. If those things are normal, there really is no indication to do an echocardiogram,” he said.
“If the patient passes out while they’re running, they pass out doing strenuous exercise, or they pass out for 10-15 minutes as opposed to 20 seconds – those are the ones that need a thorough cardiac workup. But routine passing out, waking up in seconds, those do not.”
Echocardiogram for chest pain
Children with chest pain do not need an echocardiogram unless an ECG is abnormal or the patient has a concerning history, according to the new recommendations.
Too often, Dr. Snyder said, providers treat kids as they would adults.
“Often it comes down to what you learn in medical school,” Dr. Snyder said. “In medical school, we have 6 weeks of cardiology and we had 1 hour of pediatric cardiology.”
That younger patients will clog their arteries with fatty foods and high lipids “is really exceptionally rare,” Dr. Snyder said.
Chest pain “rarely, if ever” means heart attack in younger children, he added.
A thorough history and complete physical exam are critical, “without jumping immediately to an echocardiogram, which 99.9% of the time is going to be normal,” he said.
Troponins for chest pain
In addition, a typical workup for pediatric chest pain need not include evaluating troponins unless there is a concerning history or ECG abnormalities.
Snyder notes that kids with chest pain are often brought to emergency departments that are not pediatric specific, and thus clinicians turn to the standard treatment for adults with chest pain: ECG and troponin.
“The reason we in pediatric cardiology don’t love this is that troponins tend not to be specific just for heart in kids,” Dr. Snyder said. “If someone has anginal chest pain – shortness of breath, chest pain doing anything and everything, [chest pain that] occurs when they’re exercising, feels like an elephant standing on their chest – then we do encourage troponins on those patients.”
The guidance discourages ordering troponins without careful consideration of the patient’s age and condition, he said.
This list was developed by faculty in Pediatric Cardiology at University Hospitals in Cleveland. It was revised and approved by the AAP Section on Cardiology and Cardiac Surgery and the AAP Executive Committee.
A version of this article originally appeared on Medscape.com.
the American Academy of Pediatrics explained in guidance released Nov. 2.
The AAP Section on Cardiology and Cardiac Surgery developed the recommendations as part of the Choosing Wisely campaign after reviewing evidence pertaining to practices common during pediatric visits, such as routinely ordering an electrocardiogram (ECG) as part of a sports exam.
The guidance lets physicians know what is not necessary or not indicated, with noted exceptions, Christopher S. Snyder, MD, chair of the section, said in an interview.
In all cases, family history is key, said Dr. Snyder, who is also chief of the division of pediatric cardiology at University Hospitals Cleveland Medical Center. That means taking the time necessary to ask about aunts, uncles, and all first-degree relatives, not just asking the single question of whether a patient has a family history of cardiac problems.
The following are the targeted practices and the AAP’s guidance on each.
ECG for sports participation
A screening ECG should not be ordered as part of a routine sports entry examination in otherwise healthy patients who have no symptoms and no personal or family history of cardiac disease, the committee says.
Some medical societies argue that all children who participate in sports should have an ECG, but, Dr. Snyder said, “Currently there are no data that support that, especially in the United States.”
ECGs often yield false positive findings, he noted: “About 10% of them will say the child is a little abnormal.”
That can be a particular problem in places with few or no pediatric cardiologists because kids can become sidelined from sports without access to experts who could clear them.
“In the U.S.,” he said, “we believe that the preparticipation physical exam and screening, which is routine for all high school athletes for sure and most athletes who compete in sports, is currently good enough.”
However, he warned, patients with a family history of heart disease need to see a pediatric cardiologist and “those patients need an ECG.”
The test is not perfect, though, he noted: “You could get your screening, go home, get a fever, COVID, something like that, and come back and have myocarditis and drop dead.”
ECG before ADHD therapy
Similarly, a screening ECG is not routinely needed before initiating therapy for ADHD in asymptomatic, otherwise healthy children who have no personal or family history of cardiac disease, according to the new guidance.
Dr. Snyder said that it has become routine for children to undergo an ECG before ADHD therapy, but evidence doesn’t support the practice, and with the rise in the number of ADHD diagnoses, the tests have increasingly become a burden.
Twenty years ago, the prevalence of ADHD was 3%-4%, Dr. Snyder said. It is now almost threefold higher.
The AAP committee points out that, when ECG abnormalities are identified, they rarely lead to a change in ADHD therapy. Additionally, the typical stimulants used to treat ADHD “have never shown any major effect on the heart,” Dr. Snyder said.
“Black box warnings have been put on these medications, but nothing has been found in the very routine stimulants in normal, routine doses to warrant an ECG,” he said.
Echocardiogram for syncope
The committee says routine use of echocardiograms for children with syncope is unnecessary unless a child has a concerning history or ECG abnormalities.
Most patient who have true syncope or are passing out or fainting are diagnosed through thorough family history, Dr. Snyder said.
“The vast majority of those need an ECG to rule out one other cause that can do this and a physical exam. If those things are normal, there really is no indication to do an echocardiogram,” he said.
“If the patient passes out while they’re running, they pass out doing strenuous exercise, or they pass out for 10-15 minutes as opposed to 20 seconds – those are the ones that need a thorough cardiac workup. But routine passing out, waking up in seconds, those do not.”
Echocardiogram for chest pain
Children with chest pain do not need an echocardiogram unless an ECG is abnormal or the patient has a concerning history, according to the new recommendations.
Too often, Dr. Snyder said, providers treat kids as they would adults.
“Often it comes down to what you learn in medical school,” Dr. Snyder said. “In medical school, we have 6 weeks of cardiology and we had 1 hour of pediatric cardiology.”
That younger patients will clog their arteries with fatty foods and high lipids “is really exceptionally rare,” Dr. Snyder said.
Chest pain “rarely, if ever” means heart attack in younger children, he added.
A thorough history and complete physical exam are critical, “without jumping immediately to an echocardiogram, which 99.9% of the time is going to be normal,” he said.
Troponins for chest pain
In addition, a typical workup for pediatric chest pain need not include evaluating troponins unless there is a concerning history or ECG abnormalities.
Snyder notes that kids with chest pain are often brought to emergency departments that are not pediatric specific, and thus clinicians turn to the standard treatment for adults with chest pain: ECG and troponin.
“The reason we in pediatric cardiology don’t love this is that troponins tend not to be specific just for heart in kids,” Dr. Snyder said. “If someone has anginal chest pain – shortness of breath, chest pain doing anything and everything, [chest pain that] occurs when they’re exercising, feels like an elephant standing on their chest – then we do encourage troponins on those patients.”
The guidance discourages ordering troponins without careful consideration of the patient’s age and condition, he said.
This list was developed by faculty in Pediatric Cardiology at University Hospitals in Cleveland. It was revised and approved by the AAP Section on Cardiology and Cardiac Surgery and the AAP Executive Committee.
A version of this article originally appeared on Medscape.com.
the American Academy of Pediatrics explained in guidance released Nov. 2.
The AAP Section on Cardiology and Cardiac Surgery developed the recommendations as part of the Choosing Wisely campaign after reviewing evidence pertaining to practices common during pediatric visits, such as routinely ordering an electrocardiogram (ECG) as part of a sports exam.
The guidance lets physicians know what is not necessary or not indicated, with noted exceptions, Christopher S. Snyder, MD, chair of the section, said in an interview.
In all cases, family history is key, said Dr. Snyder, who is also chief of the division of pediatric cardiology at University Hospitals Cleveland Medical Center. That means taking the time necessary to ask about aunts, uncles, and all first-degree relatives, not just asking the single question of whether a patient has a family history of cardiac problems.
The following are the targeted practices and the AAP’s guidance on each.
ECG for sports participation
A screening ECG should not be ordered as part of a routine sports entry examination in otherwise healthy patients who have no symptoms and no personal or family history of cardiac disease, the committee says.
Some medical societies argue that all children who participate in sports should have an ECG, but, Dr. Snyder said, “Currently there are no data that support that, especially in the United States.”
ECGs often yield false positive findings, he noted: “About 10% of them will say the child is a little abnormal.”
That can be a particular problem in places with few or no pediatric cardiologists because kids can become sidelined from sports without access to experts who could clear them.
“In the U.S.,” he said, “we believe that the preparticipation physical exam and screening, which is routine for all high school athletes for sure and most athletes who compete in sports, is currently good enough.”
However, he warned, patients with a family history of heart disease need to see a pediatric cardiologist and “those patients need an ECG.”
The test is not perfect, though, he noted: “You could get your screening, go home, get a fever, COVID, something like that, and come back and have myocarditis and drop dead.”
ECG before ADHD therapy
Similarly, a screening ECG is not routinely needed before initiating therapy for ADHD in asymptomatic, otherwise healthy children who have no personal or family history of cardiac disease, according to the new guidance.
Dr. Snyder said that it has become routine for children to undergo an ECG before ADHD therapy, but evidence doesn’t support the practice, and with the rise in the number of ADHD diagnoses, the tests have increasingly become a burden.
Twenty years ago, the prevalence of ADHD was 3%-4%, Dr. Snyder said. It is now almost threefold higher.
The AAP committee points out that, when ECG abnormalities are identified, they rarely lead to a change in ADHD therapy. Additionally, the typical stimulants used to treat ADHD “have never shown any major effect on the heart,” Dr. Snyder said.
“Black box warnings have been put on these medications, but nothing has been found in the very routine stimulants in normal, routine doses to warrant an ECG,” he said.
Echocardiogram for syncope
The committee says routine use of echocardiograms for children with syncope is unnecessary unless a child has a concerning history or ECG abnormalities.
Most patient who have true syncope or are passing out or fainting are diagnosed through thorough family history, Dr. Snyder said.
“The vast majority of those need an ECG to rule out one other cause that can do this and a physical exam. If those things are normal, there really is no indication to do an echocardiogram,” he said.
“If the patient passes out while they’re running, they pass out doing strenuous exercise, or they pass out for 10-15 minutes as opposed to 20 seconds – those are the ones that need a thorough cardiac workup. But routine passing out, waking up in seconds, those do not.”
Echocardiogram for chest pain
Children with chest pain do not need an echocardiogram unless an ECG is abnormal or the patient has a concerning history, according to the new recommendations.
Too often, Dr. Snyder said, providers treat kids as they would adults.
“Often it comes down to what you learn in medical school,” Dr. Snyder said. “In medical school, we have 6 weeks of cardiology and we had 1 hour of pediatric cardiology.”
That younger patients will clog their arteries with fatty foods and high lipids “is really exceptionally rare,” Dr. Snyder said.
Chest pain “rarely, if ever” means heart attack in younger children, he added.
A thorough history and complete physical exam are critical, “without jumping immediately to an echocardiogram, which 99.9% of the time is going to be normal,” he said.
Troponins for chest pain
In addition, a typical workup for pediatric chest pain need not include evaluating troponins unless there is a concerning history or ECG abnormalities.
Snyder notes that kids with chest pain are often brought to emergency departments that are not pediatric specific, and thus clinicians turn to the standard treatment for adults with chest pain: ECG and troponin.
“The reason we in pediatric cardiology don’t love this is that troponins tend not to be specific just for heart in kids,” Dr. Snyder said. “If someone has anginal chest pain – shortness of breath, chest pain doing anything and everything, [chest pain that] occurs when they’re exercising, feels like an elephant standing on their chest – then we do encourage troponins on those patients.”
The guidance discourages ordering troponins without careful consideration of the patient’s age and condition, he said.
This list was developed by faculty in Pediatric Cardiology at University Hospitals in Cleveland. It was revised and approved by the AAP Section on Cardiology and Cardiac Surgery and the AAP Executive Committee.
A version of this article originally appeared on Medscape.com.
Which behavioral health screening tool should you use—and when?
Many screening tools are available in the public domain to assess a variety of symptoms related to impaired mental health. These tools can be used to quickly evaluate for mood, suicidal ideation or behavior, anxiety, sleep, substance use, pain, trauma, memory, and cognition (TABLE). Individuals with poor mental health incur high health care costs. Those suffering from anxiety and posttraumatic stress have more outpatient and emergency department visits and hospitalizations than patients without these disorders,1,2 although use of mental health care services has been related to a decrease in the overutilization of health care services in general.3
Here we review several screening tools that can help you to identify symptoms of mental illnesses and thus, provide prompt early intervention, including referrals to psychological and psychiatric services.
