Prior to shoulder surgery, application of 3% hydrogen peroxide is a simple and inexpensive strategy to reduce the risk of postoperative cultures of Cutibacterium acnes, according to findings from a prospective randomized trial. The results were reported in an abstract scheduled for release at the annual meeting of the American Academy of Orthopaedic Surgeons. The meeting was canceled because of COVID-19.

“This approach is simple, cheap, and does not rely on patient compliance,” explained Surena Namdari, MD, associate professor of orthopedic surgery at Thomas Jefferson University, Philadelphia.

C. acnes, formerly known as Propionibacterium acnes, is increasingly seen as an important target for prevention of postoperative shoulder infections because of published reports that it is the most commonly isolated bacterium from such infections, Dr. Namdari said in an interview.

In the prospective, randomized trial, male patients scheduled for shoulder arthroscopy were recruited if they did not have active acne, history of psoriatic or eczematous lesions, or recent antibiotic use. Most of the preoperative preparation of the surgical site was the same in the experimental and control arms. This included hair clipping, application of 2% chlorhexidine, and cleansing with saturated 7.5% povidone-iodine solution surgical scrub brushes.

The difference was that 3% hydrogen peroxide–soaked gauzes were applied to perioperative skin of those randomized to the experimental group but not to controls. All patients received routine preoperative oral antibiotics as well as perioperative applications of a formulation containing 2% chlorhexidine gluconate and 70% isopropyl alcohol.

Following surgery, 11 (18.6%) of the 59 patients in the experimental arm versus 23 (34.8%) of the 66 patients randomized to the control group had positive cultures for C. acnes (P = .047), according to the trial results, which have now been published (J Shoulder Elbow Surg. 2020;29:212-6).

There were no cases of skin reactions in either the experimental or control groups.

Topical skin cleansers that contain peroxide, such as benzoyl peroxide, have been shown to have a C. acnes decolonizing effect if applied repeatedly in the days prior to surgery, but Dr. Namdari suggested the problem with this approach is that it depends on patient compliance. A prophylaxis included in the preoperative routine eliminates this potential problem.

C. acnes is an anaerobic bacterium that is part of the resident flora of the skin around several joints, including the knee and the hip, but it is particularly common in the posterior shoulder. Colonization has been found substantially more common in men than in women, according to Dr. Namdari.

The specific threat posed by C. acnes to risk of postoperative infections “is still being defined,” and this trial was not large enough to associate the reduction in postoperative C. acnes cultures with a reduced risk of an adverse clinical outcome, but Dr. Namdari says that the data do show that the nearly 50% reduction in positive cultures was achieved efficiently and inexpensively with no apparent risk.

Several previous studies have also evaluated strategies for reducing C. acnes skin burden on the basis of expected protection against postoperative infection. In one, which associated a 3-day preoperative course of benzoyl peroxide with a reduction in the skin burden of C. acnes, the authors also concluded that this approach deserves consideration in routine skin preparation for shoulder arthroplasty (J Shoulder Elbow Surg. 2018;27:1539-44).

“We believe that a preoperative skin prep protocol that reduces C. acnes load on the skin would likely lead to reduced postoperative infections,” reported the senior author, Mohit N. Gilotra, MD, assistant professor, University of Maryland, Baltimore. Contacted about the rationale for reducing C. acnes skin burden without objective evidence of an impact on postoperative infection risk, Dr. Gilotra indicated these strategies make sense.

“It seems to be true for staph infections and is a reasonable assumption to make here,” he added. “Future work will help determine how much benzoyl peroxide, hydrogen peroxide, or other skin prep can reduce surgical site infection.”

Dr. Namdari reports financial relationships with multiple device and pharmaceutical companies but none relevant to this study.

SOURCE: Namdari S et al. AAOS 2020. Abstract P0808.

Prior to shoulder surgery, application of 3% hydrogen peroxide is a simple and inexpensive strategy to reduce the risk of postoperative cultures of Cutibacterium acnes, according to findings from a prospective randomized trial. The results were reported in an abstract scheduled for release at the annual meeting of the American Academy of Orthopaedic Surgeons. The meeting was canceled because of COVID-19.

“This approach is simple, cheap, and does not rely on patient compliance,” explained Surena Namdari, MD, associate professor of orthopedic surgery at Thomas Jefferson University, Philadelphia.

C. acnes, formerly known as Propionibacterium acnes, is increasingly seen as an important target for prevention of postoperative shoulder infections because of published reports that it is the most commonly isolated bacterium from such infections, Dr. Namdari said in an interview.

In the prospective, randomized trial, male patients scheduled for shoulder arthroscopy were recruited if they did not have active acne, history of psoriatic or eczematous lesions, or recent antibiotic use. Most of the preoperative preparation of the surgical site was the same in the experimental and control arms. This included hair clipping, application of 2% chlorhexidine, and cleansing with saturated 7.5% povidone-iodine solution surgical scrub brushes.

The difference was that 3% hydrogen peroxide–soaked gauzes were applied to perioperative skin of those randomized to the experimental group but not to controls. All patients received routine preoperative oral antibiotics as well as perioperative applications of a formulation containing 2% chlorhexidine gluconate and 70% isopropyl alcohol.

Following surgery, 11 (18.6%) of the 59 patients in the experimental arm versus 23 (34.8%) of the 66 patients randomized to the control group had positive cultures for C. acnes (P = .047), according to the trial results, which have now been published (J Shoulder Elbow Surg. 2020;29:212-6).

There were no cases of skin reactions in either the experimental or control groups.

Topical skin cleansers that contain peroxide, such as benzoyl peroxide, have been shown to have a C. acnes decolonizing effect if applied repeatedly in the days prior to surgery, but Dr. Namdari suggested the problem with this approach is that it depends on patient compliance. A prophylaxis included in the preoperative routine eliminates this potential problem.

C. acnes is an anaerobic bacterium that is part of the resident flora of the skin around several joints, including the knee and the hip, but it is particularly common in the posterior shoulder. Colonization has been found substantially more common in men than in women, according to Dr. Namdari.

The specific threat posed by C. acnes to risk of postoperative infections “is still being defined,” and this trial was not large enough to associate the reduction in postoperative C. acnes cultures with a reduced risk of an adverse clinical outcome, but Dr. Namdari says that the data do show that the nearly 50% reduction in positive cultures was achieved efficiently and inexpensively with no apparent risk.

Several previous studies have also evaluated strategies for reducing C. acnes skin burden on the basis of expected protection against postoperative infection. In one, which associated a 3-day preoperative course of benzoyl peroxide with a reduction in the skin burden of C. acnes, the authors also concluded that this approach deserves consideration in routine skin preparation for shoulder arthroplasty (J Shoulder Elbow Surg. 2018;27:1539-44).

“We believe that a preoperative skin prep protocol that reduces C. acnes load on the skin would likely lead to reduced postoperative infections,” reported the senior author, Mohit N. Gilotra, MD, assistant professor, University of Maryland, Baltimore. Contacted about the rationale for reducing C. acnes skin burden without objective evidence of an impact on postoperative infection risk, Dr. Gilotra indicated these strategies make sense.

“It seems to be true for staph infections and is a reasonable assumption to make here,” he added. “Future work will help determine how much benzoyl peroxide, hydrogen peroxide, or other skin prep can reduce surgical site infection.”

Dr. Namdari reports financial relationships with multiple device and pharmaceutical companies but none relevant to this study.

SOURCE: Namdari S et al. AAOS 2020. Abstract P0808.

Prior to shoulder surgery, application of 3% hydrogen peroxide is a simple and inexpensive strategy to reduce the risk of postoperative cultures of Cutibacterium acnes, according to findings from a prospective randomized trial. The results were reported in an abstract scheduled for release at the annual meeting of the American Academy of Orthopaedic Surgeons. The meeting was canceled because of COVID-19.

“This approach is simple, cheap, and does not rely on patient compliance,” explained Surena Namdari, MD, associate professor of orthopedic surgery at Thomas Jefferson University, Philadelphia.

C. acnes, formerly known as Propionibacterium acnes, is increasingly seen as an important target for prevention of postoperative shoulder infections because of published reports that it is the most commonly isolated bacterium from such infections, Dr. Namdari said in an interview.

In the prospective, randomized trial, male patients scheduled for shoulder arthroscopy were recruited if they did not have active acne, history of psoriatic or eczematous lesions, or recent antibiotic use. Most of the preoperative preparation of the surgical site was the same in the experimental and control arms. This included hair clipping, application of 2% chlorhexidine, and cleansing with saturated 7.5% povidone-iodine solution surgical scrub brushes.

The difference was that 3% hydrogen peroxide–soaked gauzes were applied to perioperative skin of those randomized to the experimental group but not to controls. All patients received routine preoperative oral antibiotics as well as perioperative applications of a formulation containing 2% chlorhexidine gluconate and 70% isopropyl alcohol.

Following surgery, 11 (18.6%) of the 59 patients in the experimental arm versus 23 (34.8%) of the 66 patients randomized to the control group had positive cultures for C. acnes (P = .047), according to the trial results, which have now been published (J Shoulder Elbow Surg. 2020;29:212-6).

There were no cases of skin reactions in either the experimental or control groups.

Topical skin cleansers that contain peroxide, such as benzoyl peroxide, have been shown to have a C. acnes decolonizing effect if applied repeatedly in the days prior to surgery, but Dr. Namdari suggested the problem with this approach is that it depends on patient compliance. A prophylaxis included in the preoperative routine eliminates this potential problem.

C. acnes is an anaerobic bacterium that is part of the resident flora of the skin around several joints, including the knee and the hip, but it is particularly common in the posterior shoulder. Colonization has been found substantially more common in men than in women, according to Dr. Namdari.

The specific threat posed by C. acnes to risk of postoperative infections “is still being defined,” and this trial was not large enough to associate the reduction in postoperative C. acnes cultures with a reduced risk of an adverse clinical outcome, but Dr. Namdari says that the data do show that the nearly 50% reduction in positive cultures was achieved efficiently and inexpensively with no apparent risk.

Several previous studies have also evaluated strategies for reducing C. acnes skin burden on the basis of expected protection against postoperative infection. In one, which associated a 3-day preoperative course of benzoyl peroxide with a reduction in the skin burden of C. acnes, the authors also concluded that this approach deserves consideration in routine skin preparation for shoulder arthroplasty (J Shoulder Elbow Surg. 2018;27:1539-44).

“We believe that a preoperative skin prep protocol that reduces C. acnes load on the skin would likely lead to reduced postoperative infections,” reported the senior author, Mohit N. Gilotra, MD, assistant professor, University of Maryland, Baltimore. Contacted about the rationale for reducing C. acnes skin burden without objective evidence of an impact on postoperative infection risk, Dr. Gilotra indicated these strategies make sense.

“It seems to be true for staph infections and is a reasonable assumption to make here,” he added. “Future work will help determine how much benzoyl peroxide, hydrogen peroxide, or other skin prep can reduce surgical site infection.”

Dr. Namdari reports financial relationships with multiple device and pharmaceutical companies but none relevant to this study.

SOURCE: Namdari S et al. AAOS 2020. Abstract P0808.

MAUI, HAWAII – Anti-Ro52 autoantibodies are the latest and most potent of the autoantibody predictors of interstitial lung disease (ILD) discovered in patients with juvenile dermatomyositis, Anne M. Stevens, MD, PhD, said at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

In addition to detailing the autoantibody red flags for ILD in juvenile dermatomyositis (JDM), she called for “hypervigilance” in patients with systemic juvenile idiopathic arthritis (SJIA) who exhibit any of a series of risk factors for ILD.

“Most of the lung disease in kids with systemic JIA is asymptomatic until very late, but it can be reversible if we treat it. So it’s worth finding and monitoring and giving everyone PCP [pneumocystis pneumonia] prophylaxis, because they have a high incidence of PCP if they have any of those risk factors,” observed Dr. Stevens, a pediatric rheumatologist at the University of Washington, Seattle, and senior director for the adaptive immunity research program at Janssen Pharmaceuticals.
 

Autoantibodies predict ILD in JDM

Dr. Stevens highlighted recent work by Sara Sabbagh, DO, of the National Institute of Arthritis and Musculoskeletal and Skin Diseases and coinvestigators in the Childhood Myositis Heterogeneity Collaborative Study Group. They reported the presence of anti-Ro52 autoantibodies in 14% of a cohort of 302 patients with JDM as well as in 12% of 25 patients with juvenile polymyositis and in 18% of 44 youths with an overlap of juvenile connective tissue disease and myositis. In addition, 13% of patients were positive for autoantibodies previously identified as being associated with ILD in these forms of juvenile myositis: Namely, 9% of the cohort were positive for antimelanoma differentiation–associated protein 5 (anti-MDA5) autoantibodies, and antiaminoacyl tRNA synthestase (anti-Jo-1) autoantibodies were present in 4%.

A total of 33 of the 371 juvenile myositis patients had ILD based upon CT imaging, chest X-ray, dyspnea on exertion, and/or biopsy. Most patients with anti-Ro52 also had other autoantibodies associated with ILD. Indeed, 31% of patients with anti-MDA5 autoantibodies also had anti-Ro52, as did 64% of those with anti-Jo-1. After controlling for the presence of these other myositis-specific autoantibodies, auto-Ro52 autoantibodies were independently associated with ILD, which was present in 36% of those with and just 4% of those without anti-Ro52 autoantibodies.

Importantly, if a patient with JDM or another form of juvenile myositis had both anti-Ro52 and another myositis-specific autoantibody, the risk for ILD rose dramatically, climbing to 70% in patients with anti-Ro52 and anti-MDA5 autoantibodies, and to 100% in those who were both anti-Ro52- and anti-Jo-1 positive.

Patients with anti-Ro52 autoantibodies had a worse prognosis, with more severe and chronic disease, Dr. Stevens noted.
 

Novel potential treatment for ILD in JDM: JAK inhibitors

Standard treatment of ILD in JDM in all cases includes high-dose pulsed corticosteroids, intravenous immunoglobulin (IVIG), and either methotrexate or mycophenolate mofetil. Consideration should be given to adding cyclosporine, particularly when a macrophage activation syndrome component is present. In addition, several exciting recent lines of evidence suggest a potential role for Janus kinase (JAK) inhibitors in the subset of JDM patients with anti-MDA5 autoantibody-positive disease, according to Dr. Stevens.

For one, Dr. Sabbagh and colleagues have reported impressive success with the use of the JAK 1/3 inhibitor tofacitinib (Xeljanz) in two patients with anti-MDA5 autoantibody-positive refractory JDM with ILD. Both patients experienced moderate clinical improvement in disease activity in their skin, muscles, and other target organs. But particularly striking was what the investigators termed the “remarkable” improvement in ILD, including near-resolution of abnormal findings on high-resolution CT imaging and a more robust performance on pulmonary function testing.

Both of these hitherto treatment-refractory patients were able to wean or discontinue their immunosuppressive medications. The patients’ elevated blood interferon-response gene signature improved significantly in response to tofacitinib, and their problematic upregulation of STAT1 phosphorylation of CD4+ T cells and monocytes stimulated with interferon-gamma was tamed, dropping to levels typically seen in healthy individuals.

Also, French pediatric rheumatologists have identified key phenotypic and cytokine differences between 13 patients with JDM or juvenile overlap myositis who were anti-MDA5 autoantibody positive at presentation and 51 others who were not. The anti-MDA5 autoantibody–positive group had a higher frequency of ILD, arthritis, skin ulcerations, and lupus features, but milder muscle involvement than did the anti-MDA5 autoantibody–negative group. The anti-MDA5 autoantibody–positive patients demonstrated enhanced interferon-alpha signaling based upon their significantly higher serum interferon-alpha levels, compared with the anti-MDA5-negative group, and those levels decreased following treatment with improvement in symptoms.

The French investigators proposed that interferon-alpha may constitute a novel therapeutic target in the subgroup of patients with severe, refractory juvenile myositis and anti-MDA5 autoantibodies – and, as it happens, it’s known that JAK inhibitors modulate the interferon pathway.
 

Risk factors for ILD in SJIA

In the past half-dozen years or so, pediatric rheumatologists have become increasingly aware of and concerned about a new development in SJIA: the occurrence of comorbid ILD. This is a poor-prognosis disease: In a cohort from the United Kingdom, 5-year mortality from the time of diagnosis was 41%, fully 40-fold higher than in patients with SJIA only.

Patient cohorts with SJIA and ILD have unusual clinical and laboratory features that aren’t part of the typical picture in SJIA. These include acute clubbing, lymphopenia, a fixed pruritic rash, unexplained abdominal pain, peripheral eosinophilia, facial swelling, and an increased ferritin level, a hallmark of acute macrophage activation syndrome. Onset of SJIA before 2 years of age is another red flag associated with increased risk for ILD. So is trisomy 21, which is up to 50 times more prevalent in patients with SJIA and ILD than in the general population or in patients with SJIA only. Another clue is an adverse reaction to tocilizumab (Actemra).

Any of these findings warrant hypervigilance: “Be on high alert and monitor these patients for ILD much more closely,” Dr. Stevens advised.

This means ordering a CT scan, prescribing PCP prophylaxis, and regularly measuring pulmonary function, admittedly a challenge in children under 7 years old. In these younger kids, practical solutions include measuring their oxygen saturation before and after running around the room to see if it drops. A 6-minute walk test and sleep oximetry are other options.

The explanation for the abrupt arrival of ILD as part of the picture in SJIA during the past decade remains unclear. The timing coincides with a major advance in the treatment of SJIA: the arrival of biologic agents blocking interleukin-1 and -6. Could this be a serious treatment side effect?