Mood disorders
Most patients with mood disorders are treated in primary care settings.4 Quickly measuring patients’ mood symptoms can expedite treatment for those who need it. Many primary care clinics use the 9-item Patient Health Questionnaire (PHQ-9) to screen for depression.5 The US Preventive Services Task Force (USPSTF) has recommended screening for depression with adequate systems to ensure accurate diagnoses, effective treatment, and follow-up. Although the USPSTF did not specially endorse screening for bipolar disorder, it followed that recommendation with the qualifying statement, “positive screening results [for depression] should lead to additional assessment that considers severity of depression and comorbid psychological problems, alternate diagnoses, and medical conditions.”6 Thus, following a positive screen result for depression, consider using a screening tool for mood disorders to provide diagnostic clarification.
The Mood Disorder Questionnaire (MDQ) is a validated 15-item, self-administered questionnaire that takes only 5 minutes to use in screening adult patients for bipolar I disorder.7 The MDQ assesses specific behaviors related to bipolar disorder, symptom co-occurrence, and functional impairment. The MDQ has low sensitivity (58%) but good specificity (93%) in a primary care setting.8 However, the MDQ is not a diagnostic instrument. A positive screen result should prompt a more thorough clinical evaluation, if necessary, by a professional trained in psychiatric disorders.
We recommend completing the MDQ prior to prescribing antidepressants. You can also monitor a patient’s response to treatment with serial MDQ testing. The MDQ is useful, too, when a patient has unclear mood symptoms that may have features overlapping with bipolar disorder. Furthermore, we recommend screening for bipolar disorder with every patient who reports symptoms of depression, given that some pharmacologic treatments (predominately selective serotonin reuptake inhibitors) can induce mania in patients who actually have unrecognized bipolar disorder.9
Suicide
Suicide is the 10th leading cause of death among the general population. All demographic groups are impacted by suicide; however, the most vulnerable are men ages 45 to 64 years.10 Given the imminent risk to individuals who experience suicidal ideation, properly assessing and targeting suicidal risk is paramount.
The Columbia Suicide Severity Rating Scale (C-SSRS) can be completed in an interview format or as a patient self-report. Versions of the C-SSRS are available for children, adolescents, and adults. It can be used in practice with any patient who may be at risk for suicide. Specifically, consider using the C-SSRS when a patient scores 1 or greater on the PHQ-9 or when risk is revealed with another brief screening tool that includes suicidal ideation.
Continue to: The C-SSRS covers...
The C-SSRS covers 10 categories related to suicidal ideation and behavior that the clinician explores with questions requiring only Yes/No responses. The C-SSRS demonstrates moderate-to-strong internal consistency and reliability, and it has shown a high degree of sensitivity (95%) and specificity (95%) for suicidal ideation.11
Anxiety and physiologic arousal
Generalized anxiety disorder (GAD) is one of the most common anxiety disorders, with an estimated prevalence of 2.8% to 8.5% among primary care patients.12 Brief, validated screening tools such as the Generalized Anxiety Disorder–7 item (GAD-7) scale can be effective in identifying anxiety and other related disorders in primary care settings.
The GAD-7 comprises 7 items inquiring about symptoms experienced in the past 2 weeks. Scores range from 0 to 21, with cutoffs of 5, 10, and 15 indicating mild, moderate, and severe anxiety, respectively. This questionnaire is appropriate for use with adults and has strong specificity, internal consistency, and test-retest reliability.12 Specificity and sensitivity of the GAD-7 are maximized at a cutoff score of 10 or greater, both exceeding 80%.12 The GAD-7 can be used when patients report symptoms of anxiety or when one needs to screen for anxiety with new patients or more clearly understand symptoms among patients who have complex mental health concerns.
The Screen for Child Anxiety Related Disorders (SCARED) is a 41-item self-report measure of anxiety for children ages 8 to 18. The SCARED questionnaire yields an overall anxiety score, as well as subscales for panic disorder or significant somatic symptoms, generalized anxiety disorder, separation anxiety, social anxiety disorder, and significant school avoidance.13 There is also a 5-item version of the SCARED, which can be useful for brief screening in fast-paced settings when no anxiety disorder is suspected, or for children who may have anxiety but exhibit reduced verbal capacity. The SCARED has been found to have moderate sensitivity (81.8%) and specificity (52%) for diagnosing anxiety disorders in a community sample, with an optimal cutoff point of 22 on the total scale.14
Sleep
Sleep concerns are common, with the prevalence of insomnia among adults in the United States estimated to be 19.2%.15 The importance of assessing these concerns cannot be overstated, and primary care providers are the ones patients consult most often.16 The gold standard in assessing sleep disorders is a structured clinical interview, polysomnography, sleep diary, and actigraphy (home-based monitoring of movement through a device, often worn on the wrist).17,18 However, this work-up is expensive, time-intensive, and impractical in integrated care settings; thus the need for a brief, self-report screening tool to guide further assessment and intervention.
Continue to: The Insomnia Severity Index...
The Insomnia Severity Index (ISI) assesses patients’ perceptions of their insomnia. The ISI was developed to aid both in the clinical evaluation of patients with insomnia and to measure treatment outcomes. Administration of the ISI takes approximately 5 minutes, and scoring takes less than 1 minute.
The ISI is composed of 7 items that measure the severity of sleep onset and sleep maintenance difficulties, satisfaction with current sleep, impact on daily functioning, impairment observable to others, and degree of distress caused by the sleep problems. Each item is scored on a 0 to 4 Likert-type scale, and the individual items are summed for a total score of 0 to 28, with higher scores suggesting more severe insomnia. Evidence-based guidelines recommend cognitive behavioral therapy for insomnia (CBT-I) as the first-line treatment for adults with primary insomnia.19
Several validation studies have found the ISI to be a reliable measure of perceived insomnia severity, and one that is sensitive to changes in patients’ perceptions of treatment outcomes.20,21 An additional validation study confirmed that in primary care settings, a cutoff score of 14 should be used to indicate the likely presence of clinical insomnia22 and to guide further assessment and intervention.
The percentage of insomniac patients correctly identified with the ISI was 82.2%, with moderate sensitivity (82.4%) and specificity (82.1%).22 A positive predictive value of 70% was found, meaning that an insomnia disorder is probable when the ISI total score is 14 or higher; conversely, the negative predictive value was 90.2%.
Substance use and pain
The evaluation of alcohol and drug use is an integral part of assessing risky health behaviors. The 10-item Alcohol Use Disorder Identification Test (AUDIT) is a self-report tool developed by the World Health Organization.23,24 Validated in medical settings, scores of 8 or higher suggest problematic drinking.25,26 The AUDIT has demonstrated high specificity (94%) and moderate sensitivity (81%) in primary care settings.27 The AUDIT-C (items 1, 2, and 3 of the AUDIT) has also demonstrated comparable sensitivity, although slightly lower specificity, than the full AUDIT, suggesting that this 3-question screen can also be used in primary care settings.27
Continue to: Opioid medications...
Opioid medications, frequently prescribed for chronic pain, present serious risks for many patients. The Screener and Opioid Assessment for Patients with Pain–Revised (SOAPP-R) is a 24-item self-reporting scale that can be completed in approximately 10 minutes.28 A score of 18 or higher has identified 81% of patients at high risk for opioid misuse in a clinical setting, with moderate specificity (68%). Although other factors should be considered when assessing risk of opioid misuse, the SOAPP-R is a helpful and quick addition to an opioid risk assessment.
The CRAFFT Screening Tool for Adolescent Substance Use is administered by the clinician for youths ages 14 to 21. The first 3 questions ask about use of alcohol, marijuana, or other substances during the past 12 months. What follows are questions related to the young person’s specific experiences with substances in relation to Cars, Relaxation, being Alone, Forgetting, Family/Friends, and Trouble (CRAFFT). The CRAFFT has shown moderate sensitivity (76%) and good specificity (94%) for identifying any problem with substance use.29 These measures may be administered to clarify or confirm substance use patterns (ie, duration, frequency), or to determine the severity of problems related to substance use (ie, social or legal problems).
Trauma and PTSD
Approximately 7.7 million adults per year will experience posttraumatic stress disorder (PTSD) symptoms, although PTSD can affect individuals of any age.30 Given the impact that trauma can have, assess for PTSD in patients who have a history of trauma or who otherwise seem to be at risk. The Posttraumatic Stress Disorder Checklist (PCL-5) is a 20-item self-report questionnaire that screens for symptoms directly from the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for PTSD. One limitation is that the questionnaire is only validated for adults ages 18 years or older. Completion of the PCL-5 takes 5 to 10 minutes. The PCL-5 has strong internal consistency reliability (94%) and test-retest reliability (82%).31 With a cutoff score of 33 or higher,
The Child and Adolescent Trauma Screen (CATS) is used to assess for potentially traumatic events and PTSD symptoms in children and adolescents. These symptoms are based on the DSM-5, and therefore the CATS can act as a useful diagnostic aid. The CATS is also available in Spanish, with both caregiver-report (for children ages 3-6 years or 7-17 years) and self-report (for ages 7-17 years) versions. Practical use of the PCL-5 and the CATS involves screening for PTSD symptoms, supporting a provisional diagnosis of PTSD, and monitoring PTSD symptom changes during and after treatment.
Memory and cognition
Cognitive screening is a first step in evaluating possible dementia and other neuropsychological disorders. The importance of brief cognitive screening in primary care cannot be understated, especially for an aging patient population. Although the Mini Mental Status Exam (MMSE) has been widely used among health care providers and researchers, we recommend the Montreal Cognitive Assessment (MoCA).
Continue to: The MoCA is a simple...
The MoCA is a simple, standalone cognitive screening tool validated for adults ages 55 to 85 years.33 The MoCA addresses many important cognitive domains, fits on one page, and can be administered by a trained provider in 10 minutes. Research also suggests that it has strong test-retest reliability and positive and negative predictive values for mild cognitive impairment and Alzheimer dementia, and it has been found to be more sensitive than the MMSE.34 We additionally recommend the MoCA as it measures several cognitive skills that are not addressed on the MMSE, including verbal fluency and abstraction.34 Scores below 25 are suggestive of cognitive impairment and should lead to a referral for neuropsychological testing.
The MoCA’s sensitivity for detecting cognitive impairment is high (94%), and specificity is low (42%).35 To ensure consistency and accuracy in administering the MoCA, certification is now required via an online training program through www.mocatest.org.
Adapting these screening tools to practice
These tools are not meant to be used at every appointment. Every practice is different, and each clinic or physician can tailor the use of these screening tools to the needs of the patient population, as concerns arise, or in collaboration with other providers. Additionally, these screening tools can be used in both integrated care and in private practice, to prompt a more thorough assessment or to aid in—and inform—treatment. Although some physicians choose to administer certain screening tools at each clinic visit, knowing about the availability of other tools can be useful in assessing various issues.
The FIGURE can be used to aid in the clinical decision-making process.
CORRESPONDENCE
Rebecca Sewell, PsyD, Bon Secours Mercy Health, 2213 Cherry Street, Toledo, OH 4360; rebecca.sewell30@gmail.com.
1. Robinson RL, Grabner M, Palli SR, et al. Covariates of depression and high utilizers of healthcare: impact on resource use and costs. J Psychosom Res. 2016,85:35-43.
2. Fogarty CT, Sharma S, Chetty VK, et al. Mental health conditions are associated with increased health care utilization among urban family medicine patients. J Am Board Fam Med. 2008,21:398-407.
3. Weissman JD, Russell D, Beasley J, et al. Relationships between adult emotional states and indicators of health care utilization: findings from the National Health Interview Survey 2006–2014. J Psychosom Res. 2016,91:75-81.
4. Haddad M, Walters P. Mood disorders in primary care. Psychiatry. 2009,8:71-75.
5. Mitchell AJ, Yadegarfar M, Gill J, et al. Case finding and screening clinical utility of the Patient Health Questionnaire (PHQ-9 and PHQ-2) for depression in primary care: a diagnostic meta-analysis of 40 studies. BJPsych Open. 2016,2:127-138.