“It’s all association so far, and we’re not really sure why we’re seeing this association. Is it because we’re using a lot [fewer] corticosteroids now, and maybe those were preventing lung disease in the past?” Dr. Stevens speculated.

At this point, she and her fellow pediatric rheumatologists are awaiting further evidence before discussing a curb in their use of IL-1 or -6 inhibitors in patients with SJIA.

“These drugs have turned around the lives of kids with SJIA. They used to suffer through all our ineffective treatments for years, with terrible joint destruction and a pretty high mortality rate. These are great drugs for this disease, and we certainly don’t want to limit them,” she said.

Dr. Stevens reported research collaborations with Kineta and Seattle Genetics in addition to her employment at Janssen Pharmaceuticals.

bjancin@mdedge.com

MAUI, HAWAII – Anti-Ro52 autoantibodies are the latest and most potent of the autoantibody predictors of interstitial lung disease (ILD) discovered in patients with juvenile dermatomyositis, Anne M. Stevens, MD, PhD, said at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

In addition to detailing the autoantibody red flags for ILD in juvenile dermatomyositis (JDM), she called for “hypervigilance” in patients with systemic juvenile idiopathic arthritis (SJIA) who exhibit any of a series of risk factors for ILD.

“Most of the lung disease in kids with systemic JIA is asymptomatic until very late, but it can be reversible if we treat it. So it’s worth finding and monitoring and giving everyone PCP [pneumocystis pneumonia] prophylaxis, because they have a high incidence of PCP if they have any of those risk factors,” observed Dr. Stevens, a pediatric rheumatologist at the University of Washington, Seattle, and senior director for the adaptive immunity research program at Janssen Pharmaceuticals.
 

Autoantibodies predict ILD in JDM

Dr. Stevens highlighted recent work by Sara Sabbagh, DO, of the National Institute of Arthritis and Musculoskeletal and Skin Diseases and coinvestigators in the Childhood Myositis Heterogeneity Collaborative Study Group. They reported the presence of anti-Ro52 autoantibodies in 14% of a cohort of 302 patients with JDM as well as in 12% of 25 patients with juvenile polymyositis and in 18% of 44 youths with an overlap of juvenile connective tissue disease and myositis. In addition, 13% of patients were positive for autoantibodies previously identified as being associated with ILD in these forms of juvenile myositis: Namely, 9% of the cohort were positive for antimelanoma differentiation–associated protein 5 (anti-MDA5) autoantibodies, and antiaminoacyl tRNA synthestase (anti-Jo-1) autoantibodies were present in 4%.

A total of 33 of the 371 juvenile myositis patients had ILD based upon CT imaging, chest X-ray, dyspnea on exertion, and/or biopsy. Most patients with anti-Ro52 also had other autoantibodies associated with ILD. Indeed, 31% of patients with anti-MDA5 autoantibodies also had anti-Ro52, as did 64% of those with anti-Jo-1. After controlling for the presence of these other myositis-specific autoantibodies, auto-Ro52 autoantibodies were independently associated with ILD, which was present in 36% of those with and just 4% of those without anti-Ro52 autoantibodies.

Importantly, if a patient with JDM or another form of juvenile myositis had both anti-Ro52 and another myositis-specific autoantibody, the risk for ILD rose dramatically, climbing to 70% in patients with anti-Ro52 and anti-MDA5 autoantibodies, and to 100% in those who were both anti-Ro52- and anti-Jo-1 positive.

Patients with anti-Ro52 autoantibodies had a worse prognosis, with more severe and chronic disease, Dr. Stevens noted.
 

Novel potential treatment for ILD in JDM: JAK inhibitors

Standard treatment of ILD in JDM in all cases includes high-dose pulsed corticosteroids, intravenous immunoglobulin (IVIG), and either methotrexate or mycophenolate mofetil. Consideration should be given to adding cyclosporine, particularly when a macrophage activation syndrome component is present. In addition, several exciting recent lines of evidence suggest a potential role for Janus kinase (JAK) inhibitors in the subset of JDM patients with anti-MDA5 autoantibody-positive disease, according to Dr. Stevens.

For one, Dr. Sabbagh and colleagues have reported impressive success with the use of the JAK 1/3 inhibitor tofacitinib (Xeljanz) in two patients with anti-MDA5 autoantibody-positive refractory JDM with ILD. Both patients experienced moderate clinical improvement in disease activity in their skin, muscles, and other target organs. But particularly striking was what the investigators termed the “remarkable” improvement in ILD, including near-resolution of abnormal findings on high-resolution CT imaging and a more robust performance on pulmonary function testing.

Both of these hitherto treatment-refractory patients were able to wean or discontinue their immunosuppressive medications. The patients’ elevated blood interferon-response gene signature improved significantly in response to tofacitinib, and their problematic upregulation of STAT1 phosphorylation of CD4+ T cells and monocytes stimulated with interferon-gamma was tamed, dropping to levels typically seen in healthy individuals.

Also, French pediatric rheumatologists have identified key phenotypic and cytokine differences between 13 patients with JDM or juvenile overlap myositis who were anti-MDA5 autoantibody positive at presentation and 51 others who were not. The anti-MDA5 autoantibody–positive group had a higher frequency of ILD, arthritis, skin ulcerations, and lupus features, but milder muscle involvement than did the anti-MDA5 autoantibody–negative group. The anti-MDA5 autoantibody–positive patients demonstrated enhanced interferon-alpha signaling based upon their significantly higher serum interferon-alpha levels, compared with the anti-MDA5-negative group, and those levels decreased following treatment with improvement in symptoms.

The French investigators proposed that interferon-alpha may constitute a novel therapeutic target in the subgroup of patients with severe, refractory juvenile myositis and anti-MDA5 autoantibodies – and, as it happens, it’s known that JAK inhibitors modulate the interferon pathway.
 

Risk factors for ILD in SJIA

In the past half-dozen years or so, pediatric rheumatologists have become increasingly aware of and concerned about a new development in SJIA: the occurrence of comorbid ILD. This is a poor-prognosis disease: In a cohort from the United Kingdom, 5-year mortality from the time of diagnosis was 41%, fully 40-fold higher than in patients with SJIA only.

Patient cohorts with SJIA and ILD have unusual clinical and laboratory features that aren’t part of the typical picture in SJIA. These include acute clubbing, lymphopenia, a fixed pruritic rash, unexplained abdominal pain, peripheral eosinophilia, facial swelling, and an increased ferritin level, a hallmark of acute macrophage activation syndrome. Onset of SJIA before 2 years of age is another red flag associated with increased risk for ILD. So is trisomy 21, which is up to 50 times more prevalent in patients with SJIA and ILD than in the general population or in patients with SJIA only. Another clue is an adverse reaction to tocilizumab (Actemra).

Any of these findings warrant hypervigilance: “Be on high alert and monitor these patients for ILD much more closely,” Dr. Stevens advised.

This means ordering a CT scan, prescribing PCP prophylaxis, and regularly measuring pulmonary function, admittedly a challenge in children under 7 years old. In these younger kids, practical solutions include measuring their oxygen saturation before and after running around the room to see if it drops. A 6-minute walk test and sleep oximetry are other options.

The explanation for the abrupt arrival of ILD as part of the picture in SJIA during the past decade remains unclear. The timing coincides with a major advance in the treatment of SJIA: the arrival of biologic agents blocking interleukin-1 and -6. Could this be a serious treatment side effect?

“It’s all association so far, and we’re not really sure why we’re seeing this association. Is it because we’re using a lot [fewer] corticosteroids now, and maybe those were preventing lung disease in the past?” Dr. Stevens speculated.

At this point, she and her fellow pediatric rheumatologists are awaiting further evidence before discussing a curb in their use of IL-1 or -6 inhibitors in patients with SJIA.

“These drugs have turned around the lives of kids with SJIA. They used to suffer through all our ineffective treatments for years, with terrible joint destruction and a pretty high mortality rate. These are great drugs for this disease, and we certainly don’t want to limit them,” she said.

Dr. Stevens reported research collaborations with Kineta and Seattle Genetics in addition to her employment at Janssen Pharmaceuticals.

bjancin@mdedge.com

MAUI, HAWAII – Anti-Ro52 autoantibodies are the latest and most potent of the autoantibody predictors of interstitial lung disease (ILD) discovered in patients with juvenile dermatomyositis, Anne M. Stevens, MD, PhD, said at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

In addition to detailing the autoantibody red flags for ILD in juvenile dermatomyositis (JDM), she called for “hypervigilance” in patients with systemic juvenile idiopathic arthritis (SJIA) who exhibit any of a series of risk factors for ILD.

“Most of the lung disease in kids with systemic JIA is asymptomatic until very late, but it can be reversible if we treat it. So it’s worth finding and monitoring and giving everyone PCP [pneumocystis pneumonia] prophylaxis, because they have a high incidence of PCP if they have any of those risk factors,” observed Dr. Stevens, a pediatric rheumatologist at the University of Washington, Seattle, and senior director for the adaptive immunity research program at Janssen Pharmaceuticals.
 

Autoantibodies predict ILD in JDM

Dr. Stevens highlighted recent work by Sara Sabbagh, DO, of the National Institute of Arthritis and Musculoskeletal and Skin Diseases and coinvestigators in the Childhood Myositis Heterogeneity Collaborative Study Group. They reported the presence of anti-Ro52 autoantibodies in 14% of a cohort of 302 patients with JDM as well as in 12% of 25 patients with juvenile polymyositis and in 18% of 44 youths with an overlap of juvenile connective tissue disease and myositis. In addition, 13% of patients were positive for autoantibodies previously identified as being associated with ILD in these forms of juvenile myositis: Namely, 9% of the cohort were positive for antimelanoma differentiation–associated protein 5 (anti-MDA5) autoantibodies, and antiaminoacyl tRNA synthestase (anti-Jo-1) autoantibodies were present in 4%.

A total of 33 of the 371 juvenile myositis patients had ILD based upon CT imaging, chest X-ray, dyspnea on exertion, and/or biopsy. Most patients with anti-Ro52 also had other autoantibodies associated with ILD. Indeed, 31% of patients with anti-MDA5 autoantibodies also had anti-Ro52, as did 64% of those with anti-Jo-1. After controlling for the presence of these other myositis-specific autoantibodies, auto-Ro52 autoantibodies were independently associated with ILD, which was present in 36% of those with and just 4% of those without anti-Ro52 autoantibodies.

Importantly, if a patient with JDM or another form of juvenile myositis had both anti-Ro52 and another myositis-specific autoantibody, the risk for ILD rose dramatically, climbing to 70% in patients with anti-Ro52 and anti-MDA5 autoantibodies, and to 100% in those who were both anti-Ro52- and anti-Jo-1 positive.

Patients with anti-Ro52 autoantibodies had a worse prognosis, with more severe and chronic disease, Dr. Stevens noted.
 

Novel potential treatment for ILD in JDM: JAK inhibitors

Standard treatment of ILD in JDM in all cases includes high-dose pulsed corticosteroids, intravenous immunoglobulin (IVIG), and either methotrexate or mycophenolate mofetil. Consideration should be given to adding cyclosporine, particularly when a macrophage activation syndrome component is present. In addition, several exciting recent lines of evidence suggest a potential role for Janus kinase (JAK) inhibitors in the subset of JDM patients with anti-MDA5 autoantibody-positive disease, according to Dr. Stevens.

For one, Dr. Sabbagh and colleagues have reported impressive success with the use of the JAK 1/3 inhibitor tofacitinib (Xeljanz) in two patients with anti-MDA5 autoantibody-positive refractory JDM with ILD. Both patients experienced moderate clinical improvement in disease activity in their skin, muscles, and other target organs. But particularly striking was what the investigators termed the “remarkable” improvement in ILD, including near-resolution of abnormal findings on high-resolution CT imaging and a more robust performance on pulmonary function testing.

Both of these hitherto treatment-refractory patients were able to wean or discontinue their immunosuppressive medications. The patients’ elevated blood interferon-response gene signature improved significantly in response to tofacitinib, and their problematic upregulation of STAT1 phosphorylation of CD4+ T cells and monocytes stimulated with interferon-gamma was tamed, dropping to levels typically seen in healthy individuals.

Also, French pediatric rheumatologists have identified key phenotypic and cytokine differences between 13 patients with JDM or juvenile overlap myositis who were anti-MDA5 autoantibody positive at presentation and 51 others who were not. The anti-MDA5 autoantibody–positive group had a higher frequency of ILD, arthritis, skin ulcerations, and lupus features, but milder muscle involvement than did the anti-MDA5 autoantibody–negative group. The anti-MDA5 autoantibody–positive patients demonstrated enhanced interferon-alpha signaling based upon their significantly higher serum interferon-alpha levels, compared with the anti-MDA5-negative group, and those levels decreased following treatment with improvement in symptoms.

The French investigators proposed that interferon-alpha may constitute a novel therapeutic target in the subgroup of patients with severe, refractory juvenile myositis and anti-MDA5 autoantibodies – and, as it happens, it’s known that JAK inhibitors modulate the interferon pathway.
 

Risk factors for ILD in SJIA

In the past half-dozen years or so, pediatric rheumatologists have become increasingly aware of and concerned about a new development in SJIA: the occurrence of comorbid ILD. This is a poor-prognosis disease: In a cohort from the United Kingdom, 5-year mortality from the time of diagnosis was 41%, fully 40-fold higher than in patients with SJIA only.

Patient cohorts with SJIA and ILD have unusual clinical and laboratory features that aren’t part of the typical picture in SJIA. These include acute clubbing, lymphopenia, a fixed pruritic rash, unexplained abdominal pain, peripheral eosinophilia, facial swelling, and an increased ferritin level, a hallmark of acute macrophage activation syndrome. Onset of SJIA before 2 years of age is another red flag associated with increased risk for ILD. So is trisomy 21, which is up to 50 times more prevalent in patients with SJIA and ILD than in the general population or in patients with SJIA only. Another clue is an adverse reaction to tocilizumab (Actemra).

Any of these findings warrant hypervigilance: “Be on high alert and monitor these patients for ILD much more closely,” Dr. Stevens advised.

This means ordering a CT scan, prescribing PCP prophylaxis, and regularly measuring pulmonary function, admittedly a challenge in children under 7 years old. In these younger kids, practical solutions include measuring their oxygen saturation before and after running around the room to see if it drops. A 6-minute walk test and sleep oximetry are other options.

The explanation for the abrupt arrival of ILD as part of the picture in SJIA during the past decade remains unclear. The timing coincides with a major advance in the treatment of SJIA: the arrival of biologic agents blocking interleukin-1 and -6. Could this be a serious treatment side effect?

“It’s all association so far, and we’re not really sure why we’re seeing this association. Is it because we’re using a lot [fewer] corticosteroids now, and maybe those were preventing lung disease in the past?” Dr. Stevens speculated.

At this point, she and her fellow pediatric rheumatologists are awaiting further evidence before discussing a curb in their use of IL-1 or -6 inhibitors in patients with SJIA.

“These drugs have turned around the lives of kids with SJIA. They used to suffer through all our ineffective treatments for years, with terrible joint destruction and a pretty high mortality rate. These are great drugs for this disease, and we certainly don’t want to limit them,” she said.

Dr. Stevens reported research collaborations with Kineta and Seattle Genetics in addition to her employment at Janssen Pharmaceuticals.

bjancin@mdedge.com

For seriously ill patients with multidrug-resistant organisms (MDROs) in their gastrointestinal tract, performing a fecal microbiota transplant (FMT) may result in fewer and less severe infections, as well as shorter hospital stays, according to investigators.

Significant clinical improvements were observed across the group even though 59% of patients did not clear MDROs, which suggests that complete decolonization of resistant organisms may be unnecessary for patients to benefit from FMT, reported lead author Julian Marchesi, PhD, of Cardiff (Wales) University and Imperial College London (England).

“We see the quality of life for these patients is hugely improved even when we don’t get rid of the organism totally,” Dr. Marchesi said in a virtual press conference.

Although previous studies have suggested that FMT may be used to decolonize MDROs, little research has addressed other clinical outcomes, the investigators wrote in an abstract released as part of the annual Digestive Disease Week®, which was canceled because of COVID-19.

The present study involved 20 patients with MDROs, including extended-spectrum beta-lactamase Enterobacteriaceae (ESBL), carbapenemase-producing Enterobacteriaceae (CPE), or vancomycin-resistant enterococci (VRE). Approximately half of the population (n = 11) had chronic hematological disease. The other half (n = 9) had recurrent urinary tract infections with ESBL, including patients who had undergone renal transplant or had recurrent Clostridioides difficile infection.

For each transplant, 200-300 mL of fecal slurry was delivered via nasogastric tube into the small intestine. Fecal donors underwent a strict screening process that included blood, fecal, and behavioral testing.

Multiple clinical outcomes were evaluated in the 6 months leading up to FMT, then compared with outcomes in the 6 months following fecal transplant. Out of 20 patients, 17 completed the 6-month follow-up. Although only 7 of these patients (41%) were decolonized of MDROs, multiple significant clinical improvements were observed across the group, including reductions in MDRO bloodstream infections (P = .047), all bloodstream infections (P = .03), length of stay in hospital (P = .0002), and duration of carbapenem use (P = .0005). Eight out of 11 patients with hematologic disease improved enough to undergo stem cell transplantation within 6 months of FMT, and in the subgroup of patients who had undergone renal transplant, the rate of urinary tract infections was significantly improved (P = .008).

No serious adverse events were encountered during the trial, which led the investigators to conclude that FMT was safe and well tolerated, even in patients with bloodstream infections and those who were highly immunosuppressed.

Beyond clinical implications, Dr. Marchesi suggested that the study findings should influence FMT trial methodology.