6. Siu AL and US Preventive Services Task Force. Screening for depression in adults. JAMA. 2016;315:380-387.
7. Hirschfeld RM, Williams JB, Spitzer RL, et al. Development and validation of a screening instrument for bipolar spectrum disorder: the Mood Disorder Questionnaire. Am J Psychiatry. 2000;157:1873-1875.
8. Hirschfeld RM, Cass AR, Holt DC, et al. Screening for bipolar disorder in patients treated for depression in a family medicine clinic. J Am Board Fam Med. 2005;18:233-239.
9. Das AK, Olfson M, Gameroff MJ, et al. Screening for bipolar disorder in a primary care practice. JAMA. 2005;293:956-963.
10. CDC. Suicide mortality in the United States, 1999-2017. www.cdc.gov/nchs/products/databriefs/db330.htm. Accessed October 23, 2020.
11. Viguera AC, Milano N, Ralston L, et al. Comparison of electronic screening for suicidal risk with Patient Health Questionnaire Item 9 and the Columbia Suicide Severity Rating Scale in an outpatient psychiatric clinic. Psychosomatics. 2015;56:460-469.
12. Spitzer RL, Kroenke K, Williams JBW, et al. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006;166:1092-1097.
13. Birmaher B, Khetarpal S, Brent D, et al. The Screen for Child Anxiety Related Emotional Disorders (SCARED): scale construction and psychometric characteristics. J Am Acad Chil Adolesc Psychiatry. 1997;36:545-553.
14. DeSousa DA, Salum GA, Isolan LR, et al. Sensitivity and specificity of the Screen for Child Anxiety Related Emotional Disorders (SCARED): a community-based study. Child Psychiatry Hum Dev. 2013;44:391-399.
15. Ford ES, Cunningham TJ, Giles WH, et al. Trends in insomnia and excessive daytime sleepiness among U.S. adults from 2002 to 2012. Sleep Med. 2015;16:372-378.
16. Morin CM, LeBlanc M, Daley M, et al. Epidemiology of insomnia: prevalence, self-help treatments, consultations, and determinants of help-seeking behaviors. Sleep Med. 2006;7:123-130.
17. Buysse DJ, Ancoli-Israel S, Edinger JD, et al. Recommendations for a standard research assessment of insomnia. Sleep. 2006;29:1155-1173.
18. Martin JL, Hakim AD. Wrist actigraphy. Chest. 2011;139:1514-1527.
19. Riemann D, Baglioni C, Bassetti C, et al. European guideline for the diagnosis and treatment of insomnia. J Sleep Res. 2017;26:675-700.
20. Bastien CH, Vallières A, Morin CM. Validation of the Insomnia Severity Index as an outcome measure for insomnia research. Sleep Med. 2001;2:297-307.
21. Wong ML, Lau KNT, Espie CA, et al. Psychometric properties of the Sleep Condition Indicator and Insomnia Severity Index in the evaluation of insomnia disorder. Sleep Med. 2017;33:76-81.
22. Gagnon C, Bélanger L, Ivers H, et al. Validation of the Insomnia Severity Index in primary care. J Am Board Fam Med. 2013;26:701-710.
23. Saunders JB, Aasland OG, Babor TF, et al. Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO Collaborative Project on Early Detection of Persons with Harmful Alcohol Consumption. Addiction. 1993;88:791-804.
24. Selin KH. Test-retest reliability of the Alcohol Use Disorder Identification Test in a general population sample. Alcohol Clin Exp Res. 2003;27:1428-1435.
25. Bohn MJ, Babor TF, Kranzler HR. The Alcohol Use Disorders Identification Test (AUDIT): validation of a screening instrument for use in medical settings. J Stud Alcohol. 1995;56:423-432.
26. Conigrave KM, Hall WD, Saunders JB. The AUDIT questionnaire: choosing a cut-off score. Addiction. 1995;90:1349-1356.
27. Gomez A, Conde A, Santana JM, et al. Diagnostic usefulness of brief versions of Alcohol Use Identification Test (AUDIT) for detecting hazardous drinkers in primary care settings. J Stud Alcohol. 2005;66:305-308.
28. Butler SF, Fernandez K, Benoit C, et al. Validation of the revised Screener and Opioid Assessment for Patients with Pain (SOAPP-R). J Pain. 2008;9:360-372.
29. Knight JR, Sherritt L, Shrier LA, et al. Validity of the CRAFFT substance abuse screening test among adolescent clinic patients. Arch Pediatr Adolesc Med. 2002;156:607-614.
30. DHHS. Post-traumatic stress disorder (PTSD). https://archives.nih.gov/asites/report/09-09-2019/report.nih.gov/nihfactsheets/ViewFactSheetfdf8.html?csid=58&key=P#P. Accessed October 23, 2020.
31. Blevins CA, Weathers FW, Davis MT, et al. The Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5): development and initial psychometric evaluation. J Trauma Stress. 2015;28:489-498.
32. Verhey R, Chilbanda D, Gibson L, et al. Validation of the Posttraumatic Stress Disorder Checklist- 5 (PCL-5) in a primary care population with high HIV prevalence in Zimbabwe. BMC Psychiatry. 2018;18:109.
33. Nasreddine ZS, Phillips NA, Bédirian V, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005;53:695-699.
34. Stewart S, O’Riley A, Edelstein B, et al. A preliminary comparison of three cognitive screening instruments in long term care: the MMSE, SLUMS, and MoCA. Clin Gerontol. 2012;35:57-75.
35. Godefroy O, Fickl A, Roussel M, et al. Is the Montreal Cognitive Assessment superior to the Mini-Mental State Examination to detect poststroke cognitive impairment? A study with neuropsychological evaluation. Stroke. 2011;42:1712-1716.
Many screening tools are available in the public domain to assess a variety of symptoms related to impaired mental health. These tools can be used to quickly evaluate for mood, suicidal ideation or behavior, anxiety, sleep, substance use, pain, trauma, memory, and cognition (TABLE). Individuals with poor mental health incur high health care costs. Those suffering from anxiety and posttraumatic stress have more outpatient and emergency department visits and hospitalizations than patients without these disorders,1,2 although use of mental health care services has been related to a decrease in the overutilization of health care services in general.3
Here we review several screening tools that can help you to identify symptoms of mental illnesses and thus, provide prompt early intervention, including referrals to psychological and psychiatric services.
Mood disorders
Most patients with mood disorders are treated in primary care settings.4 Quickly measuring patients’ mood symptoms can expedite treatment for those who need it. Many primary care clinics use the 9-item Patient Health Questionnaire (PHQ-9) to screen for depression.5 The US Preventive Services Task Force (USPSTF) has recommended screening for depression with adequate systems to ensure accurate diagnoses, effective treatment, and follow-up. Although the USPSTF did not specially endorse screening for bipolar disorder, it followed that recommendation with the qualifying statement, “positive screening results [for depression] should lead to additional assessment that considers severity of depression and comorbid psychological problems, alternate diagnoses, and medical conditions.”6 Thus, following a positive screen result for depression, consider using a screening tool for mood disorders to provide diagnostic clarification.
The Mood Disorder Questionnaire (MDQ) is a validated 15-item, self-administered questionnaire that takes only 5 minutes to use in screening adult patients for bipolar I disorder.7 The MDQ assesses specific behaviors related to bipolar disorder, symptom co-occurrence, and functional impairment. The MDQ has low sensitivity (58%) but good specificity (93%) in a primary care setting.8 However, the MDQ is not a diagnostic instrument. A positive screen result should prompt a more thorough clinical evaluation, if necessary, by a professional trained in psychiatric disorders.
We recommend completing the MDQ prior to prescribing antidepressants. You can also monitor a patient’s response to treatment with serial MDQ testing. The MDQ is useful, too, when a patient has unclear mood symptoms that may have features overlapping with bipolar disorder. Furthermore, we recommend screening for bipolar disorder with every patient who reports symptoms of depression, given that some pharmacologic treatments (predominately selective serotonin reuptake inhibitors) can induce mania in patients who actually have unrecognized bipolar disorder.9
Suicide
Suicide is the 10th leading cause of death among the general population. All demographic groups are impacted by suicide; however, the most vulnerable are men ages 45 to 64 years.10 Given the imminent risk to individuals who experience suicidal ideation, properly assessing and targeting suicidal risk is paramount.
The Columbia Suicide Severity Rating Scale (C-SSRS) can be completed in an interview format or as a patient self-report. Versions of the C-SSRS are available for children, adolescents, and adults. It can be used in practice with any patient who may be at risk for suicide. Specifically, consider using the C-SSRS when a patient scores 1 or greater on the PHQ-9 or when risk is revealed with another brief screening tool that includes suicidal ideation.
Continue to: The C-SSRS covers...
The C-SSRS covers 10 categories related to suicidal ideation and behavior that the clinician explores with questions requiring only Yes/No responses. The C-SSRS demonstrates moderate-to-strong internal consistency and reliability, and it has shown a high degree of sensitivity (95%) and specificity (95%) for suicidal ideation.11
Anxiety and physiologic arousal
Generalized anxiety disorder (GAD) is one of the most common anxiety disorders, with an estimated prevalence of 2.8% to 8.5% among primary care patients.12 Brief, validated screening tools such as the Generalized Anxiety Disorder–7 item (GAD-7) scale can be effective in identifying anxiety and other related disorders in primary care settings.
The GAD-7 comprises 7 items inquiring about symptoms experienced in the past 2 weeks. Scores range from 0 to 21, with cutoffs of 5, 10, and 15 indicating mild, moderate, and severe anxiety, respectively. This questionnaire is appropriate for use with adults and has strong specificity, internal consistency, and test-retest reliability.12 Specificity and sensitivity of the GAD-7 are maximized at a cutoff score of 10 or greater, both exceeding 80%.12 The GAD-7 can be used when patients report symptoms of anxiety or when one needs to screen for anxiety with new patients or more clearly understand symptoms among patients who have complex mental health concerns.
The Screen for Child Anxiety Related Disorders (SCARED) is a 41-item self-report measure of anxiety for children ages 8 to 18. The SCARED questionnaire yields an overall anxiety score, as well as subscales for panic disorder or significant somatic symptoms, generalized anxiety disorder, separation anxiety, social anxiety disorder, and significant school avoidance.13 There is also a 5-item version of the SCARED, which can be useful for brief screening in fast-paced settings when no anxiety disorder is suspected, or for children who may have anxiety but exhibit reduced verbal capacity. The SCARED has been found to have moderate sensitivity (81.8%) and specificity (52%) for diagnosing anxiety disorders in a community sample, with an optimal cutoff point of 22 on the total scale.14
Sleep
Sleep concerns are common, with the prevalence of insomnia among adults in the United States estimated to be 19.2%.15 The importance of assessing these concerns cannot be overstated, and primary care providers are the ones patients consult most often.16 The gold standard in assessing sleep disorders is a structured clinical interview, polysomnography, sleep diary, and actigraphy (home-based monitoring of movement through a device, often worn on the wrist).17,18 However, this work-up is expensive, time-intensive, and impractical in integrated care settings; thus the need for a brief, self-report screening tool to guide further assessment and intervention.
Continue to: The Insomnia Severity Index...
The Insomnia Severity Index (ISI) assesses patients’ perceptions of their insomnia. The ISI was developed to aid both in the clinical evaluation of patients with insomnia and to measure treatment outcomes. Administration of the ISI takes approximately 5 minutes, and scoring takes less than 1 minute.
The ISI is composed of 7 items that measure the severity of sleep onset and sleep maintenance difficulties, satisfaction with current sleep, impact on daily functioning, impairment observable to others, and degree of distress caused by the sleep problems. Each item is scored on a 0 to 4 Likert-type scale, and the individual items are summed for a total score of 0 to 28, with higher scores suggesting more severe insomnia. Evidence-based guidelines recommend cognitive behavioral therapy for insomnia (CBT-I) as the first-line treatment for adults with primary insomnia.19
Several validation studies have found the ISI to be a reliable measure of perceived insomnia severity, and one that is sensitive to changes in patients’ perceptions of treatment outcomes.20,21 An additional validation study confirmed that in primary care settings, a cutoff score of 14 should be used to indicate the likely presence of clinical insomnia22 and to guide further assessment and intervention.
The percentage of insomniac patients correctly identified with the ISI was 82.2%, with moderate sensitivity (82.4%) and specificity (82.1%).22 A positive predictive value of 70% was found, meaning that an insomnia disorder is probable when the ISI total score is 14 or higher; conversely, the negative predictive value was 90.2%.