“We’ve got to start thinking a little bit differently in terms of how we measure the impact of FMT,” he said. “It’s not all about ... getting rid of these opportunistic pathogens. There are other quality-of-life factors that we need to measure, because they’re also important for the patient.”

Dr. Marchesi said that more research is needed to confirm findings and gain a mechanistic understanding of why patients may improve despite a lack of decolonization.

“We think we’re on a strong foundation here to take this into a clinical trial,” he said.

The research was funded by the National Institute for Health Research and the Medical Research Council. The investigators reported no conflicts of interest.

For seriously ill patients with multidrug-resistant organisms (MDROs) in their gastrointestinal tract, performing a fecal microbiota transplant (FMT) may result in fewer and less severe infections, as well as shorter hospital stays, according to investigators.

Significant clinical improvements were observed across the group even though 59% of patients did not clear MDROs, which suggests that complete decolonization of resistant organisms may be unnecessary for patients to benefit from FMT, reported lead author Julian Marchesi, PhD, of Cardiff (Wales) University and Imperial College London (England).

“We see the quality of life for these patients is hugely improved even when we don’t get rid of the organism totally,” Dr. Marchesi said in a virtual press conference.

Although previous studies have suggested that FMT may be used to decolonize MDROs, little research has addressed other clinical outcomes, the investigators wrote in an abstract released as part of the annual Digestive Disease Week®, which was canceled because of COVID-19.

The present study involved 20 patients with MDROs, including extended-spectrum beta-lactamase Enterobacteriaceae (ESBL), carbapenemase-producing Enterobacteriaceae (CPE), or vancomycin-resistant enterococci (VRE). Approximately half of the population (n = 11) had chronic hematological disease. The other half (n = 9) had recurrent urinary tract infections with ESBL, including patients who had undergone renal transplant or had recurrent Clostridioides difficile infection.

For each transplant, 200-300 mL of fecal slurry was delivered via nasogastric tube into the small intestine. Fecal donors underwent a strict screening process that included blood, fecal, and behavioral testing.

Multiple clinical outcomes were evaluated in the 6 months leading up to FMT, then compared with outcomes in the 6 months following fecal transplant. Out of 20 patients, 17 completed the 6-month follow-up. Although only 7 of these patients (41%) were decolonized of MDROs, multiple significant clinical improvements were observed across the group, including reductions in MDRO bloodstream infections (P = .047), all bloodstream infections (P = .03), length of stay in hospital (P = .0002), and duration of carbapenem use (P = .0005). Eight out of 11 patients with hematologic disease improved enough to undergo stem cell transplantation within 6 months of FMT, and in the subgroup of patients who had undergone renal transplant, the rate of urinary tract infections was significantly improved (P = .008).

No serious adverse events were encountered during the trial, which led the investigators to conclude that FMT was safe and well tolerated, even in patients with bloodstream infections and those who were highly immunosuppressed.

Beyond clinical implications, Dr. Marchesi suggested that the study findings should influence FMT trial methodology.

“We’ve got to start thinking a little bit differently in terms of how we measure the impact of FMT,” he said. “It’s not all about ... getting rid of these opportunistic pathogens. There are other quality-of-life factors that we need to measure, because they’re also important for the patient.”

Dr. Marchesi said that more research is needed to confirm findings and gain a mechanistic understanding of why patients may improve despite a lack of decolonization.

“We think we’re on a strong foundation here to take this into a clinical trial,” he said.

The research was funded by the National Institute for Health Research and the Medical Research Council. The investigators reported no conflicts of interest.

For seriously ill patients with multidrug-resistant organisms (MDROs) in their gastrointestinal tract, performing a fecal microbiota transplant (FMT) may result in fewer and less severe infections, as well as shorter hospital stays, according to investigators.

Significant clinical improvements were observed across the group even though 59% of patients did not clear MDROs, which suggests that complete decolonization of resistant organisms may be unnecessary for patients to benefit from FMT, reported lead author Julian Marchesi, PhD, of Cardiff (Wales) University and Imperial College London (England).

“We see the quality of life for these patients is hugely improved even when we don’t get rid of the organism totally,” Dr. Marchesi said in a virtual press conference.

Although previous studies have suggested that FMT may be used to decolonize MDROs, little research has addressed other clinical outcomes, the investigators wrote in an abstract released as part of the annual Digestive Disease Week®, which was canceled because of COVID-19.

The present study involved 20 patients with MDROs, including extended-spectrum beta-lactamase Enterobacteriaceae (ESBL), carbapenemase-producing Enterobacteriaceae (CPE), or vancomycin-resistant enterococci (VRE). Approximately half of the population (n = 11) had chronic hematological disease. The other half (n = 9) had recurrent urinary tract infections with ESBL, including patients who had undergone renal transplant or had recurrent Clostridioides difficile infection.

For each transplant, 200-300 mL of fecal slurry was delivered via nasogastric tube into the small intestine. Fecal donors underwent a strict screening process that included blood, fecal, and behavioral testing.

Multiple clinical outcomes were evaluated in the 6 months leading up to FMT, then compared with outcomes in the 6 months following fecal transplant. Out of 20 patients, 17 completed the 6-month follow-up. Although only 7 of these patients (41%) were decolonized of MDROs, multiple significant clinical improvements were observed across the group, including reductions in MDRO bloodstream infections (P = .047), all bloodstream infections (P = .03), length of stay in hospital (P = .0002), and duration of carbapenem use (P = .0005). Eight out of 11 patients with hematologic disease improved enough to undergo stem cell transplantation within 6 months of FMT, and in the subgroup of patients who had undergone renal transplant, the rate of urinary tract infections was significantly improved (P = .008).

No serious adverse events were encountered during the trial, which led the investigators to conclude that FMT was safe and well tolerated, even in patients with bloodstream infections and those who were highly immunosuppressed.

Beyond clinical implications, Dr. Marchesi suggested that the study findings should influence FMT trial methodology.

“We’ve got to start thinking a little bit differently in terms of how we measure the impact of FMT,” he said. “It’s not all about ... getting rid of these opportunistic pathogens. There are other quality-of-life factors that we need to measure, because they’re also important for the patient.”

Dr. Marchesi said that more research is needed to confirm findings and gain a mechanistic understanding of why patients may improve despite a lack of decolonization.

“We think we’re on a strong foundation here to take this into a clinical trial,” he said.

The research was funded by the National Institute for Health Research and the Medical Research Council. The investigators reported no conflicts of interest.

Researchers have identified Ras-guanine nucleotide-releasing factor 1 (RasGRP1) as a cause of L-DOPA–induced dyskinesia (LID) in patients with Parkinson’s disease. The conclusion is based on animal studies that were published May 1 in Science Advances. “These studies show that, if we can downregulate RasGRP1 signaling before dopamine replacement, we have an opportunity to greatly improve [patients’] quality of life,” said Srinivasa Subramaniam, PhD, of the department of neuroscience at Scripps Research in Jupiter, Fla., in a press release. Dr. Subramaniam is one of the investigators.

Parkinson’s disease results from the loss of substantia nigral projections neurons, which causes decreased levels of dopamine in the dorsal striatum. Treatment with L-DOPA reduces the disease’s motor symptoms effectively, but ultimately leads to the onset of LID. Previous data suggest that LID results from the abnormal activation of dopamine-1 (D₁)–dependent cyclic adenosine 3´,5´-monophosphate (cAMP)/protein kinase A (PKA), extracellular signal–regulated kinase (ERK), and mammalian target of rapamycin kinase complex 1 (mTORC1) signaling in the dorsal striatum.
 

Animal and biochemical data

Based on earlier animal studies, Dr. Subramaniam and colleagues hypothesized that RasGRP1 might regulate LID. To test this theory, the investigators created lesions in wild-type and RasGRP1 knockout mice to create models of Parkinson’s disease. The investigators saw similar Parkinsonian symptoms in both groups of mice on the drag, rotarod, turning, and open-field tests. After all mice received daily treatment with L-DOPA, RasGRP1 knockout mice had significantly fewer abnormal involuntary movements, compared with the wild-type mice. All aspects of dyskinesia appeared to be equally dampened in the knockout mice.

To analyze whether RasGRP1 deletion affected the efficacy of L-DOPA, the investigators subjected the treated mice to motor tests. Parkinsonian symptoms were decreased among wild-type and knockout mice on the drag and turning tests. “RasGRP1 promoted the adverse effects of L-DOPA but did not interfere with its therapeutic motor effects,” the investigators wrote. Compared with the wild-type mice, the knockout mice had no changes in basal motor behavior or coordination or amphetamine-induced motor activity.

In addition, Dr. Subramaniam and colleagues observed that RasGRP1 levels were increased in the striatum after L-DOPA injection, but not after injection of vehicle control. This and other biochemical findings indicated that striatal RasGRP1 is upregulated in an L-DOPA–dependent manner and is causally linked to the development of LID, according to the investigators.

Other observations indicated that RasGRP1 physiologically activates mTORC1 signaling, which contributes to LID. Using liquid chromatography and mass spectrometry, Dr. Subramaniam and colleagues saw that RasGRP1 acts upstream in response to L-DOPA and regulates a specific and diverse group of proteins to promote LID. When they examined a nonhuman primate model of Parkinson’s disease, they noted similar findings.
 

New therapeutic targets

“There is an immediate need for new therapeutic targets to stop LID ... in Parkinson’s disease,” said Dr. Subramaniam in a press release. “The treatments now available work poorly and have many additional unwanted side effects. We believe this [study] represents an important step toward better options for people with Parkinson’s disease.”

Future research should attempt to identify the best method of selectively reducing expression of RasGRP1 in the striatum without affecting its expression in other areas of the body, according to Dr. Subramaniam. “The good news is that in mice a total lack of RasGRP1 is not lethal, so we think that blocking RasGRP1 with drugs, or even with gene therapy, may have very few or no major side effects.”

The study was funded by grants from the National Institutes of Health. The investigators reported no conflicts of interest.

egreb@mdedge.com

SOURCE: Eshraghi M et al. Sci Adv. 2020;6:eaaz7001.

Researchers have identified Ras-guanine nucleotide-releasing factor 1 (RasGRP1) as a cause of L-DOPA–induced dyskinesia (LID) in patients with Parkinson’s disease. The conclusion is based on animal studies that were published May 1 in Science Advances. “These studies show that, if we can downregulate RasGRP1 signaling before dopamine replacement, we have an opportunity to greatly improve [patients’] quality of life,” said Srinivasa Subramaniam, PhD, of the department of neuroscience at Scripps Research in Jupiter, Fla., in a press release. Dr. Subramaniam is one of the investigators.

Parkinson’s disease results from the loss of substantia nigral projections neurons, which causes decreased levels of dopamine in the dorsal striatum. Treatment with L-DOPA reduces the disease’s motor symptoms effectively, but ultimately leads to the onset of LID. Previous data suggest that LID results from the abnormal activation of dopamine-1 (D₁)–dependent cyclic adenosine 3´,5´-monophosphate (cAMP)/protein kinase A (PKA), extracellular signal–regulated kinase (ERK), and mammalian target of rapamycin kinase complex 1 (mTORC1) signaling in the dorsal striatum.
 

Animal and biochemical data

Based on earlier animal studies, Dr. Subramaniam and colleagues hypothesized that RasGRP1 might regulate LID. To test this theory, the investigators created lesions in wild-type and RasGRP1 knockout mice to create models of Parkinson’s disease. The investigators saw similar Parkinsonian symptoms in both groups of mice on the drag, rotarod, turning, and open-field tests. After all mice received daily treatment with L-DOPA, RasGRP1 knockout mice had significantly fewer abnormal involuntary movements, compared with the wild-type mice. All aspects of dyskinesia appeared to be equally dampened in the knockout mice.

To analyze whether RasGRP1 deletion affected the efficacy of L-DOPA, the investigators subjected the treated mice to motor tests. Parkinsonian symptoms were decreased among wild-type and knockout mice on the drag and turning tests. “RasGRP1 promoted the adverse effects of L-DOPA but did not interfere with its therapeutic motor effects,” the investigators wrote. Compared with the wild-type mice, the knockout mice had no changes in basal motor behavior or coordination or amphetamine-induced motor activity.

In addition, Dr. Subramaniam and colleagues observed that RasGRP1 levels were increased in the striatum after L-DOPA injection, but not after injection of vehicle control. This and other biochemical findings indicated that striatal RasGRP1 is upregulated in an L-DOPA–dependent manner and is causally linked to the development of LID, according to the investigators.

Other observations indicated that RasGRP1 physiologically activates mTORC1 signaling, which contributes to LID. Using liquid chromatography and mass spectrometry, Dr. Subramaniam and colleagues saw that RasGRP1 acts upstream in response to L-DOPA and regulates a specific and diverse group of proteins to promote LID. When they examined a nonhuman primate model of Parkinson’s disease, they noted similar findings.
 

New therapeutic targets

“There is an immediate need for new therapeutic targets to stop LID ... in Parkinson’s disease,” said Dr. Subramaniam in a press release. “The treatments now available work poorly and have many additional unwanted side effects. We believe this [study] represents an important step toward better options for people with Parkinson’s disease.”

Future research should attempt to identify the best method of selectively reducing expression of RasGRP1 in the striatum without affecting its expression in other areas of the body, according to Dr. Subramaniam. “The good news is that in mice a total lack of RasGRP1 is not lethal, so we think that blocking RasGRP1 with drugs, or even with gene therapy, may have very few or no major side effects.”

The study was funded by grants from the National Institutes of Health. The investigators reported no conflicts of interest.

egreb@mdedge.com

SOURCE: Eshraghi M et al. Sci Adv. 2020;6:eaaz7001.

Researchers have identified Ras-guanine nucleotide-releasing factor 1 (RasGRP1) as a cause of L-DOPA–induced dyskinesia (LID) in patients with Parkinson’s disease. The conclusion is based on animal studies that were published May 1 in Science Advances. “These studies show that, if we can downregulate RasGRP1 signaling before dopamine replacement, we have an opportunity to greatly improve [patients’] quality of life,” said Srinivasa Subramaniam, PhD, of the department of neuroscience at Scripps Research in Jupiter, Fla., in a press release. Dr. Subramaniam is one of the investigators.

Parkinson’s disease results from the loss of substantia nigral projections neurons, which causes decreased levels of dopamine in the dorsal striatum. Treatment with L-DOPA reduces the disease’s motor symptoms effectively, but ultimately leads to the onset of LID. Previous data suggest that LID results from the abnormal activation of dopamine-1 (D₁)–dependent cyclic adenosine 3´,5´-monophosphate (cAMP)/protein kinase A (PKA), extracellular signal–regulated kinase (ERK), and mammalian target of rapamycin kinase complex 1 (mTORC1) signaling in the dorsal striatum.
 

Animal and biochemical data

Based on earlier animal studies, Dr. Subramaniam and colleagues hypothesized that RasGRP1 might regulate LID. To test this theory, the investigators created lesions in wild-type and RasGRP1 knockout mice to create models of Parkinson’s disease. The investigators saw similar Parkinsonian symptoms in both groups of mice on the drag, rotarod, turning, and open-field tests. After all mice received daily treatment with L-DOPA, RasGRP1 knockout mice had significantly fewer abnormal involuntary movements, compared with the wild-type mice. All aspects of dyskinesia appeared to be equally dampened in the knockout mice.

To analyze whether RasGRP1 deletion affected the efficacy of L-DOPA, the investigators subjected the treated mice to motor tests. Parkinsonian symptoms were decreased among wild-type and knockout mice on the drag and turning tests. “RasGRP1 promoted the adverse effects of L-DOPA but did not interfere with its therapeutic motor effects,” the investigators wrote. Compared with the wild-type mice, the knockout mice had no changes in basal motor behavior or coordination or amphetamine-induced motor activity.

In addition, Dr. Subramaniam and colleagues observed that RasGRP1 levels were increased in the striatum after L-DOPA injection, but not after injection of vehicle control. This and other biochemical findings indicated that striatal RasGRP1 is upregulated in an L-DOPA–dependent manner and is causally linked to the development of LID, according to the investigators.

Other observations indicated that RasGRP1 physiologically activates mTORC1 signaling, which contributes to LID. Using liquid chromatography and mass spectrometry, Dr. Subramaniam and colleagues saw that RasGRP1 acts upstream in response to L-DOPA and regulates a specific and diverse group of proteins to promote LID. When they examined a nonhuman primate model of Parkinson’s disease, they noted similar findings.
 

New therapeutic targets

“There is an immediate need for new therapeutic targets to stop LID ... in Parkinson’s disease,” said Dr. Subramaniam in a press release. “The treatments now available work poorly and have many additional unwanted side effects. We believe this [study] represents an important step toward better options for people with Parkinson’s disease.”

Future research should attempt to identify the best method of selectively reducing expression of RasGRP1 in the striatum without affecting its expression in other areas of the body, according to Dr. Subramaniam. “The good news is that in mice a total lack of RasGRP1 is not lethal, so we think that blocking RasGRP1 with drugs, or even with gene therapy, may have very few or no major side effects.”

The study was funded by grants from the National Institutes of Health. The investigators reported no conflicts of interest.

egreb@mdedge.com

SOURCE: Eshraghi M et al. Sci Adv. 2020;6:eaaz7001.

If telemedicine had not yet begun to play a significant role in your ObGyn practice, it is almost certain to now as the COVID-19 pandemic demands new ways of caring for our patients while keeping others safe from disease. According to the American College of Obstetricians and Gynecologists (ACOG), the term “telemedicine” refers to delivering traditional clinical diagnosis and monitoring via technology (see “ACOG weighs in on telehealth”).¹

Whether they realize it or not, most Ob­Gyns have practiced a simple form of telemedicine when they take phone calls from patients who are seeking medication refills. In these cases, physicians either can call the pharmacy to refill the medication or suggest patients make an office appointment to receive a new prescription (much to the chagrin of many patients—especially millennials). Physicians who acquiesce to patients’ phone requests to have prescriptions filled or to others seeking free medical advice are not compensated for these services, yet are legally responsible for their actions and advice—a situation that does not make for good medicine.

This is where telemedicine can be an important addition to an ObGyn practice. Telemedicine saves the patient the time and effort of coming to the office, while providing compensation to the physician for his/her time and advice and providing a record of the interaction, all of which makes for far better medicine. This article—the first of 3 on the subject—discusses the process of integrating telemedicine into a practice with minimal time, energy, and expense.

Telemedicine and the ObGyn practice

Many ObGyn patients do not require an in-person visit in order to receive effective care. There is even the potential to provide prenatal care via telemedicine by replacing some of the many prenatal well-care office visits with at-home care for pregnant women with low-risk pregnancies. A typical virtual visit for a low-risk pregnancy includes utilizing home monitoring equipment to track fetal heart rate, maternal blood pressure, and fundal height.²

Practices typically use telemedicine platforms to manage one or both of the following types of encounters: 1) walk-in visits through the practice’s web site; for most of these, patients tend not to care which physicians they see; their priority is usually the first available provider; and 2) appointment-based consultations, where patients schedule video chats in advance, usually with a specific provider.

Although incorporating telemedicine into a practice may seem overwhelming, it requires minimal additional equipment, interfaces easily with a practice’s web site and electronic medical record (EMR) system, increases productivity, and improves workflow. And patients generally appreciate the option of not having to travel to the office for an appointment.

Most patients and physicians are already comfortable with their mobile phones, tablets, social media, and wearable technology, such as Fitbits. Telemedicine is a logical next step. And given the current situation with COVID-19, it is really not a matter of “if,” but rather “when” to incorporate telemedicine as a communication and practice tool, and the sooner the better.

Continue to: Getting started...

Getting started

Physicians and their colleagues and staff first need to become comfortable with telemedicine technology. Physicians can begin by using video communication for other purposes, such as for conducting staff meetings. They should practice starting and ending calls and adjusting audio volume and video quality to ensure good reception.

Selecting a video platform

TABLE 1 provides a list of the most popular video providers and the advantages and disadvantages of each, and TABLE 2 shows a list of free video chat apps. Apps are available that can:

• share and mark up lab tests, magnetic resonance images, and other medical documents without exposing the entire desktop
• securely send documents over a Health Insurance Portability and Accountability Act (HIPAA)-compliant video
• stream digital device images live while still seeing patients’ faces.

Physicians should make sure their implementation team has the necessary equipment, including webcams, microphones, and speakers, and they should take the time to do research and test out a few programs before selecting one for their practice. Consider appointing a telemedicine point person who is knowledgeable about the technology and can patiently explain it to others. And keep in mind that video chatting is dependent upon a fast, strong Internet connection that has sufficient bandwidth to transport a large amount of data. If your practice has connectivity problems, consider consulting with an information technology (IT) expert.

Testing it out and obtaining feedback

Once a team is comfortable using video within the practice, it is time to test it out with a few patients and perhaps a few payers. Most patients are eager to start using video for their medical encounters. Even senior patients are often willing to try consults via video. According to a recent survey, 64% of patients are willing to see a physician over video.³ And among those who were comfortable accepting an invitation to participate in a video encounter, increasing age was actually associated with a higher likelihood to accept an invite.

Physician colleagues, medical assistants, and nurse practitioners will need some basic telemedicine skills, and physicians and staff should be prepared to make video connections seamless for patients. Usually, patients need some guidance and encouragement, such as telling them to check their spam folder for their invites if the invites fail to arrive in their email inbox, adjusting audio settings, or setting up a webcam. In the beginning, ObGyns should make sure they build in plenty of buffer time for the unexpected, as there will certainly be some “bugs” that need to be worked out.

ObGyns should encourage and collect patient feedback to such questions as:

• What kinds of devices (laptop, mobile) do they prefer using?
• What kind of networks are they using (3G, corporate, home)?
• What features do they like? What features do they have a hard time finding?
• What do they like or not like about the video experience?
• Keep track of the types of questions patients ask, and be patient as patients become acclimated to the video consultation experience.

Continue to: Streamlining online workflow...

Streamlining online workflow

Armed with feedback from patients, it is time to start streamlining online workflow. Most ObGyns want to be able to manage video visits in a way that is similar to the way they manage face-to-face visits with patients. This may mean experimenting with a virtual waiting room. A virtual waiting room is a simple web page or link that can be sent to patients. On that page, patients sign in with minimal demographic information and select one of the time slots when the physician is available. Typically, these programs are designed to alert the physicians and/or staff when a patient enters the virtual waiting room. Patients have access to the online patient queue and can start a chat or video call when both parties are ready. Such a waiting room model serves as a stepping stone for new practices to familiarize themselves with video conferencing. This approach is also perfect for practices that already have a practice management system and just want to add a video component.

Influences on practice workflow

With good time management, telemedicine can improve the efficiency and productivity of your practice. Your daily schedule and management of patients will need some minor changes, but significant alterations to your existing schedule and workflow are generally unnecessary. One of the advantages of telemedicine is the convenience of prompt care and the easy access patients have to your practice. This decreases visits to the emergency department and to urgent care centers.

Consider scheduling telemedicine appointments at the end of the day when your staff has left the office, as no staff members are required for a telemedicine visit. Ideally, you should offer a set time to communicate with patients, as this avoids having to make multiple calls to reach a patient. Another advantage of telemedicine is that you can provide care in the evenings and on weekends if you want. Whereas before you might have been fielding calls from patients during these times and not being compensated, with telemedicine you can conduct a virtual visit from any location and any computer or mobile phone and receive remuneration for your care.

And while access to care has been a problem in many ObGyn practices, many additional patients can be accommodated into a busy ObGyn practice by using telemedicine.

Telemedicine and the coronavirus

The current health care crisis makes implementing telemedicine essential. Patients who think they may have COVID-19 or who have been diagnosed need to be quarantined. Such patients can be helped safely in the comfort of their own homes without endangering others. Patients can be triaged virtually. All those who are febrile or have respiratory symptoms can continue to avail themselves of virtual visits.

According to reports in the media, COVID-19 is stretching the health care workforce to its limits and creating a shortage, both because of the sheer number of cases and because health care workers are getting sick themselves. Physicians who test positive do not have to be completely removed from the workforce if they have the ability to care for patients remotely from their homes. And not incidentally the new environment has prompted the Centers for Medicaid and Medicare Services (CMS) and private payers to initiate national payment policies that create parity between office and telemedicine visits.⁴

Continue to: Bottom line...

Bottom line

Patient-driven care is the future, and telemedicine is part of that. Patients want to have ready access to their health care providers without having to devote hours to a medical encounter that could be completed in a matter of minutes via telemedicine.

In the next article in this series, we will review the proper coding for a telemedicine visit so that appropriate compensation is gleaned. We will also review the barriers to implementing telemedicine visits. The third article is written with the assistance of 2 health care attorneys, Anjali Dooley and Nadia de la Houssaye, who are experts in telemedicine and who have helped dozens of practices and hospitals implement the technology. They provide legal guidelines for ObGyns who are considering adding telemedicine to their practice. ●

If telemedicine had not yet begun to play a significant role in your ObGyn practice, it is almost certain to now as the COVID-19 pandemic demands new ways of caring for our patients while keeping others safe from disease. According to the American College of Obstetricians and Gynecologists (ACOG), the term “telemedicine” refers to delivering traditional clinical diagnosis and monitoring via technology (see “ACOG weighs in on telehealth”).¹

Whether they realize it or not, most Ob­Gyns have practiced a simple form of telemedicine when they take phone calls from patients who are seeking medication refills. In these cases, physicians either can call the pharmacy to refill the medication or suggest patients make an office appointment to receive a new prescription (much to the chagrin of many patients—especially millennials). Physicians who acquiesce to patients’ phone requests to have prescriptions filled or to others seeking free medical advice are not compensated for these services, yet are legally responsible for their actions and advice—a situation that does not make for good medicine.

This is where telemedicine can be an important addition to an ObGyn practice. Telemedicine saves the patient the time and effort of coming to the office, while providing compensation to the physician for his/her time and advice and providing a record of the interaction, all of which makes for far better medicine. This article—the first of 3 on the subject—discusses the process of integrating telemedicine into a practice with minimal time, energy, and expense.

Telemedicine and the ObGyn practice

Many ObGyn patients do not require an in-person visit in order to receive effective care. There is even the potential to provide prenatal care via telemedicine by replacing some of the many prenatal well-care office visits with at-home care for pregnant women with low-risk pregnancies. A typical virtual visit for a low-risk pregnancy includes utilizing home monitoring equipment to track fetal heart rate, maternal blood pressure, and fundal height.²

Practices typically use telemedicine platforms to manage one or both of the following types of encounters: 1) walk-in visits through the practice’s web site; for most of these, patients tend not to care which physicians they see; their priority is usually the first available provider; and 2) appointment-based consultations, where patients schedule video chats in advance, usually with a specific provider.

Although incorporating telemedicine into a practice may seem overwhelming, it requires minimal additional equipment, interfaces easily with a practice’s web site and electronic medical record (EMR) system, increases productivity, and improves workflow. And patients generally appreciate the option of not having to travel to the office for an appointment.

Most patients and physicians are already comfortable with their mobile phones, tablets, social media, and wearable technology, such as Fitbits. Telemedicine is a logical next step. And given the current situation with COVID-19, it is really not a matter of “if,” but rather “when” to incorporate telemedicine as a communication and practice tool, and the sooner the better.

Continue to: Getting started...

Getting started

Physicians and their colleagues and staff first need to become comfortable with telemedicine technology. Physicians can begin by using video communication for other purposes, such as for conducting staff meetings. They should practice starting and ending calls and adjusting audio volume and video quality to ensure good reception.

Selecting a video platform

TABLE 1 provides a list of the most popular video providers and the advantages and disadvantages of each, and TABLE 2 shows a list of free video chat apps. Apps are available that can:

• share and mark up lab tests, magnetic resonance images, and other medical documents without exposing the entire desktop
• securely send documents over a Health Insurance Portability and Accountability Act (HIPAA)-compliant video
• stream digital device images live while still seeing patients’ faces.

Physicians should make sure their implementation team has the necessary equipment, including webcams, microphones, and speakers, and they should take the time to do research and test out a few programs before selecting one for their practice. Consider appointing a telemedicine point person who is knowledgeable about the technology and can patiently explain it to others. And keep in mind that video chatting is dependent upon a fast, strong Internet connection that has sufficient bandwidth to transport a large amount of data. If your practice has connectivity problems, consider consulting with an information technology (IT) expert.

Testing it out and obtaining feedback

Once a team is comfortable using video within the practice, it is time to test it out with a few patients and perhaps a few payers. Most patients are eager to start using video for their medical encounters. Even senior patients are often willing to try consults via video. According to a recent survey, 64% of patients are willing to see a physician over video.³ And among those who were comfortable accepting an invitation to participate in a video encounter, increasing age was actually associated with a higher likelihood to accept an invite.

Physician colleagues, medical assistants, and nurse practitioners will need some basic telemedicine skills, and physicians and staff should be prepared to make video connections seamless for patients. Usually, patients need some guidance and encouragement, such as telling them to check their spam folder for their invites if the invites fail to arrive in their email inbox, adjusting audio settings, or setting up a webcam. In the beginning, ObGyns should make sure they build in plenty of buffer time for the unexpected, as there will certainly be some “bugs” that need to be worked out.

ObGyns should encourage and collect patient feedback to such questions as:

• What kinds of devices (laptop, mobile) do they prefer using?
• What kind of networks are they using (3G, corporate, home)?
• What features do they like? What features do they have a hard time finding?
• What do they like or not like about the video experience?
• Keep track of the types of questions patients ask, and be patient as patients become acclimated to the video consultation experience.

Continue to: Streamlining online workflow...

Streamlining online workflow

Armed with feedback from patients, it is time to start streamlining online workflow. Most ObGyns want to be able to manage video visits in a way that is similar to the way they manage face-to-face visits with patients. This may mean experimenting with a virtual waiting room. A virtual waiting room is a simple web page or link that can be sent to patients. On that page, patients sign in with minimal demographic information and select one of the time slots when the physician is available. Typically, these programs are designed to alert the physicians and/or staff when a patient enters the virtual waiting room. Patients have access to the online patient queue and can start a chat or video call when both parties are ready. Such a waiting room model serves as a stepping stone for new practices to familiarize themselves with video conferencing. This approach is also perfect for practices that already have a practice management system and just want to add a video component.

Influences on practice workflow

With good time management, telemedicine can improve the efficiency and productivity of your practice. Your daily schedule and management of patients will need some minor changes, but significant alterations to your existing schedule and workflow are generally unnecessary. One of the advantages of telemedicine is the convenience of prompt care and the easy access patients have to your practice. This decreases visits to the emergency department and to urgent care centers.

Consider scheduling telemedicine appointments at the end of the day when your staff has left the office, as no staff members are required for a telemedicine visit. Ideally, you should offer a set time to communicate with patients, as this avoids having to make multiple calls to reach a patient. Another advantage of telemedicine is that you can provide care in the evenings and on weekends if you want. Whereas before you might have been fielding calls from patients during these times and not being compensated, with telemedicine you can conduct a virtual visit from any location and any computer or mobile phone and receive remuneration for your care.

And while access to care has been a problem in many ObGyn practices, many additional patients can be accommodated into a busy ObGyn practice by using telemedicine.

Telemedicine and the coronavirus

The current health care crisis makes implementing telemedicine essential. Patients who think they may have COVID-19 or who have been diagnosed need to be quarantined. Such patients can be helped safely in the comfort of their own homes without endangering others. Patients can be triaged virtually. All those who are febrile or have respiratory symptoms can continue to avail themselves of virtual visits.

According to reports in the media, COVID-19 is stretching the health care workforce to its limits and creating a shortage, both because of the sheer number of cases and because health care workers are getting sick themselves. Physicians who test positive do not have to be completely removed from the workforce if they have the ability to care for patients remotely from their homes. And not incidentally the new environment has prompted the Centers for Medicaid and Medicare Services (CMS) and private payers to initiate national payment policies that create parity between office and telemedicine visits.⁴

Continue to: Bottom line...

Bottom line

Patient-driven care is the future, and telemedicine is part of that. Patients want to have ready access to their health care providers without having to devote hours to a medical encounter that could be completed in a matter of minutes via telemedicine.

In the next article in this series, we will review the proper coding for a telemedicine visit so that appropriate compensation is gleaned. We will also review the barriers to implementing telemedicine visits. The third article is written with the assistance of 2 health care attorneys, Anjali Dooley and Nadia de la Houssaye, who are experts in telemedicine and who have helped dozens of practices and hospitals implement the technology. They provide legal guidelines for ObGyns who are considering adding telemedicine to their practice. ●

If telemedicine had not yet begun to play a significant role in your ObGyn practice, it is almost certain to now as the COVID-19 pandemic demands new ways of caring for our patients while keeping others safe from disease. According to the American College of Obstetricians and Gynecologists (ACOG), the term “telemedicine” refers to delivering traditional clinical diagnosis and monitoring via technology (see “ACOG weighs in on telehealth”).¹

Whether they realize it or not, most Ob­Gyns have practiced a simple form of telemedicine when they take phone calls from patients who are seeking medication refills. In these cases, physicians either can call the pharmacy to refill the medication or suggest patients make an office appointment to receive a new prescription (much to the chagrin of many patients—especially millennials). Physicians who acquiesce to patients’ phone requests to have prescriptions filled or to others seeking free medical advice are not compensated for these services, yet are legally responsible for their actions and advice—a situation that does not make for good medicine.

This is where telemedicine can be an important addition to an ObGyn practice. Telemedicine saves the patient the time and effort of coming to the office, while providing compensation to the physician for his/her time and advice and providing a record of the interaction, all of which makes for far better medicine. This article—the first of 3 on the subject—discusses the process of integrating telemedicine into a practice with minimal time, energy, and expense.

Telemedicine and the ObGyn practice

Many ObGyn patients do not require an in-person visit in order to receive effective care. There is even the potential to provide prenatal care via telemedicine by replacing some of the many prenatal well-care office visits with at-home care for pregnant women with low-risk pregnancies. A typical virtual visit for a low-risk pregnancy includes utilizing home monitoring equipment to track fetal heart rate, maternal blood pressure, and fundal height.²

Practices typically use telemedicine platforms to manage one or both of the following types of encounters: 1) walk-in visits through the practice’s web site; for most of these, patients tend not to care which physicians they see; their priority is usually the first available provider; and 2) appointment-based consultations, where patients schedule video chats in advance, usually with a specific provider.

Although incorporating telemedicine into a practice may seem overwhelming, it requires minimal additional equipment, interfaces easily with a practice’s web site and electronic medical record (EMR) system, increases productivity, and improves workflow. And patients generally appreciate the option of not having to travel to the office for an appointment.

Most patients and physicians are already comfortable with their mobile phones, tablets, social media, and wearable technology, such as Fitbits. Telemedicine is a logical next step. And given the current situation with COVID-19, it is really not a matter of “if,” but rather “when” to incorporate telemedicine as a communication and practice tool, and the sooner the better.

Continue to: Getting started...

Getting started

Physicians and their colleagues and staff first need to become comfortable with telemedicine technology. Physicians can begin by using video communication for other purposes, such as for conducting staff meetings. They should practice starting and ending calls and adjusting audio volume and video quality to ensure good reception.