Substance use and pain
The evaluation of alcohol and drug use is an integral part of assessing risky health behaviors. The 10-item Alcohol Use Disorder Identification Test (AUDIT) is a self-report tool developed by the World Health Organization.23,24 Validated in medical settings, scores of 8 or higher suggest problematic drinking.25,26 The AUDIT has demonstrated high specificity (94%) and moderate sensitivity (81%) in primary care settings.27 The AUDIT-C (items 1, 2, and 3 of the AUDIT) has also demonstrated comparable sensitivity, although slightly lower specificity, than the full AUDIT, suggesting that this 3-question screen can also be used in primary care settings.27
Continue to: Opioid medications...
Opioid medications, frequently prescribed for chronic pain, present serious risks for many patients. The Screener and Opioid Assessment for Patients with Pain–Revised (SOAPP-R) is a 24-item self-reporting scale that can be completed in approximately 10 minutes.28 A score of 18 or higher has identified 81% of patients at high risk for opioid misuse in a clinical setting, with moderate specificity (68%). Although other factors should be considered when assessing risk of opioid misuse, the SOAPP-R is a helpful and quick addition to an opioid risk assessment.
The CRAFFT Screening Tool for Adolescent Substance Use is administered by the clinician for youths ages 14 to 21. The first 3 questions ask about use of alcohol, marijuana, or other substances during the past 12 months. What follows are questions related to the young person’s specific experiences with substances in relation to Cars, Relaxation, being Alone, Forgetting, Family/Friends, and Trouble (CRAFFT). The CRAFFT has shown moderate sensitivity (76%) and good specificity (94%) for identifying any problem with substance use.29 These measures may be administered to clarify or confirm substance use patterns (ie, duration, frequency), or to determine the severity of problems related to substance use (ie, social or legal problems).
Trauma and PTSD
Approximately 7.7 million adults per year will experience posttraumatic stress disorder (PTSD) symptoms, although PTSD can affect individuals of any age.30 Given the impact that trauma can have, assess for PTSD in patients who have a history of trauma or who otherwise seem to be at risk. The Posttraumatic Stress Disorder Checklist (PCL-5) is a 20-item self-report questionnaire that screens for symptoms directly from the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for PTSD. One limitation is that the questionnaire is only validated for adults ages 18 years or older. Completion of the PCL-5 takes 5 to 10 minutes. The PCL-5 has strong internal consistency reliability (94%) and test-retest reliability (82%).31 With a cutoff score of 33 or higher,
The Child and Adolescent Trauma Screen (CATS) is used to assess for potentially traumatic events and PTSD symptoms in children and adolescents. These symptoms are based on the DSM-5, and therefore the CATS can act as a useful diagnostic aid. The CATS is also available in Spanish, with both caregiver-report (for children ages 3-6 years or 7-17 years) and self-report (for ages 7-17 years) versions. Practical use of the PCL-5 and the CATS involves screening for PTSD symptoms, supporting a provisional diagnosis of PTSD, and monitoring PTSD symptom changes during and after treatment.
Memory and cognition
Cognitive screening is a first step in evaluating possible dementia and other neuropsychological disorders. The importance of brief cognitive screening in primary care cannot be understated, especially for an aging patient population. Although the Mini Mental Status Exam (MMSE) has been widely used among health care providers and researchers, we recommend the Montreal Cognitive Assessment (MoCA).
Continue to: The MoCA is a simple...
The MoCA is a simple, standalone cognitive screening tool validated for adults ages 55 to 85 years.33 The MoCA addresses many important cognitive domains, fits on one page, and can be administered by a trained provider in 10 minutes. Research also suggests that it has strong test-retest reliability and positive and negative predictive values for mild cognitive impairment and Alzheimer dementia, and it has been found to be more sensitive than the MMSE.34 We additionally recommend the MoCA as it measures several cognitive skills that are not addressed on the MMSE, including verbal fluency and abstraction.34 Scores below 25 are suggestive of cognitive impairment and should lead to a referral for neuropsychological testing.
The MoCA’s sensitivity for detecting cognitive impairment is high (94%), and specificity is low (42%).35 To ensure consistency and accuracy in administering the MoCA, certification is now required via an online training program through www.mocatest.org.
Adapting these screening tools to practice
These tools are not meant to be used at every appointment. Every practice is different, and each clinic or physician can tailor the use of these screening tools to the needs of the patient population, as concerns arise, or in collaboration with other providers. Additionally, these screening tools can be used in both integrated care and in private practice, to prompt a more thorough assessment or to aid in—and inform—treatment. Although some physicians choose to administer certain screening tools at each clinic visit, knowing about the availability of other tools can be useful in assessing various issues.
The FIGURE can be used to aid in the clinical decision-making process.
CORRESPONDENCE
Rebecca Sewell, PsyD, Bon Secours Mercy Health, 2213 Cherry Street, Toledo, OH 4360; rebecca.sewell30@gmail.com.
Many screening tools are available in the public domain to assess a variety of symptoms related to impaired mental health. These tools can be used to quickly evaluate for mood, suicidal ideation or behavior, anxiety, sleep, substance use, pain, trauma, memory, and cognition (TABLE). Individuals with poor mental health incur high health care costs. Those suffering from anxiety and posttraumatic stress have more outpatient and emergency department visits and hospitalizations than patients without these disorders,1,2 although use of mental health care services has been related to a decrease in the overutilization of health care services in general.3
Here we review several screening tools that can help you to identify symptoms of mental illnesses and thus, provide prompt early intervention, including referrals to psychological and psychiatric services.
Mood disorders
Most patients with mood disorders are treated in primary care settings.4 Quickly measuring patients’ mood symptoms can expedite treatment for those who need it. Many primary care clinics use the 9-item Patient Health Questionnaire (PHQ-9) to screen for depression.5 The US Preventive Services Task Force (USPSTF) has recommended screening for depression with adequate systems to ensure accurate diagnoses, effective treatment, and follow-up. Although the USPSTF did not specially endorse screening for bipolar disorder, it followed that recommendation with the qualifying statement, “positive screening results [for depression] should lead to additional assessment that considers severity of depression and comorbid psychological problems, alternate diagnoses, and medical conditions.”6 Thus, following a positive screen result for depression, consider using a screening tool for mood disorders to provide diagnostic clarification.
The Mood Disorder Questionnaire (MDQ) is a validated 15-item, self-administered questionnaire that takes only 5 minutes to use in screening adult patients for bipolar I disorder.7 The MDQ assesses specific behaviors related to bipolar disorder, symptom co-occurrence, and functional impairment. The MDQ has low sensitivity (58%) but good specificity (93%) in a primary care setting.8 However, the MDQ is not a diagnostic instrument. A positive screen result should prompt a more thorough clinical evaluation, if necessary, by a professional trained in psychiatric disorders.
We recommend completing the MDQ prior to prescribing antidepressants. You can also monitor a patient’s response to treatment with serial MDQ testing. The MDQ is useful, too, when a patient has unclear mood symptoms that may have features overlapping with bipolar disorder. Furthermore, we recommend screening for bipolar disorder with every patient who reports symptoms of depression, given that some pharmacologic treatments (predominately selective serotonin reuptake inhibitors) can induce mania in patients who actually have unrecognized bipolar disorder.9
Suicide
Suicide is the 10th leading cause of death among the general population. All demographic groups are impacted by suicide; however, the most vulnerable are men ages 45 to 64 years.10 Given the imminent risk to individuals who experience suicidal ideation, properly assessing and targeting suicidal risk is paramount.
The Columbia Suicide Severity Rating Scale (C-SSRS) can be completed in an interview format or as a patient self-report. Versions of the C-SSRS are available for children, adolescents, and adults. It can be used in practice with any patient who may be at risk for suicide. Specifically, consider using the C-SSRS when a patient scores 1 or greater on the PHQ-9 or when risk is revealed with another brief screening tool that includes suicidal ideation.
Continue to: The C-SSRS covers...
The C-SSRS covers 10 categories related to suicidal ideation and behavior that the clinician explores with questions requiring only Yes/No responses. The C-SSRS demonstrates moderate-to-strong internal consistency and reliability, and it has shown a high degree of sensitivity (95%) and specificity (95%) for suicidal ideation.11
Anxiety and physiologic arousal
Generalized anxiety disorder (GAD) is one of the most common anxiety disorders, with an estimated prevalence of 2.8% to 8.5% among primary care patients.12 Brief, validated screening tools such as the Generalized Anxiety Disorder–7 item (GAD-7) scale can be effective in identifying anxiety and other related disorders in primary care settings.
The GAD-7 comprises 7 items inquiring about symptoms experienced in the past 2 weeks. Scores range from 0 to 21, with cutoffs of 5, 10, and 15 indicating mild, moderate, and severe anxiety, respectively. This questionnaire is appropriate for use with adults and has strong specificity, internal consistency, and test-retest reliability.12 Specificity and sensitivity of the GAD-7 are maximized at a cutoff score of 10 or greater, both exceeding 80%.12 The GAD-7 can be used when patients report symptoms of anxiety or when one needs to screen for anxiety with new patients or more clearly understand symptoms among patients who have complex mental health concerns.
The Screen for Child Anxiety Related Disorders (SCARED) is a 41-item self-report measure of anxiety for children ages 8 to 18. The SCARED questionnaire yields an overall anxiety score, as well as subscales for panic disorder or significant somatic symptoms, generalized anxiety disorder, separation anxiety, social anxiety disorder, and significant school avoidance.13 There is also a 5-item version of the SCARED, which can be useful for brief screening in fast-paced settings when no anxiety disorder is suspected, or for children who may have anxiety but exhibit reduced verbal capacity. The SCARED has been found to have moderate sensitivity (81.8%) and specificity (52%) for diagnosing anxiety disorders in a community sample, with an optimal cutoff point of 22 on the total scale.14
Sleep
Sleep concerns are common, with the prevalence of insomnia among adults in the United States estimated to be 19.2%.15 The importance of assessing these concerns cannot be overstated, and primary care providers are the ones patients consult most often.16 The gold standard in assessing sleep disorders is a structured clinical interview, polysomnography, sleep diary, and actigraphy (home-based monitoring of movement through a device, often worn on the wrist).17,18 However, this work-up is expensive, time-intensive, and impractical in integrated care settings; thus the need for a brief, self-report screening tool to guide further assessment and intervention.
Continue to: The Insomnia Severity Index...
The Insomnia Severity Index (ISI) assesses patients’ perceptions of their insomnia. The ISI was developed to aid both in the clinical evaluation of patients with insomnia and to measure treatment outcomes. Administration of the ISI takes approximately 5 minutes, and scoring takes less than 1 minute.
The ISI is composed of 7 items that measure the severity of sleep onset and sleep maintenance difficulties, satisfaction with current sleep, impact on daily functioning, impairment observable to others, and degree of distress caused by the sleep problems. Each item is scored on a 0 to 4 Likert-type scale, and the individual items are summed for a total score of 0 to 28, with higher scores suggesting more severe insomnia. Evidence-based guidelines recommend cognitive behavioral therapy for insomnia (CBT-I) as the first-line treatment for adults with primary insomnia.19
Several validation studies have found the ISI to be a reliable measure of perceived insomnia severity, and one that is sensitive to changes in patients’ perceptions of treatment outcomes.20,21 An additional validation study confirmed that in primary care settings, a cutoff score of 14 should be used to indicate the likely presence of clinical insomnia22 and to guide further assessment and intervention.
The percentage of insomniac patients correctly identified with the ISI was 82.2%, with moderate sensitivity (82.4%) and specificity (82.1%).22 A positive predictive value of 70% was found, meaning that an insomnia disorder is probable when the ISI total score is 14 or higher; conversely, the negative predictive value was 90.2%.
Substance use and pain
The evaluation of alcohol and drug use is an integral part of assessing risky health behaviors. The 10-item Alcohol Use Disorder Identification Test (AUDIT) is a self-report tool developed by the World Health Organization.23,24 Validated in medical settings, scores of 8 or higher suggest problematic drinking.25,26 The AUDIT has demonstrated high specificity (94%) and moderate sensitivity (81%) in primary care settings.27 The AUDIT-C (items 1, 2, and 3 of the AUDIT) has also demonstrated comparable sensitivity, although slightly lower specificity, than the full AUDIT, suggesting that this 3-question screen can also be used in primary care settings.27
Continue to: Opioid medications...