Selecting a video platform

TABLE 1 provides a list of the most popular video providers and the advantages and disadvantages of each, and TABLE 2 shows a list of free video chat apps. Apps are available that can:

• share and mark up lab tests, magnetic resonance images, and other medical documents without exposing the entire desktop
• securely send documents over a Health Insurance Portability and Accountability Act (HIPAA)-compliant video
• stream digital device images live while still seeing patients’ faces.

Physicians should make sure their implementation team has the necessary equipment, including webcams, microphones, and speakers, and they should take the time to do research and test out a few programs before selecting one for their practice. Consider appointing a telemedicine point person who is knowledgeable about the technology and can patiently explain it to others. And keep in mind that video chatting is dependent upon a fast, strong Internet connection that has sufficient bandwidth to transport a large amount of data. If your practice has connectivity problems, consider consulting with an information technology (IT) expert.

Testing it out and obtaining feedback

Once a team is comfortable using video within the practice, it is time to test it out with a few patients and perhaps a few payers. Most patients are eager to start using video for their medical encounters. Even senior patients are often willing to try consults via video. According to a recent survey, 64% of patients are willing to see a physician over video.³ And among those who were comfortable accepting an invitation to participate in a video encounter, increasing age was actually associated with a higher likelihood to accept an invite.

Physician colleagues, medical assistants, and nurse practitioners will need some basic telemedicine skills, and physicians and staff should be prepared to make video connections seamless for patients. Usually, patients need some guidance and encouragement, such as telling them to check their spam folder for their invites if the invites fail to arrive in their email inbox, adjusting audio settings, or setting up a webcam. In the beginning, ObGyns should make sure they build in plenty of buffer time for the unexpected, as there will certainly be some “bugs” that need to be worked out.

ObGyns should encourage and collect patient feedback to such questions as:

• What kinds of devices (laptop, mobile) do they prefer using?
• What kind of networks are they using (3G, corporate, home)?
• What features do they like? What features do they have a hard time finding?
• What do they like or not like about the video experience?
• Keep track of the types of questions patients ask, and be patient as patients become acclimated to the video consultation experience.

Continue to: Streamlining online workflow...

Streamlining online workflow

Armed with feedback from patients, it is time to start streamlining online workflow. Most ObGyns want to be able to manage video visits in a way that is similar to the way they manage face-to-face visits with patients. This may mean experimenting with a virtual waiting room. A virtual waiting room is a simple web page or link that can be sent to patients. On that page, patients sign in with minimal demographic information and select one of the time slots when the physician is available. Typically, these programs are designed to alert the physicians and/or staff when a patient enters the virtual waiting room. Patients have access to the online patient queue and can start a chat or video call when both parties are ready. Such a waiting room model serves as a stepping stone for new practices to familiarize themselves with video conferencing. This approach is also perfect for practices that already have a practice management system and just want to add a video component.

Influences on practice workflow

With good time management, telemedicine can improve the efficiency and productivity of your practice. Your daily schedule and management of patients will need some minor changes, but significant alterations to your existing schedule and workflow are generally unnecessary. One of the advantages of telemedicine is the convenience of prompt care and the easy access patients have to your practice. This decreases visits to the emergency department and to urgent care centers.

Consider scheduling telemedicine appointments at the end of the day when your staff has left the office, as no staff members are required for a telemedicine visit. Ideally, you should offer a set time to communicate with patients, as this avoids having to make multiple calls to reach a patient. Another advantage of telemedicine is that you can provide care in the evenings and on weekends if you want. Whereas before you might have been fielding calls from patients during these times and not being compensated, with telemedicine you can conduct a virtual visit from any location and any computer or mobile phone and receive remuneration for your care.

And while access to care has been a problem in many ObGyn practices, many additional patients can be accommodated into a busy ObGyn practice by using telemedicine.

Telemedicine and the coronavirus

The current health care crisis makes implementing telemedicine essential. Patients who think they may have COVID-19 or who have been diagnosed need to be quarantined. Such patients can be helped safely in the comfort of their own homes without endangering others. Patients can be triaged virtually. All those who are febrile or have respiratory symptoms can continue to avail themselves of virtual visits.

According to reports in the media, COVID-19 is stretching the health care workforce to its limits and creating a shortage, both because of the sheer number of cases and because health care workers are getting sick themselves. Physicians who test positive do not have to be completely removed from the workforce if they have the ability to care for patients remotely from their homes. And not incidentally the new environment has prompted the Centers for Medicaid and Medicare Services (CMS) and private payers to initiate national payment policies that create parity between office and telemedicine visits.⁴

Continue to: Bottom line...

Bottom line

Patient-driven care is the future, and telemedicine is part of that. Patients want to have ready access to their health care providers without having to devote hours to a medical encounter that could be completed in a matter of minutes via telemedicine.

In the next article in this series, we will review the proper coding for a telemedicine visit so that appropriate compensation is gleaned. We will also review the barriers to implementing telemedicine visits. The third article is written with the assistance of 2 health care attorneys, Anjali Dooley and Nadia de la Houssaye, who are experts in telemedicine and who have helped dozens of practices and hospitals implement the technology. They provide legal guidelines for ObGyns who are considering adding telemedicine to their practice. ●

In the midst of the coronavirus disease 2019 (COVID-19) pandemic, health care providers, including ObGyns, need up-to-date information to keep pace with the ever-changing health care crisis. Literature regarding obstetric populations is emerging in journals.^1,2 General guidance in the management of COVID-19–positive patients may also be helpful to the ObGyn provider. Although scientific journals are now publishing COVID-19 research at warp speed, those same journals tend to be too specialized for general readers.³ Mobile apps may make the information more accessible.

This app review focuses on 3 apps that provide information about the ongoing COVID-19 pandemic and detail general guidance for treatment of COVID-19–positive patients. An initial search in early April 2020 of major national health care organizations and ObGyn-specific organizational apps yielded the Centers for Disease Control and Prevention (CDC) app. A subsequent search in the app stores using the term “COVID” yielded 2 additional apps: the Osler COVID Learning Centre app and the Relief Central app.

The CDC app contains a COVID-19-specific section that highlights pertinent information for health care providers as well as a section on caring for the obstetric patient. The Osler app includes podcasts and videos on critical care for noncritical care providers. Finally, the Relief Central app contains updated information on screening and treatment for COVID-19. The TABLE features details of the 3 apps.

In the midst of the coronavirus disease 2019 (COVID-19) pandemic, health care providers, including ObGyns, need up-to-date information to keep pace with the ever-changing health care crisis. Literature regarding obstetric populations is emerging in journals.^1,2 General guidance in the management of COVID-19–positive patients may also be helpful to the ObGyn provider. Although scientific journals are now publishing COVID-19 research at warp speed, those same journals tend to be too specialized for general readers.³ Mobile apps may make the information more accessible.

This app review focuses on 3 apps that provide information about the ongoing COVID-19 pandemic and detail general guidance for treatment of COVID-19–positive patients. An initial search in early April 2020 of major national health care organizations and ObGyn-specific organizational apps yielded the Centers for Disease Control and Prevention (CDC) app. A subsequent search in the app stores using the term “COVID” yielded 2 additional apps: the Osler COVID Learning Centre app and the Relief Central app.

The CDC app contains a COVID-19-specific section that highlights pertinent information for health care providers as well as a section on caring for the obstetric patient. The Osler app includes podcasts and videos on critical care for noncritical care providers. Finally, the Relief Central app contains updated information on screening and treatment for COVID-19. The TABLE features details of the 3 apps.

In the midst of the coronavirus disease 2019 (COVID-19) pandemic, health care providers, including ObGyns, need up-to-date information to keep pace with the ever-changing health care crisis. Literature regarding obstetric populations is emerging in journals.^1,2 General guidance in the management of COVID-19–positive patients may also be helpful to the ObGyn provider. Although scientific journals are now publishing COVID-19 research at warp speed, those same journals tend to be too specialized for general readers.³ Mobile apps may make the information more accessible.

This app review focuses on 3 apps that provide information about the ongoing COVID-19 pandemic and detail general guidance for treatment of COVID-19–positive patients. An initial search in early April 2020 of major national health care organizations and ObGyn-specific organizational apps yielded the Centers for Disease Control and Prevention (CDC) app. A subsequent search in the app stores using the term “COVID” yielded 2 additional apps: the Osler COVID Learning Centre app and the Relief Central app.

The CDC app contains a COVID-19-specific section that highlights pertinent information for health care providers as well as a section on caring for the obstetric patient. The Osler app includes podcasts and videos on critical care for noncritical care providers. Finally, the Relief Central app contains updated information on screening and treatment for COVID-19. The TABLE features details of the 3 apps.

A majority of adults are reluctant to visit health care providers unless the visit is related to COVID-19, according to survey conducted at the end of April.

When asked how likely they were to visit a variety of health care settings for treatment not related to the coronavirus, 62% of respondents said it was unlikely that they would go to a hospital, 64% wouldn’t go to a specialist, and 65% would avoid walk-in clinics, digital media company Morning Consult reported May 4.

The only setting with less than a majority on the unlikely-to-visit side was primary physicians, who managed to combine a 39% likely vote with a 13% undecided/no-opinion tally, Morning Consult said after surveying 2,201 adults on April 29-30 (margin of error, ±2 percentage points).

As to when they might feel comfortable making such an in-person visit with their primary physician, 24% of respondents said they would willing to go in the next month, 14% said 2 months, 18% said 3 months, 13% said 6 months, and 10% said more than 6 months, the Morning Consult data show.

“Hospitals, despite being overburdened in recent weeks in coronavirus hot spots such as New York City, have reported dips in revenue as a result of potential patients opting against receiving elective surgeries out of fear of contracting COVID-19,” Morning Consult wrote, and these poll results suggest that “health care companies could continue to feel the pinch as long as the coronavirus lingers.”
 

rfranki@mdedge.com

A majority of adults are reluctant to visit health care providers unless the visit is related to COVID-19, according to survey conducted at the end of April.

When asked how likely they were to visit a variety of health care settings for treatment not related to the coronavirus, 62% of respondents said it was unlikely that they would go to a hospital, 64% wouldn’t go to a specialist, and 65% would avoid walk-in clinics, digital media company Morning Consult reported May 4.

The only setting with less than a majority on the unlikely-to-visit side was primary physicians, who managed to combine a 39% likely vote with a 13% undecided/no-opinion tally, Morning Consult said after surveying 2,201 adults on April 29-30 (margin of error, ±2 percentage points).

As to when they might feel comfortable making such an in-person visit with their primary physician, 24% of respondents said they would willing to go in the next month, 14% said 2 months, 18% said 3 months, 13% said 6 months, and 10% said more than 6 months, the Morning Consult data show.

“Hospitals, despite being overburdened in recent weeks in coronavirus hot spots such as New York City, have reported dips in revenue as a result of potential patients opting against receiving elective surgeries out of fear of contracting COVID-19,” Morning Consult wrote, and these poll results suggest that “health care companies could continue to feel the pinch as long as the coronavirus lingers.”
 

rfranki@mdedge.com

A majority of adults are reluctant to visit health care providers unless the visit is related to COVID-19, according to survey conducted at the end of April.

When asked how likely they were to visit a variety of health care settings for treatment not related to the coronavirus, 62% of respondents said it was unlikely that they would go to a hospital, 64% wouldn’t go to a specialist, and 65% would avoid walk-in clinics, digital media company Morning Consult reported May 4.

The only setting with less than a majority on the unlikely-to-visit side was primary physicians, who managed to combine a 39% likely vote with a 13% undecided/no-opinion tally, Morning Consult said after surveying 2,201 adults on April 29-30 (margin of error, ±2 percentage points).

As to when they might feel comfortable making such an in-person visit with their primary physician, 24% of respondents said they would willing to go in the next month, 14% said 2 months, 18% said 3 months, 13% said 6 months, and 10% said more than 6 months, the Morning Consult data show.

“Hospitals, despite being overburdened in recent weeks in coronavirus hot spots such as New York City, have reported dips in revenue as a result of potential patients opting against receiving elective surgeries out of fear of contracting COVID-19,” Morning Consult wrote, and these poll results suggest that “health care companies could continue to feel the pinch as long as the coronavirus lingers.”
 

rfranki@mdedge.com

On June 17, 1775, American colonists, defending a forward redoubt on Breed’s Hill, ran out of gunpowder, and their position was overrun by British troops. The Battle of Bunker Hill resulted in the death of 140 colonists and 226 British soldiers, setting the stage for major combat throughout the colonies. American colonists lacked many necessary weapons. They had almost no gunpowder, few field cannons, and no warships. Yet, they fought on with the weapons at hand for 6 long years.

In the spring of 2020, American society has been shaken by the COVID-19 pandemic. Hospitals have been overrun with thousands of people infected with the disease. Some hospitals are breaking under the crush of intensely ill people filling up and spilling out of intensive care units. We are in a war, fighting a viral disease with a limited supply of weapons. We do not have access to the most powerful medical munitions: easily available rapid testing, proven antiviral medications, and an effective vaccine. Nevertheless, clinicians and patients are courageous, and we will continue the fight with the limited weapons we have until the pandemic is brought to an end.

Who is infected with SARS-CoV-2?

Rapid high-fidelity testing for SARS-CoV-2 nucleic acid sequences would be the best approach to identifying people with COVID-19 disease. At the beginning of the pandemic, testing was strictly rationed because of lack of reagents and test swabs. Clinicians were permitted to test only a minority of people who had symptoms. Asymptomatic individuals were not eligible to be tested. This terribly flawed approach to screening permitted a vast army of SARS-CoV-2–positive asymptomatic and mildly symptomatic people to circulate unchecked in the general population, infecting dozens of other people, some of whom developed moderate or severe disease. The Centers for Disease Control and Prevention (CDC) has reported on 7 independent clusters of COVID-19 disease, each of which appear to have been caused by one asymptomatic infected individual.⁶ Another cluster of COVID-19 disease from China appears to have been caused by one asymptomatic infected individual.⁷ Based on limited data, it appears that there may be a 1- to 3-day window where an individual with COVID-19 may be asymptomatic and able to infect others. I suspect that we will soon discover, based on testing for the presence of high-titre anti SARS-CoV-2 antibodies, that many people with no history of illness and people with mild respiratory symptoms had an undiagnosed COVID-19 infection.

As testing capacity expands we likely will be testing all women, including asymptomatic women, before they arrive at the hospital for childbirth or gynecologic surgery, as well as all inpatients and women with respiratory symptoms having an ambulatory encounter.

With expanded testing capability, some pregnant women who were symptomatic and tested positive for SARS-CoV-2 have had sequential long-term follow-up testing. A frequent observation is that over one to two weeks the viral symptoms resolve and the nasopharyngeal test becomes negative for SARS-CoV-2 on multiple sequential tests, only to become positive at a later date. The cause of the positive-negative-negative-positive test results is unknown, but it raises the possibility that once a person tests positive for SARS-CoV-2, they may be able to transmit the infection over many weeks, even after viral symptoms resolve.

Continue to: COVID-19: Respiratory droplet or aerosol transmission?

COVID-19: Respiratory droplet or aerosol transmission?

Respiratory droplets are large particles (> 5 µm in diameter) that tend to be pulled to the ground or furniture surfaces by gravity. Respiratory droplets do not circulate in the air for an extended period of time. Droplet nuclei are small particles less than 5 µm in diameter. These small particles may become aerosolized and float through the air for an extended period of time. The CDC and WHO believe that under ordinary conditions, SARS-CoV-2 is transmitted through respiratory droplets and contact routes.² In an analysis of more than 75,000 COVID-19 cases in China there were no reports of transmission by aerosolized airborne virus. Therefore, under ordinary conditions, surgical masks, face shields, gowns, and gloves provide a high level of protection from infection.⁸

In contrast to the WHO’s perspective, Dr. Harvey Fineberg, Chair of the National Academies of Sciences, Engineering, and Medicine’s Standing Committee on Emerging Infectious Diseases and 21st Century Health Threats, wrote a letter to the federal Office of Science and Technology Policy warning that normal breathing might generate aerosolization of the SARS-CoV-2 virus and result in airborne transmission.⁹ A report from the University of Nebraska Medical Center supports the concept of airborne transmission of SARS-CoV-2. In a study of 13 patients with COVID-19, room surfaces, toilet facilities, and air had evidence of viral contamination.¹⁰ The investigators concluded that disease spreads through respiratory droplets, person-to-person touch, contaminated surfaces, and airborne routes. Other investigators also have reported that aersolization of SARS-CoV-2 may occur.¹¹ Professional societies recommend that all medical staff caring for potential or confirmed COVID-19 patients should use personal protective equipment (PPE), including respirators (N95 respirators) when available. Importantly, all medical staff should be trained in and adhere to proper donning and doffing of PPE. The controversy about the modes of transmission of SARS-CoV-2 will continue, but as clinicians we need to work within the constraints of the equipment we have.

Certain medical procedures and devices are known to generate aerosolization of respiratory secretions. These procedures and devices include: bronchoscopy, intubation, extubation, cardiopulmonary resuscitation, nebulization, high-flow oxygen masks, and continuous- and bilevel-positive airway pressure devices. When aerosols are generated during the care of a patient with COVID-19, surgical masks are not sufficient protection against infection. When an aerosol is generated maximal protection of health care workers from viral transmission requires use of a negative-pressure room and an N95 respirator or powered air-purifying respirator (PAPR) device. However, negative-pressure rooms, N95 masks, and PAPRs are in very short supply or are unavailable in some health systems. We are lucky at our hospital that all of the labor rooms can be configured to operate in a negative-pressure mode, limiting potential airborne spread of the virus on the unit. Many hospitals restrict the use of N95 masks to anesthesiologists, leaving nurses, ObGyns, and surgical technicians without the best protective equipment, risking their health. As one action to reduce aerosolization of virus, obstetricians can markedly reduce the use of oxygen masks and nasal cannulas by laboring women.