Opioid medications, frequently prescribed for chronic pain, present serious risks for many patients. The Screener and Opioid Assessment for Patients with Pain–Revised (SOAPP-R) is a 24-item self-reporting scale that can be completed in approximately 10 minutes.28 A score of 18 or higher has identified 81% of patients at high risk for opioid misuse in a clinical setting, with moderate specificity (68%). Although other factors should be considered when assessing risk of opioid misuse, the SOAPP-R is a helpful and quick addition to an opioid risk assessment.
The CRAFFT Screening Tool for Adolescent Substance Use is administered by the clinician for youths ages 14 to 21. The first 3 questions ask about use of alcohol, marijuana, or other substances during the past 12 months. What follows are questions related to the young person’s specific experiences with substances in relation to Cars, Relaxation, being Alone, Forgetting, Family/Friends, and Trouble (CRAFFT). The CRAFFT has shown moderate sensitivity (76%) and good specificity (94%) for identifying any problem with substance use.29 These measures may be administered to clarify or confirm substance use patterns (ie, duration, frequency), or to determine the severity of problems related to substance use (ie, social or legal problems).
Trauma and PTSD
Approximately 7.7 million adults per year will experience posttraumatic stress disorder (PTSD) symptoms, although PTSD can affect individuals of any age.30 Given the impact that trauma can have, assess for PTSD in patients who have a history of trauma or who otherwise seem to be at risk. The Posttraumatic Stress Disorder Checklist (PCL-5) is a 20-item self-report questionnaire that screens for symptoms directly from the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for PTSD. One limitation is that the questionnaire is only validated for adults ages 18 years or older. Completion of the PCL-5 takes 5 to 10 minutes. The PCL-5 has strong internal consistency reliability (94%) and test-retest reliability (82%).31 With a cutoff score of 33 or higher,
The Child and Adolescent Trauma Screen (CATS) is used to assess for potentially traumatic events and PTSD symptoms in children and adolescents. These symptoms are based on the DSM-5, and therefore the CATS can act as a useful diagnostic aid. The CATS is also available in Spanish, with both caregiver-report (for children ages 3-6 years or 7-17 years) and self-report (for ages 7-17 years) versions. Practical use of the PCL-5 and the CATS involves screening for PTSD symptoms, supporting a provisional diagnosis of PTSD, and monitoring PTSD symptom changes during and after treatment.
Memory and cognition
Cognitive screening is a first step in evaluating possible dementia and other neuropsychological disorders. The importance of brief cognitive screening in primary care cannot be understated, especially for an aging patient population. Although the Mini Mental Status Exam (MMSE) has been widely used among health care providers and researchers, we recommend the Montreal Cognitive Assessment (MoCA).
Continue to: The MoCA is a simple...
The MoCA is a simple, standalone cognitive screening tool validated for adults ages 55 to 85 years.33 The MoCA addresses many important cognitive domains, fits on one page, and can be administered by a trained provider in 10 minutes. Research also suggests that it has strong test-retest reliability and positive and negative predictive values for mild cognitive impairment and Alzheimer dementia, and it has been found to be more sensitive than the MMSE.34 We additionally recommend the MoCA as it measures several cognitive skills that are not addressed on the MMSE, including verbal fluency and abstraction.34 Scores below 25 are suggestive of cognitive impairment and should lead to a referral for neuropsychological testing.
The MoCA’s sensitivity for detecting cognitive impairment is high (94%), and specificity is low (42%).35 To ensure consistency and accuracy in administering the MoCA, certification is now required via an online training program through www.mocatest.org.
Adapting these screening tools to practice
These tools are not meant to be used at every appointment. Every practice is different, and each clinic or physician can tailor the use of these screening tools to the needs of the patient population, as concerns arise, or in collaboration with other providers. Additionally, these screening tools can be used in both integrated care and in private practice, to prompt a more thorough assessment or to aid in—and inform—treatment. Although some physicians choose to administer certain screening tools at each clinic visit, knowing about the availability of other tools can be useful in assessing various issues.
The FIGURE can be used to aid in the clinical decision-making process.
CORRESPONDENCE
Rebecca Sewell, PsyD, Bon Secours Mercy Health, 2213 Cherry Street, Toledo, OH 4360; rebecca.sewell30@gmail.com.
1. Robinson RL, Grabner M, Palli SR, et al. Covariates of depression and high utilizers of healthcare: impact on resource use and costs. J Psychosom Res. 2016,85:35-43.
2. Fogarty CT, Sharma S, Chetty VK, et al. Mental health conditions are associated with increased health care utilization among urban family medicine patients. J Am Board Fam Med. 2008,21:398-407.
3. Weissman JD, Russell D, Beasley J, et al. Relationships between adult emotional states and indicators of health care utilization: findings from the National Health Interview Survey 2006–2014. J Psychosom Res. 2016,91:75-81.
4. Haddad M, Walters P. Mood disorders in primary care. Psychiatry. 2009,8:71-75.
5. Mitchell AJ, Yadegarfar M, Gill J, et al. Case finding and screening clinical utility of the Patient Health Questionnaire (PHQ-9 and PHQ-2) for depression in primary care: a diagnostic meta-analysis of 40 studies. BJPsych Open. 2016,2:127-138.
6. Siu AL and US Preventive Services Task Force. Screening for depression in adults. JAMA. 2016;315:380-387.
7. Hirschfeld RM, Williams JB, Spitzer RL, et al. Development and validation of a screening instrument for bipolar spectrum disorder: the Mood Disorder Questionnaire. Am J Psychiatry. 2000;157:1873-1875.
8. Hirschfeld RM, Cass AR, Holt DC, et al. Screening for bipolar disorder in patients treated for depression in a family medicine clinic. J Am Board Fam Med. 2005;18:233-239.
9. Das AK, Olfson M, Gameroff MJ, et al. Screening for bipolar disorder in a primary care practice. JAMA. 2005;293:956-963.
10. CDC. Suicide mortality in the United States, 1999-2017. www.cdc.gov/nchs/products/databriefs/db330.htm. Accessed October 23, 2020.
11. Viguera AC, Milano N, Ralston L, et al. Comparison of electronic screening for suicidal risk with Patient Health Questionnaire Item 9 and the Columbia Suicide Severity Rating Scale in an outpatient psychiatric clinic. Psychosomatics. 2015;56:460-469.
12. Spitzer RL, Kroenke K, Williams JBW, et al. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006;166:1092-1097.
13. Birmaher B, Khetarpal S, Brent D, et al. The Screen for Child Anxiety Related Emotional Disorders (SCARED): scale construction and psychometric characteristics. J Am Acad Chil Adolesc Psychiatry. 1997;36:545-553.
14. DeSousa DA, Salum GA, Isolan LR, et al. Sensitivity and specificity of the Screen for Child Anxiety Related Emotional Disorders (SCARED): a community-based study. Child Psychiatry Hum Dev. 2013;44:391-399.
15. Ford ES, Cunningham TJ, Giles WH, et al. Trends in insomnia and excessive daytime sleepiness among U.S. adults from 2002 to 2012. Sleep Med. 2015;16:372-378.
16. Morin CM, LeBlanc M, Daley M, et al. Epidemiology of insomnia: prevalence, self-help treatments, consultations, and determinants of help-seeking behaviors. Sleep Med. 2006;7:123-130.
17. Buysse DJ, Ancoli-Israel S, Edinger JD, et al. Recommendations for a standard research assessment of insomnia. Sleep. 2006;29:1155-1173.
18. Martin JL, Hakim AD. Wrist actigraphy. Chest. 2011;139:1514-1527.
19. Riemann D, Baglioni C, Bassetti C, et al. European guideline for the diagnosis and treatment of insomnia. J Sleep Res. 2017;26:675-700.
20. Bastien CH, Vallières A, Morin CM. Validation of the Insomnia Severity Index as an outcome measure for insomnia research. Sleep Med. 2001;2:297-307.
21. Wong ML, Lau KNT, Espie CA, et al. Psychometric properties of the Sleep Condition Indicator and Insomnia Severity Index in the evaluation of insomnia disorder. Sleep Med. 2017;33:76-81.
22. Gagnon C, Bélanger L, Ivers H, et al. Validation of the Insomnia Severity Index in primary care. J Am Board Fam Med. 2013;26:701-710.
23. Saunders JB, Aasland OG, Babor TF, et al. Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO Collaborative Project on Early Detection of Persons with Harmful Alcohol Consumption. Addiction. 1993;88:791-804.
24. Selin KH. Test-retest reliability of the Alcohol Use Disorder Identification Test in a general population sample. Alcohol Clin Exp Res. 2003;27:1428-1435.
25. Bohn MJ, Babor TF, Kranzler HR. The Alcohol Use Disorders Identification Test (AUDIT): validation of a screening instrument for use in medical settings. J Stud Alcohol. 1995;56:423-432.
26. Conigrave KM, Hall WD, Saunders JB. The AUDIT questionnaire: choosing a cut-off score. Addiction. 1995;90:1349-1356.
27. Gomez A, Conde A, Santana JM, et al. Diagnostic usefulness of brief versions of Alcohol Use Identification Test (AUDIT) for detecting hazardous drinkers in primary care settings. J Stud Alcohol. 2005;66:305-308.
28. Butler SF, Fernandez K, Benoit C, et al. Validation of the revised Screener and Opioid Assessment for Patients with Pain (SOAPP-R). J Pain. 2008;9:360-372.
29. Knight JR, Sherritt L, Shrier LA, et al. Validity of the CRAFFT substance abuse screening test among adolescent clinic patients. Arch Pediatr Adolesc Med. 2002;156:607-614.
30. DHHS. Post-traumatic stress disorder (PTSD). https://archives.nih.gov/asites/report/09-09-2019/report.nih.gov/nihfactsheets/ViewFactSheetfdf8.html?csid=58&key=P#P. Accessed October 23, 2020.
31. Blevins CA, Weathers FW, Davis MT, et al. The Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5): development and initial psychometric evaluation. J Trauma Stress. 2015;28:489-498.
32. Verhey R, Chilbanda D, Gibson L, et al. Validation of the Posttraumatic Stress Disorder Checklist- 5 (PCL-5) in a primary care population with high HIV prevalence in Zimbabwe. BMC Psychiatry. 2018;18:109.
33. Nasreddine ZS, Phillips NA, Bédirian V, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005;53:695-699.
34. Stewart S, O’Riley A, Edelstein B, et al. A preliminary comparison of three cognitive screening instruments in long term care: the MMSE, SLUMS, and MoCA. Clin Gerontol. 2012;35:57-75.
35. Godefroy O, Fickl A, Roussel M, et al. Is the Montreal Cognitive Assessment superior to the Mini-Mental State Examination to detect poststroke cognitive impairment? A study with neuropsychological evaluation. Stroke. 2011;42:1712-1716.
1. Robinson RL, Grabner M, Palli SR, et al. Covariates of depression and high utilizers of healthcare: impact on resource use and costs. J Psychosom Res. 2016,85:35-43.
2. Fogarty CT, Sharma S, Chetty VK, et al. Mental health conditions are associated with increased health care utilization among urban family medicine patients. J Am Board Fam Med. 2008,21:398-407.
3. Weissman JD, Russell D, Beasley J, et al. Relationships between adult emotional states and indicators of health care utilization: findings from the National Health Interview Survey 2006–2014. J Psychosom Res. 2016,91:75-81.
4. Haddad M, Walters P. Mood disorders in primary care. Psychiatry. 2009,8:71-75.
5. Mitchell AJ, Yadegarfar M, Gill J, et al. Case finding and screening clinical utility of the Patient Health Questionnaire (PHQ-9 and PHQ-2) for depression in primary care: a diagnostic meta-analysis of 40 studies. BJPsych Open. 2016,2:127-138.
6. Siu AL and US Preventive Services Task Force. Screening for depression in adults. JAMA. 2016;315:380-387.
7. Hirschfeld RM, Williams JB, Spitzer RL, et al. Development and validation of a screening instrument for bipolar spectrum disorder: the Mood Disorder Questionnaire. Am J Psychiatry. 2000;157:1873-1875.
8. Hirschfeld RM, Cass AR, Holt DC, et al. Screening for bipolar disorder in patients treated for depression in a family medicine clinic. J Am Board Fam Med. 2005;18:233-239.
9. Das AK, Olfson M, Gameroff MJ, et al. Screening for bipolar disorder in a primary care practice. JAMA. 2005;293:956-963.
10. CDC. Suicide mortality in the United States, 1999-2017. www.cdc.gov/nchs/products/databriefs/db330.htm. Accessed October 23, 2020.
11. Viguera AC, Milano N, Ralston L, et al. Comparison of electronic screening for suicidal risk with Patient Health Questionnaire Item 9 and the Columbia Suicide Severity Rating Scale in an outpatient psychiatric clinic. Psychosomatics. 2015;56:460-469.
12. Spitzer RL, Kroenke K, Williams JBW, et al. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006;166:1092-1097.
13. Birmaher B, Khetarpal S, Brent D, et al. The Screen for Child Anxiety Related Emotional Disorders (SCARED): scale construction and psychometric characteristics. J Am Acad Chil Adolesc Psychiatry. 1997;36:545-553.
14. DeSousa DA, Salum GA, Isolan LR, et al. Sensitivity and specificity of the Screen for Child Anxiety Related Emotional Disorders (SCARED): a community-based study. Child Psychiatry Hum Dev. 2013;44:391-399.
15. Ford ES, Cunningham TJ, Giles WH, et al. Trends in insomnia and excessive daytime sleepiness among U.S. adults from 2002 to 2012. Sleep Med. 2015;16:372-378.
16. Morin CM, LeBlanc M, Daley M, et al. Epidemiology of insomnia: prevalence, self-help treatments, consultations, and determinants of help-seeking behaviors. Sleep Med. 2006;7:123-130.
17. Buysse DJ, Ancoli-Israel S, Edinger JD, et al. Recommendations for a standard research assessment of insomnia. Sleep. 2006;29:1155-1173.
18. Martin JL, Hakim AD. Wrist actigraphy. Chest. 2011;139:1514-1527.
19. Riemann D, Baglioni C, Bassetti C, et al. European guideline for the diagnosis and treatment of insomnia. J Sleep Res. 2017;26:675-700.
20. Bastien CH, Vallières A, Morin CM. Validation of the Insomnia Severity Index as an outcome measure for insomnia research. Sleep Med. 2001;2:297-307.
21. Wong ML, Lau KNT, Espie CA, et al. Psychometric properties of the Sleep Condition Indicator and Insomnia Severity Index in the evaluation of insomnia disorder. Sleep Med. 2017;33:76-81.
22. Gagnon C, Bélanger L, Ivers H, et al. Validation of the Insomnia Severity Index in primary care. J Am Board Fam Med. 2013;26:701-710.
23. Saunders JB, Aasland OG, Babor TF, et al. Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO Collaborative Project on Early Detection of Persons with Harmful Alcohol Consumption. Addiction. 1993;88:791-804.
24. Selin KH. Test-retest reliability of the Alcohol Use Disorder Identification Test in a general population sample. Alcohol Clin Exp Res. 2003;27:1428-1435.
25. Bohn MJ, Babor TF, Kranzler HR. The Alcohol Use Disorders Identification Test (AUDIT): validation of a screening instrument for use in medical settings. J Stud Alcohol. 1995;56:423-432.
26. Conigrave KM, Hall WD, Saunders JB. The AUDIT questionnaire: choosing a cut-off score. Addiction. 1995;90:1349-1356.
27. Gomez A, Conde A, Santana JM, et al. Diagnostic usefulness of brief versions of Alcohol Use Identification Test (AUDIT) for detecting hazardous drinkers in primary care settings. J Stud Alcohol. 2005;66:305-308.
28. Butler SF, Fernandez K, Benoit C, et al. Validation of the revised Screener and Opioid Assessment for Patients with Pain (SOAPP-R). J Pain. 2008;9:360-372.
29. Knight JR, Sherritt L, Shrier LA, et al. Validity of the CRAFFT substance abuse screening test among adolescent clinic patients. Arch Pediatr Adolesc Med. 2002;156:607-614.
30. DHHS. Post-traumatic stress disorder (PTSD). https://archives.nih.gov/asites/report/09-09-2019/report.nih.gov/nihfactsheets/ViewFactSheetfdf8.html?csid=58&key=P#P. Accessed October 23, 2020.
31. Blevins CA, Weathers FW, Davis MT, et al. The Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5): development and initial psychometric evaluation. J Trauma Stress. 2015;28:489-498.
32. Verhey R, Chilbanda D, Gibson L, et al. Validation of the Posttraumatic Stress Disorder Checklist- 5 (PCL-5) in a primary care population with high HIV prevalence in Zimbabwe. BMC Psychiatry. 2018;18:109.
33. Nasreddine ZS, Phillips NA, Bédirian V, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005;53:695-699.
34. Stewart S, O’Riley A, Edelstein B, et al. A preliminary comparison of three cognitive screening instruments in long term care: the MMSE, SLUMS, and MoCA. Clin Gerontol. 2012;35:57-75.
35. Godefroy O, Fickl A, Roussel M, et al. Is the Montreal Cognitive Assessment superior to the Mini-Mental State Examination to detect poststroke cognitive impairment? A study with neuropsychological evaluation. Stroke. 2011;42:1712-1716.
Pfizer vaccine data show 90% efficacy in early results
A vaccine candidate against SARS-CoV-2 has been found to be 90% effective in preventing COVID-19 in trial volunteers who were without evidence of prior infection of the virus, results from an interim analysis of a phase 3 study demonstrated.
BTN162b2, a messenger RNA–based vaccine candidate that requires two doses, is being developed by Pfizer and BioNTech SE independently of the Trump administration’s Operation Warp Speed. A global phase 3 clinical trial of BTN162b2 began on July 27 and has enrolled 43,538 participants to date; 42% of enrollees have racially and ethnically diverse backgrounds.
According to a press release issued by the two companies, 38,955 trial volunteers had received a second dose of either vaccine or placebo as of Nov. 8. An interim analysis of 94 individuals conducted by an independent data monitoring committee (DMC) found that the vaccine efficacy rate was above 90% 7 days after the second dose. This means that protection was achieved 28 days after the first vaccine dose.
“It’s promising in that it validates the genetic strategy – whether it’s mRNA vaccines or DNA vaccines,” Paul A. Offit, MD, told Medscape Medical News. Offit is a member of the US Food and Drug Administraiton’s COVID-19 Vaccine Advisory Committee. “All of them have the same approach, which is that they introduce the gene that codes for the coronavirus spike protein into the cell. Your cell makes the spike protein, and your immune system makes antibodies to the spike protein. At least in these preliminary data, which involved 94 people getting sick, it looks like it’s effective. That’s good. We knew that it seemed to work in experimental animals, but you never know until you put it into people.”
According to Pfizer and BioNTech SE, a final data analysis is planned once 164 confirmed COVID-19 cases have accrued. So far, the DMC has not reported any serious safety concerns. It recommends that the study continue to collect safety and efficacy data as planned. The companies plan to apply to the FDA for emergency use authorization soon after the required safety milestone is achieved.
Pfizer CEO Albert Bourla, DVM, PhD, added in a separate press release, “It’s important to note that we cannot apply for FDA Emergency Use Authorization based on these efficacy results alone. More data on safety is also needed, and we are continuing to accumulate that safety data as part of our ongoing clinical study.
“We estimate that a median of two months of safety data following the second and final dose of the vaccine candidate – required by FDA’s guidance for potential Emergency Use Authorization – will be available by the third week of November.”
Offit, professor of pediatrics in the Division of Infectious Diseases at the Children’s Hospital of Philadelphia, said that, if BTN162b2 is approved, administering it will be tricky. “This particular vaccine has to be shipped and stored at –70° C or –80° C, which we’ve never done before in this country,” he said. “That means maintaining the product on dry ice. That’s going to be a challenge for distribution, I think.”
Good news, but…
In the press release, BioNTech SE’s cofounder and CEO, Ugur Sahin, MD, characterized the findings as “a victory for innovation, science and a global collaborative effort. When we embarked on this journey 10 months ago this is what we aspired to achieve. Especially today, while we are all in the midst of a second wave and many of us in lockdown, we appreciate even more how important this milestone is on our path towards ending this pandemic and for all of us to regain a sense of normality.”
President-elect Joe Biden also weighed in, calling the results “excellent news” in a news release.
“At the same time, it is also important to understand that the end of the battle against COVID-19 is still months away,” he said. “This news follows a previously announced timeline by industry officials that forecast vaccine approval by late November. Even if that is achieved, and some Americans are vaccinated later this year, it will be many more months before there is widespread vaccination in this country.
“Today’s news does not change this urgent reality. Americans will have to rely on masking, distancing, contact tracing, hand washing, and other measures to keep themselves safe well into next year,” Biden added.
This article first appeared on Medscape.com.
A vaccine candidate against SARS-CoV-2 has been found to be 90% effective in preventing COVID-19 in trial volunteers who were without evidence of prior infection of the virus, results from an interim analysis of a phase 3 study demonstrated.
BTN162b2, a messenger RNA–based vaccine candidate that requires two doses, is being developed by Pfizer and BioNTech SE independently of the Trump administration’s Operation Warp Speed. A global phase 3 clinical trial of BTN162b2 began on July 27 and has enrolled 43,538 participants to date; 42% of enrollees have racially and ethnically diverse backgrounds.
According to a press release issued by the two companies, 38,955 trial volunteers had received a second dose of either vaccine or placebo as of Nov. 8. An interim analysis of 94 individuals conducted by an independent data monitoring committee (DMC) found that the vaccine efficacy rate was above 90% 7 days after the second dose. This means that protection was achieved 28 days after the first vaccine dose.
“It’s promising in that it validates the genetic strategy – whether it’s mRNA vaccines or DNA vaccines,” Paul A. Offit, MD, told Medscape Medical News. Offit is a member of the US Food and Drug Administraiton’s COVID-19 Vaccine Advisory Committee. “All of them have the same approach, which is that they introduce the gene that codes for the coronavirus spike protein into the cell. Your cell makes the spike protein, and your immune system makes antibodies to the spike protein. At least in these preliminary data, which involved 94 people getting sick, it looks like it’s effective. That’s good. We knew that it seemed to work in experimental animals, but you never know until you put it into people.”
According to Pfizer and BioNTech SE, a final data analysis is planned once 164 confirmed COVID-19 cases have accrued. So far, the DMC has not reported any serious safety concerns. It recommends that the study continue to collect safety and efficacy data as planned. The companies plan to apply to the FDA for emergency use authorization soon after the required safety milestone is achieved.
Pfizer CEO Albert Bourla, DVM, PhD, added in a separate press release, “It’s important to note that we cannot apply for FDA Emergency Use Authorization based on these efficacy results alone. More data on safety is also needed, and we are continuing to accumulate that safety data as part of our ongoing clinical study.
“We estimate that a median of two months of safety data following the second and final dose of the vaccine candidate – required by FDA’s guidance for potential Emergency Use Authorization – will be available by the third week of November.”
Offit, professor of pediatrics in the Division of Infectious Diseases at the Children’s Hospital of Philadelphia, said that, if BTN162b2 is approved, administering it will be tricky. “This particular vaccine has to be shipped and stored at –70° C or –80° C, which we’ve never done before in this country,” he said. “That means maintaining the product on dry ice. That’s going to be a challenge for distribution, I think.”
Good news, but…
In the press release, BioNTech SE’s cofounder and CEO, Ugur Sahin, MD, characterized the findings as “a victory for innovation, science and a global collaborative effort. When we embarked on this journey 10 months ago this is what we aspired to achieve. Especially today, while we are all in the midst of a second wave and many of us in lockdown, we appreciate even more how important this milestone is on our path towards ending this pandemic and for all of us to regain a sense of normality.”
President-elect Joe Biden also weighed in, calling the results “excellent news” in a news release.
“At the same time, it is also important to understand that the end of the battle against COVID-19 is still months away,” he said. “This news follows a previously announced timeline by industry officials that forecast vaccine approval by late November. Even if that is achieved, and some Americans are vaccinated later this year, it will be many more months before there is widespread vaccination in this country.