Universal use of surgical masks and mouth-nose coverings

During the entire COVID-19 pandemic, PPE has been in short supply, including severe shortages of N95 masks, PAPRs, and in some health systems, surgical masks, gowns, eye protection, and face shields. Given the severe shortages, some clinicians have needed to conserve PPE, using the same PPE across multiple patient encounters and across multiple work shifts.

Given that the virus is transmitted by respiratory droplets and contaminated surfaces, use of face coverings, including surgical masks, face shields, and gloves is critically important. Scrupulous hand hygiene is a simple approach to reducing infection risk. In my health system, all employees are required to wear a surgical mask, all day every day, requiring distribution of 35,000 masks daily.¹² We also require every patient and visitor to our health care facilities to use a face mask. The purpose of the procedure or surgical mask is to prevent presymptomatic spread of COVID-19 from an asymptomatic health care worker to an uninfected patient or a colleague by reducing the transmission of respiratory droplets. Another benefit is to protect the uninfected health care worker from patients and colleagues who are infected and not yet diagnosed with COVID-19. The CDC now recommends that all people wear a mouth and nose covering when they are outside of their residence. America may become a nation where wearing masks in public becomes a routine practice. Since SARS-CoV-2 is transmitted by respiratory droplets, social distancing is an important preventive measure.

Continue to: Obstetric care...

Obstetric care

Can it be repeated too often? No. Containing COVID-19 disease requires social distancing, fastidious hand hygiene, and using a mask that covers the mouth and nose.

Pregnant women should be advised to assiduously practice social distancing and to wear a face covering or mask in public. Hand hygiene should be emphasized. Pregnant women with children should be advised to not allow their children to play with non‒cohabiting children because children may be asymptomatic vectors for COVID-19.

Pregnant health care workers should stop face-to-face contact with patients after 36 weeks’ gestation to avoid a late pregnancy infection that might cause the mother to be separated from her newborn. Based on data currently available, pregnancy in the absence of another risk factor is not a major risk factor for developing severe COVID-19 disease.¹³

Hyperthermia is a common feature of COVID-19. Acetaminophen is recommended treatment to suppress pyrexia during pregnancy.

The COVID-19 pandemic has transformed prenatal care from a series of face-to-face encounters at a health care facility to telemedicine either by telephone or a videoconferencing portal. Many factors contributed to the rapid switch to telemedicine, including orders by governors to restrict unnecessary travel, patients’ fear of contracting COVID-19 at their clinicians’ offices, clinicians’ fear of contracting COVID-19 from patients, and insurers’ rapid implementation of policies to pay for telemedicine visits. Most prenatal visits can be provided through telemedicine as long as the patient has a home blood pressure cuff and can reliably use the instrument. In-person visits may be required for blood testing, ultrasound assessment, anti-Rh immunoglobulin administration, and group B streptococcal infection screening. One regimen is to limit in-person prenatal visits to encounters at 12, 20, 28, and 36 weeks’ gestation when blood testing and ultrasound examinations are needed. The postpartum visit also may be conducted using telemedicine.

Pregnant women with COVID-19 and pneumonia are reported to have high rates of preterm birth less than 37 weeks (41%) and preterm prelabor rupture of membranes (19%).¹⁴

The rate of vertical transmission from mother to fetus is probably very low (<1%).¹⁵ However, based on serological studies, an occasional newborn has been reported to have IgM and IgG antibodies to the SARS-CoV-2 nucleoprotein at birth.^16,17

Pregnant women should be consistently and regularly screened for symptoms of an upper respiratory infection, including: fever, new cough, new runny nose or nasal congestion, new sore throat, shortness of breath, muscle aches, and anosmia. A report of any of these symptoms should result in nucleic acid testing of a nasal swab for SARS-CoV-2 of all pregnant women. Given limited testing resources, however, symptomatic pregnant women with the following characteristics should be prioritized for testing: if the woman is more than 36 weeks pregnant, intrapartum, or in the hospital after delivery. Ambulatory pregnant women with symptoms who do not need medical care should quarantine themselves at home, if possible, or at another secure location away from their families. In some regions, testing of ambulatory patients with upper respiratory symptoms is limited.

All women scheduled for induction or cesarean delivery (CD) and their support person should have a symptom screen 24 to 48 hours before arrival to the hospital and should be rescreened prior to entry to labor and delivery. In this situation if the pregnant woman screens positive, she should be tested for SARS-CoV-2, and if the test result is positive, the scheduled induction and CD should be rescheduled, if possible. All hospitalized women and their support persons should be screened for symptoms daily. If the pregnant woman screens positive she should have a nucleic acid test for SARS-CoV-2. If the support person screens positive, he or she should be sent home.

Systemic glucocorticoids may worsen the course of COVID-19. For pregnant women with COVID-19 disease, betamethasone administration should be limited to women at high risk for preterm delivery within 7 days and only given to women between 23 weeks to 33 weeks 6 days of gestation. Women at risk for preterm delivery at 34 weeks to 36 weeks and 6 days of gestation should not be given betamethasone.

If cervical ripening is required, outpatient regimens should be prioritized.

One support person plays an important role in optimal labor outcome and should be permitted at the hospital. All support persons should wear a surgical or procedure mask.

Nitrous oxide for labor anesthesia should not be used during the pandemic because it might cause aerosolization of respiratory secretions, endangering health care workers. Neuraxial anesthesia is an optimal approach to labor anesthesia.

Labor management and timing of delivery does not need to be altered during the COVID-19 pandemic. However, pregnant women with moderate or severe COVID-19 disease who are not improving may have a modest improvement in respiratory function if they are delivered preterm.

At the beginning of the COVID pandemic, the CDC recommended separation of a COVID-positive mother and her newborn until the mother’s respiratory symptoms resolved. However, the CDC now recommends that, for a COVID-positive mother, joint decision-making should be used to decide whether to support the baby rooming-in with the mother or to practice separation of mother and baby at birth to reduce the risk for postnatal infection from mother to newborn. There is no evidence that breast milk contains virus that can cause an infection. One option is for the mother who recently tested positive for SARS-CoV-2 to provide newborn nutrition with expressed breast milk.

Pregnant women with COVID-19 may be at increased risk for venous thromboembolism. Some experts recommend that hospitalized pregnant women and postpartum women with COVID-19 receive thromboembolism prophylaxis.
The Chinese Centers for Disease Control and Prevention described a classification system for COVID-19 disease, including 3 categories¹⁸:

• mild: no dyspnea, no pneumonia, or mild pneumonia
• severe: dyspnea, respiratory frequency ≥ 30 breaths per minute, blood oxygen saturation ≤ 93%, lung infiltrates > 50% within 48 hours of onset of symptoms
• critical: respiratory failure, septic shock, or multiple organ dysfunction or failure.

Among 72,314 cases in China, 81% had mild disease, 14% had severe disease, and 5% had critical disease. In a report of 118 pregnant women in China, 92% of the women had mild disease; 8% had severe disease (hypoxemia), one of whom developed critical disease requiring mechanical ventilation.¹⁹ In this cohort, the most common presenting symptoms were fever (75%), cough (73%), chest tightness (18%), fatigue (17%), shortness of breath (7%), diarrhea (7%), and headache (6%). Lymphopenia was present in 44% of the women.

Severe and critical COVID-19 disease are associated with elevations in D-dimer, C-reactive protein, troponin, ferritin, and creatine phosphokinase levels. These markers return to the normal range with resolution of disease.

Continue to: Gynecologic care...

Gynecologic care

Gynecologists are highly impacted by the COVID-19 pandemic. Most state governments have requested that all elective surgery be suspended for the duration of the pandemic in order to redeploy health resources to the care of COVID-19 patients. Except for high-priority gynecologic surgery, including cancer surgery, treatment of heavy vaginal bleeding, and surgical care of ectopic pregnancy and miscarriage, most gynecologic surgery has ceased.

All office visits for routine gynecologic care have been suspended. Video and telephone visits can be used for contraceptive counseling and prescribing and for managing problems associated with the menopause, endometriosis, and vaginitis. Cervical cancer screening can be deferred for 3 to 6 months, depending on patient risk factors.

Medicines to treat COVID-19 infections

There are many highly effective medicines to manage HIV infection and medicines that cure hepatitis C. There is an urgent need to develop precision medicines to treat this disease. Early in the pandemic some experts thought that hydroxychloroquine might be helpful in the treatment of COVID-19 disease. But recent evidence suggests that hydroxychloroquine is probably not an effective treatment. As the pandemic has evolved, there is evidence that remdesivir may have modest efficacy in treating COVID-19 disease.²⁰ Remdesivir has received emergency-use authorization by the FDA to treat COVID-19 infection.

Remdesivir

Based on expert opinion, in the absence of high-quality clinical trial evidence, our current practice is to offer pregnant women with severe or critical COVID-19 disease treatment with remdesivir.

Remdesivir (Gilead Sciences, Inc) is a nucleoside analog that inhibits RNA synthesis. A dose regimen for remdesivir is a 200-mg loading dose given intravenously, followed by 100 mg daily given intravenously for 5 to 10 days. Remdesivir may cause elevation of hepatic enzymes. Remdesivir has been administered to a few pregnant women to treat Ebola and Marburg virus disease.²¹

Experts in infectious disease are important resources for determining optimal medication regimens for the treatment of COVID-19 disease in pregnant women.

Continue to: Convalescent serum...

Convalescent serum

There are no high-quality studies demonstrating the efficacy of convalescent serum for treatment of COVID-19. A small case series suggests that there may be modest benefit to treatment of people with severe COVID-19 disease with convalescent serum.²²

Testing for anti-SARS-CoV-2 IgM and IgG antibodies

We may have a serious problem in our current approach to detecting COVID-19 disease. Based on measurement of IgM and IgG antibodies to SARS-CoV-2 nucleocapsid protein, our current nucleic acid tests for SARS-CoV-2 may detect less than 80% of infections early in the course of disease. In two studies of IgM and IgG antibodies to the SARS-CoV-2 nucleocapsid protein, a single polymerase chain reaction test for SARS-CoV-2 had less than a 60% sensitivity for detecting the virus.^23,24 During the second week of COVID-19 illness, IgM or IgG antibodies were detected in greater than 89% of infected patients.²³ Severe disease resulted in high concentrations of antibody.

When testing for IgM and IgG antibodies is widely available, it may become an option to test all health care workers. This will permit the assignment of those health care workers with the highest levels of antibody to frontline duties with COVID-19 patients during the next disease outbreak, likely to occur at some point during the next 12 months.

A COVID-19 vaccine

Dozens of research teams, including pharmaceutical and biotechnology companies and many academic laboratories, are working on developing and testing vaccines to prevent COVID-19 disease. An effective vaccine would reduce the number of people who develop severe disease during the next outbreak, reducing deaths, avoiding a shutdown of the country, and allowing the health systems to function normally. A vaccine is unlikely to be widely available until sometime early in 2021.

Facing COVID-19 well-being and mental health

SARS-CoV-2, like all viral particles, is incredibly small. Remarkably, it has changed permanently life on earth. COVID-19 is affecting our physical health, psychological well-being, economics, and patterns of social interaction. As clinicians it is difficult to face a viral enemy that cannot be stopped from causing the death of more than 100,000 people, including some of our clinical colleagues, within a short period of time.

Dr. Russ Harris, an Australian acceptance commitment therapist, has written an ebook (http://www.commpsych.com/wp-content/uploads/FACE_COVID-1.pdf) and produced an animated YouTube video, titled FACE COVID (https://www.youtube.com/watch?v=BmvNCdpHUYM), which describes a systematic approach to deal with the challenge of the pandemic. He advises a 9-step approach:

• F—focus on what is in your control
• A—acknowledge your thoughts and feelings
• C—come back to a focus on your body
• E—engage in what you are doing
• C—commit to acting effectively based on your core values
• O—opening up to difficult feelings and being kind to yourself and others
• V—values should guide your actions
• I—identify resources for help, assistance, support, and advice
• D—disinfect and practice social distancing.

This war will come to an end

During the American Revolution, colonists faced housing and food insecurity, epidemics of typhus and smallpox, traumatic injury including amputation of limbs, and a complete disruption of normal life activities. They persevered and, against the odds, successfully concluded the war. Unlike the colonists, who did not know if their conflict would end with success or failure, we clinicians know that the COVID-19 pandemic will end. We also know that eventually the global community of clinicians will develop and deploy the effective weapons we need to prevent a recurrence of this traumatic pandemic: population-wide testing for both the SARS-CoV-2 virus and serologic testing for IgG and IgM antibodies to the virus, effective antiviral medications, and a potent vaccine. ●

On June 17, 1775, American colonists, defending a forward redoubt on Breed’s Hill, ran out of gunpowder, and their position was overrun by British troops. The Battle of Bunker Hill resulted in the death of 140 colonists and 226 British soldiers, setting the stage for major combat throughout the colonies. American colonists lacked many necessary weapons. They had almost no gunpowder, few field cannons, and no warships. Yet, they fought on with the weapons at hand for 6 long years.

In the spring of 2020, American society has been shaken by the COVID-19 pandemic. Hospitals have been overrun with thousands of people infected with the disease. Some hospitals are breaking under the crush of intensely ill people filling up and spilling out of intensive care units. We are in a war, fighting a viral disease with a limited supply of weapons. We do not have access to the most powerful medical munitions: easily available rapid testing, proven antiviral medications, and an effective vaccine. Nevertheless, clinicians and patients are courageous, and we will continue the fight with the limited weapons we have until the pandemic is brought to an end.

Who is infected with SARS-CoV-2?

Rapid high-fidelity testing for SARS-CoV-2 nucleic acid sequences would be the best approach to identifying people with COVID-19 disease. At the beginning of the pandemic, testing was strictly rationed because of lack of reagents and test swabs. Clinicians were permitted to test only a minority of people who had symptoms. Asymptomatic individuals were not eligible to be tested. This terribly flawed approach to screening permitted a vast army of SARS-CoV-2–positive asymptomatic and mildly symptomatic people to circulate unchecked in the general population, infecting dozens of other people, some of whom developed moderate or severe disease. The Centers for Disease Control and Prevention (CDC) has reported on 7 independent clusters of COVID-19 disease, each of which appear to have been caused by one asymptomatic infected individual.⁶ Another cluster of COVID-19 disease from China appears to have been caused by one asymptomatic infected individual.⁷ Based on limited data, it appears that there may be a 1- to 3-day window where an individual with COVID-19 may be asymptomatic and able to infect others. I suspect that we will soon discover, based on testing for the presence of high-titre anti SARS-CoV-2 antibodies, that many people with no history of illness and people with mild respiratory symptoms had an undiagnosed COVID-19 infection.

As testing capacity expands we likely will be testing all women, including asymptomatic women, before they arrive at the hospital for childbirth or gynecologic surgery, as well as all inpatients and women with respiratory symptoms having an ambulatory encounter.

With expanded testing capability, some pregnant women who were symptomatic and tested positive for SARS-CoV-2 have had sequential long-term follow-up testing. A frequent observation is that over one to two weeks the viral symptoms resolve and the nasopharyngeal test becomes negative for SARS-CoV-2 on multiple sequential tests, only to become positive at a later date. The cause of the positive-negative-negative-positive test results is unknown, but it raises the possibility that once a person tests positive for SARS-CoV-2, they may be able to transmit the infection over many weeks, even after viral symptoms resolve.

Continue to: COVID-19: Respiratory droplet or aerosol transmission?

COVID-19: Respiratory droplet or aerosol transmission?

Respiratory droplets are large particles (> 5 µm in diameter) that tend to be pulled to the ground or furniture surfaces by gravity. Respiratory droplets do not circulate in the air for an extended period of time. Droplet nuclei are small particles less than 5 µm in diameter. These small particles may become aerosolized and float through the air for an extended period of time. The CDC and WHO believe that under ordinary conditions, SARS-CoV-2 is transmitted through respiratory droplets and contact routes.² In an analysis of more than 75,000 COVID-19 cases in China there were no reports of transmission by aerosolized airborne virus. Therefore, under ordinary conditions, surgical masks, face shields, gowns, and gloves provide a high level of protection from infection.⁸

In contrast to the WHO’s perspective, Dr. Harvey Fineberg, Chair of the National Academies of Sciences, Engineering, and Medicine’s Standing Committee on Emerging Infectious Diseases and 21st Century Health Threats, wrote a letter to the federal Office of Science and Technology Policy warning that normal breathing might generate aerosolization of the SARS-CoV-2 virus and result in airborne transmission.⁹ A report from the University of Nebraska Medical Center supports the concept of airborne transmission of SARS-CoV-2. In a study of 13 patients with COVID-19, room surfaces, toilet facilities, and air had evidence of viral contamination.¹⁰ The investigators concluded that disease spreads through respiratory droplets, person-to-person touch, contaminated surfaces, and airborne routes. Other investigators also have reported that aersolization of SARS-CoV-2 may occur.¹¹ Professional societies recommend that all medical staff caring for potential or confirmed COVID-19 patients should use personal protective equipment (PPE), including respirators (N95 respirators) when available. Importantly, all medical staff should be trained in and adhere to proper donning and doffing of PPE. The controversy about the modes of transmission of SARS-CoV-2 will continue, but as clinicians we need to work within the constraints of the equipment we have.