“Today’s news does not change this urgent reality. Americans will have to rely on masking, distancing, contact tracing, hand washing, and other measures to keep themselves safe well into next year,” Biden added.
This article first appeared on Medscape.com.
A vaccine candidate against SARS-CoV-2 has been found to be 90% effective in preventing COVID-19 in trial volunteers who were without evidence of prior infection of the virus, results from an interim analysis of a phase 3 study demonstrated.
BTN162b2, a messenger RNA–based vaccine candidate that requires two doses, is being developed by Pfizer and BioNTech SE independently of the Trump administration’s Operation Warp Speed. A global phase 3 clinical trial of BTN162b2 began on July 27 and has enrolled 43,538 participants to date; 42% of enrollees have racially and ethnically diverse backgrounds.
According to a press release issued by the two companies, 38,955 trial volunteers had received a second dose of either vaccine or placebo as of Nov. 8. An interim analysis of 94 individuals conducted by an independent data monitoring committee (DMC) found that the vaccine efficacy rate was above 90% 7 days after the second dose. This means that protection was achieved 28 days after the first vaccine dose.
“It’s promising in that it validates the genetic strategy – whether it’s mRNA vaccines or DNA vaccines,” Paul A. Offit, MD, told Medscape Medical News. Offit is a member of the US Food and Drug Administraiton’s COVID-19 Vaccine Advisory Committee. “All of them have the same approach, which is that they introduce the gene that codes for the coronavirus spike protein into the cell. Your cell makes the spike protein, and your immune system makes antibodies to the spike protein. At least in these preliminary data, which involved 94 people getting sick, it looks like it’s effective. That’s good. We knew that it seemed to work in experimental animals, but you never know until you put it into people.”
According to Pfizer and BioNTech SE, a final data analysis is planned once 164 confirmed COVID-19 cases have accrued. So far, the DMC has not reported any serious safety concerns. It recommends that the study continue to collect safety and efficacy data as planned. The companies plan to apply to the FDA for emergency use authorization soon after the required safety milestone is achieved.
Pfizer CEO Albert Bourla, DVM, PhD, added in a separate press release, “It’s important to note that we cannot apply for FDA Emergency Use Authorization based on these efficacy results alone. More data on safety is also needed, and we are continuing to accumulate that safety data as part of our ongoing clinical study.
“We estimate that a median of two months of safety data following the second and final dose of the vaccine candidate – required by FDA’s guidance for potential Emergency Use Authorization – will be available by the third week of November.”
Offit, professor of pediatrics in the Division of Infectious Diseases at the Children’s Hospital of Philadelphia, said that, if BTN162b2 is approved, administering it will be tricky. “This particular vaccine has to be shipped and stored at –70° C or –80° C, which we’ve never done before in this country,” he said. “That means maintaining the product on dry ice. That’s going to be a challenge for distribution, I think.”
Good news, but…
In the press release, BioNTech SE’s cofounder and CEO, Ugur Sahin, MD, characterized the findings as “a victory for innovation, science and a global collaborative effort. When we embarked on this journey 10 months ago this is what we aspired to achieve. Especially today, while we are all in the midst of a second wave and many of us in lockdown, we appreciate even more how important this milestone is on our path towards ending this pandemic and for all of us to regain a sense of normality.”
President-elect Joe Biden also weighed in, calling the results “excellent news” in a news release.
“At the same time, it is also important to understand that the end of the battle against COVID-19 is still months away,” he said. “This news follows a previously announced timeline by industry officials that forecast vaccine approval by late November. Even if that is achieved, and some Americans are vaccinated later this year, it will be many more months before there is widespread vaccination in this country.
“Today’s news does not change this urgent reality. Americans will have to rely on masking, distancing, contact tracing, hand washing, and other measures to keep themselves safe well into next year,” Biden added.
This article first appeared on Medscape.com.
Proposed Medicare rule would expand CGM coverage
A new proposed rule from the Centers for Medicare & Medicaid Services (CMS) would expand coverage for continuous glucose monitors (CGMs) under Medicare to include devices that aren’t approved for making treatment decisions.
If accepted, the proposed rule would classify all approved CGMs as durable medical equipment under Medicare Part B and establish payment amounts for all related supplies. The move primarily affects Medtronic’s Guardian Connect System, which has not been approved by the U.S. Food and Drug Administration to replace the need for fingersticks in determining insulin or other glucose-lowering medication dosing.
Two other CGM systems, the Dexcom G6 and Abbott Libre, have “therapeutic” indications and are, therefore, already covered under Medicare, as is the combined insulin pump–CGM Tandem Diabetes Care Control-IQ Technology system.
According to a CMS statement, “CGMs that are not approved for use in making diabetes treatment decisions can be used to alert beneficiaries about potentially dangerous glucose levels while they sleep and that they should further test their glucose levels using a blood glucose monitor. ... This proposal would give Medicare beneficiaries and their physicians a wider range of technology and devices to choose from in managing diabetes.”
Sean Salmon, executive vice president and president of the Diabetes Group at Medtronic said in an interview that the company is “very encouraged” by the proposal. “Importantly, the proposed rule would enable continuity of therapy for people on Medtronic insulin pumps aging into Medicare – including Medtronic hybrid closed loop systems, which automatically adjust insulin delivery based on readings from the integrated CGM.”
The type 1 diabetes research and advocacy organization JDRF also applauded the proposed rule, noting in a statement, “CGM technology can be an integral component of artificial pancreas systems and important on its own to significantly improve diabetes management and enable users to avoid potential crises and risks for long-term complications. JDRF is heartened by this proposed change as it has long advocated for coverage, affordability and choice of all therapies to help ensure people with T1D have what they need to survive.”
The proposal is part of a broader set of proposed changes to Medicare Durable Medical Equipment, Prosthetics, Orthotic Devices and Supplies (DMEPOS) coverage and payment policies. Comments on the entire document can be submitted through Jan. 4, 2021 to the Federal Register.
A new proposed rule from the Centers for Medicare & Medicaid Services (CMS) would expand coverage for continuous glucose monitors (CGMs) under Medicare to include devices that aren’t approved for making treatment decisions.
If accepted, the proposed rule would classify all approved CGMs as durable medical equipment under Medicare Part B and establish payment amounts for all related supplies. The move primarily affects Medtronic’s Guardian Connect System, which has not been approved by the U.S. Food and Drug Administration to replace the need for fingersticks in determining insulin or other glucose-lowering medication dosing.
Two other CGM systems, the Dexcom G6 and Abbott Libre, have “therapeutic” indications and are, therefore, already covered under Medicare, as is the combined insulin pump–CGM Tandem Diabetes Care Control-IQ Technology system.
According to a CMS statement, “CGMs that are not approved for use in making diabetes treatment decisions can be used to alert beneficiaries about potentially dangerous glucose levels while they sleep and that they should further test their glucose levels using a blood glucose monitor. ... This proposal would give Medicare beneficiaries and their physicians a wider range of technology and devices to choose from in managing diabetes.”
Sean Salmon, executive vice president and president of the Diabetes Group at Medtronic said in an interview that the company is “very encouraged” by the proposal. “Importantly, the proposed rule would enable continuity of therapy for people on Medtronic insulin pumps aging into Medicare – including Medtronic hybrid closed loop systems, which automatically adjust insulin delivery based on readings from the integrated CGM.”
The type 1 diabetes research and advocacy organization JDRF also applauded the proposed rule, noting in a statement, “CGM technology can be an integral component of artificial pancreas systems and important on its own to significantly improve diabetes management and enable users to avoid potential crises and risks for long-term complications. JDRF is heartened by this proposed change as it has long advocated for coverage, affordability and choice of all therapies to help ensure people with T1D have what they need to survive.”
The proposal is part of a broader set of proposed changes to Medicare Durable Medical Equipment, Prosthetics, Orthotic Devices and Supplies (DMEPOS) coverage and payment policies. Comments on the entire document can be submitted through Jan. 4, 2021 to the Federal Register.
A new proposed rule from the Centers for Medicare & Medicaid Services (CMS) would expand coverage for continuous glucose monitors (CGMs) under Medicare to include devices that aren’t approved for making treatment decisions.
If accepted, the proposed rule would classify all approved CGMs as durable medical equipment under Medicare Part B and establish payment amounts for all related supplies. The move primarily affects Medtronic’s Guardian Connect System, which has not been approved by the U.S. Food and Drug Administration to replace the need for fingersticks in determining insulin or other glucose-lowering medication dosing.
Two other CGM systems, the Dexcom G6 and Abbott Libre, have “therapeutic” indications and are, therefore, already covered under Medicare, as is the combined insulin pump–CGM Tandem Diabetes Care Control-IQ Technology system.
According to a CMS statement, “CGMs that are not approved for use in making diabetes treatment decisions can be used to alert beneficiaries about potentially dangerous glucose levels while they sleep and that they should further test their glucose levels using a blood glucose monitor. ... This proposal would give Medicare beneficiaries and their physicians a wider range of technology and devices to choose from in managing diabetes.”
Sean Salmon, executive vice president and president of the Diabetes Group at Medtronic said in an interview that the company is “very encouraged” by the proposal. “Importantly, the proposed rule would enable continuity of therapy for people on Medtronic insulin pumps aging into Medicare – including Medtronic hybrid closed loop systems, which automatically adjust insulin delivery based on readings from the integrated CGM.”
The type 1 diabetes research and advocacy organization JDRF also applauded the proposed rule, noting in a statement, “CGM technology can be an integral component of artificial pancreas systems and important on its own to significantly improve diabetes management and enable users to avoid potential crises and risks for long-term complications. JDRF is heartened by this proposed change as it has long advocated for coverage, affordability and choice of all therapies to help ensure people with T1D have what they need to survive.”
The proposal is part of a broader set of proposed changes to Medicare Durable Medical Equipment, Prosthetics, Orthotic Devices and Supplies (DMEPOS) coverage and payment policies. Comments on the entire document can be submitted through Jan. 4, 2021 to the Federal Register.
Cystic fibrosis patients’ vulnerability to COVID-19 infection: Preliminary data ease fears
But early results suggest that social distance measures and perhaps the younger average age of individuals with CF have prevented a severe impact on this patient population.
Not all of the news is good. Some research suggests that posttransplant individuals may be at greater risk of severe outcomes. However, researchers warned that the data are too sparse to draw firm conclusions, and ongoing analyses of patient registries and other sources should lend greater insight into the burden of COVID-19 among individuals with CF. Those were some of the conclusions presented at a session of the virtual North American Cystic Fibrosis Conference.
D.B. Sanders, MD, who is a pediatric pulmonologist at Riley Hospital for Children and the Indiana University, both in Indianapolis, presented data from the Cystic Fibrosis Foundation’s Patient Registry, which includes patients in the United States. As in other populations, he showed that health care use has gone down among individuals with CF. From April to September 2019, 81% of clinical encounters were in the clinic and 12% in the hospital. Over the same period in 2020, those numbers dropped to 35% and 4%, respectively, with 30% by phone or computer. In-person health care use rebounded somewhat between July 1 and Sept. 16, with 53% of encounters at the clinic, 5% at the hospital, and 28% conducted virtually. There were also dips in forced expiratory volume in one second (FEV1) and microbiology testing, from about 90% occurring during health encounters at the end of 2019 to fewer than 10% of encounters by April.
As of Aug. 17, Dr. Sanders reported that 3,048 individuals with CF had been tested for COVID-19, with 174 positive results.
Racial and ethnic disparities in positive test results seen in other populations were also observable among individuals with CF. Several groups made up a higher proportion of COVID-19–positive CF patients than the general CF population, including Hispanics (18% vs. 9%), Blacks (7% vs. 5%), and individuals with FEV1 value less than 40% predicted (14% vs. 8%).
As of Sept. 17, there had been 51 hospitalizations and two deaths in the United States among 212 individuals with CF who tested positive for COVID-19, with increasing numbers that mirror trends in the U.S. population. One death occurred in a patient with advanced lung disease, the other in a post–lung transplant patient. “Thankfully [the numbers are] not higher, but this is being followed very closely,” said Dr. Sanders during his presentation.