Certain medical procedures and devices are known to generate aerosolization of respiratory secretions. These procedures and devices include: bronchoscopy, intubation, extubation, cardiopulmonary resuscitation, nebulization, high-flow oxygen masks, and continuous- and bilevel-positive airway pressure devices. When aerosols are generated during the care of a patient with COVID-19, surgical masks are not sufficient protection against infection. When an aerosol is generated maximal protection of health care workers from viral transmission requires use of a negative-pressure room and an N95 respirator or powered air-purifying respirator (PAPR) device. However, negative-pressure rooms, N95 masks, and PAPRs are in very short supply or are unavailable in some health systems. We are lucky at our hospital that all of the labor rooms can be configured to operate in a negative-pressure mode, limiting potential airborne spread of the virus on the unit. Many hospitals restrict the use of N95 masks to anesthesiologists, leaving nurses, ObGyns, and surgical technicians without the best protective equipment, risking their health. As one action to reduce aerosolization of virus, obstetricians can markedly reduce the use of oxygen masks and nasal cannulas by laboring women.

Universal use of surgical masks and mouth-nose coverings

During the entire COVID-19 pandemic, PPE has been in short supply, including severe shortages of N95 masks, PAPRs, and in some health systems, surgical masks, gowns, eye protection, and face shields. Given the severe shortages, some clinicians have needed to conserve PPE, using the same PPE across multiple patient encounters and across multiple work shifts.

Given that the virus is transmitted by respiratory droplets and contaminated surfaces, use of face coverings, including surgical masks, face shields, and gloves is critically important. Scrupulous hand hygiene is a simple approach to reducing infection risk. In my health system, all employees are required to wear a surgical mask, all day every day, requiring distribution of 35,000 masks daily.¹² We also require every patient and visitor to our health care facilities to use a face mask. The purpose of the procedure or surgical mask is to prevent presymptomatic spread of COVID-19 from an asymptomatic health care worker to an uninfected patient or a colleague by reducing the transmission of respiratory droplets. Another benefit is to protect the uninfected health care worker from patients and colleagues who are infected and not yet diagnosed with COVID-19. The CDC now recommends that all people wear a mouth and nose covering when they are outside of their residence. America may become a nation where wearing masks in public becomes a routine practice. Since SARS-CoV-2 is transmitted by respiratory droplets, social distancing is an important preventive measure.

Continue to: Obstetric care...

Obstetric care

Can it be repeated too often? No. Containing COVID-19 disease requires social distancing, fastidious hand hygiene, and using a mask that covers the mouth and nose.

Pregnant women should be advised to assiduously practice social distancing and to wear a face covering or mask in public. Hand hygiene should be emphasized. Pregnant women with children should be advised to not allow their children to play with non‒cohabiting children because children may be asymptomatic vectors for COVID-19.

Pregnant health care workers should stop face-to-face contact with patients after 36 weeks’ gestation to avoid a late pregnancy infection that might cause the mother to be separated from her newborn. Based on data currently available, pregnancy in the absence of another risk factor is not a major risk factor for developing severe COVID-19 disease.¹³

Hyperthermia is a common feature of COVID-19. Acetaminophen is recommended treatment to suppress pyrexia during pregnancy.

The COVID-19 pandemic has transformed prenatal care from a series of face-to-face encounters at a health care facility to telemedicine either by telephone or a videoconferencing portal. Many factors contributed to the rapid switch to telemedicine, including orders by governors to restrict unnecessary travel, patients’ fear of contracting COVID-19 at their clinicians’ offices, clinicians’ fear of contracting COVID-19 from patients, and insurers’ rapid implementation of policies to pay for telemedicine visits. Most prenatal visits can be provided through telemedicine as long as the patient has a home blood pressure cuff and can reliably use the instrument. In-person visits may be required for blood testing, ultrasound assessment, anti-Rh immunoglobulin administration, and group B streptococcal infection screening. One regimen is to limit in-person prenatal visits to encounters at 12, 20, 28, and 36 weeks’ gestation when blood testing and ultrasound examinations are needed. The postpartum visit also may be conducted using telemedicine.

Pregnant women with COVID-19 and pneumonia are reported to have high rates of preterm birth less than 37 weeks (41%) and preterm prelabor rupture of membranes (19%).¹⁴

The rate of vertical transmission from mother to fetus is probably very low (<1%).¹⁵ However, based on serological studies, an occasional newborn has been reported to have IgM and IgG antibodies to the SARS-CoV-2 nucleoprotein at birth.^16,17

Pregnant women should be consistently and regularly screened for symptoms of an upper respiratory infection, including: fever, new cough, new runny nose or nasal congestion, new sore throat, shortness of breath, muscle aches, and anosmia. A report of any of these symptoms should result in nucleic acid testing of a nasal swab for SARS-CoV-2 of all pregnant women. Given limited testing resources, however, symptomatic pregnant women with the following characteristics should be prioritized for testing: if the woman is more than 36 weeks pregnant, intrapartum, or in the hospital after delivery. Ambulatory pregnant women with symptoms who do not need medical care should quarantine themselves at home, if possible, or at another secure location away from their families. In some regions, testing of ambulatory patients with upper respiratory symptoms is limited.

All women scheduled for induction or cesarean delivery (CD) and their support person should have a symptom screen 24 to 48 hours before arrival to the hospital and should be rescreened prior to entry to labor and delivery. In this situation if the pregnant woman screens positive, she should be tested for SARS-CoV-2, and if the test result is positive, the scheduled induction and CD should be rescheduled, if possible. All hospitalized women and their support persons should be screened for symptoms daily. If the pregnant woman screens positive she should have a nucleic acid test for SARS-CoV-2. If the support person screens positive, he or she should be sent home.

Systemic glucocorticoids may worsen the course of COVID-19. For pregnant women with COVID-19 disease, betamethasone administration should be limited to women at high risk for preterm delivery within 7 days and only given to women between 23 weeks to 33 weeks 6 days of gestation. Women at risk for preterm delivery at 34 weeks to 36 weeks and 6 days of gestation should not be given betamethasone.

If cervical ripening is required, outpatient regimens should be prioritized.

One support person plays an important role in optimal labor outcome and should be permitted at the hospital. All support persons should wear a surgical or procedure mask.

Nitrous oxide for labor anesthesia should not be used during the pandemic because it might cause aerosolization of respiratory secretions, endangering health care workers. Neuraxial anesthesia is an optimal approach to labor anesthesia.

Labor management and timing of delivery does not need to be altered during the COVID-19 pandemic. However, pregnant women with moderate or severe COVID-19 disease who are not improving may have a modest improvement in respiratory function if they are delivered preterm.

At the beginning of the COVID pandemic, the CDC recommended separation of a COVID-positive mother and her newborn until the mother’s respiratory symptoms resolved. However, the CDC now recommends that, for a COVID-positive mother, joint decision-making should be used to decide whether to support the baby rooming-in with the mother or to practice separation of mother and baby at birth to reduce the risk for postnatal infection from mother to newborn. There is no evidence that breast milk contains virus that can cause an infection. One option is for the mother who recently tested positive for SARS-CoV-2 to provide newborn nutrition with expressed breast milk.

Pregnant women with COVID-19 may be at increased risk for venous thromboembolism. Some experts recommend that hospitalized pregnant women and postpartum women with COVID-19 receive thromboembolism prophylaxis.
The Chinese Centers for Disease Control and Prevention described a classification system for COVID-19 disease, including 3 categories¹⁸:

• mild: no dyspnea, no pneumonia, or mild pneumonia
• severe: dyspnea, respiratory frequency ≥ 30 breaths per minute, blood oxygen saturation ≤ 93%, lung infiltrates > 50% within 48 hours of onset of symptoms
• critical: respiratory failure, septic shock, or multiple organ dysfunction or failure.

Among 72,314 cases in China, 81% had mild disease, 14% had severe disease, and 5% had critical disease. In a report of 118 pregnant women in China, 92% of the women had mild disease; 8% had severe disease (hypoxemia), one of whom developed critical disease requiring mechanical ventilation.¹⁹ In this cohort, the most common presenting symptoms were fever (75%), cough (73%), chest tightness (18%), fatigue (17%), shortness of breath (7%), diarrhea (7%), and headache (6%). Lymphopenia was present in 44% of the women.

Severe and critical COVID-19 disease are associated with elevations in D-dimer, C-reactive protein, troponin, ferritin, and creatine phosphokinase levels. These markers return to the normal range with resolution of disease.

Continue to: Gynecologic care...

Gynecologic care

Gynecologists are highly impacted by the COVID-19 pandemic. Most state governments have requested that all elective surgery be suspended for the duration of the pandemic in order to redeploy health resources to the care of COVID-19 patients. Except for high-priority gynecologic surgery, including cancer surgery, treatment of heavy vaginal bleeding, and surgical care of ectopic pregnancy and miscarriage, most gynecologic surgery has ceased.

All office visits for routine gynecologic care have been suspended. Video and telephone visits can be used for contraceptive counseling and prescribing and for managing problems associated with the menopause, endometriosis, and vaginitis. Cervical cancer screening can be deferred for 3 to 6 months, depending on patient risk factors.

Medicines to treat COVID-19 infections

There are many highly effective medicines to manage HIV infection and medicines that cure hepatitis C. There is an urgent need to develop precision medicines to treat this disease. Early in the pandemic some experts thought that hydroxychloroquine might be helpful in the treatment of COVID-19 disease. But recent evidence suggests that hydroxychloroquine is probably not an effective treatment. As the pandemic has evolved, there is evidence that remdesivir may have modest efficacy in treating COVID-19 disease.²⁰ Remdesivir has received emergency-use authorization by the FDA to treat COVID-19 infection.

Remdesivir

Based on expert opinion, in the absence of high-quality clinical trial evidence, our current practice is to offer pregnant women with severe or critical COVID-19 disease treatment with remdesivir.

Remdesivir (Gilead Sciences, Inc) is a nucleoside analog that inhibits RNA synthesis. A dose regimen for remdesivir is a 200-mg loading dose given intravenously, followed by 100 mg daily given intravenously for 5 to 10 days. Remdesivir may cause elevation of hepatic enzymes. Remdesivir has been administered to a few pregnant women to treat Ebola and Marburg virus disease.²¹

Experts in infectious disease are important resources for determining optimal medication regimens for the treatment of COVID-19 disease in pregnant women.

Continue to: Convalescent serum...

Convalescent serum

There are no high-quality studies demonstrating the efficacy of convalescent serum for treatment of COVID-19. A small case series suggests that there may be modest benefit to treatment of people with severe COVID-19 disease with convalescent serum.²²

Testing for anti-SARS-CoV-2 IgM and IgG antibodies

We may have a serious problem in our current approach to detecting COVID-19 disease. Based on measurement of IgM and IgG antibodies to SARS-CoV-2 nucleocapsid protein, our current nucleic acid tests for SARS-CoV-2 may detect less than 80% of infections early in the course of disease. In two studies of IgM and IgG antibodies to the SARS-CoV-2 nucleocapsid protein, a single polymerase chain reaction test for SARS-CoV-2 had less than a 60% sensitivity for detecting the virus.^23,24 During the second week of COVID-19 illness, IgM or IgG antibodies were detected in greater than 89% of infected patients.²³ Severe disease resulted in high concentrations of antibody.

When testing for IgM and IgG antibodies is widely available, it may become an option to test all health care workers. This will permit the assignment of those health care workers with the highest levels of antibody to frontline duties with COVID-19 patients during the next disease outbreak, likely to occur at some point during the next 12 months.

A COVID-19 vaccine

Dozens of research teams, including pharmaceutical and biotechnology companies and many academic laboratories, are working on developing and testing vaccines to prevent COVID-19 disease. An effective vaccine would reduce the number of people who develop severe disease during the next outbreak, reducing deaths, avoiding a shutdown of the country, and allowing the health systems to function normally. A vaccine is unlikely to be widely available until sometime early in 2021.

Facing COVID-19 well-being and mental health

SARS-CoV-2, like all viral particles, is incredibly small. Remarkably, it has changed permanently life on earth. COVID-19 is affecting our physical health, psychological well-being, economics, and patterns of social interaction. As clinicians it is difficult to face a viral enemy that cannot be stopped from causing the death of more than 100,000 people, including some of our clinical colleagues, within a short period of time.

Dr. Russ Harris, an Australian acceptance commitment therapist, has written an ebook (http://www.commpsych.com/wp-content/uploads/FACE_COVID-1.pdf) and produced an animated YouTube video, titled FACE COVID (https://www.youtube.com/watch?v=BmvNCdpHUYM), which describes a systematic approach to deal with the challenge of the pandemic. He advises a 9-step approach:

• F—focus on what is in your control
• A—acknowledge your thoughts and feelings
• C—come back to a focus on your body
• E—engage in what you are doing
• C—commit to acting effectively based on your core values
• O—opening up to difficult feelings and being kind to yourself and others
• V—values should guide your actions
• I—identify resources for help, assistance, support, and advice
• D—disinfect and practice social distancing.

This war will come to an end

During the American Revolution, colonists faced housing and food insecurity, epidemics of typhus and smallpox, traumatic injury including amputation of limbs, and a complete disruption of normal life activities. They persevered and, against the odds, successfully concluded the war. Unlike the colonists, who did not know if their conflict would end with success or failure, we clinicians know that the COVID-19 pandemic will end. We also know that eventually the global community of clinicians will develop and deploy the effective weapons we need to prevent a recurrence of this traumatic pandemic: population-wide testing for both the SARS-CoV-2 virus and serologic testing for IgG and IgM antibodies to the virus, effective antiviral medications, and a potent vaccine. ●

On June 17, 1775, American colonists, defending a forward redoubt on Breed’s Hill, ran out of gunpowder, and their position was overrun by British troops. The Battle of Bunker Hill resulted in the death of 140 colonists and 226 British soldiers, setting the stage for major combat throughout the colonies. American colonists lacked many necessary weapons. They had almost no gunpowder, few field cannons, and no warships. Yet, they fought on with the weapons at hand for 6 long years.

In the spring of 2020, American society has been shaken by the COVID-19 pandemic. Hospitals have been overrun with thousands of people infected with the disease. Some hospitals are breaking under the crush of intensely ill people filling up and spilling out of intensive care units. We are in a war, fighting a viral disease with a limited supply of weapons. We do not have access to the most powerful medical munitions: easily available rapid testing, proven antiviral medications, and an effective vaccine. Nevertheless, clinicians and patients are courageous, and we will continue the fight with the limited weapons we have until the pandemic is brought to an end.

Who is infected with SARS-CoV-2?

Rapid high-fidelity testing for SARS-CoV-2 nucleic acid sequences would be the best approach to identifying people with COVID-19 disease. At the beginning of the pandemic, testing was strictly rationed because of lack of reagents and test swabs. Clinicians were permitted to test only a minority of people who had symptoms. Asymptomatic individuals were not eligible to be tested. This terribly flawed approach to screening permitted a vast army of SARS-CoV-2–positive asymptomatic and mildly symptomatic people to circulate unchecked in the general population, infecting dozens of other people, some of whom developed moderate or severe disease. The Centers for Disease Control and Prevention (CDC) has reported on 7 independent clusters of COVID-19 disease, each of which appear to have been caused by one asymptomatic infected individual.⁶ Another cluster of COVID-19 disease from China appears to have been caused by one asymptomatic infected individual.⁷ Based on limited data, it appears that there may be a 1- to 3-day window where an individual with COVID-19 may be asymptomatic and able to infect others. I suspect that we will soon discover, based on testing for the presence of high-titre anti SARS-CoV-2 antibodies, that many people with no history of illness and people with mild respiratory symptoms had an undiagnosed COVID-19 infection.

As testing capacity expands we likely will be testing all women, including asymptomatic women, before they arrive at the hospital for childbirth or gynecologic surgery, as well as all inpatients and women with respiratory symptoms having an ambulatory encounter.

With expanded testing capability, some pregnant women who were symptomatic and tested positive for SARS-CoV-2 have had sequential long-term follow-up testing. A frequent observation is that over one to two weeks the viral symptoms resolve and the nasopharyngeal test becomes negative for SARS-CoV-2 on multiple sequential tests, only to become positive at a later date. The cause of the positive-negative-negative-positive test results is unknown, but it raises the possibility that once a person tests positive for SARS-CoV-2, they may be able to transmit the infection over many weeks, even after viral symptoms resolve.

Continue to: COVID-19: Respiratory droplet or aerosol transmission?

COVID-19: Respiratory droplet or aerosol transmission?

Respiratory droplets are large particles (> 5 µm in diameter) that tend to be pulled to the ground or furniture surfaces by gravity. Respiratory droplets do not circulate in the air for an extended period of time. Droplet nuclei are small particles less than 5 µm in diameter. These small particles may become aerosolized and float through the air for an extended period of time. The CDC and WHO believe that under ordinary conditions, SARS-CoV-2 is transmitted through respiratory droplets and contact routes.² In an analysis of more than 75,000 COVID-19 cases in China there were no reports of transmission by aerosolized airborne virus. Therefore, under ordinary conditions, surgical masks, face shields, gowns, and gloves provide a high level of protection from infection.⁸

In contrast to the WHO’s perspective, Dr. Harvey Fineberg, Chair of the National Academies of Sciences, Engineering, and Medicine’s Standing Committee on Emerging Infectious Diseases and 21st Century Health Threats, wrote a letter to the federal Office of Science and Technology Policy warning that normal breathing might generate aerosolization of the SARS-CoV-2 virus and result in airborne transmission.⁹ A report from the University of Nebraska Medical Center supports the concept of airborne transmission of SARS-CoV-2. In a study of 13 patients with COVID-19, room surfaces, toilet facilities, and air had evidence of viral contamination.¹⁰ The investigators concluded that disease spreads through respiratory droplets, person-to-person touch, contaminated surfaces, and airborne routes. Other investigators also have reported that aersolization of SARS-CoV-2 may occur.¹¹ Professional societies recommend that all medical staff caring for potential or confirmed COVID-19 patients should use personal protective equipment (PPE), including respirators (N95 respirators) when available. Importantly, all medical staff should be trained in and adhere to proper donning and doffing of PPE. The controversy about the modes of transmission of SARS-CoV-2 will continue, but as clinicians we need to work within the constraints of the equipment we have.

Certain medical procedures and devices are known to generate aerosolization of respiratory secretions. These procedures and devices include: bronchoscopy, intubation, extubation, cardiopulmonary resuscitation, nebulization, high-flow oxygen masks, and continuous- and bilevel-positive airway pressure devices. When aerosols are generated during the care of a patient with COVID-19, surgical masks are not sufficient protection against infection. When an aerosol is generated maximal protection of health care workers from viral transmission requires use of a negative-pressure room and an N95 respirator or powered air-purifying respirator (PAPR) device. However, negative-pressure rooms, N95 masks, and PAPRs are in very short supply or are unavailable in some health systems. We are lucky at our hospital that all of the labor rooms can be configured to operate in a negative-pressure mode, limiting potential airborne spread of the virus on the unit. Many hospitals restrict the use of N95 masks to anesthesiologists, leaving nurses, ObGyns, and surgical technicians without the best protective equipment, risking their health. As one action to reduce aerosolization of virus, obstetricians can markedly reduce the use of oxygen masks and nasal cannulas by laboring women.

Universal use of surgical masks and mouth-nose coverings

During the entire COVID-19 pandemic, PPE has been in short supply, including severe shortages of N95 masks, PAPRs, and in some health systems, surgical masks, gowns, eye protection, and face shields. Given the severe shortages, some clinicians have needed to conserve PPE, using the same PPE across multiple patient encounters and across multiple work shifts.

Given that the virus is transmitted by respiratory droplets and contaminated surfaces, use of face coverings, including surgical masks, face shields, and gloves is critically important. Scrupulous hand hygiene is a simple approach to reducing infection risk. In my health system, all employees are required to wear a surgical mask, all day every day, requiring distribution of 35,000 masks daily.¹² We also require every patient and visitor to our health care facilities to use a face mask. The purpose of the procedure or surgical mask is to prevent presymptomatic spread of COVID-19 from an asymptomatic health care worker to an uninfected patient or a colleague by reducing the transmission of respiratory droplets. Another benefit is to protect the uninfected health care worker from patients and colleagues who are infected and not yet diagnosed with COVID-19. The CDC now recommends that all people wear a mouth and nose covering when they are outside of their residence. America may become a nation where wearing masks in public becomes a routine practice. Since SARS-CoV-2 is transmitted by respiratory droplets, social distancing is an important preventive measure.

Continue to: Obstetric care...

Obstetric care

Can it be repeated too often? No. Containing COVID-19 disease requires social distancing, fastidious hand hygiene, and using a mask that covers the mouth and nose.

Pregnant women should be advised to assiduously practice social distancing and to wear a face covering or mask in public. Hand hygiene should be emphasized. Pregnant women with children should be advised to not allow their children to play with non‒cohabiting children because children may be asymptomatic vectors for COVID-19.

Pregnant health care workers should stop face-to-face contact with patients after 36 weeks’ gestation to avoid a late pregnancy infection that might cause the mother to be separated from her newborn. Based on data currently available, pregnancy in the absence of another risk factor is not a major risk factor for developing severe COVID-19 disease.¹³

Hyperthermia is a common feature of COVID-19. Acetaminophen is recommended treatment to suppress pyrexia during pregnancy.

The COVID-19 pandemic has transformed prenatal care from a series of face-to-face encounters at a health care facility to telemedicine either by telephone or a videoconferencing portal. Many factors contributed to the rapid switch to telemedicine, including orders by governors to restrict unnecessary travel, patients’ fear of contracting COVID-19 at their clinicians’ offices, clinicians’ fear of contracting COVID-19 from patients, and insurers’ rapid implementation of policies to pay for telemedicine visits. Most prenatal visits can be provided through telemedicine as long as the patient has a home blood pressure cuff and can reliably use the instrument. In-person visits may be required for blood testing, ultrasound assessment, anti-Rh immunoglobulin administration, and group B streptococcal infection screening. One regimen is to limit in-person prenatal visits to encounters at 12, 20, 28, and 36 weeks’ gestation when blood testing and ultrasound examinations are needed. The postpartum visit also may be conducted using telemedicine.

Pregnant women with COVID-19 and pneumonia are reported to have high rates of preterm birth less than 37 weeks (41%) and preterm prelabor rupture of membranes (19%).¹⁴

The rate of vertical transmission from mother to fetus is probably very low (<1%).¹⁵ However, based on serological studies, an occasional newborn has been reported to have IgM and IgG antibodies to the SARS-CoV-2 nucleoprotein at birth.^16,17

Pregnant women should be consistently and regularly screened for symptoms of an upper respiratory infection, including: fever, new cough, new runny nose or nasal congestion, new sore throat, shortness of breath, muscle aches, and anosmia. A report of any of these symptoms should result in nucleic acid testing of a nasal swab for SARS-CoV-2 of all pregnant women. Given limited testing resources, however, symptomatic pregnant women with the following characteristics should be prioritized for testing: if the woman is more than 36 weeks pregnant, intrapartum, or in the hospital after delivery. Ambulatory pregnant women with symptoms who do not need medical care should quarantine themselves at home, if possible, or at another secure location away from their families. In some regions, testing of ambulatory patients with upper respiratory symptoms is limited.

All women scheduled for induction or cesarean delivery (CD) and their support person should have a symptom screen 24 to 48 hours before arrival to the hospital and should be rescreened prior to entry to labor and delivery. In this situation if the pregnant woman screens positive, she should be tested for SARS-CoV-2, and if the test result is positive, the scheduled induction and CD should be rescheduled, if possible. All hospitalized women and their support persons should be screened for symptoms daily. If the pregnant woman screens positive she should have a nucleic acid test for SARS-CoV-2. If the support person screens positive, he or she should be sent home.

Systemic glucocorticoids may worsen the course of COVID-19. For pregnant women with COVID-19 disease, betamethasone administration should be limited to women at high risk for preterm delivery within 7 days and only given to women between 23 weeks to 33 weeks 6 days of gestation. Women at risk for preterm delivery at 34 weeks to 36 weeks and 6 days of gestation should not be given betamethasone.

If cervical ripening is required, outpatient regimens should be prioritized.

One support person plays an important role in optimal labor outcome and should be permitted at the hospital. All support persons should wear a surgical or procedure mask.

Nitrous oxide for labor anesthesia should not be used during the pandemic because it might cause aerosolization of respiratory secretions, endangering health care workers. Neuraxial anesthesia is an optimal approach to labor anesthesia.

Labor management and timing of delivery does not need to be altered during the COVID-19 pandemic. However, pregnant women with moderate or severe COVID-19 disease who are not improving may have a modest improvement in respiratory function if they are delivered preterm.

At the beginning of the COVID pandemic, the CDC recommended separation of a COVID-positive mother and her newborn until the mother’s respiratory symptoms resolved. However, the CDC now recommends that, for a COVID-positive mother, joint decision-making should be used to decide whether to support the baby rooming-in with the mother or to practice separation of mother and baby at birth to reduce the risk for postnatal infection from mother to newborn. There is no evidence that breast milk contains virus that can cause an infection. One option is for the mother who recently tested positive for SARS-CoV-2 to provide newborn nutrition with expressed breast milk.

Pregnant women with COVID-19 may be at increased risk for venous thromboembolism. Some experts recommend that hospitalized pregnant women and postpartum women with COVID-19 receive thromboembolism prophylaxis.
The Chinese Centers for Disease Control and Prevention described a classification system for COVID-19 disease, including 3 categories¹⁸:

• mild: no dyspnea, no pneumonia, or mild pneumonia
• severe: dyspnea, respiratory frequency ≥ 30 breaths per minute, blood oxygen saturation ≤ 93%, lung infiltrates > 50% within 48 hours of onset of symptoms
• critical: respiratory failure, septic shock, or multiple organ dysfunction or failure.

Among 72,314 cases in China, 81% had mild disease, 14% had severe disease, and 5% had critical disease. In a report of 118 pregnant women in China, 92% of the women had mild disease; 8% had severe disease (hypoxemia), one of whom developed critical disease requiring mechanical ventilation.¹⁹ In this cohort, the most common presenting symptoms were fever (75%), cough (73%), chest tightness (18%), fatigue (17%), shortness of breath (7%), diarrhea (7%), and headache (6%). Lymphopenia was present in 44% of the women.

Severe and critical COVID-19 disease are associated with elevations in D-dimer, C-reactive protein, troponin, ferritin, and creatine phosphokinase levels. These markers return to the normal range with resolution of disease.

Continue to: Gynecologic care...

Gynecologic care

Gynecologists are highly impacted by the COVID-19 pandemic. Most state governments have requested that all elective surgery be suspended for the duration of the pandemic in order to redeploy health resources to the care of COVID-19 patients. Except for high-priority gynecologic surgery, including cancer surgery, treatment of heavy vaginal bleeding, and surgical care of ectopic pregnancy and miscarriage, most gynecologic surgery has ceased.

All office visits for routine gynecologic care have been suspended. Video and telephone visits can be used for contraceptive counseling and prescribing and for managing problems associated with the menopause, endometriosis, and vaginitis. Cervical cancer screening can be deferred for 3 to 6 months, depending on patient risk factors.

Medicines to treat COVID-19 infections

There are many highly effective medicines to manage HIV infection and medicines that cure hepatitis C. There is an urgent need to develop precision medicines to treat this disease. Early in the pandemic some experts thought that hydroxychloroquine might be helpful in the treatment of COVID-19 disease. But recent evidence suggests that hydroxychloroquine is probably not an effective treatment. As the pandemic has evolved, there is evidence that remdesivir may have modest efficacy in treating COVID-19 disease.²⁰ Remdesivir has received emergency-use authorization by the FDA to treat COVID-19 infection.

Remdesivir

Based on expert opinion, in the absence of high-quality clinical trial evidence, our current practice is to offer pregnant women with severe or critical COVID-19 disease treatment with remdesivir.

Remdesivir (Gilead Sciences, Inc) is a nucleoside analog that inhibits RNA synthesis. A dose regimen for remdesivir is a 200-mg loading dose given intravenously, followed by 100 mg daily given intravenously for 5 to 10 days. Remdesivir may cause elevation of hepatic enzymes. Remdesivir has been administered to a few pregnant women to treat Ebola and Marburg virus disease.²¹

Experts in infectious disease are important resources for determining optimal medication regimens for the treatment of COVID-19 disease in pregnant women.

Continue to: Convalescent serum...

Convalescent serum

There are no high-quality studies demonstrating the efficacy of convalescent serum for treatment of COVID-19. A small case series suggests that there may be modest benefit to treatment of people with severe COVID-19 disease with convalescent serum.²²

Testing for anti-SARS-CoV-2 IgM and IgG antibodies

We may have a serious problem in our current approach to detecting COVID-19 disease. Based on measurement of IgM and IgG antibodies to SARS-CoV-2 nucleocapsid protein, our current nucleic acid tests for SARS-CoV-2 may detect less than 80% of infections early in the course of disease. In two studies of IgM and IgG antibodies to the SARS-CoV-2 nucleocapsid protein, a single polymerase chain reaction test for SARS-CoV-2 had less than a 60% sensitivity for detecting the virus.^23,24 During the second week of COVID-19 illness, IgM or IgG antibodies were detected in greater than 89% of infected patients.²³ Severe disease resulted in high concentrations of antibody.

When testing for IgM and IgG antibodies is widely available, it may become an option to test all health care workers. This will permit the assignment of those health care workers with the highest levels of antibody to frontline duties with COVID-19 patients during the next disease outbreak, likely to occur at some point during the next 12 months.

A COVID-19 vaccine

Dozens of research teams, including pharmaceutical and biotechnology companies and many academic laboratories, are working on developing and testing vaccines to prevent COVID-19 disease. An effective vaccine would reduce the number of people who develop severe disease during the next outbreak, reducing deaths, avoiding a shutdown of the country, and allowing the health systems to function normally. A vaccine is unlikely to be widely available until sometime early in 2021.

Facing COVID-19 well-being and mental health

SARS-CoV-2, like all viral particles, is incredibly small. Remarkably, it has changed permanently life on earth. COVID-19 is affecting our physical health, psychological well-being, economics, and patterns of social interaction. As clinicians it is difficult to face a viral enemy that cannot be stopped from causing the death of more than 100,000 people, including some of our clinical colleagues, within a short period of time.

Dr. Russ Harris, an Australian acceptance commitment therapist, has written an ebook (http://www.commpsych.com/wp-content/uploads/FACE_COVID-1.pdf) and produced an animated YouTube video, titled FACE COVID (https://www.youtube.com/watch?v=BmvNCdpHUYM), which describes a systematic approach to deal with the challenge of the pandemic. He advises a 9-step approach:

• F—focus on what is in your control
• A—acknowledge your thoughts and feelings
• C—come back to a focus on your body
• E—engage in what you are doing
• C—commit to acting effectively based on your core values
• O—opening up to difficult feelings and being kind to yourself and others
• V—values should guide your actions
• I—identify resources for help, assistance, support, and advice
• D—disinfect and practice social distancing.

This war will come to an end

During the American Revolution, colonists faced housing and food insecurity, epidemics of typhus and smallpox, traumatic injury including amputation of limbs, and a complete disruption of normal life activities. They persevered and, against the odds, successfully concluded the war. Unlike the colonists, who did not know if their conflict would end with success or failure, we clinicians know that the COVID-19 pandemic will end. We also know that eventually the global community of clinicians will develop and deploy the effective weapons we need to prevent a recurrence of this traumatic pandemic: population-wide testing for both the SARS-CoV-2 virus and serologic testing for IgG and IgM antibodies to the virus, effective antiviral medications, and a potent vaccine. ●

The Food and Drug Administration has issued an Emergency Use Authorization (EUA) for the VentFree Respiratory Muscle Stimulator in order to potentially reduce the number of days adult patients, including those with COVID-19, require mechanical ventilation, according to a press release from Liberate Medical.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

In comparison with mechanical ventilation, which is invasive and commonly weakens the breathing muscles, the VentFree system uses noninvasive neuromuscular electrical stimulation to contract the abdominal wall muscles in synchrony with exhalation during mechanical ventilation, according to the press release. This allows patients to begin treatment during the early stages of ventilation while they are sedated and to continue until they are weaned off of ventilation.

A pair of pilot randomized, controlled studies, completed in Europe and Australia, showed that VentFree helped to reduce ventilation duration and ICU length of stay, compared with placebo stimulation. The FDA granted VentFree Breakthrough Device status in 2019.

“We are grateful to the FDA for recognizing the potential of VentFree and feel privileged to have the opportunity to help patients on mechanical ventilation during the COVID-19 pandemic,” Angus McLachlan PhD, cofounder and CEO of Liberate Medical, said in the press release.

VentFree has been authorized for use only for the duration of the current COVID-19 emergency, as it has not yet been approved or cleared for usage by primary care providers.

lfranki@mdedge.com

The Food and Drug Administration has issued an Emergency Use Authorization (EUA) for the VentFree Respiratory Muscle Stimulator in order to potentially reduce the number of days adult patients, including those with COVID-19, require mechanical ventilation, according to a press release from Liberate Medical.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

In comparison with mechanical ventilation, which is invasive and commonly weakens the breathing muscles, the VentFree system uses noninvasive neuromuscular electrical stimulation to contract the abdominal wall muscles in synchrony with exhalation during mechanical ventilation, according to the press release. This allows patients to begin treatment during the early stages of ventilation while they are sedated and to continue until they are weaned off of ventilation.

A pair of pilot randomized, controlled studies, completed in Europe and Australia, showed that VentFree helped to reduce ventilation duration and ICU length of stay, compared with placebo stimulation. The FDA granted VentFree Breakthrough Device status in 2019.

“We are grateful to the FDA for recognizing the potential of VentFree and feel privileged to have the opportunity to help patients on mechanical ventilation during the COVID-19 pandemic,” Angus McLachlan PhD, cofounder and CEO of Liberate Medical, said in the press release.

VentFree has been authorized for use only for the duration of the current COVID-19 emergency, as it has not yet been approved or cleared for usage by primary care providers.

lfranki@mdedge.com

The Food and Drug Administration has issued an Emergency Use Authorization (EUA) for the VentFree Respiratory Muscle Stimulator in order to potentially reduce the number of days adult patients, including those with COVID-19, require mechanical ventilation, according to a press release from Liberate Medical.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

In comparison with mechanical ventilation, which is invasive and commonly weakens the breathing muscles, the VentFree system uses noninvasive neuromuscular electrical stimulation to contract the abdominal wall muscles in synchrony with exhalation during mechanical ventilation, according to the press release. This allows patients to begin treatment during the early stages of ventilation while they are sedated and to continue until they are weaned off of ventilation.

A pair of pilot randomized, controlled studies, completed in Europe and Australia, showed that VentFree helped to reduce ventilation duration and ICU length of stay, compared with placebo stimulation. The FDA granted VentFree Breakthrough Device status in 2019.

“We are grateful to the FDA for recognizing the potential of VentFree and feel privileged to have the opportunity to help patients on mechanical ventilation during the COVID-19 pandemic,” Angus McLachlan PhD, cofounder and CEO of Liberate Medical, said in the press release.

VentFree has been authorized for use only for the duration of the current COVID-19 emergency, as it has not yet been approved or cleared for usage by primary care providers.

lfranki@mdedge.com