One encouraging bit of news was that hospitalizations among individuals with CF have dropped since the start of the pandemic. “I think this shows how good our families are at socially distancing, wearing masks, and now that they not being exposed to viruses, I think we’re seeing the fruits of this with fewer hospitalizations,” said Dr. Sanders. He noted that it’s possible some of the decline could have been to reluctance to go to the hospital, and the introduction of triple combination cystic fibrosis transmembrane conductance regulator modulator therapy has also likely contributed. “We were already seeing fewer hospitalizations even before the pandemic hit,” he said.
At the session, Rebecca Cosgriff, director of data and quality improvement at the Cystic Fibrosis Trust in the United Kingdom, presented an international perspective on COVID-19 cases among individuals with CF. At the beginning of the pandemic, the Cystic Fibrosis Global Registry Harmonization Group recruited country coordinators to collect anonymized data on infections, hospitalizations, and other outcomes. In April, the group published its initial findings from 40 cases in eight countries, which concluded that these cases generally resembled the broader population in clinical course, which assuaged initial fears.
Ms. Cosgriff reported on results from a second round of data collection with a cutoff date of June 19, which expanded to 19 countries and included many from South America and more in Europe. The network encompassed about 85,000 individuals with CF, and tallied 181 cases of COVID-19. A total of 149 cases were nontransplant, and 32 were posttransplant (28 lung only). Fully 15% of the nontransplant group were over age 40 years, compared with 41% in the transplant group. Homozygous F508del mutations were more common in the posttransplant group (59% vs. 36%). However, lung function, as estimated by the best FEV1 measured in the previous year prior to infection, differed between the nontransplant (73%) and posttransplant (80%) COVID-19 patients.
Across all age groups, hospitalizations were more common in patients with best FEV1 percentage predicted values less than 70% (P = .001). Ms. Cosgriff also expressed concern about the posttransplant group. “Across all outcomes that might be indicative of infection severity – hospitalization, ICU admission, new supplementary oxygen, and non-invasive ventilation – the proportion of the posttransplant group was higher across the board,” she said during her presentation.
There were seven deaths. Ms. Cosgriff noted that there were too few deaths to analyze trends, but she presented a slide showing characteristics of deceased patients. “Factors like being post–lung transplant, being male, having less FEV1 than predicted, being over 40, or having CF-related diabetes, all appear pretty frequently amongst the cohort of people who died,” she said.
Overall, the results of these surveys are encouraging, suggesting that early fears that COVID-19 cases could be more severe among individuals with CF may not have been borne out so far. Dr. Sanders noted in his talk that there aren’t enough cases in the U.S. cohort to show links to risk factors with statistical significance. “But thankfully we’re not seeing a host of negative outcomes,” he said.
Dr. Sanders and Ms Cosgriff have no relevant financial disclosures.
But early results suggest that social distance measures and perhaps the younger average age of individuals with CF have prevented a severe impact on this patient population.
Not all of the news is good. Some research suggests that posttransplant individuals may be at greater risk of severe outcomes. However, researchers warned that the data are too sparse to draw firm conclusions, and ongoing analyses of patient registries and other sources should lend greater insight into the burden of COVID-19 among individuals with CF. Those were some of the conclusions presented at a session of the virtual North American Cystic Fibrosis Conference.
D.B. Sanders, MD, who is a pediatric pulmonologist at Riley Hospital for Children and the Indiana University, both in Indianapolis, presented data from the Cystic Fibrosis Foundation’s Patient Registry, which includes patients in the United States. As in other populations, he showed that health care use has gone down among individuals with CF. From April to September 2019, 81% of clinical encounters were in the clinic and 12% in the hospital. Over the same period in 2020, those numbers dropped to 35% and 4%, respectively, with 30% by phone or computer. In-person health care use rebounded somewhat between July 1 and Sept. 16, with 53% of encounters at the clinic, 5% at the hospital, and 28% conducted virtually. There were also dips in forced expiratory volume in one second (FEV1) and microbiology testing, from about 90% occurring during health encounters at the end of 2019 to fewer than 10% of encounters by April.
As of Aug. 17, Dr. Sanders reported that 3,048 individuals with CF had been tested for COVID-19, with 174 positive results.
Racial and ethnic disparities in positive test results seen in other populations were also observable among individuals with CF. Several groups made up a higher proportion of COVID-19–positive CF patients than the general CF population, including Hispanics (18% vs. 9%), Blacks (7% vs. 5%), and individuals with FEV1 value less than 40% predicted (14% vs. 8%).
As of Sept. 17, there had been 51 hospitalizations and two deaths in the United States among 212 individuals with CF who tested positive for COVID-19, with increasing numbers that mirror trends in the U.S. population. One death occurred in a patient with advanced lung disease, the other in a post–lung transplant patient. “Thankfully [the numbers are] not higher, but this is being followed very closely,” said Dr. Sanders during his presentation.
One encouraging bit of news was that hospitalizations among individuals with CF have dropped since the start of the pandemic. “I think this shows how good our families are at socially distancing, wearing masks, and now that they not being exposed to viruses, I think we’re seeing the fruits of this with fewer hospitalizations,” said Dr. Sanders. He noted that it’s possible some of the decline could have been to reluctance to go to the hospital, and the introduction of triple combination cystic fibrosis transmembrane conductance regulator modulator therapy has also likely contributed. “We were already seeing fewer hospitalizations even before the pandemic hit,” he said.
At the session, Rebecca Cosgriff, director of data and quality improvement at the Cystic Fibrosis Trust in the United Kingdom, presented an international perspective on COVID-19 cases among individuals with CF. At the beginning of the pandemic, the Cystic Fibrosis Global Registry Harmonization Group recruited country coordinators to collect anonymized data on infections, hospitalizations, and other outcomes. In April, the group published its initial findings from 40 cases in eight countries, which concluded that these cases generally resembled the broader population in clinical course, which assuaged initial fears.
Ms. Cosgriff reported on results from a second round of data collection with a cutoff date of June 19, which expanded to 19 countries and included many from South America and more in Europe. The network encompassed about 85,000 individuals with CF, and tallied 181 cases of COVID-19. A total of 149 cases were nontransplant, and 32 were posttransplant (28 lung only). Fully 15% of the nontransplant group were over age 40 years, compared with 41% in the transplant group. Homozygous F508del mutations were more common in the posttransplant group (59% vs. 36%). However, lung function, as estimated by the best FEV1 measured in the previous year prior to infection, differed between the nontransplant (73%) and posttransplant (80%) COVID-19 patients.
Across all age groups, hospitalizations were more common in patients with best FEV1 percentage predicted values less than 70% (P = .001). Ms. Cosgriff also expressed concern about the posttransplant group. “Across all outcomes that might be indicative of infection severity – hospitalization, ICU admission, new supplementary oxygen, and non-invasive ventilation – the proportion of the posttransplant group was higher across the board,” she said during her presentation.
There were seven deaths. Ms. Cosgriff noted that there were too few deaths to analyze trends, but she presented a slide showing characteristics of deceased patients. “Factors like being post–lung transplant, being male, having less FEV1 than predicted, being over 40, or having CF-related diabetes, all appear pretty frequently amongst the cohort of people who died,” she said.
Overall, the results of these surveys are encouraging, suggesting that early fears that COVID-19 cases could be more severe among individuals with CF may not have been borne out so far. Dr. Sanders noted in his talk that there aren’t enough cases in the U.S. cohort to show links to risk factors with statistical significance. “But thankfully we’re not seeing a host of negative outcomes,” he said.
Dr. Sanders and Ms Cosgriff have no relevant financial disclosures.
But early results suggest that social distance measures and perhaps the younger average age of individuals with CF have prevented a severe impact on this patient population.
Not all of the news is good. Some research suggests that posttransplant individuals may be at greater risk of severe outcomes. However, researchers warned that the data are too sparse to draw firm conclusions, and ongoing analyses of patient registries and other sources should lend greater insight into the burden of COVID-19 among individuals with CF. Those were some of the conclusions presented at a session of the virtual North American Cystic Fibrosis Conference.
D.B. Sanders, MD, who is a pediatric pulmonologist at Riley Hospital for Children and the Indiana University, both in Indianapolis, presented data from the Cystic Fibrosis Foundation’s Patient Registry, which includes patients in the United States. As in other populations, he showed that health care use has gone down among individuals with CF. From April to September 2019, 81% of clinical encounters were in the clinic and 12% in the hospital. Over the same period in 2020, those numbers dropped to 35% and 4%, respectively, with 30% by phone or computer. In-person health care use rebounded somewhat between July 1 and Sept. 16, with 53% of encounters at the clinic, 5% at the hospital, and 28% conducted virtually. There were also dips in forced expiratory volume in one second (FEV1) and microbiology testing, from about 90% occurring during health encounters at the end of 2019 to fewer than 10% of encounters by April.
As of Aug. 17, Dr. Sanders reported that 3,048 individuals with CF had been tested for COVID-19, with 174 positive results.
Racial and ethnic disparities in positive test results seen in other populations were also observable among individuals with CF. Several groups made up a higher proportion of COVID-19–positive CF patients than the general CF population, including Hispanics (18% vs. 9%), Blacks (7% vs. 5%), and individuals with FEV1 value less than 40% predicted (14% vs. 8%).
As of Sept. 17, there had been 51 hospitalizations and two deaths in the United States among 212 individuals with CF who tested positive for COVID-19, with increasing numbers that mirror trends in the U.S. population. One death occurred in a patient with advanced lung disease, the other in a post–lung transplant patient. “Thankfully [the numbers are] not higher, but this is being followed very closely,” said Dr. Sanders during his presentation.
One encouraging bit of news was that hospitalizations among individuals with CF have dropped since the start of the pandemic. “I think this shows how good our families are at socially distancing, wearing masks, and now that they not being exposed to viruses, I think we’re seeing the fruits of this with fewer hospitalizations,” said Dr. Sanders. He noted that it’s possible some of the decline could have been to reluctance to go to the hospital, and the introduction of triple combination cystic fibrosis transmembrane conductance regulator modulator therapy has also likely contributed. “We were already seeing fewer hospitalizations even before the pandemic hit,” he said.
At the session, Rebecca Cosgriff, director of data and quality improvement at the Cystic Fibrosis Trust in the United Kingdom, presented an international perspective on COVID-19 cases among individuals with CF. At the beginning of the pandemic, the Cystic Fibrosis Global Registry Harmonization Group recruited country coordinators to collect anonymized data on infections, hospitalizations, and other outcomes. In April, the group published its initial findings from 40 cases in eight countries, which concluded that these cases generally resembled the broader population in clinical course, which assuaged initial fears.
Ms. Cosgriff reported on results from a second round of data collection with a cutoff date of June 19, which expanded to 19 countries and included many from South America and more in Europe. The network encompassed about 85,000 individuals with CF, and tallied 181 cases of COVID-19. A total of 149 cases were nontransplant, and 32 were posttransplant (28 lung only). Fully 15% of the nontransplant group were over age 40 years, compared with 41% in the transplant group. Homozygous F508del mutations were more common in the posttransplant group (59% vs. 36%). However, lung function, as estimated by the best FEV1 measured in the previous year prior to infection, differed between the nontransplant (73%) and posttransplant (80%) COVID-19 patients.
Across all age groups, hospitalizations were more common in patients with best FEV1 percentage predicted values less than 70% (P = .001). Ms. Cosgriff also expressed concern about the posttransplant group. “Across all outcomes that might be indicative of infection severity – hospitalization, ICU admission, new supplementary oxygen, and non-invasive ventilation – the proportion of the posttransplant group was higher across the board,” she said during her presentation.
There were seven deaths. Ms. Cosgriff noted that there were too few deaths to analyze trends, but she presented a slide showing characteristics of deceased patients. “Factors like being post–lung transplant, being male, having less FEV1 than predicted, being over 40, or having CF-related diabetes, all appear pretty frequently amongst the cohort of people who died,” she said.
Overall, the results of these surveys are encouraging, suggesting that early fears that COVID-19 cases could be more severe among individuals with CF may not have been borne out so far. Dr. Sanders noted in his talk that there aren’t enough cases in the U.S. cohort to show links to risk factors with statistical significance. “But thankfully we’re not seeing a host of negative outcomes,” he said.
Dr. Sanders and Ms Cosgriff have no relevant financial disclosures.
FROM NACFC 2020